Health Technology Assessment 2006; Vol. 10: No.

16
Health Technology Assessment 2006; Vol. 10: No. 16

Systematic review of the effectiveness

and cost-effectiveness of HealOzone
for the treatment of occlusal pit/fissure
caries and root caries

HealOzone for the treatment of occlusal pit/fissure caries and root caries
M Brazzelli, L McKenzie, S Fielding, C Fraser,
J Clarkson, M Kilonzo and N Waugh
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Systematic review of the effectiveness
and cost-effectiveness of HealOzone
for the treatment of occlusal pit/fissure
caries and root caries

M Brazzelli,1* L McKenzie,2 S Fielding,3 C Fraser,1

J Clarkson,4 M Kilonzo2 and N Waugh3
1
Health Services Research Unit, Institute of Applied Health Sciences,
University of Aberdeen, UK
2
Health Economics Research Unit, Institute of Applied Health Sciences,
University of Aberdeen, UK
3
Department of Public Health, Institute of Applied Health Sciences,
University of Aberdeen, UK
4
Dental Health Services Research Unit, MacKenzie Building, Dundee, UK

* Corresponding author. Current affiliation: Department of Clinical Neurosciences,

University of Edinburgh, Western General Hospital, UK

Declared competing interests of authors: none

Published May 2006

This report should be referenced as follows:

Brazzelli M, McKenzie L, Fielding S, Fraser C, Clarkson J, Kilonzo M, et al. Systematic

review of the effectiveness and cost-effectiveness of HealOzone for the treatment of
occlusal pit/fissure caries and root caries. Health Technol Assess 2006;10(16).

Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE,

Excerpta Medica/EMBASE and Science Citation Index Expanded (SciSearch) and
Current Contents/Clinical Medicine.
 NHS R&D HTA Programme

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 Health Technology Assessment 2006; Vol. 10: No. 16

Abstract
Systematic review of the effectiveness and cost-effectiveness of
HealOzone for the treatment of occlusal pit/fissure caries and
root caries
M Brazzelli,1* L McKenzie,2 S Fielding,3 C Fraser,1 J Clarkson,4 M Kilonzo2
and N Waugh3
1
Health Services Research Unit, Institute of Applied Health Sciences, University of Aberdeen, UK
2
Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, UK
3
Department of Public Health, Institute of Applied Health Sciences, University of Aberdeen, UK
4
Dental Health Services Research Unit, MacKenzie Building, Dundee, UK
* Corresponding author. Current affiliation: Department of Clinical Neurosciences, University of Edinburgh,
Western General Hospital, UK

Objectives: To assess the effectiveness and cost-
effectiveness of HealOzone (CurOzone USA Inc.,
Ontario, Canada) for the management of pit and fissure
caries, and root caries. The complete HealOzone
procedure involves the direct application of ozone gas
to the caries lesion on the tooth surface, the use of a
remineralising solution immediately after application of
ozone and the supply of a patient kit, which consists
of toothpaste, oral rinse and oral spray all containing
fluoride.
Data sources: Electronic databases up to May 2004
(except Conference Papers Index, which were
searched up to May 2002).
Review methods: A systematic review of the
effectiveness of HealOzone for the management of
tooth decay was carried out. A systematic review of
existing economic evaluations of ozone for dental caries
was also planned but no suitable studies were
identified. The economic evaluation included in the
industry submission was critically appraised and
summarised. A Markov model was constructed to
explore possible cost-effectiveness aspects of
HealOzone in addition to current management of
dental caries.
Results: Five full-text reports and five studies
published as abstracts met the inclusion criteria. The
five full-text reports consisted of two randomised
controlled trials (RCTs) assessing the use of HealOzone
for the management of primary root caries and two
doctoral theses of three unpublished randomised trials
assessing the use of HealOzone for the management of
occlusal caries. Of the abstracts, four assessed the
effects of HealOzone for the management of occlusal
caries and one the effects of HealOzone for the
management of root caries. Overall, the quality of the
studies was modest, with many important
methodological aspects not reported (e.g. concealment
of allocation, blinding procedures, compliance of
patients with home treatment). In particular, there
were some concerns about the choice of statistical
analyses. In most of the full-text studies analyses were
undertaken at lesion level, ignoring the clustering of
lesions within patients. The nature of the
methodological concerns was sufficient to raise doubts
about the validity of the included studies findings.
A quantitative synthesis of results was deemed
inappropriate. On the whole, there is not enough
evidence from published RCTs on which to judge the
effectiveness of ozone for the management of both
occlusal and root caries. The perspective adopted for
the study was that of the NHS and Personal Social
Services. The analysis, carried out over a 5-year
period, indicated that treatment using current
management plus HealOzone cost more than current
management alone for non-cavitated pit and fissure
caries (40.49 versus 24.78), but cost less for non-
cavitated root caries (14.63 versus 21.45). Given
the limitations of the calculations these figures should
be regarded as illustrative, not definitive. It was not
possible to measure health benefits in terms of
quality-adjusted life-years, due to uncertainties around
the evidence of clinical effectiveness, and to the fact
that the adverse events avoided are transient (e.g. pain
from injection of local anaesthetic, fear of the drill).
One-way sensitivity analysis was applied to the model.
However, owing to the limitations of the economic iii

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 Abstract
analysis, this should be regarded as merely speculative.
For non-cavitated pit and fissure caries, the HealOzone
option was always more expensive than current
management when the probability of cure using the
HealOzone option was 70% or lower. For non-
cavitated root caries the costs of the HealOzone
comparator were lower than those of current
management only when cure rates from HealOzone
were at least 80%. The costs of current management
were higher than those of the HealOzone option
when the cure rate for current management was 40%
or lower. One-way sensitivity analysis was also
performed using similar NHS Statement of Dental
Remuneration codes to those that are used in the
industry submission. This did not alter the results for
non-cavitated pit fissure caries as the discounted net
iv
present value of current management remained lower
than that of the HealOzone comparator (22.65
versus 33.39).
Conclusions: Any treatment that preserves teeth and
avoids fillings is welcome. However, the current
evidence base for HealOzone is insufficient to conclude
that it is a cost-effective addition to the management
and treatment of occlusal and root caries. To make a
decision on whether HealOzone is a cost-effective
alternative to current preventive methods for the
management of dental caries, further research into its
clinical effectiveness is required. Independent RCTs of
the effectiveness and cost-effectiveness of HealOzone
for the management of occlusal caries and root caries
need to be properly conducted with adequate design,
outcome measures and methods for statistical analyses.
 Health Technology Assessment 2006; Vol. 10: No. 16

Contents
List of abbreviations .................................. vii Budget implications to the NHS ............... 37

Executive summary .................................... ix 7 Discussion ................................................... 41

Main results ................................................ 41
1 Aim of the review ...................................... 1 Need for further research .......................... 41

2 Background ................................................ 3 8 Conclusion .................................................. 43

Dental caries ............................................... 3
Current service provision ........................... 7 Acknowledgements .................................... 45
Description of new intervention ................ 11
Key questions .............................................. 12 References .................................................. 47

3 Effectiveness ............................................... 13 Appendix 1 Literature search

Methods for reviewing effectiveness .......... 13 strategies ..................................................... 51
Results ........................................................ 14
Discussion of results and conclusions on Appendix 2 Data extraction form ............. 55
the evidence for and against the
intervention ................................................ 21 Appendix 3 Checklist for the quality
assessment of randomised controlled
4 Systematic review of economic trials ............................................................ 59
evaluations ................................................. 23
Methods ...................................................... 23 Appendix 4 Characteristics of included
Results ........................................................ 23 studies: full-text reports ............................. 61
Review of industry submission ................... 24
Appendix 5 Characteristics of included
5 Economic analysis ...................................... 29 studies: abstracts ......................................... 71
Methods for economic analysis .................. 29
Results ........................................................ 33 Appendix 6 Structure of the economic
Discussion ................................................... 36 model ......................................................... 75

6 Implications for the NHS .......................... 37 Health Technology Assessment reports

National Service Framework ...................... 37 published to date ....................................... 81
Health targets ............................................. 37
Fair access ................................................... 37 Health Technology Assessment
Equity issues ............................................... 37 Programme ................................................ 93

v
 Health Technology Assessment 2006; Vol. 10: No. 16

List of abbreviations

ANOVA analysis of variance NICE National Institute for Health

and Clinical Excellence
CDC Centers for Disease Control and
Prevention NPV net present value

CI confidence interval ns not significant

DFS decayed and filled surfaces NS not stated

DMFS decayed, missing and filled ORCA European Organisation for

surfaces Caries Research

DMFT decayed, missing and filled PRCL primary root carious lesion
teeth
QALY quality-adjusted life-years
ECM electrical conductance
measurement QLF quantitative light-induced
fluorescence
FDA Food and Drug Administration
QOTI/FOTI quantitative fibre-optic
GDS General Dental Services transillumination

IADR International Association for RCT randomised controlled trial

Dental Research
SD standard deviation
ITT intention-to-treat
SDR NHS Statement of Dental
NCHS National Centre for Health Remuneration
Statistics
TACT tuned aperture computed
NHANES III USA National Health and tomography
Nutrition Examination Survey
UCD ultrasound caries detector
NHS EED NHS Economic Evaluation
Database USPHS US Public Health Service
criteria

All abbreviations that have been used in this report are listed here unless the abbreviation is well known (e.g. NHS), or
it has been used only once, or it is a non-standard abbreviation used only in figures/tables/appendices in which case
the abbreviation is defined in the figure legend or at the end of the table.

vii

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Executive summary
Background
Dental caries is a chronic disease caused by the
localised and progressive demineralisation of the
hard tissues of the coronal and root surfaces of the
teeth. Caries location, development and
progression depend on a range of environmental,
social and genetic factors, and vary greatly among
individuals.
Despite the decline in the prevalence of dental
caries observed in the high-income countries
during the past few decades as a consequence of
the increased availability of fluoride products and
improved oral hygiene, dental caries is still a
common disease experienced by almost 80% of
children by the age of 18 years and by almost 90%
of adults.
The current management of early non-cavitated
occlusal and root caries, and cavitated root caries,
which are still accessible to cleaning, is based on
non-operative preventive strategies that include
information on oral hygiene, dietary advice, use of
topically applied fluorides and application of
sealants. For cavitated occlusal caries and cavitated
root caries that are not easily accessible to
cleaning, restorative interventions are adopted
(drilling and filling).
HealOzone (CurOzone USA Inc., Ontario,
Canada) has recently been proposed as a novel
method for the treatment of dental caries. It is
suggested that HealOzone may reverse, arrest or
slow the progression of dental caries. The
complete HealOzone procedure involves the direct
application of ozone gas to the caries lesion on the
tooth surface, the use of a remineralising solution
immediately after application of ozone and the
supply of a patient kit, which consists of
toothpaste, oral rinse and oral spray all containing
fluoride.
Objective
The review aims to assess the effectiveness and cost-
effectiveness of HealOzone for the management of
pit and fissure caries, and root caries.
Queens Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 16
Methods
Electronic searches were conducted to identify
published and unpublished studies. The following
databases were searched: MEDLINE (1966 to
May 2004), EMBASE (1980 to May 2004),
MEDLINE Extra (17 May 2004), Science Citation
Index (1981 to May 2004), BIOSIS (1985 to
May 2004), AMED (1985 to May 2004), Cochrane
Library (Issue 2, 2004) National Research Register
(Issue 2, 2004), Current Controlled Trials (18 May
2004), Clinical Trials (18 May 2004), SCI
Proceedings (1991 to May 2004), Conference
Papers Index (1982 to May 2002), ZETOC
conferences (1993 to May 2004) and IADR
meeting abstracts (2002 to 2004). Two reviewers
independently assessed the methodological quality
of included studies and extracted data. Criteria for
assessment of study quality included method and
unit of randomisation, concealment of allocation,
comparability of groups at baseline, blinding
procedures, number of withdrawals/dropouts and
completeness of assessment at follow-up.
A systematic review of the effectiveness of
HealOzone for the management of tooth decay
was carried out. A systematic review of existing
economic evaluations of ozone for dental caries
was also planned but no suitable studies were
identified. The economic evaluation included in
the industry submission was critically appraised
and summarised.
A Markov model was constructed to explore
possible cost-effectiveness aspects of HealOzone in
addition to current management of dental caries.
Results
Number and quality of studies, and
direction of evidence
Five full-text reports and five studies published as
abstracts met the inclusion criteria. Of these, only
one was published in a refereed journal, but it
lacked some study details. The remaining studies
were PhD theses, unpublished reports or
conference proceedings. The five full-text reports
consisted of two randomised controlled trials
ix
 Executive summary
(RCTs) assessing the use of HealOzone for the
management of primary root caries and two PhD
theses of three unpublished randomised trials
assessing the use of HealOzone for the
management of occlusal caries. Of the five studies
published as abstracts, four assessed the effects of
HealOzone for the management of occlusal caries
and one the effects of HealOzone for the
management of root caries.
Overall, the quality of the studies was modest, with
many important methodological aspects not
reported (e.g. concealment of allocation, blinding
procedures, compliance of patients with home
treatment). In particular, there were some
concerns about the choice of statistical analyses. In
most of the full-text studies analyses were
undertaken at lesion level, ignoring the clustering
of lesions within patients. The nature of the
methodological concerns was sufficient to raise
doubts about the validity of the included studies
findings. A quantitative synthesis of results was
deemed inappropriate.
Summary of benefits
Root caries
Two studies (one published and one unpublished)
assessing the use of HealOzone for the
management of primary non-cavitated root caries
reported high success rates for ozone-treated
lesions and no significant changes in the control
lesions, despite application of topical fluoride.
This is puzzling, since topical fluoride is known to
be effective. Results of cavitated root lesions were
poorly defined and reported in one of these two
studies. Cavitated lesions did not seem to benefit
from ozone application.
One unpublished study showed that fissure
sealants preceded by the application of ozone for
the preventive treatment of non-cavitated root
lesions were more likely to remain intact (61%
versus 42%, p < 0.05).
Pit and fissure caries
One unpublished study did not show any
significant benefits of HealOzone for the
management of non-cavitated pit and fissure
lesions in the permanent dentition. Similarly, a
small unpublished pilot study did not show any
significant differences between cavitated occlusal
lesions treated with or without ozone, apart from
an improvement in the hardness and visual clinical
indices. In contrast, findings from conference
proceedings (which provide little detail for the
assessment of their methodological quality and
x therefore are of little use in systematic reviews)
reported very high success rates (from 86.6% to
99% of reversal of caries).
Adding ozone to a fissure sealant did not seem to
produce better sealant retention in occlusal lesions
extending 24 mm into dentine.
Data on the use of HealOzone for the treatment of
occlusal lesion in the deciduous dentition were
available from only one unpublished study. An
overall reduction in clinical severity scores was
reported for non-cavitated occlusal lesions in
primary molars treated with ozone.
On the whole, there is not enough evidence from
published RCTs on which to judge the
effectiveness of ozone for the management of both
occlusal and root caries.
Costs
The perspective adopted for the study was that of
the NHS and Personal Social Services. The
analysis, carried out over a 5-year period, indicated
that treatment using current management plus
HealOzone cost more than current management
alone for non-cavitated pit and fissure caries
(40.49 versus 24.78), but cost less for non-
cavitated root caries (14.63 versus 21.45). Given
the limitations of the calculations these figures
should be regarded as illustrative, not definitive.
Cost per quality-adjusted life-year
It was not possible to measure health benefits in
terms of quality-adjusted life-years. This was
mainly due to uncertainties around the evidence
of clinical effectiveness, and to the fact that the
adverse events avoided are transient (e.g. pain
from injection of local anaesthetic, fear the drill).
Sensitivity analyses
One-way sensitivity analysis was applied to the
model. However, owing to the limitations of the
economic analysis, this should be regarded as
merely speculative. For non-cavitated pit and
fissure caries, the HealOzone option was always
more expensive than current management when
the probability of cure using the HealOzone option
was 70% or lower. For non-cavitated root caries the
costs of the HealOzone comparator were lower
than those of current management only when cure
rates from HealOzone were at least 80%. The costs
of current management were higher than those of
the HealOzone option when the cure rate for
current management was 40% or lower.
One-way sensitivity analysis was also performed
using similar NHS Statement of Dental

Remuneration codes to those that are used in the
industry submission. This did not alter the results
for non-cavitated pit fissure caries as the
discounted net present value of current
management remained lower than that of the
HealOzone comparator (22.65 versus 33.39).
Conclusions
Any treatment that preserves teeth and avoids
fillings is welcome. However, the current evidence
base for HealOzone is insufficient to conclude that
it is a cost-effective addition to the management
and treatment of occlusal and root caries.
Limitations of the calculations
The economic analysis was severely constrained by
the uncertainty over clinical effectiveness, and it
could be argued that such analysis was
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Health Technology Assessment 2006; Vol. 10: No. 16
inappropriate. It was done merely to illustrate the
key factors involved in economic modelling. The
long-term effects of HealOzone are unknown and
the assumption that reversed caries remains
inactive may not be reliable.
Recommendations for research
To make a decision on whether HealOzone is a
cost-effective alternative to current preventive
methods for the management of dental caries,
further research into its clinical effectiveness is
required. Independent RCTs of the effectiveness
and cost-effectiveness of HealOzone for the
management of occlusal caries and root caries
need to be properly conducted with adequate
design, outcome measures and methods for
statistical analyses.
xi
 Health Technology Assessment 2006; Vol. 10: No. 16

Chapter 1
Aim of the review
he review aims to assess the effectiveness and USA Inc., Ontario, Canada) for the management
T cost-effectiveness of HealOzone (CurOzone of both pit and fissure caries, and root caries.

Queens Printer and Controller of HMSO 2006. All rights reserved.


Chapter 2
Background
Dental caries
Aetiology, pathology and prognosis
Dental caries (tooth decay) is a chronic disease
caused by the localised and progressive
demineralisation of the hard tissues of the coronal
and root surfaces of the teeth. The
demineralisation is caused by the interaction of
acid-producing oral microorganisms (in particular
Streptococcus mutans, Lactobacillus and Actinomyces
species) with dietary carbohydrates (sugar).
Caries occurs when the natural dynamic balance
between mineralisation and demineralisation of
dental tissues is disrupted. The process begins on
the surface of the enamel (outer surface of the
tooth; see Figure 1). In enamel caries, the lesion
may reverse or arrest by remineralisation. If
remineralisation does not occur, the lesion may
penetrate the enamel and consequently result in
the formation of a cavity, which may progress
through the dentine and the pulp of the tooth. In
the absence of treatment, dental caries may
ultimately destroy the tooth. Caries location,
development and progression are influenced by a
range of environmental, social and genetic factors,
and vary greatly among individuals. In most
individuals dental caries tend to progress slowly
over time, with lesions often taking more than
2 years to cavitate, although in some it can take a
shorter time. Conversely, some lesions never
cavitate.
According to the anatomical location of carious
lesions, it is possible to differentiate between
coronal lesions, which may affect the pits and
fissures or the smooth surfaces of a tooth, and root
lesions, which affect the exposed root cementum
and dentine. Root caries occurs in the same
manner as coronal caries, but demineralisation
begins at a higher pH and it is more common in
older people. The term primary caries is used to
indicate lesions on the unrestored surfaces of
teeth, while caries that develops adjacent to a
filling is referred to as recurrent or secondary
caries. Hidden caries is a term used to identify
carious lesions in the dentine that are not detected
by visual examination but are large enough to be
identified radiographically. According to their
activity, carious lesions may be classified as active
Queens Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 16
or inactive/arrested. A lesion that is considered to
be progressive is described as active, whereas a
lesion that has stopped further progression is
described as arrested. This distinction is clinically
important as arrested lesions do not require any
further preventive interventions.
The occlusal surfaces (pits and fissures) of teeth
are particularly susceptible to dental caries owing
to their morphological structure (minute
dimensions of pits and fissures) and because
microbial plaque is more likely to grow in these
areas (plaque stagnation). The teeth are more
prone to plaque stagnation during eruption.
Occlusal caries is seen more often in molar teeth
than in premolar or anterior teeth.
The incidence of root caries begins at about
3040 years of age and tends to increase
thereafter. Root caries is most prevalent in the
elderly because when people get older and retain
their natural teeth, their gums tend to recede and
expose the root surfaces. According to the
published NHS Plan for Modernising NHS
Enamel
Dentine
Crown
Pulp containing
blood vessels
and nerves
Gum (gingiva)
Neck
Bone
Periodontal
membrane
Root
Cementum
Root canal
Opening at tip
of root
FIGURE 1 Structure of a sound tooth. Reproduced with
permission from www.mydr.com.au. Copyright CMPMedica
Australia 2005. 3
 Background
Dentistry, nearly 90% of people aged over
65 years show some signs of gum disease
compared with 14% of 1624 year olds.1
Significance in terms of ill-health
Impact on patients quality of life
Dental caries may have a significant impact on an
individuals life. The most common consequences
of untreated lesions are discomfort and pain.
Restorative dental treatments can now be provided
pain free, apart from the pain of the local
anaesthetic injection. However, for some people
restorative treatments are associated with fear and
anxiety, which, may become barriers to dental
attendance. Treatment avoidance can subsequently
lead to further progression of caries which, in
turn, may cause more distress and long-term
complications. Gross decay may lead to
disturbances in eating and sleeping patterns
because of pain. Psychological distress can arise
from the embarrassment and self-consciousness of
having missing or decayed teeth, especially in the
anterior dentition. Communication problems may
ultimately occur as a possible result of tooth loss.
In addition to human cost, dental caries can be
costly for the patients receiving treatment. For
many patients NHS charges can be expensive,
especially for those who earn just enough to
disqualify them from exemption or remission of
charges. Moreover, where provision of NHS
dentistry is patchy, patients may have to depend
on private dental care.
Impact on the NHS
Treatments for dental care carry considerable costs
for both the NHS and society. NHS General
Dental Services (GDS) data reveal that the total
number of claims in England and Wales for dental
interventions in the financial year 2002/03 was 34
million. Almost half (48%) of claims were for
treatments requiring no dental intervention (i.e.
examination, simple scaling, X-ray, fissure sealant,
topical fluoride). The total number of teeth filled
was about 19 million, while the number of teeth
with roots filled was just over one million. Overall,
the total gross fees authorised was 1634 million.
The care and treatment for children accounted for
27% (461 million) of all gross fees authorised.
Epidemiology
There has been a significant reduction in dental
caries since the 1970s in industrialised countries,
due to environmental and educational factors such
as the increased use of fluoride in public water
supplies, dentifrices and dental products;
4 improved oral hygiene and prophylaxis; dietary
counselling; and increased access to dental care.
Nevertheless, dental caries is still a common
disease, experienced by almost 80% of children by
the age of 18 and by almost 90% of adults.2
Prevalence in children
Since the significant decline in the 1970s and
1980s, it seems that over the past 20 years caries
prevalence rates have become relatively stable.2
The 2003 Childrens Dental Health Survey
commissioned by the UK Health Departments
provides the most recent estimate of the
prevalence of dentine decay in children in
England and Wales.3 The 2003 survey is the fourth
in a series of dental health surveys carried out
every 10 years since 1973. The criteria used in the
survey to assess dental caries were the following:
filled decay, otherwise sound: teeth with
amalgam, or other fillings that had no cavitated
dentine caries present
obvious decay experience: all teeth with
cavitated dentine caries, restorations with
cavitated dentine caries, teeth with filled decay
(otherwise sound) and teeth extracted due to
caries. The term relates to the DMFT (decayed,
missing, and filled teeth) dental decay index.
The preliminary findings of this survey indicate
that:
there has not been a substantial change in the
proportion of 5- and 8-year-olds who presented
with obvious decay in the primary (milk) teeth
between the 1993 and 2003 dental survey
(Table 1)
the proportion of filled primary teeth as well as
the proportion of the total obvious decay
experience represented by filled primary teeth
in 5- and 8-year-olds has declined since 1983,
indicating a decline in restorative interventions
(Table 1)
the mean number of primary teeth with obvious
decay has decreased since 1983 in 5- and
8-year-olds (Table 2), but the mean number of
primary teeth with obvious decay among
children with decay has not changed
considerably since 1993, apart from the decline
in the number of filled teeth in the 8-year-olds
(Table 3)
the proportion of 8-, 12- and 15-year-olds with
obvious tooth decay and cavities into dentine in
permanent teeth has decreased considerably
since 1983 (Figures 2 and 3)
the proportion of filled permanent teeth has
declined considerably since 1983 in 12- and
15-year-olds, but not in 8-year-olds (Figure 4)
 Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 1 Percentage of children with obvious tooth decay in TABLE 3 Mean number of primary teeth with obvious tooth
primary teeth by age (Childrens Dental Health in the United decay in children with obvious decay experience by age
Kingdom, 2003)3 (Childrens Dental Health in the United Kingdom, 2003)3

Year Year

Tooth condition 1983 1993 2003 Tooth condition 1993 2003

Percentage of children: Mean number of teeth

Obvious decay experience Teeth with cavities into dentine
5-year-olds 50 45 43 5-year-olds 3.1 3.2
8-year-olds 70 61 57 8-year-olds 2.1 2.3
Teeth with cavities into dentine Filled decay (otherwise sound)
5-year-olds 41 40 40 5-year-olds 0.6 0.6
8-year-olds 49 50 50 8-year-olds 1.1 0.9
Filled decay (otherwise sound) Obvious decay experience
5-year-olds 23 15 12 5-year-olds 3.7 3.8
8-year-olds 47 33 26 8-year-olds 3.2 3.2
Filled teeth as a proportion of total obvious decay
experience
5-year-olds 28 17 15 TABLE 4 Proportion of children with obvious tooth decay in
8-year-olds 50 35 28 permanent teeth by age (Childrens Dental Health in the United
Kingdom, 2003)3

TABLE 2 Mean number of primary teeth with obvious tooth Year

decay by age (Childrens Dental Health in the United Kingdom,
Tooth condition 1983 1993 2003
2003)3
Percentage of children:
Year Filled teeth as a proportion of total obvious decay
experience
Tooth condition 1983 1993 2003 8-year-olds 58 37 52
12-year-olds 70 58 70
Mean number of teeth
15-year-olds 74 68 77
Teeth with cavities into dentine
5-year-olds 1.3 1.4 1.4
8-year-olds 1.2 1.3 1.3
Filled decay (otherwise sound)
5-year-olds 0.5 0.3 0.2
presented with tooth decay in permanent or
8-year-olds 1.2 0.7 0.5 primary teeth. The proportion of children with
untreated caries in permanent or primary teeth
Obvious decay experience
was 29% for the 68-year-olds and 20% for the
5-year-olds 1.8 1.7 1.6
8-year-olds 2.3 2.0 1.8 15-year-olds (Figure 5).

Dental caries is not evenly distributed across the

the proportion of the total obvious decay
experience represented by the number of filled
permanent teeth in 8-, 12- and 15-year-olds has
increased since 1993, indicating an increase in
restorative interventions (Table 4).
These findings are consistent with those found by
the USA Third National Health and Nutrition
Examination Survey (NHANES III), Centers for
Disease Control and Prevention (CDC), National
Centre for Health Statistics (NCHS)4 and the
National Survey of Dental Caries in US School
Children 19861987, where 52% of children aged
68 years and 61% of children aged 15 years
child population, with about 26% of children (worst
cases) presenting with 75% of all carious lesions.6
This can be interpreted in the light of the fact that
dental caries is a disease of lifestyle with strong
socio-economic and geographical differences. The
use of deprivation categories in the assessment of
Scottish schoolchildren aged 5 years is a good
example of how measures of socio-economic status
may correlate with dental caries experience
(Figure 6).5 The link between social status and
prevalence of caries is also supported by the data
from the National Childrens Dental Health Survey
carried out in the UK in 1993 (Figure 7).7
Prevalence in adults
Fewer prevalence data are available for adults. 5

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 Background

100
90
80
70
60 1983
% 50
1993
40
2003
30
20
10
0
8 12 15
Age (years)

FIGURE 2 Proportion of children with obvious decay experience in permanent teeth by age (Childrens Dental Health in the United
Kingdom, 2003)3

45
40
35
30
% 25 1983
20 1993
15 2003
10
5
0
8 12 15
Age (years)

FIGURE 3 Proportion of children with cavities into dentine in permanent teeth by age (Childrens Dental Health in the United
Kingdom, 2003)3

90
80
70
60
50 1983
%
40 1993
30 2003
20
10
0
8 12 15
Age (years)

6 FIGURE 4 Proportion of children with filled permanent teeth by age (Childrens Dental Health in the United Kingdom, 2003)3
 Health Technology Assessment 2006; Vol. 10: No. 16

70 Tooth decay
60 Untreated caries
50
40
%
30
20
10
0
68 15
Age (years)

FIGURE 5 Proportion of children with tooth decay and untreated caries by age (NHANES III)4

5.0
4.5
4.0
Number of DMFT

3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
1 2 3 4 5 6 7
Deprivation categories

FIGURE 6 Caries distribution by socio-economic deprivation categories (DEPCAT) in Scottish schoolchildren aged 5 years.5 DEPCAT 1
= most affluent postcode sections. DECAT 7 = most deprived postcode sectors.

According to the UK 1998 Adult Dental Health
Survey,8 adults had an average of 1.5 decayed or
unsound teeth (teeth with visual or cavitated caries
or those with an unsound restoration) and 55%
had at least one decayed or unsound tooth. The
numbers of adults with decayed or unsound teeth
varied according to the regions surveyed. The
proportion of dentate adults with tooth decay in
England, Wales, Scotland and Northern Ireland is
shown in Figure 8.
The mean proportion of filled permanent teeth
ranged from 9% for people aged 1624 years to
39% for people aged 4554 years (Figure 9).
Overall, 66% of the adult population showed at
least one tooth with a root surface that was
exposed, worn, decayed or filled. Overall, root
surface fillings were found in 43% of people aged
65 and older.
Similarly, in the USA, NHANES III Phase 1
found evidence of coronal carious lesions in 94%
of the studied population. The mean score for
decayed and filled surfaces (DFS) on permanent
teeth in adults was 22.2. Carious lesions were
found in 23% of all dentate adults and in 47% of
people aged 65 years and over (NHANES III
19981991).4
Current service provision
Current management of dental caries
Increasing emphasis has been recently dedicated
to the provision of caries prevention and 7

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 Background

3.5
3.0
Number of DMFT

2.5
2.0 I, II, III non-manual
1.5 III manual
1.0 IV, V
0.5
0
12 15
Age (years)

FIGURE 7 Average number of decayed, missing or filled teeth in adolescents in the UK by social class (National Childrens Dental
Health Survey, 1993)7

60

50

40

% 30

20

10

0
England Wales Scotland Northern
Ireland

FIGURE 8 Proportion of adults with decaying or unsound teeth by country (United Kingdom Adult Dental Health Survey, 1998)8

40
35
30
25
% 20
15
10
5
0
1624 2534 3544 4554 5564 65 All

Age (years)

8 FIGURE 9 Mean proportion of filled teeth by age (United Kingdom Adult Dental Health Survey, 1998)8

management strategies. In particular, attention to
risk assessment and to preventive non-operative
methods for assisting remineralisation of early
caries has been advocated. Despite the
acknowledged importance for the prevention of
caries, non-operative, preventive treatments are
not fully funded by the NHS at present. Changes
are likely to be introduced with the
implementation of the new contract in 2006.
Efficient management of dental caries depends on
the knowledge of patients dental and medical
history and risk assessment, correct identification
of carious lesions and identification of the best
treatment options for dental caries. A thorough
dental and medical history provides information
about patients previous experience of dental
caries, number of active lesions and factors that
may affect caries activity (e.g. general oral
hygiene, diet and sugar intake, exposure to
fluoride, salivary flow rate, certain medical
conditions and medications). Caries risk
assessment aims at identifying high-risk
individuals who may benefit more from preventive
treatments, and low-risk individuals for whom
restorative treatments could be delayed. Carious
lesions are first identified on the basis of the
findings of the clinical examination (visual
criteria). For visual detection of occlusal caries and
for predicting their activity and severity, the
ranked scoring system described by Ekstrand and
colleagues9 is recognised as a valid and reliable
tool, although mainly used in clinical research. For
assessing the extent and severity of root caries the
tactile criteria of soft, leathery and hard on
probing are commonly used in dental practice and
dental research. Radiographic investigations (X-
rays) have been widely used for decades as an
adjunct to clinical examination to estimate the
depth of occlusal lesions into dentine or to
identify lesions that are hidden from clinical
examination. More recently, other quantitative,
more advanced methods have been proposed for
the diagnosis of dental caries. These include
methods based on:
digital radiology [e.g. digital image
enhancement, digital subtraction radiography,
tuned aperture computed tomography (TACT)]
visible light [e.g. quantitative fibre-optic
transillumination (QOTI/FOTI), quantitative
light-induced fluorescence (QLF)]
laser fluorescence (e.g. DIAGNOdent)
electrical current [e.g. electrical conductance
measurement (ECM)]
ultrasound [e.g. ultrasound caries detector
(UCD)].
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Health Technology Assessment 2006; Vol. 10: No. 16
However, with the exception of digital radiology,
these diagnostic procedures are not widely used in
dental practice. Some procedures need further
investigation (e.g. QOTI/FOTI, QLF) or further
development (e.g. UCD) before their use could be
recommended in dental practice. Others are
prone to false-positive measurements (e.g. small
amount of plaque identified as a carious lesion by
DIAGNOdent) or unreliable findings (e.g. because
of inadequate tooth isolation during ECM),10
which require a careful interpretation and
sometimes correction by the dentist. In particular,
to the authors knowledge the validity of
DIAGNOdent as an instrument for detecting
occlusal caries has yet to be demonstrated in in
vivo studies.
Treatment of early caries (non-cavitated pit and
fissure caries and root caries)
Treatment options for early caries include the
following:
provision of information about oral hygiene
dietary assessment and advice
fluoride-delivery methods
application of chlorhexidine
pit and fissure sealants
recall at regular intervals.
Oral hygiene
Instructions on oral hygiene aim at improving
personal removal of plaque by toothbrushing.
Regular toothbrushing in children may help to
reduce the incidence of caries,11 and children
whose level of oral hygiene is good experience less
decay.12 Despite the lack of evidence on the
effectiveness of oral hygiene instructions,13
toothbrushing, together with the use of fluoride
toothpaste and the advice of reducing sugar intake,
is usually recommended in the dental practice for
maintaining a good level of oral hygiene.
Dietary assessment and advice
Evidence from epidemiological and experimental
studies indicates that frequent consumption of
fermentable carbohydrates is associated with
prevalence of dental caries. For some patients the
frequency of intake of a certain type of food may
primarily contribute to their caries risk and
modification of this factor may be sufficient to
change their risk. The dietcaries association is,
however, complex and needs to be evaluated not
only on the basis of the quantity and type of
fermentable carbohydrates consumed, but also
considering several other background factors such
as age, total food intake, dietary habits, salivary
flow rate, use and type of medications, and use of 9
 Background
fluoride products. Dietary assessment is usually
recommended in patients with multiple active
lesions. In contrast, no diet modifications are
suggested for patients with inactive caries. The
dentist, however, may still provide information on
how unhealthy dietary habits may become a
problem, especially when associated with a poor
level of oral hygiene.14
Fluoride-delivery methods
Use of fluoride-delivery products and water
fluoridation are among the factors that have
contributed to the observed progressive
improvement in oral health since the 1970s.
Evidence indicates that fluoridation of the water
supply is associated with an increased proportion
of children without caries and a reduction in the
number of teeth affected by caries.1,15,16 Topical
fluoride-delivery methods in the form of
toothpastes, mouth rinses, gels or varnishes are
effective measures to prevent dental caries. Their
effectiveness has been established on evidence
from randomised trials and more recently from a
series of Cochrane systematic reviews of
randomised trials.1722 Overall, fluoride toothpaste
is the cheapest and the most widespread method
to control dental caries.2325 A recent randomised,
double-blind, clinical trial examined the anticaries
effectiveness of fluoride dentifrices containing
1700, 2200 and 2800 ppm fluoride ion compared
with a 1100 ppm fluoride control toothpaste, in
schoolchildren aged 615 years.24 The 1-year
results demonstrated significant caries reductions
for higher fluoride dentifrices for all tooth
surfaces, but in particular for occlusal surfaces.24
The use of fluoride mouth rinses and gels, as an
adjunct to fluoride toothpaste, is usually advised
for individuals at high risk of developing caries.
Fluoride varnish is used to provide fluoride
delivery to specific tooth sites and surfaces and is
usually applied at intervals of 3 or 6 months. A
recent systematic review by Marinho and
colleagues17 looked at the effectiveness of fluoride
varnish in preventing dental caries in children and
adults and commented on the ability of fluoride
varnish to promote remineralisation of early
caries. The included studies also considered non-
cavitated incipient enamel lesions, clinically
visible as white spots or discoloured fissures, which
would be included among those lesions eligible for
ozone application. The treatment effect was
measured in terms of prevented fraction (mean
increment in caries in controls minus mean
increment in fluoride group divided by the mean
increment in the controls). For the seven studies
that contributed to the main meta-analysis, the
10 decayed, missing and filled surfaces (DMFS)
prevented fraction pooled estimate was 0.46 [95%
confidence interval (CI) 0.30 to 0.63, p < 0.0001],
indicating a substantial benefit and demonstrating
that fluoride varnish alone can result in reversal of
early caries. Similarly, the meta-analysis of the
three studies assessing the effect of fluoride
varnish on deciduous teeth suggested a 0.33%
(95% CI 0.19% to 0.48%, p < 0.0001) reduction in
DMFS. Another recent systematic review26 of
selected caries prevention methods reached
similar conclusions, demonstrating that there is a
fair body of evidence on the effectiveness of
fluoride varnish to arrest or reverse non-cavitated
carious lesions in permanent teeth. Other fluoride
products such as fluoride supplements (e.g.
fluoride tablets or drops) are regarded as less
effective methods of delivering fluoride because
they rely entirely upon patient compliance. Their
use is usually limited to high-risk categories of
children, adults and, particularly, elderly people.27
Application of chlorhexidine
The effectiveness of chlorhexidine as an
antimicrobial for preventing progression of non-
cavitated caries has yet to be established. Current
evidence is derived mainly from small studies
evaluating the effects of different forms of
chlorhexidine (varnish, gel or rinse) in
combination with other concomitant preventive
measures.26,28
Pit and fissure sealants
Pits and fissures are sealed to prevent caries
development.28 Evidence indicates that caries does
not progress as long as the sealant remains in
place.29,30 Sealant applications may be suitable for
both young children and older patients.31
Materials that are currently used to seal a lesion
include different types of composite resin and
glass ionomer cement. The resin-based sealants
are divided into generations according to their
mechanism for polymerisation and their content.
The first generation sealants which were activated
by ultraviolet light are no longer available and the
most recently developed fourth generation
sealants contain fluoride. The effectiveness of
resin sealants for the prevention of caries in the
permanent teeth of children and adolescents was
demonstrated by Ahovuo-Saloranta and
colleagues32 in a recent Cochrane systematic
review. The review compared second, third and
fourth generation resin-based sealants or glass
ionomer sealants with a control (no sealant) and
compared one type of fissure sealant with another
type. The focus of the review was on prevention,
and the children and adolescents included did not
seem to present with obvious caries. The review

concluded that resin-based sealants are effective in
preventing caries of the occlusal surfaces of
permanent molars. Reduction of caries ranged
from 86% at 12 months to 57% at 4854 months.
Resin sealant retention was good across studies
and sealants were retained completely in 79% and
92% of cases at 12 months. Sealant retention
decreased with time and at 36 months ranged
from 61 to 80%. Evidence on the effects of glass
ionomer-based sealants was less convincing.
Treatment of cavitated pit and fissure caries and
root caries
For lesions that have progressed to the stage of
cavity, restorative interventions are often used to
remove the decayed tissue and fill the cavity to aid
plaque control. However, cavitated root lesions
that are still accessible to cleaning need not always
be filled because cleaning alone can arrest caries.
A number of different materials can be used to
restore a tooth. These include composite resin,
glass ionomer cement and amalgam. Amalgam is
still the material of choice for large restoration of
molar teeth. Root caries are usually restored with
composite resin or glass ionomer cement.
According to the NHS Dental Review
20022003,33 in the quarter ending December
2002 the number of teeth filled was 4,896,951 and
on average one tooth was filled for every two
claims (55%). Overall, restorations showed a
median survival interval to next restorative
intervention of just over 8 years. The main factors
associated with different likelihoods of re-
intervention were the age of the patient at the
date of restoration, the position of the tooth and
the type/material of restoration.33
Description of new intervention
Rationale
The antimicrobial effects of ozone gas (O3) have
been known for many years. Direct application of
ozone gas to the coronal or root tooth surface is
claimed to have a sterilising effect. In particular,
ozone is claimed to stop the action of the
acidogenic and aciduric micro-organisms
responsible for the tooth decay. It is consequently
alleged to be able to reverse, arrest or slow down
the progression of dental caries. It is also
maintained that ozone is useful for reducing the
microbial flora in cavitated lesions, before fillings
are inserted.
Development of HealOzone
The ozone unit for dental use was initially
developed by CurOzone Inc. (Canada) and
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Health Technology Assessment 2006; Vol. 10: No. 16
subsequently manufactured under licence and
distributed by KaVo-Dental GmbH & Co.
(Germany) under the name HealOzone. Its use
has been pioneered by Professor Edward Lynch
and his team at Queens University in Belfast,
Northern Ireland, and Barts and the London
Queen Marys School of Medicine and Dentistry
in London, UK. HealOzone is a certified
Medical Device [Conformit Europene (CE)
marked] for the management of occlusal pit and
fissure caries, and root caries. According to the
manufacturer, 294 HealOzone units (as at June
2004) are currently in use in dental practices in
the UK and more than one million people have
already received HealOzone treatment. The
HealOzone technology has not yet received Food
and Drug Administration (FDA) approval in the
USA.
The new version of HealOzone (Mark3) was
launched in July 2004. According to the
manufacturer previous models can be upgraded to
the most recent technical functions.
HealOzone procedure
The HealOzone procedure consists of a package,
which includes the application of ozone gas, the
use of remineralising agents, a patient kit and
information on oral hygiene. The HealOzone
device comprises an air filter, a vacuum pump, an
ozone generator, a handpiece fitted with a sealing
silicone cup and a flexible hose. The silicone cups
are available in a range of five sizes from 3 to
8 mm in diameter. The HealOzone unit requires
high-voltage power to generate ozone from the air
and to convert ozone back to oxygen when the
process is completed. The air is exposed to high-
voltage current to generate ozone at a
concentration of 2100 ppm 10% and passes
through the instrument hose and handpiece. The
flow of air into the system, the delivery of ozone to
the tooth and the removal of ozone from the
system after completion of treatment are achieved
by a vacuum pump, which works at an adjustable
flow rate of 615 cm3 per minute to maintain the
ozone concentration at 2100 ppm.
The procedure usually takes between 20 and 120
seconds per tooth. Immediately after ozone
application the tooth surface is treated with a
remineralising solution (reductant) containing
fluoride, calcium, zinc, phosphate and xylitol
dispensed from a 2-ml ampoule. The reductant is
supplied in packs of 100 ampoules. Patients are
also supplied with a patient kit, which consists of
toothpaste, oral rinse and oral spray, all
containing fluoride, calcium, zinc, phosphate and 11
 Background
xylitol, and aims to enhance the remineralisation
process. HealOzone application for the treatment
of non-cavitated lesions is usually repeated at 3
and 6 months. There is no clear information on
how delivery of ozone at the correct concentration
can be ensured by the device.
Key questions
This review aims to answer the following
questions:
For the management of pit and fissure caries, is
the HealOzone procedure more effective than
the combination of oral hygiene, dietary
12
advice, chlorhexidine/fluoride varnish and
fissure sealant? If so, is it a cost-effective
alternative?
For the management of non-cavitated root
caries, is the HealOzone procedure more
clinically effective than the combination of oral
hygiene, dietary advice and varnish? If so, is it
cost-effective?
For the management of cavitated caries, how
often, if at all, is HealOzone procedure an
alternative to fillings?
For the management of cavitated caries, does
the application of ozone gas and of a re-
mineralising solution to the cavity before
restoration prolong the life of a filling? If so, is
it cost-effective?

Chapter 3
Effectiveness
Methods for reviewing
effectiveness
Search strategy
Initial database searches were undertaken to
identify relevant systematic reviews and other
evidence-based reports. Several websites were also
consulted to obtain background information. Full
details of the main sources consulted are listed in
Appendix 1.
Electronic searches were conducted to identify
published and unpublished studies on the clinical
and cost-effectiveness of ozone therapy for dental
caries. The electronic databases searched are
detailed in Table 5. Full details of the search
strategies are documented in Appendix 1. It was
anticipated that there was a small body of research
available, therefore a sensitive search strategy for
clinical effectiveness studies was undertaken to
retrieve all useful information on ozone therapy
for dental caries. Additional searches were carried
out for economic data and these are detailed in
Chapter 4. In addition, selected conferences
proceedings that were not available electronically
were handsearched. These were International
Association for Dental Research (IADR) conference
proceedings for 19992001 and the annual
European Organisation for Caries Research (ORCA)
Congresses 20002003. Research abstracts,
published on industry and users websites (KaVo
Dental, CurOzone USA, HealOzone and
TABLE 5 Electronic databases searched
Database
MEDLINE/EMBASE/MEDLINE Extra multifile search
Science Citation Index (SCI)
BIOSIS
AMED
Cochrane Controlled Trials Register (CCTR)
National Research Register (NRR)
Current Controlled Trials (CCT)
Clinical Trials
SCI Proceedings
Conference Papers Index
ZETOC Conferences
IADR Meetings Abstracts
Queens Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 16
DentalOzone; see Appendix 1 for full details),
were also identified. Reference lists of included
studies were also checked for additional study
reports.
Inclusion and exclusion criteria
All citations identified by the search strategy were
assessed for relevance by two reviewers. Copies of
the full-text, published papers of those considered
to be relevant were then obtained. It was decided
that studies reported in languages other than
English would be identified but not included in
the review.
For clinical effectiveness assessment, included
studies were randomised controlled trials (RCTs)
of ozone treatment (HealOzone) versus at least
one comparator (nil, placebo or active treatment).
Data from studies other than randomised trials
were collected but not included in the review. The
outcome measures were required to be measures of
clinical effectiveness (e.g. reversal/progression of
caries). Only in vivo studies involving human
subjects were deemed to be suitable for inclusion,
while studies reporting in vitro results were
excluded. Studies were also excluded if their
follow-up was less than 6 months or did not report
clinically relevant outcome measures.
Data extraction strategy
A data abstraction form was designed (Appendix
2) to collect details from each individual study.
Coverage
MEDLINE: 1966 to May Week 1 2004
EMBASE: 1980 to Week 20 2004
MEDLINE: Extra: 17 May 2004
1981 to 16 May 2004
1985 to 12 May 2004
1985 to May 2004
Cochrane Library, Issue 2, 2004
Issue 2, 2004
18 May 2004
18 May 2004
1991 to 15 May 2004
1982 to May 2002
1993 to May 2004
2002 to 2004
13
 Effectiveness
TABLE 6 Number of screened and selected reports according to database searched
Database searched Number screened
MEDLINE/EMBASE/MEDLINE Extra
SCI
BIOSIS
CENTRAL
IADR abstracts
Handsearch
Websites
Other databases
Total
These included the type of study design, number
of participants and their characteristics,
intervention characteristics, caries information
including location and severity of lesion, patient
outcomes such as reversal/progression of caries,
and any reported adverse events.
In particular, the outcomes sought for the
included studies were as follows:
(a) Non-cavitated caries
reversal of caries
progression of caries
utilisation of dental services (e.g. visits to dental
care units; duration of dental treatment)
adverse events
patient-centred measures (e.g. patient
satisfaction and preference, relief of
pain/discomfort)
quality of life.
(b) Cavitated caries
time to restorative interventions
need for further restorative interventions and
length of time between restorations
symptoms of pulpal pathology.
Inclusion criteria were assessed independently by
two reviewers. Any disagreements were resolved by
consensus or referred to a third reviewer.
Reviewers were not blinded to the names of study
authors, institutions or publications.
Quality assessment strategy
Two reviewers assessed the methodological quality
of all included studies and any disagreements were
resolved by discussion. The quality assessment of
RCTs was formally assessed using a published
checklist modified by the reviewers for the
14 purpose of this review.34 The checklist consisted of
Number selected Included studies
46 4 1
38 7 1
38 1 0
8 1 0
175 43 12
14 2
15 5
26 0 0
331 85 21
12 questions, which focus on the following
methodological aspects: method of randomisation,
unit of randomisation, concealment of allocation,
comparability of groups at baseline, blinding
procedures, number of withdrawals/dropouts and
completeness of assessment at follow-up.
For each question a Yes, No or Unclear answer
was required. The quality assessment checklist is
presented in Appendix 3.
Results
Quantity and quality of research
available
After removing duplicates a total of 331 reports
was identified (Table 6): 78% (257) were abstracts
and 22% (74) were full-text reports. Eighty-five
reports (seven full-text papers and 78 abstracts)
were selected for full assessment, of which 21
(three full-text papers and 18 abstracts) met the
predefined criteria for inclusion in the review. In
addition, two reports, both PhD theses, were
identified from reference lists. All 23 identified
reports were written in English.
Number of studies identified
In total, five studies reported in five full-text
papers and 13 abstracts, and five studies reported
only as abstracts, met the inclusion criteria for
studies of clinical effectiveness. In case of multiple
publications the report with the longest follow-up
time and/or largest sample size was chosen as the
main source of information.
Number and type of studies excluded
After identifying duplicates, several studies were
excluded as they did not meet the inclusion
criteria. The main reasons for exclusion, together
with the corresponding number of studies
excluded are listed in Table 7.

TABLE 7 Number of studies and reasons for exclusion
Reason for exclusion
Follow-up less than 6 months
No HealOzone treatment; other experiments involving ozone
No measures of clinical effectiveness
HealOzone used on extracted teeth (in vitro studies)
Evaluation of diagnostic tests for detection of dental caries; no clinical effectiveness
measures
Time studies, no clinical effectiveness measures
Discussion paper, no comparative information on clinical effectiveness
Costs, no clinical effectiveness measures
No random allocation
Patients attitudes, no effectiveness measures
Studies not involving ozone
Number and type of studies included
The five full-text studies consisted of two RCTs
assessing the use of HealOzone for the
management of primary root caries one
published trial by Holmes35 and one unpublished
trial by Baysan and Lynch,36 and two PhD theses
assessing the use of HealOzone for the
management of pit and fissure caries, one by
Abu-Nabaa37 reporting two unpublished trials
and one by Abu-Salem38 reporting one
unpublished trial.
Root caries studies
Holmes (2003): this published randomised
trial35,39,40 of management of primary non-
cavitated root caries had two treatment groups:
ozone plus reductant plus patient care kit versus
air treatment plus reductant plus patient care kit.
This study was set in a general dental practice.
Baysan and Lynch (2004): this unpublished
randomised trial on cavitated and non-cavitated
root caries36,4144 had four treatment groups:
ozone plus reductant versus reductant only, and
ozone plus sealant versus sealant only. It recruited
patients who attended the School of Dentistry in
Belfast.
Pit and fissure caries studies
Abu-Nabaa PhD thesis37 included two randomised
studies: a main study (Abu-Nabaa, 2003) and a
pilot study (Abu-Nabaa pilot study, 2003), which
are considered separately as they do not include
the same patient population. The main study
assessed exclusively non-cavitated occlusal lesions,
whereas the pilot study included cavitated occlusal
lesions. Patients were recruited from the School of
Dentistry in Belfast for both the main and pilot
studies.
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Health Technology Assessment 2006; Vol. 10: No. 16
Number of studies/abstracts
17
14
6
4
5
3
1
1
2
7
4
The Abu-Nabaa main study37,4550 had four
treatment groups: ozone plus reductant versus air
treatment plus reductant, and ozone plus
reductant plus sealant versus reductant plus
sealant only. It involved 90 patients with 254
lesions.
The Abu-Nabaa pilot study37,51,52 had two
treatment groups: ozone plus reductant versus
reductant only. It involved eight patients with 34
lesions.
The Abu-Salem study38 had two treatment groups:
HealOzone plus reductant versus reductant only. It
recruited 21 patients with 74 lesions, from Belfast
primary schools.
Of the five studies published only as abstracts,
four assessed the effects of HealOzone for the
management of occlusal pit and fissure carious
lesions,5356 and one assessed the effects of
HealOzone on primary root carious lesions.57
Tabulation of quality of studies, characteristics of
studies and evidence rating
The characteristics of the five full-text studies
(type and number of participants and carious
lesions, details of study design, inclusion criteria,
characteristics of intervention and main results)
are shown in Appendix 4.
Method of randomisation was reported in three
studies.35,37,38 Concealment of allocation was not
specified in any of the included studies. One study
was described as double blind35 and another study
stated that outcome assessment was undertaken by
a blinded examiner.38 In particular, the double-
blind study by Holmes was reported to involve
three dentists: the first dentist performed the 15
 Effectiveness
initial assessment of primary root carious lesions;
the second randomised the lesions to treatment
groups; the first then treated and assessed the
result without knowing which were given ozone
and which air, using a modified HealOzone
machine; the third dentist independently assessed
lesions in 15 patients. The practicality of the
entire process is, however, doubtful. Holmes is the
only author of the study and the other assessors
are neither listed as authors nor acknowledged in
the paper.
It was unclear whether blinding procedures were
secured in the remaining three included studies.
The total number of people in the studies was
287, with a total of 768 carious lesions. Across the
studies, the ages of the participant groups ranged
from 7 to 82 years. Only three studies provided
information on the gender of the participants.3638
The length of follow-up ranged from 6 to
21 months.
Each study involved either two or four
intervention groups. Ozone was always used in
combination with other active interventions (i.e.
ozone plus reductant, ozone plus reductant plus
patient care kit, ozone plus sealant, ozone plus
reductant plus sealant) and compared to the same
intervention without ozone or to a sham
procedure (air treatment). The dosage of ozone
treatment varied between studies. In the Baysan
and Lynch study,36 the Abu-Salem study38 and the
Abu-Nabaa main study,37 ozone was administered
for 10 seconds, whereas in the Holmes study35 and
the Abu-Nabaa pilot study37 ozone was
administered for 40 seconds. In all studies ozone
applications were repeated at some point before
the final follow-up. None of the included studies
provided information on the model/version of the
HealOzone device.
The main outcome measure was reversal of
caries. This included the proportion of carious
lesions becoming hard and, for some of the
included studies, the proportion of lesions
reversing from leathery to leathery approaching
hard texture, but not necessarily hardening. The
proportion of lesions that deteriorated from
leathery to soft was also recorded, although not
consistently. Where appropriate the proportion of
intact sealants was documented. Changes in the
ECM and DIAGNOdent readings were also
reported in the identified studies, but not
considered in this review, owing to the
unreliability of their measurements (i.e. high-false
positive rates) and poor correlation with clinical
16 outcomes.58
In the majority of the included studies, data
analysis was conducted at the level of the lesion.
Holmes used 2 statistics, but did not specify
whether they were for related samples (i.e.
McNemar 2 test). In the Baysan and Lynch
study no information was provided on the
choice of statistical test used. In both Abu-Nabaa
studies the unit of analysis was tooth-pair, but
it was unclear whether the occurrence of
multiple pairs of lesions per mouth was taken
into account. Abu-Salem used a mixed-effects
analysis of variance (ANOVA) with random
effects for patient and teeth within patient,
and fixed effects for group and time of
treatment.
The characteristics of the five studies published as
abstracts are shown in Appendix 5.
Tabulation of results and assessment of
effectiveness
The clinical effectiveness results are presented
according to type of carious lesions (root caries
results are presented separately from occlusal
caries results). Within this categorisation studies
results are presented according to:
type of outcome measures
type of publication (results of full-text studies
are presented separately from results of studies
published as conference proceedings)
type of dentition (treatment results of primary
teeth are presented separately from treatment
results of permanent teeth).
It was planned to undertake further statistical
analyses of the data reported in the full-text
studies and when appropriate to combine them
quantitatively. However, owing to the limited raw
data provided, this proved unfeasible. The
p-values of statistical analyses in the results section
are those originally quoted by the studies authors.
However, as the data were not analysed as paired
data on a patient basis, their validity and
reliability are open to question.
Primary root carious lesions
Two full-text studies by Holmes35 and Baysan and
Lynch36 and one abstract by Lynch and
colleagues57 assessed the use of ozone for the
management of primary non-cavitated root
carious lesions. The Baysan and Lynch study also
included the assessment of a non-specified
number of cavitated root lesions. In the Holmes
studies the clinical criteria of soft, leathery and
hard were adopted for the assessment of carious
lesions, whereas in the Baysan and Lynch study
 Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 8 Results of root carious lesions

Ozone final follow-up Control final follow-up

No. (%) No. (%)

PRCLs becoming hard

Baysan and Lynch, 200436 (12 months)a NR (47) NR (0)
Holmes, 200335 (18 months)b 87/87 (100) 1/87 (1)
PRCLs becoming less severe (from index 2 to 1)
Baysan and Lynch, 200436 (12 months)a NR (52) NR (12)
PRCLs becoming soft
Holmes, 200335 (18 months)b 0/87 (0) 32/87 (37)

NR, not reported (the denominator was not clearly reported in the study, so the number of caries cannot be calculated,
hence only percentages are given).
a
Baysan and Lynch: non-cavitated and cavitated primary root carious lesions.
b
Holmes: non-cavitated primary root carious lesions.

TABLE 9 Results of the Holmes study at each recall visit35

Ozone at follow-up Control at follow-up

No. (%) No. (%)

PRCLs becoming hard

12 months 85/87 (98) 1/87 (1)
18 months 87/87 (100) 1/87 (1)
21 months 81/81 (100) 6/81 (8)
PRCLs remaining leathery
12 months 2/87 (2) 65/87 (75)
18 months 0/87 (0) 54/87 (62)
21 months 0/81 (0) 65/81 (80)
PRCLs becoming soft
12 months 0/87 (0) 21/87 (24)
18 months 0/87 (0) 32/87 (37)
21 months 0/81 (0) 10/81 (12)

lesions were classified according to a five-point between three degrees of leathery seemed rather
severity index as follows: artificial.

0 all hard lesions
1 leathery lesions considered to be small, easily
cleanable and approaching a hard texture
2 leathery lesions judged to be shallow and
where the surface of the exposed sound dentine
could be easily maintained plaque free
3 leathery lesions judged to be in surfaces that
were difficult to maintain plaque free, and large,
cavitated leathery lesions where pulpal
integrity was judged to be at risk
4 all soft lesions.
No information was provided on the validity and
reproducibility of the above severity index, or on
how lesions were clinically identified as leathery
soft or hard. In particular, the distinction
Change in clinical severity Table 8 shows for each of
the included studies the proportions of carious
lesions that according to the studies authors
reversed (became hard), improved (became less
severe) or deteriorated in the ozone-treated group
and the control group. The Holmes study35
reported that 100% of ozone-treated primary root
carious lesions (PRCLs) had reversed by
18 months, while 37% of PRCLs in the control
group had worsened from leathery to soft and 1%
had reversed. However, comparisons of results at
different follow-up points show some
inconsistencies in the way data were reported
(Table 9). In particular, the results at 21 months
(published as an abstract) showed an increase in
the number of control lesions that stabilised 17

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 Effectiveness
(from 54/87 at 18 months to 65/81 at 21 months)
and a subsequent decrease in the number of
control lesions that had become soft (from 32/87
at 18 months to 10/81 at 21 months), indicating
an improvement over time in lesions receiving
treatment other than ozone. No comments on
these changes were provided by the authors.
In the Baysan and Lynch study,36 47% of the
ozone-treated lesions had arrested by 12 months,
whereas none had become hard in the control
group (p < 0.001), and 52% had reversed from
index 2 (leathery) to index 1 (leathery
approaching hard texture) in the ozone group
compared with 12% of lesions in the control group
(p < 0.001). So, if one combines the approaching
hard (from index 2 to 1) and hard lesions (from
index 2 to 0), 99% of lesions improved, as in the
Holmes study. This study included both cavitated
and non-cavitated root lesions, but results were not
clearly presented according to the type of lesions
and it is unclear how many cavitated and non-
cavitated lesions were assessed in each
intervention group. Only one figure in the paper
presented results for both types of lesions in the
ozone group: the percentage of cavitated lesions
that had reversed (become hard) decreased from
9.1% at 1 month to 1.4% at 9 months, indicating
an increase/progression in the severity of cavitated
root lesions treated with ozone. No statistical
analysis was undertaken by the authors, no
corresponding data were given for the control
group, and no comments on reversal/progression
of cavitated lesions were provided in the text of
the paper.
In addition, the abstract by Lynch and
colleagues57 indicated that 80% (48/60) of non-
cavitated PRCLs treated with ozone reversed from
severity index 4 to 3, whereas none of the soft
lesions in the control group significantly changed,
and that 94% (189/200) of leathery lesions became
hard and arrested in the ozone group, whereas
those in the control group did not significantly
change.
Marginal adaptation of the root sealant The Baysan
and Lynch study36 also assessed the effects of
ozone with or without a fissure sealant using the
modified US Public Health Service (USPHS)
criteria. In the ozone plus sealant group 61% of
sealants were retained compared with 42% in the
sealant only group (p < 0.05) at 12 months.
It is worth noticing that both groups had the
same other active interventions such as reductant,
18 patient care kits and sealants. The very low
improvement rates in the control groups are
therefore surprising.
Summary: root carious lesions The two full-text
studies assessing the use of ozone for root carious
lesions both report very high success rates with
ozone and very low improvement rates in the
controls.
Fissure sealants after application of ozone for the
preventive treatment of non-cavitated root lesions
are more likely to remain intact (61% versus 42%,
p < 0.05).
Pit and fissure carious lesions
The three remaining studies the Abu-Nabaa
main study (2003),37 Abu-Nabaa pilot study
(2003)37 and Abu-Salem (2004) study38 assessed
the effects of ozone on pit and fissure carious
lesions. Both Abu-Nabaa studies involved patients
aged over 12 years with primary lesions in the
permanent posterior teeth, while the Abu-Salem
study involved children 79 years old with carious
lesions in the posterior primary teeth. The
Abu-Nabaa main study and the Abu-Salem study
assessed non-cavitated lesions, while the
Abu-Nabaa pilot study included lesions with
cavitation.
Change in clinical severity: permanent dentition
Results of full-text studies Tables 10 and 11 illustrate
the results of the Abu-Nabaa main study.37
Clinical severity of non-cavitated pit and fissure
lesions was assessed using the criteria described by
Ekstrand and colleagues (0 = least severe, 1, 2, 3,
4 = most severe).9 The change in severity score is
calculated as the score at follow-up minus the
score at baseline. Thus, a negative change
indicates an improvement, while a positive change
implies a worsening of lesion severity. The mean
change from baseline in clinical severity score at
12 months was not significantly different
(p = 0.112) between the two intervention groups:
ozone (10 seconds) plus reductant group versus
reductant only group (Table 10).
It was also reported that a greater proportion of
ozone-treated lesions improved or stabilised
compared with control lesions at all recalls
(Table 11). However, statistical analyses of these
data were not provided. The relationship between
clinical severity score and the need for future
fillings was not explained.
No significant difference in the clinical severity
score was found between the ozone and control
groups in the Abu-Nabaa main study. The
 Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 10 Mean change in clinical severity score of pit/fissure lesions from baseline (Abu-Nabaa main study)37

Ozone group Control group p-Value

Change in clinical severity score (n = 106) (n = 106)

Mean change from baseline 0.283 0.443 0.112

Standard deviation 0.64 0.74
Standard error 0.06 0.07

TABLE 11 Percentage of pit/fissure lesions that improved, remained stable, or increased in clinical severity at each recall visit (Abu-
Nabaa main study)37

Month(s) of Treatment Decreased severity Stable Increased severity

follow-up group (improvement) (worsening)

1 Ozone 11.4% 74.6% 14.0%

Control 5.3% 81.6% 13.2%
3 Ozone 17.7% 63.9% 18.5%
Control 8.4% 73.1% 17.6%
6 Ozone 10.8% 55.9% 33.3%
Control 5.9% 59.8% 34.3%
9 Ozone 7.8% 57.8% 34.5%
Control 6.9% 56.0% 37.1%
12 Ozone 7.4% 56.5% 36.1%
Control 5.6% 48.6% 45.8%

reported proportions of lesions improved,
stabilised and deteriorated appeared similar
between groups, but no statistical analyses were
undertaken and the clinical relevance of these
findings was not explained in terms of fillings
avoided.
Abu-Nabaa pilot study In the Abu-Nabaa pilot
study,37 17 lesions (with cavitation) were treated
with ozone plus reductant and 17 reserved as
controls (reductant only) in eight patients.
Outcomes were measured using Ekstrand and
colleagues clinical index9 as well as the following
clinical indices: hardness index (hard, leathery,
soft), visual index (sound, arrested, active),
cavitation score (1 = no cavitation,
2 = microcavitation, 3 = frank cavitation), colour
index (normal, yellow, light brown, grey, dark
brown, black), frosted enamel measure (mm),
stained enamel measure (mm) and perceived
treatment need index (e.g. requiring no
intervention, requiring preventive resin
restoration, requiring drilling and filling).
Thirteen lesions in the treatment group and 12
lesions in the control group were assessed at
6 months. Lesions treated with ozone showed a
significant reduction in the hardness and visual
indices (Table 12). No significant differences
between groups were found for any other indices
or for the Ekstrand clinical index (p > 0.05).
This study was only a pilot study, which did not
add much to the results of the Abu-Nabaa main
study.37
Results of abstracts The abstracts gave little detail of
studies, their methodology could not be easily
assessed and therefore their findings must be
interpreted with caution. They are included here
for completeness and as a guide to emerging
research.
Three abstracts compared pit and fissure lesions
receiving ozone (at different concentrations) with
pit and fissure lesions receiving no-ozone
treatment.5456 Their results are presented in
Table 13. The proportion of lesions reported as
clinically reversed, the extent of which was not
specified, ranged from 86.6 to 99% in the ozone-
treated groups. All studies reported that no
significant clinical changes were observed in the
control group, but no numerical information was
given.
Another abstract53 compared the use of ozone
versus conventional treatment in 35 patients, each
with two occlusal lesions extending
radiographically 24 mm into dentine. The
authors defined the occlusal lesions as non-
cavitated, but lesions 24 mm into dentine on
radiographs are likely to have small cavities that 19

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 Effectiveness

TABLE 12 Number of pit/fissure lesions showing a reduction in the clinical indices at 6 months (Abu-Nabaa pilot study)37

Colour index

Hardness indexa Visual indexb Cavitation scorec Darkerd Lightere Perceived

treatment needf

Treatment 11/13 (84.6%) 8/13 (61.5%) 6/13 (46.2%) 3/13 (23.1%) 2/13 (15.4%) 12/13 (92%)
Control 4/12 (33.3%) 1/12 (8.3%) 5/12 (41.7%) 2/12 (16.7%) 6/12 (50%) 9/12 (75%)
p-Value <0.05 <0.05 ns 0.084 (ns) 0.16 (ns)
a
The proportion of lesions becoming hard
b
The proportion of lesions with increasing score
c
The proportion of lesions with reduction in cavity score
d
The proportion of darker lesions
e
The proportion of lighter lesions
f
The proportion of lesions with a reduced treatment need

TABLE 13 Reversal of pit/fissure caries: findings from abstracts

Ozone at follow-up Control at follow-up

No. (%) No. (%)

Holmes 200354 (12 months) 1918/1937 (99) 0/427 (0)

Hamid, 200355 (6 months) 80/92 (86.9) 0/92 (0)
Megighian and Bertolini, 200456 (6 months) p < 0.05 0/80 (0)
(220 lesions treated)

trap plaque and are likely to progress unless
cleaned thoroughly. The ozone-treated lesions
received ozone for 40 seconds and application of a
glass ionomer preventive sealing, which was
subsequently replaced with a posterior composite
at 3 months. The control lesions received
conventional drilling and filling (posterior
composite). All the ozone-treated lesions were
reported to have reversed at 3 months. Six
complaints (17.1%) of postoperative sensitivity were
reported after conventional drilling and filling at
6 months compared with none after ozone
treatment (p < 0.05). Postoperative sensitivity is,
however, a measure commonly used to assess large
carious lesions and it is questionable whether it
should be used for early carious lesions. Moreover,
complaints of postoperative sensitivity after
occlusal restorations are rare.
Clinical reversal of caries: primary dentition One
full-text study assessed the use of ozone for the
treatment of non-cavitated primary posterior teeth
in children aged 79 years.38 Occlusal lesions were
assigned to receive ozone for 10 seconds followed
by a reductant or a reductant only. The proportion
of lesions that improved, remained stable or
deteriorated in each intervention group was not
20 provided and the clinical severity findings were
only presented graphically. The graph showed a
steady increase in the mean change from baseline
clinical severity scores for the control group,
compared with an initial slight decrease and a
subsequent levelling in the ozone group at
12 months. The overall changes in the clinical
severity scores9 were analysed using a mixed-
effects ANOVA. This analysis assumed that
patients and teeth within patients had a random
effect, while group and time of treatment had a
fixed effect. There was overall little reduction in
clinical severity scores in the ozone-treated group,
while an overall increase was observed in the
control group. There was a statistically significant
effect of treatment upon clinical severity scores
with time (p < 0.01).
Sealant retention The Abu-Nabaa main study37
also assessed the use of ozone for 10 seconds with
and without a fissure sealant. No sealants were
reported to be lost in either the ozone plus sealant
group or the sealant-only group. The percentage
of partial loss in the ozone plus sealant group at
12 months was 32.7%, and in the sealant-only
group was 29.8%, with no significant differences
between groups (this indicates similar rates of
reinterventions between groups for repairing
partial sealant loss).

Discussion of results and
conclusions on the evidence for
and against the intervention
Only a limited number of RCTs (five full-text
reports and five studies reported as abstracts) were
available for assessing the effects of ozone for the
management of root carious lesions and pit and
fissure carious lesions. Of these only one was
published in a refereed journal, but lacked some
study details, while the remaining studies were
derived from PhD theses, unpublished reports or
conference proceedings. All full-text studies with
the exception of the Holmes study were conducted
by the same research team that developed the
procedure, led by Professor Lynch of Queens
University, but Holmes was at one time part of the
same group, having done his PhD in Belfast. The
methodological quality varied across studies and
information on method of randomisation,
concealment of allocation, blinding procedures
and statistical methods was lacking in many of
them. Therefore, interpretation of studies results
was not straightforward. A quantitative synthesis of
results was not feasible owing to the differences
among studies regarding intervention, dosage of
ozone and outcome measures.
There were some concerns over the
appropriateness of the methods of analysis
adopted by study investigators. All studies in this
review were of a hierarchical structure, although
not necessarily treated as such for analysis.
Specific types of analysis are required when data
have a hierarchical structure. The hierarchy occurs
as smaller units, such as lesions or teeth, are
clustered together within a larger unit, the patient.
In most studies included in this review, the
statistical analysis was carried out at the lesion
level. However, two lesions within one patient are
not strictly independent, so analysis at the lesion
level is inappropriate. A more suitable statistical
analysis takes into account the hierarchical
clustering of lesions within a subject.59
In the simple case of two lesions per person, one
receiving control and one receiving the ozone
treatment, paired data are produced. In this case,
the appropriate paired analysis would be a
McNemar 2 test for dichotomous data,
a Wilcoxon signed rank test for ordinal data and
a paired t-test for continuous data. The choice of
statistical tests that ignore the pairing of the data
is more conservative and may fail to detect
important differences found by paired analysis.59
In the case of more than two lesions per subject,
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Health Technology Assessment 2006; Vol. 10: No. 16
multilevel modelling procedures would need to
be used.
Baysan and Lynch36 stated that statistical tests
were used, but they did not specify which
particular tests. Holmes used 2 tests, but did not
specify whether they were McNemar 2 tests.
Abu-Nabaa37 (main and pilot studies) recognised
the fact that there were pairs of teeth. However, in
some cases there were multiple pairs of teeth per
person and it is not clear whether this was taken
into account. Abu-Salem38 used analysis of
variance for a mixed effects model. This type of
analysis is hierarchical in nature, with one
component for the patients and one for the tooth
within the patient. However, as not enough
information was provided by the author it was not
possible to determine whether the statistical
analysis was conducted appropriately.
For primary non-cavitated root caries both the
Holmes study35 and the Baysan and Lynch study36
reported high success rates for ozone-treated
lesions compared with control lesions. However,
the lack of reversal of caries among controls
receiving conventional treatment (reductant)
known to be efficacious is puzzling.
Cavitated root lesions did not seem to benefit
from ozone application, showing indeed a
negative effect over time, but no formal statistical
analysis was presented.
Treatment results of pit and fissure caries of
permanent teeth were not consistent across
studies. The Abu-Nabaa main study did not show
any significant differences between non-cavitated
lesions treated with or without ozone. Similarly,
the Abu-Nabaa pilot study,37 which included
lesions with cavitation, did not demonstrate any
significant effect of ozone apart from an
improvement in the hardness and visual clinical
indices. In contrast, results from conference
proceedings (methodologically less reliable)
provided very high success rates (from 86.6% to
100% of reversal of caries).
Data on the use of ozone for the treatment
of primary teeth were available from only one
study, which suggested an overall reduction in
clinical severity scores for non-cavitated occlusal
lesions in primary molars treated with ozone
(p < 0.01).38
The adjunct of ozone to a fissure sealant produced
a better sealant retention in root carious lesions
(61% of sealant retention versus 42%, p < 0.05),36 21
 Effectiveness
but not in pit and fissure carious lesions (32.7%
versus 29.8%).37
On the whole, and despite the differences
reported in some studies (e.g. Holmes), there are
as yet insufficient published full-text studies (only
one refereed journal article) to provide convincing
evidence on the effectiveness of ozone for the
management of caries.
This review was done independently of the
Cochrane systematic review on ozone therapy for
the treatment of dental caries,60 which concluded
that at present there is no reliable evidence on the
effectiveness of ozone applications to arrest or
reverse the decay process. The present version of
the Cochrane review does not include the Holmes
(2003) and Abu-Salem (2004) studies.
22
Important subgroup differences
There are not enough data on which to assess the
effects of ozone on cavitated caries in the
permanent dentition (both occlusal caries and root
caries) or on non-cavitated occlusal caries in the
deciduous dentition (only one study involved
children with primary teeth38). No data are
available on cavitated occlusal caries in deciduous
teeth, secondary caries or high-risk patient
categories.
Adverse effects of intervention
None of the studies reported any adverse events in
the intervention group.

Chapter 4
Systematic review of economic evaluations
Methods
Search strategies
In addition to the electronic searches and
handsearches detailed in Chapter 3, a search of
the NHS Economic Evaluation Database (NHS
EED) and the Health Management Information
Consortium was undertaken for economic
evaluations of ozone for dental caries. Details of
the searches are provided in Appendix 1.
Studies that reported both costs and outcomes of
HealOzone compared with any of the comparators
were sought. The manufacturers submission to the
National Institute for Health and Clinical
Excellence (NICE) was also scanned for relevant
economic evidence.
Inclusion and exclusion criteria
To be included, studies needed to compare
HealOzone with any of the existing comparators
in terms of their costs and effectiveness. Studies
reported in languages other than English were
identified from the literature searches, but would
not be included in the review unless a structured
abstract was available from NHS EED. A single
economist assessed all abstracts for relevance. Full-
text papers were then obtained for all studies that
appeared potentially relevant and were formally
assessed for relevance.
Data abstraction
The following data were extracted for each
included study:
study characteristics:
research question
study design
comparison
setting
basis of costing
characteristics of the study population or of the
populations that formed the basis of data used
in a modelling exercise:
numbers receiving or randomised to each
intervention
dates to which data of effectiveness and costs
relate
duration of follow-up for both effectiveness and
costs
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Health Technology Assessment 2006; Vol. 10: No. 16
results
summary of effectiveness and costs (point
estimate and, if reported, range or standard
deviation)
summary of cost-effectiveness/utility (point
estimate and, if reported, range or standard
deviation)
sensitivity analysis
conclusions as reported by the authors of the
study.
Quality assessment
A single economist assessed the quality of included
studies using a published checklist.61 The
questions were set out on a standard form
generated before the review.
Data synthesis
Data from included studies were assessed and
summarised by a single economist, and
interpreted alongside the results of the systematic
review of effectiveness so that conclusions could be
drawn on the relative efficiency of HealOzone
compared with alternative treatments.
Results
The search revealed no published economic
evaluations of HealOzone. One published trial was
found which discussed the costs and effectiveness
of the management of primary root caries with
HealOzone.35 However, since the cost information
is limited to estimates of the total cost of dentistry,
with no detail of costs and consequences of the
alternatives, the study did not meet all of the
methodological criteria listed in Table 14 to be
classified as an economic evaluation and therefore
was not further reviewed. Two abstracts
concerning studies on the costs and benefits of
HealOzone for dental caries were found, but did
not provide sufficient details of study design or
data for the purpose of this review.62,63 However,
the industry submission from KaVo Dental (August
2004) provided an economic evaluation. The
remainder of this section provides a summary and
critique of that submission.
The unpublished industry submission from KaVo
Dental Ltd, UK (KaVo: Clinical and cost 23
 Systematic review of economic evaluations
TABLE 14 Quality assessment of the economic evaluation presented in the industry submission by KaVo
Quality component
1. Was a well-defined question posed in an answerable form?
2. Was a comprehensive description of the competing
alternatives given (i.e. can you tell who did what, to
whom, where and how often)?
3. Was there evidence that the programmes effectiveness
had been established?
4. Were all the important and relevant costs and
consequences for each alternative identified?
5. Were costs and consequences measured accurately in
appropriate physical units?
6. Were costs and consequences valued credibly?
7. Were costs and consequences adjusted for differential
timing?
8. Was an incremental analysis of costs and consequences
of alternatives performed?
9. Was allowance made for uncertainty in the estimates of
costs and consequences?
10. Did the presentation and discussion of study results
include all issues of concern to users?
C-PCF, cavitated pit and fissure caries; NC-PCF, non-cavitated pit and fissure caries; QALY, quality-adjusted life-year;
RC, root caries.
effectiveness of HealOzone for the treatment and
management of dental caries, 2004) included an
economic model of HealOzone compared with
current treatment for non-cavitated pit and fissure
caries, cavitated pit and fissure caries, and root
caries. Both a base-case and a probabilistic analysis
were included. The submission comprised both a
text document and supporting Excel spreadsheets.
Table 14 provides a summarised assessment of the
KaVo industry submission based on the ten critical
appraisal components.61
Review of industry submission
The first part of this section provides a summary
of the methods and results from the economic
evaluation of HealOzone reported in the industry
submission. This is followed by a critical review of
24 the evaluation.
Assessment and comments
Yes
Yes: current treatments were defined as:
NC-PFC: sealants
C-PFC: glass ionomer, composite resin and amalgam
restoration
RC: glass ionomer and composite resin restoration
Limited owing to short follow-up of included studies and
inability to compare/combine results from more than one
study owing to differences in study characteristics. None
of the studies used specifically considered C-PFC,
although the model does include such effectiveness data
based on assumptions outlined in the following critique
Yes: the base-case analysis assumes that the capital
cost of HealOzone is borne by dental practices. This
assumption is varied for sensitivity analysis
Yes
Not always: see critique of QALY estimation
Yes: a discount rate of 3.5% was used
Yes: see critique
Yes
Yes
Summary of the industry submission
The submission by KaVo included a cost-
effectiveness analysis over a 5-year time horizon of
HealOzone treatment versus current management
for non-cavitated pit and fissure caries, cavitated
pit and fissure caries, and cavitated root caries.
The current management treatments were defined
as follows:
non-cavitated pit and fissure caries: sealants
cavitated pit and fissure caries: glass ionomer,
composite resin and amalgam fillings
root caries glass ionomer and composite resin
restorations.
These comparators were identified from the
expert opinion of four dentists. The submission
does not consider preventive treatments such as
oral hygiene or advice on diet along with surface
applications of fluoride and sealants as a
comparator. The intervention with HealOzone is

defined as an initial treatment with HealOzone
followed by 12 weeks of treatment with
mineralising toothpaste, oral rinse and spray, with
the possible addition of restorative treatments. An
opinion survey of 243 dentists practising
HealOzone treatment was used to estimate the
proportion of teeth that would require additional
restorative treatment at the same time as the
HealOzone application or at any time
subsequently, but only 48 provided usable
responses.
Effectiveness data were obtained from a review of
published evidence for HealOzone and the
current management of dental caries. Clinical
outcomes included caries progression and reversal.
Costs included those of comparators plus costs of
rerestorations avoided. The costs of each current
treatment comparator were estimated from
published data for the treatments defined above.
All cost data were estimated from the perspective
of the NHS and were presented in UK pounds
sterling () at 2003 prices. Their method was to
translate the treatments into relevant treatment
codes listed in the Statement of Dental
Remuneration (SDR codes)64 and then to use
GDS65 data to identify the total annual numbers of
such treatments. These data are presented
separately for patients aged less than 18 years and
those aged 18 years and over. The same source
(GDS) gives annual total treatment costs which,
when combined with annual treatment numbers,
gave a unit cost per treatment item. These figures
were adjusted to take account of SDR codes
relating to more than one tooth and more than
one type of caries. The unit cost estimates do not
appear to differentiate between primary
restorations on virgin tooth surfaces and
secondary restorations, the latter being outside the
scope of the study since these would be unsuitable
for treatment with HealOzone. Finally, these unit
cost estimates were adjusted to reflect the fact that
patients under 18 years receive free NHS dental
care and those aged 18 years and over pay 80% of
their NHS dental fees, unless they are eligible for
free treatment. It was assumed that the dental
practice and not the NHS would fund the capital
cost and running cost of the actual HealOzone
device.
Using these unit cost estimates the industry model
assesses the annual cost to the NHS for each
comparator. To estimate the annual cost to the
NHS of the HealOzone comparator the industry
submission carried out a survey of dentists to
estimate the proportion of teeth currently treated
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Health Technology Assessment 2006; Vol. 10: No. 16
for either non-cavitated pit and fissure caries,
cavitated pit and fissure caries or root caries that
would be suitable for treatment with HealOzone.
This survey also asked dentists to estimate the
proportion of HealOzone-treated teeth that would
require some restorative treatment either at the
time of HealOzone treatment or sometime
afterwards. These restorative treatments were
defined similarly to current management
treatments for each caries type.
The unit cost of HealOzone treatment was based
on the cost of patient consumables and dentists
time (in practice, a dentist is remunerated by a fee
per item of service as listed in the SDR and these
fees are intended to reflect the costs incurred by
dental practices). Using the results of a
questionnaire survey of dentists who use
HealOzone in their own dental practice the
estimated unit cost for a course of HealOzone-
treatment was then adjusted to reflect the
estimated percentages of HealOzone-treated teeth
that would require additional restorative
treatment. On the basis of responses to this
questionnaire an additional cost of restoration
(using current management in addition to
HealOzone) was applied to 44% of non-cavitated
pit and fissure caries, 84% of cavitated pit and
fissure caries and 47% of root caries.
The cost to the NHS of HealOzone also took into
account the proportion of treatment fees paid by
the NHS rather than by patients as described
above for current treatment costs. The unit cost
for a course of HealOzone procedure was based on
an assumption of more than one HealOzone
application per course of treatment. The model
used a mean of 2.5 HealOzone applications per
course of treatment (range 14). This was based
on data from KaVo Dental.
An additional cost was added to reflect the
weighted average cost per tooth year of
rerestorations avoided. This was based on data
from a study that reported the average cost per
tooth year of restoration in teeth previously filled
with amalgam or composite resin for each type of
caries over 5 and 10 years. When calculating the
cost of rerestorations avoided the costs of the
original restoration are removed to avoid double
counting.66
The model uses rates of caries progression and
regression taken from a variety of unpublished
and published clinical studies. The mean values
for annual rates of caries progression for the
current treatments assumed in the industry 25
 Systematic review of economic evaluations
submission, along with the study reference from
which these values were obtained, are: non-
cavitated pit and fissure caries 0%,67 cavitated pit
and fissure caries 4.9%,6870 and root caries
3.9%.68,69
The progression rates cited for HealOzone were
all 0%, taken from studies with follow-up of
321 months.35,40,42,44,53,71,72
Caries reversal rates for non-HealOzone
treatments were assumed to be zero. The industry
submission does cite a 15% reversal rate found in
a study reporting the use of varnish
(chlorhexidine), but this value was excluded from
the industry submission on the grounds that such
varnish is not cited in the SDR codes. Rates of
caries reversal in teeth treated with HealOzone
were derived from 11 studies with follow-up times
ranging from 3 to 21 months. The annualised
mean values used for base-case analysis were: non-
cavitated pit and fissure caries 93.3%,53,55 cavitated
pit and fissure caries 79.0%,7277 and root caries
84.5%.35,40,42,44,57,71
Although no evidence was available to estimate
underlying QALY scores, the industry submission
model estimated alternative cost per QALY
thresholds of between 10,000 and 40,000
assuming quality of life benefits from 1 day to
1 month. The assumptions for QALY estimates
were utility gains of 0.01, 0.02, 0.05 and 0.1 for
restorations avoided.
The model was run to provide results using base-
case data. The deterministic base-case analysis
used mean values from the minimum and
maximum values inputted for each parameter.
Both one-way analysis and multivariate sensitivity
analysis were also conducted. Stochastic analysis
was conducted using Monte Carlo simulation over
10,000 cycles. Random numbers were used to
select data inputs from those provided.
Results
The average baseline figure estimated in the
industry model, across all caries types, for the
incremental cost to the NHS per tooth treated
with HealOzone was 6.24. Allowing for the cost
of rerestorations avoided (see earlier description),
the net incremental cost per tooth treated with
HealOzone was minus 9.70. The industry model
also resulted in an estimated NHS cost of 61 per
case of caries progression avoided (for all caries
types) using a 5-year model time horizon, and
assuming up to 35 cases per 1000 avoided per
26 year (152 over 5 years). An estimated 846 cases of
caries reversal per 100 cases treated with
HealOzone were reported, with an estimated NHS
cost case of per caries reversal of 7.38, again for
all caries types.
The estimated minimum utility gain (at 0.095) to
achieve a cost per QALY of 30,000 was found to
be for the use of HealOzone for root caries
treatment. This was estimated using alternative
cost-effectiveness acceptability thresholds based on
varying the length of time over which a utility gain
was accrued.
Sensitivity analysis indicated that the main drivers
of cost and cost-effectiveness were numbers of
teeth treated per treatment session and the
numbers of treatments per course of therapy.
Multivariate analysis revealed that despite
uncertainty around the cost of HealOzone,
HealOzone would be likely to be cost-effective
over a 10-year follow-up period.
The report also discusses the wider implications to
the NHS, impact on patient health and equity
issues. The results of the economic evaluation are
used to estimate the budget impact to the NHS
from the use of HealOzone technology for all
caries treatment of all eligible teeth. The figures
include both initial treatment costs and the
estimated costs of rerestorations avoided. On this
basis, an annual net incremental cost of 48.1
million in year 1, reducing to 11.8 million by
year 5, was estimated for HealOzone. These
results assume that the capital and running
costs of the HealOzone device are funded by
dental practices, with no contribution from the
NHS apart from the fee for service. If the
exchequer provided additional funds for the
device this would cost the NHS an additional
110.4 million, assuming one device per dental
practice in England and Wales. Additional
annual servicing costs are estimated at 10.8
million.
Although the evaluation does not include patient
health as an outcome in the model, the results
include a brief description of possible effects on
patient health, based on studies of patient
attitudes to dental treatment.
Equity issues are also briefly discussed in the
results. The report cites evidence suggesting a link
between caries incidence and deprivation, and
that deprived populations would be one group less
likely to benefit from HealOzone technology as
long as it is only available through private dental
treatment.

Critique of industry submission
On the whole, the economic evaluation submitted
by KaVo Ltd is based on reasonable economic
evaluation methodology. Nevertheless, a number
of concerns can be raised relating to the choice of
comparators and the quality of data used to
parameterise the economic model.
The comparators used in the industry submission
for non-cavitated caries were based on restorative
treatment of caries. The evaluation did not
consider preventive measures for early caries.
However, the management of non-cavitated caries
rarely requires fillings, as it is now well established
that preventive treatments for early lesions can be
effective in reversing and arresting further
progression of caries. Furthermore, HealOzone
has been cited as being most effective in the role
of prevention and early management of lesions.78
It would therefore have been appropriate for the
industry model to include conservative treatments
aimed at ensuring reversal of early caries as
additional comparators for non-cavitated caries.
The HealOzone comparator includes an
assumption about the proportions of teeth that
would require additional treatment to HealOzone
treatment alone. These assumptions are taken
from a survey of 243 dentists who currently use
HealOzone, of whom only 48 provided usable
responses. Given the absence of robust, objective
clinical data, options to obtain relevant model
parameter values are limited. Nonetheless, such
data are potentially biased and unreliable and the
considerable uncertainty would be reduced if
actual clinical evidence were to exist. This was a
non-randomised survey of opinion and cannot
therefore be interpreted as having a strong
evidence source. It does not appear that any
random selection process was used to recruit
dentists for the survey, and therefore it is unclear
whether any attempt was made to obtain a
balanced opinion.
The industry evaluation of implications to the
NHS includes an assumption about the numbers
of teeth suitable for treatment with HealOzone.
These figures were again estimated from
information taken from a survey of dentists who
are users of HealOzone.
The assumption concerning the funding of the
capital cost of providing a HealOzone device in
dental surgeries was that this would not affect the
fee for service. In reality, however, it would be
expected that any additional contribution by the
NHS towards capital costs incurred by dental
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Health Technology Assessment 2006; Vol. 10: No. 16
practices would be offset by lowering subsequent
fees paid to dentists for the associated therapy.
Estimates of caries progression and reversal rates
were extracted from a range of studies of varying
degrees of quality, including published and
unpublished RCTs, conference abstracts and PhD
theses. Some of the limitations of these data
sources are discussed in Chapter 3. Caries
progression rates for current management were
extracted from studies that did not include
HealOzone as a comparator and the patient mix
may be different. Caries progression rates for
HealOzone were estimated from studies with
follow-up periods from as little as 3 months, all of
which claimed a 0% caries progression rate. Other
studies show higher caries progression rates.
Selecting the most favourable studies biases the
results.
Rates of caries reversal with current management
were assumed to be zero despite a 15% reversal
rate being reported in one study. This rate was
excluded from the analysis on the grounds that it
was associated with the application of
chlorhexidine varnish and this was assumed by the
authors of the industry report not to be a standard
NHS dental treatment. However, dentists
commonly rank application of varnish among
treatments for sensitive cementum or dentine
(code 3631 in the SDR).
Source data for caries reversal associated with the
use of HealOzone came from 14 studies, three of
which had follow-up of less than 3 months. Only
the latter were included in the sensitivity analysis.
The remaining 11 studies differed in design and
quality. For non-cavitated pit and fissure caries
effectiveness data were extracted from studies with
36-month follow-up.53,55 For cavitated pit and
fissure caries, despite finding no available
evidence, data from five studies were used in the
model. The assumption used to justify this is the
following:
None of the available studies specifically describes
the treatment of cavitated pit and fissure caries. In the
absence of such detail, the studies presented in this
section refer to carious lesions, which are deemed to
require drilling and filling. While non-cavitated caries
may be treated in this way, drilling and filling is the
conventional treatment for cavitated caries and it is
therefore assumed that these studies included a
proportion of cavitated caries. (KaVo Dental, 2004).
A further concern is that, although the industry
submission report does acknowledge the limitation
of combining data from more than one study, 27
 Systematic review of economic evaluations
given the disparity in inclusion/exclusion criteria
and other study characteristics, the reversal rates
and progression rates used as the mean rates for
base-case analysis were calculated using the results
from more than one study.
Estimates of the cost of rerestorations avoided
are based on a number of assumptions and the
report does acknowledge the absence of
published data for rates of future rerestorations.
Instead, the model uses published data for the
average cost per tooth year of rerestoration in
teeth previously filled with amalgam or
composite resin over 5 and 10 years (KaVo
industry submission, 2004). It is unclear in the
report exactly how estimates of the numbers of
future rerestorations would be avoided as a
result of HealOzone treatment, although the
report does provide estimates for the cost of such
rerestorations avoided. Given the considerable
uncertainty surrounding the rate of rerestorations,
28
the figures used should be interpreted with care.
Realistically, such data could only be obtained
from the outcomes of a long-term study of the
effectiveness of the relevant comparators. QALY
estimates are included in the economic evaluation,
but are not based on quality of life data. Instead,
assumptions concerning the amount of utility gain
and duration of gain were used to derive QALY
thresholds. Given the short duration of any
potential intermittent change in quality of life,
along with the high degree of uncertainty
surrounding any estimates of QALY scores, the
additional information value of such QALY
thresholds is dubious.
Although the economic evaluation in the industry
submission is well presented, the choice of
comparator is questionable and considerable
uncertainty surrounds many of the parameter
values used in the model. Therefore, their results
overestimate the benefits of HealOzone.

Chapter 5
Economic analysis
iven the current state of the clinical
G effectiveness evidence, with little published in
full in peer-reviewed journals, it could be argued
that economic analysis is premature. However,
NICE always requests some attempt at economic
appraisal, if only to clarify the data deficits.
Therefore, the following analysis has been
produced more as illustrative modelling than as
hard evidence.
Methods for economic analysis
The economic evaluation aimed to assess the cost-
effectiveness of HealOzone relative to the
alternative interventions for the treatment of both
occlusal pit and fissure caries and root caries. As
identified in the previous section, economic
evaluations of HealOzone versus conventional
treatments of dental caries were virtually non-
existent at the time of this review. This section
provides an economic evaluation using cost-
effectiveness analysis and presents economic
models of the treatment of non-cavitated pit and
fissure caries, and root caries. They compare
current management versus current management
plus HealOzone. The results over the extended
period must be qualified by the fact that follow-up
data on HealOzone are limited to 2 years. The
results reported in this section should be
interpreted on the understanding that they
entirely depend on the model parameters and
assumptions made. The authors recommend that
the model be rerun in the future if evidence on
clinical effectiveness is published.
Markov model framework
This section presents a description of the Markov
model developed for the assessment, and of the
parameters that were common across all models.
Key parameters specific to each model and
results are then presented separately for each
comparator. The section concludes with a
summary of the results for all comparators and of
the factors deemed to be most critical in affecting
the results.
Markov modelling techniques were used to assess
the cost-effectiveness of HealOzone plus current
management, relative to the standard current
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Health Technology Assessment 2006; Vol. 10: No. 16
management of dental caries. A Markov model is
composed of a set of defined health states among
which a patient can move over successive periods
and is run using a hypothetical cohort of patients.
The model incorporates both the logical and
temporal sequences of treatment, including the
events that follow from the initial treatment
procedure and the outcomes for the patient that
are associated with each possible scenario or
clinical pathway. Transition probabilities are used
to allow patients to move within and between
these states of health. A patient can only be in one
state of health at any time and can only make one
transition per cycle. A relevant period is chosen
for the length of a cycle and the cycles then link
together to form a Markov chain. The length of
cycle used in this study was 1 year. When the
model is run over the defined number of cycles, a
discounted net present value (NPV) for the cost of
an intervention is calculated, determined by the
occurrence of different states and the length of
time in various states.
The models were designed to estimate a typical
patients costs and outcomes for the alternative
treatments over a 5-year period. A 5-year time
horizon was chosen to facilitate comparison with
the results from the industry model. Figure 10
summarises the basic structure of the model.
Similar models were developed to carry out the
analysis for non-cavitated pit and fissure caries,
and non-cavitated root caries
Non-cavitated pit and fissure caries
The model for non-cavitated pit and fissure caries
compares current management strategies (i.e.
watchful waiting, oral hygiene/removal of plaque,
fluoride applications and sealants) versus the same
strategy plus HealOzone.
Non-cavitated root caries
The model for non-cavitated root caries compares
current management strategies (i.e. removal of
plaque, topical fluorides, chlorhexidine and a
sealant) versus the same strategy plus HealOzone.
Model pathways
The pathways for each model were developed in
accordance with the protocol for the assessment
along with expert opinion from members of a 29
 Economic analysis
Early caries initial
treatment
Current management (watchful
waiting, oral hygiene/plaque
removal, fluoride, sealants)
Reversal of caries
Progression of caries
Tooth filled
Progression of caries
FIGURE 10 Model for primary non-cavitated pit and fissure caries
local dental school. All models have simplified
clinical event pathways, but are designed to reflect
those clinical events of importance to the
evaluation (Figures 1518 in Appendix 6).
Non-cavitated pit and fissure caries and root
caries
Following initial treatment carious lesions may
either reverse or not reverse. Lesions that do not
show reversal of caries progression after the initial
intervention require additional treatment. This is a
further application of the initial preventive/non-
restorative treatment or a restorative treatment (i.e.
drilling and filling). In those receiving further
preventive/non-restorative treatments, caries can
again be reversed or treated with filling (Figure 10).
The event pathway is split into two mutually
exclusive events, the reversal (cure) of caries and
no reversal of caries. The arrows between these
states represent the possible transitions between
them. Movement between the different states is
governed by the transition probabilities, such as
the chance of the caries reversing. The absorbing
state in this model is a tooth with a filling. While
30 this is not an absorbing state in reality, given the
Current management plus
HealOzone
Reversal of caries
Initial treatment
repeated
Reversal of caries
Tooth filled
5-year timescale of the model, and that a typical
filling would last longer than 5 years, no states
beyond filling were included. It was assumed that
once a tooth was cured it remained in a cured state
for the rest of the 5 years. TREEAGE DATA 4.0
software (TREEAGE Software, 2001) was used to
construct the model.
Estimation of parameters
Probabilities
The time horizon considered in the Markov model
was a maximum of 5 years. The outcome
considered in the economic evaluation was the
numbers of carious lesions cured. The main
probabilities used in the model were the rates of
reversal (cure) of caries. These rates were derived
from the effectiveness study (Chapter 3) and
consultation with dental practitioners. The
probability of cure rates (Table 15) obtained from
the effectiveness studies and used in the first run
of the economic model were: HealOzone 0.074
(7.4%) for the non-cavitated pit and fissure
caries37 and 0.98 (98%)35 for the non-cavitated
root caries. The rates used for current
management were 0.056 (5.6%)37 for non-
 Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 15 Probabilities used in the economic model

Intervention Probability Source

HealOzone cure rate (non-cavitated pit fissures) 0.074 Table 11, Chapter 3
Current management cure rate (non-cavitated pit fissures) 0.056 Table 11, Chapter 3
HealOzone cure rate (non-cavitated root caries) 0.98 Table 9, Chapter 3
Current management cure rate (non-cavitated root caries) 0.01 Table 9, Chapter 3
Percentage being retreated with initial treatment 0.50 Discussions with expert
Percentage being retreated with filling 0.50 Discussions with expert

TABLE 16 Unit cost per itema

Type Current treatment (SDR code) Cost ()

Non-cavitated pit and fissure caries

Hygiene/diet advice (0601) 7.70
Chlorhexidine gel/varnish or fluoride varnish (3631) 4.60
Fissure sealant (0701) 6.95
Total (sum of above) 19.25
Non-cavitated root caries
Hygiene/diet advice (0601) 7.70
Chlorhexidine gel/varnish or fluoride varnish (3631) 4.60
Total (sum of above) 12.30
Cavitated pit and fissure caries
Sealant only (1441) 6.95
Composite resin (1442) 9.80
Glass-ionomer (1443) 10.55
Amalgam (1401 or 1421) 7.15
(posterior)
14.15
(anterior)
Total (average of above) 16.98
HealOzone (No SDR code) 20
(estimate)
a
Costs are those that would be incurred by the NHS and exclude patient contributions to dental fees. Further details of
cost calculations are presented in Appendix 6.

cavitated pit and fissure caries and 0.01(1%) for Costs

non-cavitated root caries.35 These values, which
are highly favourable to HealOzone, were different
to those used in the industry model, which
aggregated data from a number of studies, some
of which did not meet the inclusion criteria
specified in this review. In the absence of any
alternative information, it was assumed for the
purposes of the model that, following initial
treatment, there was a 0.50 (50%) chance of
subsequent treatment being the same treatment as
the initial one received or a filling.
The root caries cure rates are taken from the
Holmes study,54 the results of which seem
puzzling; they reflect a best possible case for
HealOzone.
The perspective adopted for the study is that of
the NHS and Personal Social Services. The unit
costs of dental treatments were taken directly from
cost data published by the NHS.65 Table 16
provides details of the different treatments with
corresponding codes from the NHS SDR for each
treatment item. Unit costs are listed for each
treatment item and represent the fee paid by the
NHS to the dentist for each item of service.
Resource-use data were identified from existing
literature, reports from manufacturers and advice
from experts in this field. Based on existing
evidence and clinical opinion, patients were
assumed to visit the dentist every 6 months. Cost
data were measured in pounds sterling () for the 31

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 Economic analysis
TABLE 17 Weighted average costs used in the modela
Intervention
Current management
Non-cavitated pit and fissure caries
Non-cavitated root caries
Current management plus HealOzone
Non-cavitated pit and fissure caries
Non-cavitated root caries
Restorative interventions
Filling
a
Costs are those that would be incurred by the NHS excluding patient contributions to dental fees.
year 2004. As specified by the guidelines for
conducting health technology assessment, cost-
effectiveness results should reflect the present
value of the stream of costs and benefit accruing
over the time horizon of the analysis.79 To make
the analysis consistent with the model used in the
industry submission the analysis was carried out
over a period of 5 years. An annual discount rate
of 3.5% was applied to both costs and benefits
accrued, the rate currently specified in the HTA
guidelines.79
The per-item fee for service paid by the NHS was
used as a proxy for costs to the NHS of current
management. Under the current NHS dental
system patients pay 80% of the dentists fee, with
the remaining 20% being paid by the exchequer
(except that there is a maximum charge for a
course of dental treatment of 366). Some
patients, including all those less than 18 years old,
are entitled to free treatment and the exchequer
pays the full cost of treatment. Recent figures
report that 25% of all claims for patients aged 18
years and over were exempt from patient
charges.65 The other 75% of claims for patients
aged 18 and over therefore include a patient
contribution at 80% of the amount of the claim
and an NHS contribution of 20%. Taking these
data into account, the average net NHS
contribution equates to 40% [25% + (20% of
75%)] of any NHS dental claim for patients aged
18 and over. As children (persons under 18 years
of age) are exempt from paying NHS dental
treatment fees, the full cost of all claims for those
less than 18 years old was used as the cost to the
NHS. The data used in the industry model
indicated that the NHS contribution to those aged
32 18 and over was 52%.
Cost ()
Under 18 Over 18 Weighted
19.25 7.70 9.02
12.30 4.92 6.09
39.25 15.70 20.03
32.30 12.92 17.10
19.67 7.87 12.75
In the absence of separate effectiveness data for
adults and children it was decided to combine all
age groups for the base-case analysis. A two-stage
process was required to weight the unit costs to
represent a mixed population of adults and
children. Further details of the stages involved in
the cost calculations are reported in Appendix 6.
Published statistics65 indicate that adults and
children do not receive similar proportions of each
treatment item among the different treatment
items listed in Table 16. The first stage was
therefore to calculate the percentage mix of
children and adults for each identified SDR
component of the treatment. These proportions
were then weighted by the amount that the NHS
contributed using the figures described earlier, at
100% of the amount of a claim per child and 40%
per adult. Following this two-stage weighting
process, the adjusted costs to the NHS used in the
model were 9.02 for the non-cavitated pit and
fissure caries and 6.09 for non-cavitated root
caries, and a filling was estimated at 12.75.
Details of the costs are included in Table 17.
The costs of HealOzone were calculated using the
existing NHS methods and information from the
manufacturer. Most of the studies indicated that
HealOzone treatment is given at the start, and
repeated at 3 and 6 months. The cost of
HealOzone therefore took into account that
patients could receive between one and three
applications. The cost of HealOzone treatment
also included that of current management as
HealOzone was considered as an additional
treatment and not as a stand-alone treatment. The
weighted average cost of current management
plus HealOzone treatment used in the model was
20.03 for non-cavitated pit and fissure caries and

17.10 for non-cavitated root caries. These values
were not similar to those used in the industry
model as they focused on costs and benefits to the
NHS in England and Wales as a whole, rather
than on costs and benefits faced by the average
patient.
Quality of life
It was not possible to measure health benefits in
terms of QALYs. This was mainly because the
adverse events avoided are transient: a few
seconds pain from injection of local anaesthetic;
the anxiety/fear of having a drill and numbness
until the local anaesthesia wears off.
Sensitivity analysis
As every economic analysis contains some degree
of uncertainty, imprecision or methodological
controversy, and this one more than most, a
sensitivity analysis was performed. Given the
limited effectiveness data for estimating rates of
caries reversal, the models were rerun using
different probability values of reversal of caries.
Assumptions were also made about what items to
include in each of the interventions and sensitivity
analysis was performed using different codes to
determine the costs, namely the SDR codes used
in the industry submission.
Results
The analysis, carried out over a 5-year period
using the data reported in the trials, indicated that
treatment using current management plus
HealOzone cost more than current management
alone for non-cavitated pit and fissure caries
(40.49 versus 24.78), but cost less for non-
cavitated root caries (14.63 versus 21.45). For
non-cavitated pit and fissure caries 91.8% of the
teeth treated using current management received
a filling and 8.2% of teeth were cured. For teeth
treated with current management plus
HealOzone, 89.2% received fillings and 10.8%
were cured. This was different from the results of
the Cochrane review by Ahovuo-Saloranta and
colleagues,32 which reported that the reduction in
caries ranged from 86% at 12 months to 57% at
4854 months. This review focused, however, on
the prevention (and not the treatment) of tooth
decay in children and adolescents who presented
with no obvious caries. Based on the Holmes
study,54 1.5% of teeth were cured at 5 years in the
non-cavitated root caries group treated with
current management and 98.5% teeth were filled,
while 99.9% of teeth were cured by the
combination of current management and
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Health Technology Assessment 2006; Vol. 10: No. 16
HealOzone and 0.01% were filled. The present
authors remain sceptical about these results.
Sensitivity analysis
There was very little suitable evidence on the
effectiveness of the HealOzone comparator. One-
way sensitivity analysis was applied to the model to
assess the robustness of the results to variations in
the underlying data. The probability of caries
being cured was varied for each comparator
separately, using the baseline cure rate for the
alternative comparator. These results indicated
that when higher probability cure rates were used
the proportion of teeth filled was lower at
12 months. These results were similar to those of
the Cochrane review by Ahovuo-Saloranta and
colleagues.32 However, as the focus of the
Cochrane review was on the prevention of dental
decay in the permanent teeth of children and
adolescents, the extrapolation of its results to an
adult population with dental caries might be
questionable.
The results of the one-way sensitivity analyses are
illustrated in Figures 1114 and presented in
tabular form in Appendix 6 (Tables 2932).
In Figure 11 the costs refer to those of current
management when the baseline cure rates of
HealOzone are used (0.074). The discounted NPV
for the cost of HealOzone was 40.49. The above
results indicate that the discounted NPV of the
cost of the HealOzone comparator, using baseline
parameter values for HealOzone, was higher than
that of current management at any probability of
cure with current management. This is mainly
attributable to the fact that the baseline cure rate
used in the model is less than 10%. The results
also indicate that as the probability of cure rate
increases, the cost reduces and the number of
teeth filled also reduces.
In Figure 12 the costs refer to those of HealOzone
plus current management when the baseline
annual cure rate of current management is used
(0.056). The discounted NPV for the cost of
current management was 24.78. Varying the
probability of the cure rates of HealOzone plus
current management, and using the baseline cure
rate probability for current management,
indicated that the HealOzone option was always
more expensive than current management when
the probability of cure using the HealOzone
option was 70% or lower.
In Figure 13 the costs of HealOzone reflect the
costs when the baseline probability of cure of 33
 Economic analysis

45.00

40.00

35.00
Current management
30.00
HealOzone
NPV ()

25.00

20.00

15.00

10.00

5.00

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Probability of current management cure rate

FIGURE 11 One-way sensitivity analysis for non-cavitated pit and fissure caries: discounted NPV of each comparator at alternative
cure rates for current management, holding the baseline cure rate for HealOzone plus current management constant

45.00
Current management
40.00 HealOzone

35.00

30.00
NPV ()

25.00

20.00

15.00

10.00

5.00

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Probability of HealOzone cure rate

FIGURE 12 One-way sensitivity analysis for non-cavitated pit and fissure caries: discounted NPV of each comparator at alternative
cure rates for HealOzone plus current management, holding the baseline cure rate for current management constant

current management (0.01) was used and the
probability of cure of HealOzone management was
varied accordingly. The one-way sensitivity analysis
results show that discounted NPVs for the costs of
current management plus HealOzone were lower
than those of current management only when cure
rates from current management plus HealOzone
34 were at least 80% and above.
In Figure 14 the costs of current management reflect
the costs when the baseline probability of cure of
HealOzone (0.98) was used and the probability of
cure of current management was varied accordingly.
The discounted NPVs for the costs of current
management were higher than those of current
management plus HealOzone when the cure rate
for current management was 40% or lower.
 Health Technology Assessment 2006; Vol. 10: No. 16

45.00
Current management
40.00
HealOzone
35.00

30.00

25.00
NPV ()

20.00

15.00

10.00

5.00

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Probability of HealOzone cure rate

FIGURE 13 One-way sensitivity analysis for non-cavitated root caries: discounted NPV of each comparator at alternative cure rates
for HealOzone plus current management, holding the baseline cure rate for current management constant

25.00

Current management

20.00 HealOzone

15.00
NPV ()

10.00

5.00

0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Probability of current management cure rate

FIGURE 14 One-way sensitivity analysis for non-cavitated root caries: discounted NPV of each comparator at alternative cure rates
for current management, holding the baseline cure rate for HealOzone plus current management constant 35

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 Economic analysis
TABLE 18 Industry submission model inputs for annual treatment items and cost for patients under 18 years of agea
Procedure
Non-cavitated pit and fissure caries
Fissure sealant: sealant only
Fissure sealant: composite resin
Fissure sealant: composite resin and glass ionomer
Root caries
Composite/synthetic: one filling
Composite/synthetic: two or more fillings
Glass ionomer: one filling
Glass ionomer: two or more fillings
a
The current costs of treatment were estimated using the GDS treatment items reported for the year ending March 2003
(KaVo Dental Ltd, industry submission, 2004, p. 62).
One-way sensitivity analysis was also carried out
using similar SDR codes to those used in the
industry submission. Table 18 shows the SDR codes
used by the industry for patients under 18 years of
age. The figures for those over 18 years were
similar. This did not alter the results for non-
cavitated pit fissure caries as the discounted NPV
of current management remained lower than that
of the HealOzone comparator (22.65 versus
33.39). These results could be attributed to the
fact that it was assumed that patients received the
same treatment as the initial one and the cost of
current management plus HealOzone is much
higher than that of current management alone,
given that HealOzone is an additional treatment
rather than an alternative treatment. Results using
the SDR codes used for non-cavitated root caries
in the industry model gave similar results to those
in the base-case analysis. HealOzone cost less than
current management (17.66 versus 30.41).
Discussion
The economic analysis was greatly constrained by
the uncertainty over clinical effectiveness;
36
SDR code Unit cost ()
1441 6.50
1442 9.15
1444 13.71
1421 13.22
1421 10.32
1426 12.08
1426 8.22
therefore, the results should be regarded mainly as
illustrations of the key variables and hence
interpreted cautiously as they reflect the
parameter values and assumptions used in the
model. A further constraint was the lack of long-
term data on the effectiveness of HealOzone (it is
not known whether caries that is reversed will
always stay in the inactive/arrested state or
whether future treatments will be required). To
attempt to model longer term effects the available
12-month data were extrapolated to 5 years. It is
not known at this stage whether this assumption is
valid. Another possible area of uncertainty was
related to whether the response to HealOzone
treatment would increase with increasing dose
levels.
It was not possible to model the treatment of
cavitated caries since no effectiveness data on
direct comparisons were available. The analysis
was carried out on a hypothetical cohort of teeth
with carious lesions and did into take into account
the proportion of teeth that are unsuitable for
HealOzone treatment. Further research is
therefore necessary to support a complete
economic evaluation.

Chapter 6
Implications for the NHS
National Service Framework
The majority of general dental practitioners in the
UK are contracted to the NHS through GDS,
although, as independent contractors, dentists
who offer NHS treatment may also offer certain
treatments on a private basis. Dentists receive
fixed fees per item of treatment for adults, while
for children they receive a combination of fixed
fees per item and capitation fees. Under this NHS
system patients can pay up to 80% of the cost of
their treatment up to a maximum cost of around
366. Some patients are entitled to free NHS
dental treatment, including children, young
people in full-time education, pregnant women
and those with a child under 1 year old, and
people on low incomes. The costs of running a
dental practice, including capital costs of
equipment, are met by the dental practice rather
than the NHS, and recovered from the fee for
service charges paid by the patients and the NHS.
In addition to dentists contracted to provide NHS
treatment, some of whom also offer private
treatment, there are many dentists in the UK who
only provide treatment on a private basis.
Currently, HealOzone treatment is only available
as a private treatment from a limited number of
dentists.
Health targets
There are no specific health targets, although in
England the Department of Health set a target to
reduce tooth decay in 5-year-olds to low levels by
2003, while in Wales the official target was to
achieve no more than 48% of 5-year-olds having
tooth decay by 2002.80
The new Base Dental Contract (based on the
personal dental services model) will be introduced
for all practices in April 2006. The new contract
will be more likely to have a greater preventive
and capitation element.81
Fair access
At the time of writing HealOzone treatment was
only available through private dental care and it
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Health Technology Assessment 2006; Vol. 10: No. 16
was estimated that there were 294 HealOzone
units in the UK (at June 2004). Were ozone
therapy to be made available, provision of
HealOzone units would have to be increased much
beyond this to allow all suitable patients fair access
to the treatment.
Equity issues
The availability of HealOzone treatment is
currently limited to those people who are able
and willing to pay for the treatment privately.
However, in the present state of knowledge, it
cannot be said that people suffer by being unable
to afford it.
Budget implications to the NHS
At present, HealOzone is only available to patients
through private dental care. The aim of this
section is to estimate what the implications would
be to the NHS if HealOzone were made available
as an NHS dental service.
The models used in the economic evaluation
described in Chapter 5 considered the costs and
effectiveness of current treatment with and without
the addition of HealOzone for arresting the
progression of dental caries (further details of
these cost calculations are presented in Appendix
6). The evaluation does not consider those teeth
with carious lesions, which would be unsuitable for
HealOzone therapy. These could be considered in
the estimated implications to the NHS for the
total population of teeth with carious lesions if
estimated numbers of such teeth were available. To
achieve this it is necessary to make assumptions
about the proportion of teeth currently treated for
caries that would be suitable for alternative
HealOzone treatment. This proportion would be
used to calculate the total annual number of
treated teeth.
Data from GDS provide statistics for the numbers
of teeth treated by SDR code in a year for adults
and children in England and Wales. At the time of
writing the latest available GDS data were those
pertaining to the year ending March 2003. 37
 Implications for the NHS
TABLE 19 NHS annual cost for treatment of non-cavitated pit and fissure caries
Current management
HealOzone plus current management
Net difference in cost
Net difference in cost per tooth treated initially
TABLE 20 NHS annual cost for treatment of non-cavitated root caries
Current management
HealOzone plus current management
Net difference in cost
Net difference in cost per tooth treated initially
The following results were calculated by
combining the GDS data with assumptions about
the SDR codes relevant to each caries type to
estimate annual numbers of teeth treated for non-
cavitated pit and fissure caries and non-cavitated
root caries. Again, teeth with cavitated caries were
not considered given the absence of evidence on
the effectiveness of HealOzone as a comparator
treatment for cavitated caries.
Non-cavitated pit and fissure caries
The discounted NPV for the cost over 5 years of
teeth treated initially with current management or
HealOzone plus current management was
reported in Chapter 5. These figures were
combined with the numbers of teeth treated
initially using annual GDS data for the SDR codes
in the present treatment definitions. The results
should, however, be interpreted with extreme
caution given that they are based on the limited
effectiveness data available for the economic
analysis, as reported in Chapters 3 and 5 of this
report.
The total discounted NPV over 5 years for treating
non-cavitated primary fissure caries was estimated
at 8,565,765 for current management and
13,996,280 for HealOzone therapy (Table 19).
The base-case results showed that by 5 years
fillings were present in 91.8% of teeth treated with
current management compared with 89.2% of
teeth treated with HealOzone plus current
management. Using these figures the incremental
cost per tooth treated would be 15.71, at an
initial total cost to the NHS of 5,430,515. The
incremental cost over 5 years for the HealOzone
comparator compared with current management
38 (13,996,2808,565,765 ) was divided by the
NPV of treatment cost over 5 years ()
8,565,765
13,996,280
5,430,515
15.71
NPV of treatment cost over 5 years ()
7,371,882
5,876,885
1,494,997
4.35
difference in numbers of teeth filled at 5 years for
the HealOzone comparator and current
management (308,340317,327). The incremental
cost per filling avoided, using these assumptions,
would be estimated at 604.23.
The industry submission estimates for the
percentage of teeth currently treated that would
be suitable for HealOzone, obtained from the
opinion of current users of HealOzone, were 92%
for non-cavitated pit and fissure caries, 76% for
cavitated pit and fissure caries, and 76% for root
caries. These figures were derived from Table 15 in
the industry submission.
Non-cavitated root caries
The total discounted NPV over 5 years for treating
non-cavitated root caries, using the best case for
HealOzone again, would be estimated at
7,371,882 for current management and
5,876,885 for HealOzone therapy. The net
difference in these two costs shows that
HealOzone therapy would save the NHS 4.35 per
tooth treated initially with HealOzone in addition
to current management for root caries, a total cost
saving over 5 years of 1,494,997 (Table 20).
These figures are estimated using base-case values
for caries reversal rates. Limited suitable
effectiveness data were available for reversal rates
of root caries, apart from a single study reporting
reversal rates of 1% for current management and
98% for HealOzone treatment. Given the extreme
values of reversal rates for the comparators, based
on the limited effectiveness data available at the
time of analysis, these results need to be
interpreted with caution. It was only possible to
carry out limited one-way sensitivity analyses,

varying cure rates separately for the HealOzone
and current management comparators (see
Chapter 5). From the results of the sensitivity
analyses it can be seen that the net difference in
cost per tooth treated initially was higher for
current management unless the probability of cure
for the HealOzone comparator was lower than
approximately 80%.
It is advisable that the reader interprets all such
results merely as an illustration of possible
scenarios. In the light of limited evidence on
effectiveness, a more detailed analysis of budget
implications was not considered likely to add any
useful information to the evaluation.
The cost implications over time are difficult to
ascertain since there are many uncertain factors to
take into account. Further research is required to
model the cost implications over time, taking into
account the cost of rerestorations beyond the
lifetime of first fillings and their effects over time
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Health Technology Assessment 2006; Vol. 10: No. 16
on the tooth population. For example, it is
unknown how long an arrested carious lesion
remains inactive. Any prospective trial should have
sufficient follow-up to allow for this.
Importantly, the above results are based on the
authors assumptions for the management of the
different types of caries.
In addition, it is difficult to estimate the actual
cost of HealOzone to the NHS. Assuming that
patients who pay some of their dental treatment
fees are willing to pay no more than current
treatment for the same condition initially, what
would the cost-effectiveness ratio be? Would
patients opt for this treatment if it was more
expensive?
Finally, would patients be given a choice for caries
management or would dentists have to follow
some guidelines about the best treatment? This
has implications on the numbers of teeth treated.
39

Chapter 7
Discussion
Main results
Clinical effectiveness
The literature on ozone treatment is still at a
relatively early stage, in the sense that only one
paper has been published in full in a refereed
journal. Most of the reports are available only in
abstract form, as conference proceedings, and
inevitably give few details. Many trials are still very
short term and none of the studies has followed
up the patients after they have stopped ozone
treatment for a reasonable length of time. It is also
worthwhile remembering that caries is a dynamic
process: a lesion can remineralise without the
need for any intervention, and the rate of caries
progression can be very slow.
HealOzone is supposed to kill the microorganisms
(bacteria) responsible for dental plaque formation.
However, unless patients have improved their
plaque control and eliminated the causes of the
increased numbers of microorganisms, the plaque
will re-form and the lesion will progress again.
This raises the question of whether HealOzone is
a reasonable preventive technology. Furthermore,
treatments based on HealOzone would need to be
repeated for an indeterminate numbers of years to
be beneficial, with obvious cost implications.
The available evidence is conflicting, with the root
caries treatment showing much better results than
treatment for pit and fissure caries. However, the
results are surprising, partly because the ozone
group did so well, with 99% cure or improvement,
but mainly because the control group performed
very badly, despite receiving the same care
package (oral hygiene, topical fluoride, etc.) but
without the application of ozone. Compliance of
patients with treatment, however, was not assessed
in the included studies.
In particular, it proved difficult to identify the
additional role of ozone gas from the patient kit
or the synergistic effect between ozone and the
patient kit, which contained, among other
elements, fluoride and xyliton. It would have been
useful, for example, to know the effects of ozone
alone, namely ozone gas, together with the
patients normal brushing or how HealOzone
compares to professional plaque control (the
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Health Technology Assessment 2006; Vol. 10: No. 16
removal of plaque by a dentist or hygienist), which
has been used effectively in the management of
dental caries in adults. A recent study assessing the
outcomes of a 30-year preventive programme
based on professional and self-performed plaque
control has shown how high standards of oral
hygiene are associated with a very low incidence of
dental caries and periodontal disease in adults.82
Cost-effectiveness
If HealOzone led to a reduction in future fillings,
then the extra cost might be justified. The authors
do not believe that the evidence base yet supports
that.
Need for further research
Nearly all the research to date comes from the
same group who developed and pioneered the
procedure, and have the greatest experience in its
use. There is a need for large, well-conducted
RCTs to assess the effectiveness and cost-
effectiveness of HealOzone for the management of
both occlusal and root caries. In particular, future
trials:
should be conducted by independent research
teams
should be properly randomised so that an equal
number of lesions, or paired lesions, per mouth
are allocated to intervention groups
should apply appropriate statistical methods for
the analysis of paired-data on a patient basis;
should use validated and reproducible criteria
for the assessment of caries
should measure relevant outcomes such as
reduction in caries incidence over a reasonable
period (at least 2 years, but realistically much
longer)
should mask participants and outcome assessors
should provide both a statistical and a clinical
interpretation of their findings
should conform to the CONSORT guidelines
for the reporting of RCTs.83
Owing to the natural history of the caries process,
any future trial would need to include a very long
follow-up, which would have a significant impact
on trial costs. 41
 Discussion
There also appears to be a need for evaluation of
the different methods of assessing caries severity.
The base case could be clinical examination, with
the marginal benefits and costs of more
sophisticated techniques assessed. Although the
economic evaluation was not able to provide
results that could be used by decision-makers, it
was a valuable exercise in highlighting the paucity
of good quality data on key parameters. In
particular, the paucity of suitable data from
published clinical trials comparing the
effectiveness of HealOzone with appropriate
comparators restricted the scope of the economic
model. No comparable quality of life data were
available for the comparators, thus limiting the
range of outcomes available for an evaluation.
These gaps in the data needed to undertake an
informative economic evaluation of HealOzone
can only be filled through further research in the
form of prospective RCTs.
To provide adequate information to assess the
cost-effectiveness of HealOzone, any future
economic evaluation of HealOzone should feature
the following characteristics:
42
It should be based on data from properly
conducted RCTs of HealOzone versus
appropriate comparators (e.g. no treatment or
current management).
Follow-up of patients should be long enough to
allow identification of both short-term and
long-term resource use and effectiveness.
Outcome data must include both short-term
and long-term rates of caries reversal, caries
progression, retreatment and/or rerestoration.
Separate consideration is needed for cavitated
and non-cavitated caries.
Sufficient power is needed to allow for robust
subgroup analyses for deciduous and
permanent teeth, and for variation in caries
severity.
An estimate of the unit cost of HealOzone to
the NHS should be based on calculations
similar to those underlying the SDR figures for
current dental treatments provided by the NHS.
Factors affecting patients quality of life should
be considered, both at the point of treatment
and during follow-up (e.g. the effect on quality
of life due to pain from toothache).
 Health Technology Assessment 2006; Vol. 10: No. 16

Chapter 8
Conclusion
ny treatment that preserves teeth and avoids conclude that it is a cost-effective addition to the
A fillings is welcome. However, the current
evidence base for HealOzone is insufficient to
management and treatment of occlusal and root
caries.

43

Queens Printer and Controller of HMSO 2006. All rights reserved.


Acknowledgements
rateful thanks to Heather Mackintosh for her
G secretarial support.
The views and opinions expressed are those of the
authors and do not necessarily reflect those of the
funding bodies.
Publication information
The Aberdeen Health Technology Assessment
Group is part of the Institute of Applied Health
Sciences (IAHS). The Institute of Applied Health
Sciences within the College of Medicine and Life
Sciences of the University of Aberdeen is made up
of discrete but methodologically related research
groups. The HTA Group is drawn mainly from the
Health Services Research Unit, the Department of
Public Health and the Health Economics
Research Unit.
The HTA Group carries out independent health
technology assessment reports (TARs) for the UK
HTA Programme, which commissions TARs for
the National Institute for Health and Clinical
Excellence (NICE) and other bodies, such as the
National Screening Committee. In addition, a
Queens Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 16
joint venture between the Health Services
Research Unit at Aberdeen and the Medical Care
Research Unit at Sheffield University forms the
Review Body for Interventional Procedures
(ReBIP) Programme within NICE. ReBIP
undertakes systematic reviews and, where
appropriate, establishes UK registries to collect
and analyse data on the efficacy and safety of
selected procedures.
Contribution of authors
Miriam Brazzelli (Research Fellow) and Shona
Fielding (Medical Statistician) completed the
review of effectiveness. Lynda McKenzie (Research
Fellow) conducted the review of economic
evaluations. Lynda McKenzie and Mary Kilonzo
(Research Fellow) conducted the economic
evaluation. Cynthia Fraser (Information Scientist)
developed and ran the search strategies. Norman
Waugh (Professor of Public Health) provided
oversight and contributed to drafting the review.
Jan Clarkson (Honary Consultant in Paediatric
Dentistry) provided clinical advice and
commented on the draft review.
45

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 Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 1
Literature search strategies
Sources searched for systematic Search strategies used to identify
reviews, other evidence-based reports assessing ozone therapy
reports and background for dental caries
information MEDLINE (1966 to week 1 2004),
Databases EMBASE (1980 to week 20 2004),
Cochrane Database of Systematic Reviews (CDSR). (MEDLINE Extra 17 May 2004)
The Cochrane Library (Issue 2, 2004). Ovid Multifile Search.
Database of Abstracts of Reviews of Effectiveness URL: http://gateway.ovid.com/athens
(NHS Centre for Reviews and Dissemination), 1 (healozone or curazone).tw.
April 2004. 2 ozone/ (14334)
HTA Database (NHS Centre for Reviews and 3 (ozone or o3).tw.
Dissemination), April 2004. 4 (oxidat$ or oxidis$).tw.
Trip database. URL: http://www.tripdatabase.com/. 5 or/2-4
Accessed May 2004. 6 exp tooth demineralization/ use mesz
7 dental caries/ use emez
Websites 8 demineralization/ use emez
The Dental, Oral and Craniofacial Data Resource 9 Dental Caries Susceptibility/ use mesz
Center (DRC). URL: http://drc.nidcr.nih.gov/ 10 Dental Enamel Solubility/
default.htm. Accessed July 2004. 11 (caries or carious).tw.
National Center for Health Statistics. 12 ((tooth or teeth or dental or dentine or enamel
URL: http://www.cdc.gov/nchs/nhanes.htm. or root? or occlusal) adj5 decay$).tw.
Accessed July 2004. 13 ((tooth or teeth or dental or dentine or enamel
British Association for the Study of Community or root? or occlusal) adj5 cavit$).tw.
Dentistry. URL: http://www.bascd.org/ Accessed 14 ((tooth or teeth or dental or root? or dentine or
July 2004. occlusal or enamel or cavitated) adj5
KaVo Dental Ltd. URL: http://www.kavo.com/En/ lesion?).tw.
default.asp. Accessed April 2004. 15 ((tooth or teeth or dental or dentine or
CurOzone USA Inc. enamel) adj5 (minerali$ or deminerali$ or
URL: http://www.curozone.com/. Accessed April reminerali$)).tw.
2004. 16 or/6-15
DentalOzone. London: Dental Clinique. 17 1 or (5 and 16)
URL: http://www.dentalozone.co.uk/. Accessed 18 human/
April 2004. 19 animal/ use mesz
HealOzone. Dr Julian Holmes. URL: 20 nonhuman/ use emez
http://www.the-o-zone.cc/. Accessed April 2004. 21 (19 or 20) not 18
NHS Dental Practice Board. 22 17 not 21
URL: http://www.dpb.nhs.uk/gds/index.shtml. 23 remove duplicates from 22
Accessed July 2004.
Department of Health.
URL: http://www.dh.gov.uk/Home/fs/en.
Accessed April 2004.

51

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 Appendix 1

Science Citation Index 1981 to 16 May AMED (1985 to May 2004)

2004) Ovid. URL: http://gateway.ovid.com/
Web of Science Proceedings 1990 to athens
15 May 2004) 1 (healozone or curazone).tw
Web of Knowledge. 2 (ozone or o3).tw.
URL: http://wok.mimas.ac.uk/ 3 (oxidat$ or oxidis$).tw.
#1 TS= (Healozone or curazone) 4 or/2-3
#2 TS= (ozone or o3) 5 (caries or carious).tw
#3 TS=(oxidat* or oxidis*) 6 ((tooth or teeth or dental or dentine or enamel
#4 #2 or #3 or root? or occlusal) adj5 decay$).tw
#5 TS=(caries or carious) 7 ((tooth or teeth or dental or dentine or enamel
#6 TS=((tooth or teeth or dental or dentine or or root? or occlusal) adj5 cavit$).tw
enamel or root* or occlusal) SAME decay*) 8 ((tooth or teeth or dental or root? or dentine or
#7 TS=((tooth or teeth or dental or root* or occlusal or enamel or cavitated) adj5 lesion?).tw
dentine or occlusal or enamel or cavitated) 9 ((tooth or teeth or dental or dentine or
SAME lesion*) enamel) adj5 (minerali$ or deminerali$ or
#8 TS=((tooth or teeth or dental or dentine or reminerali$)).tw
enamel or root* or occlusal) SAME cavit*) 10 or/5-9
#9 TS=(( tooth or teeth or dental or dentine or 11 1 or (4 and 10)
enamel) SAME (minerali* OR deminerali* 12
OR reminerali*))
#10 #5 OR #6 OR #7 OR #8 OR #9 Cochrane Library Issue 2, 2004
#11 #4 AND #10 URL: http://www.update-software.com/
#12 #1 OR #11 clibng/cliblogon.htm
National Research Register
BIOSIS (1985 to 12 May 2004) (Issue 2, 2004)
Edina. URL: http://edina.ac.uk/biosis/ URL: http://www.update-
(tn: (humans)) and (((al: (healozone)) or al: software.com/National/
(curazone)) or ((((al: (oxidat*)) or al: (oxidis*)) or #1. (healozone or curazone)
((al: (ozone)) or al: (o3))) and ((((((al: (caries)) or #2. OZONE single term (MeSH)
al: (carious)) or ((((al: (root n5 decay*)) or al: #3. (ozone or o3)
(roots n5 decay*)) or (((al: (dentine n5 decay*)) or #4. (oxidat* or oxidis*)
al: (enamel n5 decay*)) or al: (occlusal n5 #5. (#2 or #3 or #4)
decay*))) or (((al: (tooth n5 decay*)) or al: (teeth #6. TOOTH DEMINERALIZATION explode
n5 decay*)) or al: (dental n5 decay*)))) or ((((al: tree 1 (MeSH)
(root n5 cavit*)) or al: (roots n5 cavit*)) or (((al: #7. DENTAL CARIES SUSCEPTIBILITY single
(dentine n5 cavit*)) or al: (occlusal n5 cavit*)) or term (MeSH)
al: (enamel n5 cavit*))) or (((al: (tooth n5 cavi*)) #8. DENTAL ENAMEL SOLUBILITY single
or al: (teeth n5 cavit*)) or al: (dental n5 cavit*)))) term (MeSH)
or (((((al: (root n5 lesion*)) or al: (roots n5 #9. (caries or carious)
lesion*)) or (((al: (dentine n5 lesion*)) or al: #10. ((tooth or teeth or dental or dentine or
(enamel n5 lesion*)) or al: (occlusal n5 lesion*))) enamel or root* or occlusal) and decay*)
or (((al: (tooth n5 lesion*)) or al: (teeth n5 #11. ((tooth or teeth or dental or dentine or
lesion*)) or al: (dental n5 lesion*))) or (al: enamel or root* or occlusal) and cavit*)
(cavitated n5 lesion*)))) or ((((((al: (tooth n5 #12. ((tooth or teeth or dental or dentine or
minerali*)) or al: (tooth n5 reminerali*)) or al: enamel or root* or occlusal or cavitated) and
(tooth n5 deminerali*)) or (((al: (teeth n5 lesion*)
mineral*)) or al: (teeth n5 reminerali*)) or al: #13. ((tooth or teeth or dental or dentine or
(teeth n5 deminerali*))) or (((al: (dent* n5 enamel) and (mineralis* or demineralis* or
minerali*)) or al: (dent* n5 reminerali*)) or al: remineralis*))
(dent* n5 deminerali*))) or (((al: (enamel n5 #14. ((tooth or teeth or dental or dentine or
minerali*)) or al: (enamel n5 reminerali*)) or al: enamel) and (mineraliz* or demineraliz* or
(enamel n5 deminerali*)))))) remineraliz*))
#15. (#6 or #7 or #8 or #9 or #10 or #11 or
#12 or #13 or #14)
#16. (#5 and #15)
52 #17. (#1 or #16)
 Health Technology Assessment 2006; Vol. 10: No. 16

DARE, NHS Economic Evaluation IARD/AADR/CADR 82nd General Session,

Database and HTA Databases Honolulu, March2004
(April 2004) AADR 32nd Annual Meeting and Exhibition, San
NHS Centre for Reviews and Antonio, March 2003
Dissemination IADR 81st General Session, Goteberg 2003
URL: http://nhscrd.york.ac.uk/ IADR, Irish Division Annual Meeting, Belfast,
welcome.htm 2004
Ozone or healozone or oxid* - all fields BSDR Ann Scientific Meeting, Birmingham, April
Dental or caries or carious all fields 2004

Clinical Trials (18 May 2004) ozone or healozone or oxid*

URL: http://clinicaltrials.gov/ct/gui/c/r
Current Controlled Trials (18 May Handsearching
2004)
URL: http://www.controlled-trials.com/ Journal of Dental Research
Ozone or healozone or oxid* all fields Vol. 79 (Special Issue 2000): 78th General Session
of IADR, Washington, USA, April 2000.
Health Management Information Vol. 79(5) 2000: British Section: Annual Scientific
Consortium (May 2004) Session, Lancaster, UK, April 2000; Irish Section:
1 (healozone or curazone).tw. Annual Scientific Meeting, Newcastle, Ireland,
2 dental caries/ January 1999.
3 (caries or carious).tw. Vol. 80 (Special Issue, AADR Abstracts, January
4 ((tooth or teeth or dental or dentine or enamel 2001): 30th Annual Meeting AADR/25th Annual
or root? or occlusal) adj1 decay$).tw. Meeting CADR, Chicago, USA, March 2001.
5 ((tooth or teeth or dental or dentine or enamel Vol. 80(4) (April 2001): British Society for Dental
or root? or occlusal) adj1 cavit$).tw. Research and Irish Division, Continental
6 ((tooth or teeth or dental or dentine or enamel European (1999 and 2000).
or cavitated) adj1 lesion?).tw.
7 ((tooth or teeth or dental or dentine or Caries Research
enamel) adj1 (minerali$ or deminerali$ or Vol. 37(4): 50th Annual ORCA Congress, Konstanz
reminerali$)).tw. Germany, July 2003.
8 or/1-7 Vol. 36(3): 49th Annual ORCA Congress, Naantali
9 limit 8 to yr=1995 2004 Finland, July 2002.
Vol. 35(4): 48th Annual ORCA Congress, Graz,
Conference Papers Index (1982 to Austria, July 2001.
May 2002) Vol 34(4): 47th Annual ORCA Congress, Alghero,
Cambridge Scientific Abstracts Sardinia, July 2000.
URL: http://www.csa1.co.uk/
KW=(healozone or curazone) or (KW=(ozone or
oxidat* or oxidis*) and KW=(caries or carious or Websites
dental)) or (KW=(ozone or oxidat* or oxidis*)
and KW=(teeth or tooth or cavit*)) or KaVo Dental Ltd. URL: http://www.kavo.com/En/
(KW=(ozone or oxidat* or oxidis*) and default.asp. Accessed April 2004.
KW=(occlusal or decay* or lesion*)) CurOzone USA Inc.
URL: http://www.curozone.com/. Accessed April
Zetoc Conference Search (1993 to 2004.
May 2004) DentalOzone. London: Dental Clinique.
MIMAS URL: http://zetoc.mimas.ac.uk/ URL: http://www.dentalozone.co.uk/. Accessed
Ozone or healoaone or oxid* and (conference: April 2004.
dental or dentist or caries) HealOzone. Dr Julian Holmes.
URL: http://www.the-o-zone.cc. Accessed April
IADR Meeting abstracts 2004.
URL: http://www.iadr.com/Meetings/
index.html
IARD/AADR/CADR 80th General Session, San
Diego, March 2002 53

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 Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 2
Data extraction form
HEALOZONE TECHNOLOGY ASSESSMENT REVIEW

DATA EXTRACTION FORM

Reviewer ID: Date information extracted:

Study Details

Study ID: _____________________________________________

Study identifier: _______________________________________

(Surname of first author + year of publication)

Study origin: _________________________________________

Language: ____________________________________________

Published Unpublished

Full text Abstract only

Study Design

RCT Other __________________________________________

Quasi RCT

Observational Study

For RCTs only: What is the unit of randomisation?

Patient

Tooth/lesion

Tooth/lesion pair

55

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 Appendix 2

Participants

Number of eligible patients: Number of patients randomised:

Inclusion criteria: Exclusion criteria:

Interventions

Type of intervention Number of participants

Group 1:

Group 2:

Group 3:

Patient Characteristics

Intervention 1 Intervention 2 Intervention 3 Total

Age (mean, range)
Sex (M/F)
Permanent/Deciduous teeth
Primary or Secondary caries
Comparability at baseline

Characteristics of the intervention

Location of trial centre(s):

Source of participants:

Method of recruitment:

56
 Health Technology Assessment 2006; Vol. 10: No. 16

Method of randomisation:

Dosage of HealOzone application:

Repeated applications:

Was a reductant applied? If yes, what was its formulation?

Did patient receive the aftercare kit (e.g. toothpaste, mouth rinse and spray)?

Length of follow-up:

Compliance with the treatment:

Number lost to follow-up:

Caries Information

Method of caries examination:

Tooth location, lesion location, and type of lesion:

Severity of caries:

Outcomes

Intervention 1 Intervention 2 Intervention 3

Non-cavitated caries

Reversal of caries

Progression of caries

Utilisation of dental resources

57

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 Appendix 2

Adverse reactions

Patientcentred measures (e.g. patient

satisfaction and preference, relief of
pain/discomfort)

Quality of life

Cavitated caries

Time to restorative interventions

Need for further restorative

interventions

Symptoms of pulpal pathology

Other comments

58
 Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 3
Checklist for the quality assessment of randomised
controlled trials
(adapted from Verhagen, 199834)

Criteria Yes No Unclear Comments

1. Was the assignment to the treatment groups really random?

Adequate approaches to sequence generation
computer-generated random tables

random number tables

Inadequate approaches to sequence generation

use of alternation, case record numbers, birth dates or week days

2. Was the unit of randomisation clear?

3. Was the treatment allocation concealed?
Adequate approaches to concealment of randomisation
centralised or pharmacy-controlled randomisation

serially-numbered identical containers

on-site computer based system with a randomisation sequence that is

not readable until allocation

other approaches with robust methods to prevent foreknowledge of

the allocation sequence to clinicians and patients

Inadequate approaches to concealment of randomisation
use of alternation, case record numbers, birth dates or week days

open random numbers lists

serially numbered envelopes (even sealed opaque envelopes can be

subject to manipulation)
4. Were the groups similar at baseline in terms of prognostic factors?
5. Were the eligibility criteria specified?
6. Were the groups treated in the same way apart from the
intervention received?
7. Was the outcome assessor blinded to the treatment allocation?
8. Was the care provider blinded?
9. Were the patients blinded?
10. Were the point estimates and measures of variability presented
for the primary outcome measures?
11. Was the withdrawal/dropout rate likely to cause bias?
12. Did the analyses include an intention-to-treat analysis?

59

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 Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 4
Characteristics of included studies:
full-text reports

61

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62
TABLE 21 Characteristics of full-text reports

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
Appendix 4

of participants and criteria

carious lesions

Root caries: permanent dentition

Baysan and Lynch, n =79 (220 primary Design: RCT Two or four Group 1: cleaning of the Reversal of caries, groups 1 and 2: The number of lesions in
200436,4144 cavitated and non- (unpublished) primary non- tooth surface, application of at 12 months 47% of PRCLs each intervention group was
(Belfast, UK) cavitated root carious cavitated and O3 + reductant reversed from severity index 1 to not clearly reported
Unit of
lesions) cavitated root The procedure was 0 (hard) in the ozone group,
randomisation: All subjects enrolled in the
carious lesions repeated after 1 month while none became hard in the
Age, mean SD (range): lesion study received preventive
with severity without ozone and at control group (p < 0.001). 52%
65 14.76 (3072) years advice, including oral
Method of index II 3 months with ozone of lesions reversed from 2 to 1 in
hygiene and dietary advice,
Gender (M/F): 49/30 randomisation: (leathery the ozone group compared with
Group 2: reductant only. and were given a toothbrush
NS lesions) 11.6% in the control group
Tooth and lesion location: The procedure was and toothpaste (Natural
root surface lesions. (p < 0.001)
Concealment of repeated after 1 month and White, Natural White Inc.,
allocation: NS at the 3-month follow-up Cavitated lesions in the ozone USA, 1100 ppm F)
Caries risk assessment:
NS group did not show the same
Blinding: unclear Group 3: O3 + sealant (Seal Unclear whether cleaning of
& Protect, Dentsply, trend of improvement of non-
the root surface was
ITT: no cavitated lesions. Percentage of
Germany) performed before treatment
Length of follow- lesions that became hard
The procedure was in groups 2, 3 and 4
up: 12 months decreased from 9.1 at 1 month to
repeated at 3 months. 1.4 at 9 months, suggesting It was reported that subjects
Lost at follow-up: Sealants were reapplied only worsening of cavitated carious who presented with any
five subjects if a partial or complete loss lesions. Data for the control form of discomfort were
of the sealant was suspected group were not given immediately treated with
Comparability of
groups at Group 4: sealant only (Seal conventional drilling and
Marginal adaptation of the root
baseline: unclear & Protect, Dentsply, filling procedures, but no
sealant (modified USPHS criteria):
Germany) further information was
Setting: general 61% intact sealants in the
Sealants were reapplied provided
dental practices O3 + sealant group compared
after 1 and 3 months only if with 26.1% in the sealant-only Methods for statistical
a partial or complete loss of group (p < 0.001) analyses not clearly
the sealant was suspected reported. Unclear whether
Significant differences in the
Reductant formulation: the results were adjusted
changes in both the ECM readings
Sodium fluoride (1100 ppm for covariates/risk factors
and DIAGNOdent readings in the
F), xylitol, sodium benzoate, ozone and control groups Emphasis on non-cavitated
among other active (p < 0.001) lesions
ingredients
Ozone dosage: 10 seconds Adverse events: none observed

continued
 TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
carious lesions

Caries assessment: ECM III

(Lode Diagnostics BV, The
Netherlands), DIAGNodent
(KaVo, Germany) and
clinical criteria. The severity
of lesions was assessed on a
four-point scale (0 = hard
lesions; 4 = soft lesions). In
addition, modified USPHS
criteria were used for
assessing groups 3 and 4
Assessors/operators: single
operator (A. Baysan)
Ozone device output: NS

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continued
Health Technology Assessment 2006; Vol. 10: No. 16

63
64
TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
Appendix 4

carious lesions

Holmes, 200335,39,40 n = 89 (178 primary non- Design: RCT Adults with Group 1: application of O3 18 months follow-up. All subjects enrolled in the
(Berkshire, UK) cavitated root carious two leathery + reductant + patient care study received information
Unit of Reversal of caries: 87/87 lesions in
lesions, 89 lesions in each non-cavitated kit on oral hygiene, brushing
randomisation: the ozone group reversed
group) PRCLs techniques and diet. In
lesion Group 2: air treatment + (became hard) compared with
particular, all subjects
Age, mean SD (range): reductant only + patient 1/87 in the control group
Method of received instructions on
70.8 6 (6082) care kit (p < 0.01)
randomisation: how to use the
Tooth and lesion computer- Repeated applications of O3 Progression of caries: 32/87 remineralising toothpaste
location: leathery roof generated + reductant at 3, 6, 12 and lesions in the control group twice a day, the mineral
surface lesions (severity random tables 18 months worsened from leathery to soft mouthwash twice a day and
index II) and 54/87 did not change the remineralising spray four
Concealment of Reductant formulation:
Caries risk assessment: xylitol, fluoride, calcium, Adverse events: none observed times a day
allocation: NS
NS phosphate and zinc (no All subjects were offered a
Blinding: double
concentrations provided) pharmacological treatment,
blind
Ozone dosage: 40 seconds which they all accepted as
ITT: no an alternative to the
Caries assessment: ECM traditional drilling and filling.
Length of follow-
(Lode Diagnostics BV, The No details of the
up: 3, 6, 12, 18
Netherlands), DIAGNodent pharmacological treatment
and 21 months
(KaVo, Germany) and were provided
Lost at follow-up: visual/tactile examination
two at 18 months method The two dentists who
allocated subjects to
Comparability of Assessors/operators: the intervention groups and
groups at ozone treatment was assessed severity of lesions,
baseline: unclear applied by a different and the third dentist who
operator to the one assessed reproducibility of
Setting: general
recording the severity of data, were not
dental practice
lesions. Unclear whether acknowledged in the paper
the operator who assessed
outcomes was the same one The 21-month findings
who did allocated subjects published in abstract format
to intervention groups. A (Holmes, 200440 seem to
contradict those reported in
sample of 15 subjects (30
the full text
lesions) was examined by a
third dentist to test
reproducibility of results
continued
 TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
carious lesions

Ozone device output: it was

reported that the
HealOzone unit was fitted
with a modified control
integrated electronic chip.
Unclear whether this
modified chip could allow
better calibration and
monitoring of ozone doses

Queens Printer and Controller of HMSO 2006. All rights reserved.

continued
Health Technology Assessment 2006; Vol. 10: No. 16

65
66
TABLE 21 Characteristics of full-text reports (contd)
Author(s) No. and characteristics Design
of participants and
carious lesions
Pit and fissure caries: permanent dentition
Abu-Nabaa, 2003, n = 90
main study37,4550 (258 primary occlusal pit
(Belfast, UK) and fissure carious
lesions)
Age: 79 subjects between
12 and 31 years, 8
subjects between 32 and
41 years, and 3 subjects
>41 years
Gender (M/F): 35/55
Tooth and lesion location:
all posterior teeth in the
upper and lower jaws.
Central grooves and pits
were the most commonly
observed lesions
Caries risk assessment:
NS
Inclusion Interventions Results Notes and caveats
criteria
Appendix 4
Design: RCT Males and Before treatment all lesions Groups 1 and 2 All subjects enrolled in the
(unpublished) females were disclosed and cleaned study received preventive
Reversal of caries: no significant
>12 years old with an air-abrasive system advice and were given a
Unit of differences between groups in the
with primary (PROPHYflex 2, KaVo, toothbrush and toothpaste
randomisation: mean change from baseline:
occlusal pit Germany) (Natural White; Natural
lesion Group 1: 0.283 (0.64)
and fissure White Inc., UK, 1100 ppm F)
Group 1: application of O3 Group 2: 0.443 (0.74);
Method of carious lesions
+ reductant (p = 0.112) Sealant was reapplied if
randomisation: in at least two
necessary and O3 application
random sampling teeth of the Group 2: reductant ECM values: no significant
repeated
digit tables permanent only/control differences in the mean change
posterior from baseline values between Subjects attendance to
Concealment of Group 3: O3 + reductant +
dentition, groups: follow-up visits varied. The
allocation: NS fissure sealant (Guardian,
which were Group 1 (109 lesions): mean loge number of subjects assessed
Kerr)
Blinding: unclear accessible for change 0.020 (1.4) by ECM differed from the
the diagnostic Group 4: reductant + Group 2 (109 lesions): 0.073 number of subjects assessed
ITT: no
procedures sealant (1.61) (p = 0.75) by DIAGNOdent at follow-
Length of follow- up visits
Reductant formulation: Excluding teeth with baseline
up: 1, 3, 6, 9 and
Sodium fluoride (1100 ppm ECM score 0:
12 months
F), xylitol and zinc chloride Group 1 (77 lesions): 0.327 (1.32)
Lost at follow-up: among other active Group 2 (69 lesions): 0.073
32 subjects ingredients (1.37); p = 0.54
Comparability of Ozone dosage: 10 seconds DIAGNOdent values: no
groups at baseline: significant differences between
Caries assessment: ECM
more severe groups (p > 0.05) at any follow-
(Lode Diagnostics BV, The
lesions (index
Netherlands), DIAGNodent up visits
scores of 2 and 3)
(KaVo, Germany) and Groups 3 and 4
in the treatment
clinical severity (Ekstrand,
group (p = 0.055). Secondary caries: no significant
1998).9 In addition, modified
More molars in the differences between groups (two
USPHS criteria +
treatment group secondary caries in the ozone
radiographic assessments
than in the control group and two secondary caries
were used for assessing
group. in the control group)
groups 3 and 4
Setting: general
dental practice
continued
 TABLE 21 Characteristics of full-text reports (contd)
Author(s) No. and characteristics Design Inclusion Interventions
of participants and criteria
carious lesions
Assessors/operators: three
operators were reported to
assess radiographs. A single
operator assessed the
lesions and interpreted ECM
and DIAGNOdent findings
(L. Abu-Nabaa)
Ozone device output: NS
Queens Printer and Controller of HMSO 2006. All rights reserved.
67
Results Notes and caveats
Sealant retention: partial loss in
the margins of the sealants in
32.7% in the O3 + sealant group
compared with 29.8% in the
sealant-only group (p > 0.05)
No significant differences in terms
of fissure sealant colour and
radiographic depth of
radiolucency between groups
continued
Health Technology Assessment 2006; Vol. 10: No. 16
68
TABLE 21 Characteristics of full-text reports (contd)

Author(s) No. and characteristics Design Inclusion Interventions Results Notes and caveats
of participants and criteria
Appendix 4

carious lesions

Abu-Nabaa, 2003, n=8 Design: RCT Males and Before treatment all lesions Clinical severity scores: not All subjects enrolled in the
pilot study37,51,52 (38 occlusal pit and fissure (unpublished) females were disclosed and cleaned significant differences between study received preventive
(Belfast, UK) lesions, 19 in each group) >12 years old with an air-abrasive system groups at any follow-up visits advice and were given a
Unit of
with primary (PROPHYflex 2, KaVo, (p > 0.05) toothbrush and toothpaste
randomisation:
occlusal pit Germany) (1100 ppm F)
lesion ECM and DIAGNOdent readings:
and fissure
Group 1: application of O3 no significant differences between
Method of carious lesions
+ reductant groups (p > 0.05)
randomisation: in at least two
random sampling teeth of the Group 2: reductant only Clinical indices
digit tables permanent Hardness index score: 11 lesions
At 3 months group 1
posterior in the ozone group became
Concealment of received another application
dentition, harder compared with four in the
allocation: NS of O3
which were control group (p < 0.05)
Blinding: unclear accessible for Reductant formulation: Two lesions in the control group
the diagnostic sodium fluoride became softer
ITT: no
procedures (1100 ppm F), xylitol and
Change in the visual index score:
Length of follow- zinc chloride among other
eight teeth in the treatment
up: 1, 3 and active ingredients
group changed positively at the
6 months
Ozone dosage: 40 seconds 6-month follow-up compared
Lost at follow-up: with one tooth in the control
Caries assessment: ECM
unclear group (p < 0.05)
(Lode Diagnostics BV, The
Comparability of Netherlands), DIAGNOdent Change in the cavitation score:
groups at baseline: (KaVo, Germany), and six teeth had a decreased cavity
more severe clinical criteria (Ekstrand,score in the ozone group
lesions (index 1998)9 compared with five teeth in the
score of 3) in the control group. The difference
Assessors/operators:
control group
Unclear. It would seem that between intervention groups was
Setting: general a single operator assessed not significant (p > 0.05)
dental practice the lesions and interpreted Change in colour: no significant
ECM and DIAGNOdent differences between groups
findings (L. Abu-Nabaa) (p > 0.05)
Ozone device output: 33% Change in frosted enamel and
of the outcome expected undermined enamel: no significant
differences between groups
(p > 0.05)
continued
 TABLE 21 Characteristics of full-text reports (contd)
Author(s) No. and characteristics Design
of participants and
carious lesions
Pit and fissure caries: primary dentition
Abu-Salem, 200438 n = 21
(Belfast, UK) (74 non-cavitated occlusal
carious lesions in primary
molars)
Age range: 79 years
(7 years 28%, 8 years
48%, 9 years 24%)
Gender (M/F): 9/21
Caries risk assessment:
NS
Queens Printer and Controller of HMSO 2006. All rights reserved.
NS, not stated; ITT, intention-to-treat, O3, ozone gas.
69
Design: RCT (unpublished)
Unit of randomisation:
lesion
Method of randomisation:
computer-generated
random tables
Concealment of allocation:
NS
Blinding: examiner blinded
to results of previous tests
and outcomes of previous
records
ITT: no
Length of follow-up: 3, 6, 9
and 12 months
Lost at follow-up: four
subjects (16 lesions)
Comparability of groups at
baseline: there was a
significant difference in
mean DIAGNOdent scores
at baseline (p < 0.01).
Lesions in ozone group
appeared to be more
severe than those in the
control group.
Setting: general dental
practice
Inclusion Interventions Results Notes and caveats
criteria
Children Before treatment, teeth 12-month follow-up All subjects received
79 years old were cleaned using the preventive advice and
Clinical severity scores:
with at least PROPHYflex-2 system for were given a
overall there was a little
two carious 5 seconds toothbrush (Brilliant,
reduction in clinical
lesions in the soft toothbrush;
Group 1: O3 + reductant severity scores in the
posterior Brilliant Products, UK)
ozone group and an
primary teeth Group 2: reductant only and toothpaste
increase in scores in the
and absence Reductant formulation: (Natural White, Natural
control group. There was
of occlusal White Inc., UK
sodium benzoate a significant effect of
restoration, (1100 ppm F), xylitol, zinc 1100 ppm F) at each
treatment on clinical
fissure recall to be used
chloride and sodium citrate severity scores over time
sealants, throughout the study
among other active (mixed models ANOVA
hypoplastic ingredients p < 0.01) The mean loge ECM
pits and
readings, mean
fractures Ozone dosage: 10 seconds Log ECM and
DIAGNOdent readings,
extending into DIAGNOdent readings:
Caries assessment: ECM ECM scores,
dentine or there was a significant
(Lode Diagnostics BV, The DIAGNOdent scores
cavitations effect of time and
Netherlands), DIAGNOdent and clinical severity
resulting from treatment on the mean
(KaVo, Germany) and index were analysed
carious attack clinical criteria (Ekstrand,
loge ECM readings
using ANOVA (mixed
on the (p < 0.001) and the mean
1998)9 effect model)
occlusal DIAGNOdent readings
surface (p < 0.001). There was Results reported in a
also an overall significant format that did not
effect of time and allow any further
treatment on ECM scores analysis
(p < 0.001) and an overall
increase in the
DIAGNOdent scores in
the control group
compared with the ozone
group (p < 0.05)
Health Technology Assessment 2006; Vol. 10: No. 16
 Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 5
Characteristics of included studies:
abstracts

71

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72
TABLE 22 Characteristics of abstracts

Author(s) No. of participants Design Inclusion Interventions Results Notes

(no. and type of criteria
Appendix 5

lesions)

Root caries
Lynch et al., 260 (two PRCLs: 60 Design: RCT Two primary Group 1: O3 (260 lesions) Reversal of caries:
200457 (Belfast, subjects with two soft root carious Soft lesions: at 6 months, 48/60 of
Unit of Group 2: no treatment
UK) PRCLs and 200 with lesions ozone-treated soft PRCLs had
randomisation: lesion (260 lesions)
two leathery non- reversed (from index 4 to 3), no
cavitated PRCLs, least Concealment of Ozone dosage: NS significant changes in control soft
severe category) allocation: NS lesions (p < 0.01)
Caries assessment: clinical
Blinding: blinded assessment Leathery lesions: 189/200 of
outcome assessor ozone-treated PRCLs had
reversed from index 1 to 0 (hard
ITT: no
to arrested), no significant
Length of follow-up: changes for control lesions
6 months (p < 0.01)
Lost at follow-up: NS Adverse events: none observed
Setting: NS

Pit and fissure caries

Holmes and Lynch, 38 (76 non-cavitated Design: RCT Two non- Group 1: air abrasion + O3 No post-operative sensitivity was Progression of caries in the
200453 (Belfast, occlusal caries lesions) cavitated early + mineral wash + glass associated with ozone treatment, conventional treatment
Unit of
UK) occlusal ionomer sealant. After 3 while 6/35 subjects in the group not reported
randomisation: lesion
carious lesions months the glass ionomer conventional treatment group
Sensitivity is a measure
Concealment of with sealant was dissected and complained of some post-
used to assess large necrotic
allocation: NS radiographic replaced with a posterior operative sensitivity
lesions and it is considered
radiolucencies composite
Blinding: NS Reversal of caries: at 3 months all inappropriate for assessing
extending
Group 2: conventional ozone dentine caries was hard early carious lesions
ITT: no 24 mm into
drilling and filling using and required no additional
Length of follow-up: dentine posterior composite removal
6 months
Ozone dosage: 40 seconds Adverse events: none observed
Lost at follow-up:
Caries assessment:
three subjects
radiographic and clinical
Setting: general dental assessment
practice

continued
 TABLE 22 Characteristics of abstracts (contd)

Author(s) No. of participants Design Inclusion Interventions Results Notes

(no. and type of criteria
lesions)

Holmes, 200354 376 (2364 primary non- Design: RCT Primary Group 1: O3 treatment Reversal of caries: 99% in the A total of 1937/2364
(Berkshire, UK) cavitated occlusal fissure occlusal ozone group (1918 lesions); the received ozone application.
Unit of Group 2: no treatment
lesions) fissure lesions control lesions did not change Unclear how many lesions
randomisation: lesion
with caries Ozone dosage: 10, 20, 30 or significantly were randomly allocated to
Concealment of judged to 40 seconds depending on each group (unbalanced
The DIAGNOdent values
allocation: NS extend 2 mm the clinical severity. randomisation?)
correlated with the clinical
into dentine Applications were repeated
Blinding: NS findings (p < 0.01)
(1170 teeth) every 3 months if reversal
ITT: no had not occurred Adverse events: none observed
Length of follow-up: Caries assessment:
12 months DIAGNOdent (KaVo,
Germany) and clinical
Lost at follow-up: 61
assessment
Setting: general dental
practice

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Hamid, 200355 184 (184 non-cavitated Design: RCT Primary early Group 1: O3 treatment Reversal of caries: 86.6% in the
(London, UK) pit and fissure carious occlusal (92 lesions) ozone group; the control lesions
Unit of
lesions) pit/fissure did not change significantly
randomisation: patient Group 2: no treatment
lesions with (p < 0.05)
(92 lesions)
Concealment of caries
The DIAGNOdent values
allocation: NS extending up Ozone dosage: 40 seconds
correlated with the clinical
to 1 mm into at baseline and at 3 months
Blinding: NS findings
dentine Caries assessment: clinical
ITT: unclear Adverse events: none observed
assessment and
Length of follow-up: DIAGNOdent (KaVo,
6 months Germany)
Lost at follow-up:
unclear
Setting: NS

continued
Health Technology Assessment 2006; Vol. 10: No. 16

73
74
TABLE 22 Characteristics of abstracts (contd)

Author(s) No. of participants Design Inclusion Interventions Results Notes

(no. and type of criteria
Appendix 5

lesions)

Megighian and 80 (300 pit and fissure Design: randomised Pit and fissure Group 1: O3 (220 lesions) Reversal of caries: ozone-treated Unclear whether the
Bertolini, 200456 carious lesions) clinical trial carious lesions lesions clinically reversed proportion of lesions that
Group 2: no treatment (80
(Verona, Italy) (p < 0.05), while control lesions clinically reversed or
Unit of lesions)
did not showed a reduction in
randomisation: lesion
Ozone dosage: 20, 30 or 40 DIAGNOdent readings
DIAGNOdent: significant overall
Concealment of seconds according to clinical were all ozone-treated
reduction in readings for ozone-
allocation: NS severity lesions or included some
treated lesions, while control
Caries assessment: clinical control lesions
Blinding: double blind lesions showed an increase in
assessment and DIAGNOdent readings
ITT: no
DIAGNOdent (KaVo,
85% of teeth clinically reversed
Length of follow-up: Germany)
and showed a DIAGNOdent
6 months
reduction
Lost at follow-up: NS
Setting: private
practice, Italy
 Health Technology Assessment 2006; Vol. 10: No. 16

Appendix 6
Structure of the economic model
Decision models to assess costs
and benefits of HealOzone
The four models depicted in Figures 1518 have a
similar structure; therefore, only current
management plus HealOzone is described here.
Markov models can be used to estimate costs and
consequences that occur over a series of years (in
this study up to 5 years). At the beginning of the
first year each patient receives current
management plus HealOzone and hence a
probability of 1 is attached. At the end of the first
year there is a chance that the patients are cured
(caries are reversed) or they have progressed. If

Cure
Current management Cured post current management plus HealOzone
probcurel
plus HealOzone
Retreatment
1 Retreatment
Progress probretreat
# New treatment
Filled tooth
#
Cured post current
management plus HealOzone
Current management
plus HealOzone 0
M Cured
Cured post retreatment
Retreatment probcure
0 Progress
Filled tooth
1-probcurel
Cured post retreatment
0
Filled tooth
0

FIGURE 15 Decision model to assess the cost and benefits of current management plus HealOzone of non-cavitated root caries
(Markov model)

Cure
Cured post current management
probcure
Current management
Retreatment
1 Retreatment
Progress probretreat
# New treatment
Filled tooth
#
Cured post current management

Current management 0
M Cured
Cured post retreatment
Retreatment probcure
0 Progress
Filled tooth
1-probcure
Cured post retreatment
0
Filled tooth
0

FIGURE 16 Decision model to assess the costs and benefits of current management of non-cavitated root caries 75

Queens Printer and Controller of HMSO 2006. All rights reserved.

 Appendix 6

Cure
Cured post current management
probcure
Current management
Retreatment
1 Retreatment
Progress probretreat
# New treatment
Filled tooth
#
Cured post current management

Current management 0
M Cured
Cured post retreatment
Retreatment probcure
0 Progress
Filled tooth
1-probcure
Cured post retreatment
0
Filled tooth
0

FIGURE 17 Decision model to assess the costs and benefits of current management of non-cavitated pit and fissure caries

Cure
Current management Cured post current management plus HealOzone
probcurel
plus HealOzone
Retreatment
1 Retreatment
Progress probretreat
# New treatment
Filled tooth
#
Cured post current
management plus HealOzone
Current management
plus HealOzone 0
M Cured
Cured post retreatment
Retreatment probcurel
0 Progress
Filled tooth
1-probcurel
Cured post retreatment
0
Filled tooth
0

FIGURE 18 Decision model to assess the costs and benefits of current management plus HealOzone of non-cavitated pit and fissure
caries

they have progressed there is a chance that they
receive the same treatment or a new treatment
(filling). The chance of a patient being cured is
pbcure1 and not being cured is 1-pbcure1. The
chance that a patient will receive the same
treatment is probretreat. In the model it is
assumed that the patient has a 50% chance of
receiving the same treatment or having a filling. If
the first treatment fails the patient moves to the
76 third branch or the fifth branch. The probability
of cure does not change in the third branch and
those who go into the third branch are either
cured or filled. The filled tooth state is a terminal
state and patients do not leave it. The model also
assumes that when a patient is cured they remain
cured for as long as the model runs.
Details of cost calculations are shown in
Tables 2330.
 Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 23 Annual treatment numbers for non-cavitated caries based on each relevant SDR code by age group for year ending March
200365

Treatment No. of Total teeth

SDR code numbers caries types No. of teeth treated

Age <18 years

Non-cavitated pit and fissure caries 601 3,930 2 1 1,965
3631 2,393 2 1 1,196.5
701 73 1 1 73
Total 3,234.5
Non-cavitated root caries 601 3,930 2 1 1,965
3631 2,393 2 1 1,196.5
Total 3,161.5

Age 18 years
Non-cavitated pit and fissure caries 601 11,728 2 1 5,864
3631 669,304 2 1 334,652
701 1,922 1 1 1,922
Total 342,438
Non-cavitated root caries 601 11,728 2 1 5,864
3631 669,304 2 1 334,652
Total 340,516

Where one SDR code was relevant to more than one type of caries the published treatment numbers were divided by the
number of relevant types of caries. Similar adjustments were provided for the numbers of teeth to which any one SDR code
applied.

TABLE 24 Percentage teeth treated by age group of patient, based on numbers in Table 23

SDR code <18 years (%) 18 years (%)

Non-cavitated pit and fissure caries 601 25.1 74.9

3631 0.4 99.6
701 3.7 96.3
Non-cavitated root caries 601 25.1 74.9
3631 0.4 99.6

TABLE 25 Calculation for cost to NHS based on 100% treatment items paid for those <18 years and 40% all treatment items paid
for those 18 years

NHS cost ()

SDR code <18 years 18 years Unit cost <18 years 18 years Weighted
() average NHS
fee across all
age ()

Non-cavitated pit and 601 25.1% 74.9% 7.70 7.70 3.08 4.24
fissure caries 3631 0.4% 99.6% 4.60 4.60 1.84 1.85
701 3.7% 96.3% 6.95 6.95 2.78 2.93
Total 19.25 7.70 9.02
Non-cavitated root caries 601 25.1% 74.9% 7.70 7.70 3.08 4.24
3631 0.4% 99.6% 4.60 4.60 1.84 1.85
Total 12.30 4.92 6.09

77

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 Appendix 6

TABLE 26 Cost calculations for treatment of cavitated caries

SDR code Total annual Annual No. of No. of Total teeth

treatment treatment caries teeth treated
numbers numbers types

Age <18 years

Cavitated pit and fissure caries 1441 1,025,404 1 1
1442 201,308 1 1 201,308
1443 163,379 1 1 163,379
Anterior teeth 1401a 557,753 278,876.5 1 1 278,876.5
Posterior teeth 1421a 386,061 193,030.5 1 1 193,030.5
1421a 35,681 17,840.5 1 2 35,681
Age 18 years
Cavitated pit and fissure caries 1441 147,980 1 1 147,980
1442 86,667 1 1 86,667
1443 68,353 1 1 68,353
1401a 1,671,224 835,612 1 1 835,612
1421a 4,141,954 2,070,977 1 1 2,070,977
1421a 346,816 173,408 1 2 346,816

Figures assume a treatment mix of SDR codes 1441, 1442 and 1443 plus either 1401 or 1421. All patients also receive SDR
code 0101 (initial dental assessment).
It is also assumed that 50% of treatments are for anterior and 50% for posterior teeth.
a
50% mix assumed.

TABLE 27 Steps used to calculate the mean cost of a filling when different proportions of children and adults receive different
treatment mixes by SDR code

% treatment for NHS cost ()

cavitated caries (fillings)

SDR <18 years 18 years Unit cost <18 years 18 years Weighted
code () average NHS
fee across all
age ()

1441 87.4 12.6 6.95 6.95 2.78 6.42

1442 69.9 30.1 9.80 9.80 3.92 8.03
1443 70.5 29.5 10.55 10.55 4.22 8.68
1401a 25.0 75.0 7.50 7.50 3.00 4.13
1421a 8.5 91.5 14.15 14.15 5.66 6.38
1421a 9.3 90.6 14.15 14.15 5.66 6.45
63.10 63.10 25.24 40.10
Overall % mix children/adults
for fillings and mean cost per filling 45.1 54.9 12.62 12.62 5.05 8.02
Initial dental assessment 101 100 100 7.05 7.05 2.82 4.73
Total average cost per filling visit 19.67 7.87 12.75
a
50% mix assumed.

78
 Health Technology Assessment 2006; Vol. 10: No. 16

TABLE 28 HealOzone cost calculations

% who have caries

treatmenta
Cost to NHS ()
1st year initial treatment Unit cost <18 years 18 years <18 years 18 years Weighted
option () average cost
to NHS ()

Non-cavitated pit and fissure caries

Currentb 19.25 19.25 7.70 9.02
HealOzone 20.00 20.00 8.00 25.1 74.9 11.01
Current + HealOzone 39.25 15.70 20.03
Non-cavitated root caries
Currentb 12.30 12.30 4.92 6.09
HealOzone 20.00 20.00 8.00 25.1 74.9 11.01
Current + HealOzone 32.30 12.92 17.10
a
Non-cavitated pit and fissure caries treatment or non-cavitated root caries treatment (see Table 25).
b
See Tables 24 and 25.

Non-cavitated pit and fissure caries

The combined cost of HealOzone and current management is 40.49 and the cost of current
management alone is 24.78.

TABLE 29 Results of one-way sensitivity analysis for non-cavitated pit fissure caries (current management versus current management
and HealOzone) holding current management plus HealOzone cost constant

Current Additional cost of

Probability Proportion cured Proportion filled management HealOzone HealOzone

0 0 1 26.06 40.49 14.43

0.1 0.015 0.985 23.81 40.49 16.68
0.2 0.145 0.855 21.67 40.49 18.82
0.3 0.28 0.72 19.66 40.49 20.83
0.4 0.405 0.595 17.77 40.49 22.72
0.5 0.52 0.48 16.00 40.49 24.49
0.6 0.625 0.375 14.36 40.49 26.13
0.7 0.72 0.28 12.84 40.49 27.65
0.8 0.805 0.195 11.44 40.49 29.05
0.9 0.88 0.12 10.17 40.49 30.32
1 1 0 9.02 40.49 31.47

TABLE 30 Results of one-way sensitivity analysis for non-cavitated pit fissure caries (current management versus current management
and HealOzone) holding current management cost constant

Current Additional cost of

Probability Proportion cured Proportion filled management HealOzone HealOzone

0 0 1 24.78 42.58 17.80

0.1 0.015 0.985 24.78 39.77 14.99
0.2 0.145 0.855 24.78 37.08 12.30
0.3 0.28 0.72 24.78 34.52 9.74
0.4 0.405 0.595 24.78 32.08 7.30
0.5 0.52 0.48 24.78 29.76 4.98
0.6 0.625 0.375 24.78 27.57 2.79
0.7 0.72 0.28 24.78 25.50 0.72
0.8 0.805 0.195 24.78 23.55 1.23
0.9 0.88 0.12 24.78 21.73 3.05
1 1 0 24.78 20.03 4.75
79

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 Appendix 6

Non-cavitated root caries

The combined cost of HealOzone and current management is 14.63 and the cost of current
management alone is 21.45 (Tables 31 and 32).

TABLE 31 Results of one-way sensitivity analysis for non-cavitated root caries (current management versus current management and
HealOzone) holding current management cost constant

Current Additional cost of

Probability Proportion cured Proportion filled management HealOzone HealOzone

0 0 1 21.45 38.18 16.73

0.1 0.145 0.855 21.45 35.52 14.07
0.2 0.28 0.72 21.45 32.98 11.53
0.3 0.405 0.595 21.45 30.57 9.12
0.4 0.52 0.48 21.45 28.27 6.82
0.5 0.625 0.375 21.45 26.10 4.65
0.6 0.72 0.28 21.45 24.06 2.61
0.7 0.805 0.195 21.45 22.13 0.68
0.8 0.88 0.12 21.45 20.33 1.12
0.9 0.945 0.055 21.45 18.65 2.80
1 1 0 21.45 17.10 4.35

TABLE 32 Results of one-way sensitivity analysis for non-cavitated root caries (current management versus current management and
HealOzone) holding current management plus HealOzone cost constant

Current Additional cost of

Probability Proportion cured Proportion filled management HealOzone HealOzone

0 0 1 21.67 14.63 7.04

0.1 0.145 0.855 19.56 14.63 4.93
0.2 0.28 0.72 17.57 14.63 2.94
0.3 0.405 0.595 15.70 14.63 1.07
0.4 0.52 0.48 13.96 14.63 0.67
0.5 0.625 0.375 12.34 14.63 2.29
0.6 0.72 0.28 10.84 14.63 3.79
0.7 0.805 0.195 9.47 14.63 5.16
0.8 0.88 0.12 8.22 14.63 6.41
0.9 0.945 0.055 7.09 14.63 7.54
1 1 0 6.09 14.63 8.54

80

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of reversible contraceptives: two
systematic reviews to assess relative
effectiveness, acceptability, tolerability
and cost-effectiveness.
By French RS, Cowan FM, Mansour
DJA, Morris S, Procter T, Hughes D,
et al.
No. 8
An introduction to statistical methods
for health technology assessment.
A review by White SJ, Ashby D,
Brown PJ.
No. 9
Disease-modifying drugs for multiple
sclerosis: a rapid and systematic
review.
By Clegg A, Bryant J, Milne R.
No. 10
Publication and related biases.
A review by Song F, Eastwood AJ,
Gilbody S, Duley L, Sutton AJ.
No. 11
Cost and outcome implications of the
organisation of vascular services.
By Michaels J, Brazier J, Palfreyman
S, Shackley P, Slack R.
No. 12
Monitoring blood glucose control in
diabetes mellitus: a systematic review.
By Coster S, Gulliford MC, Seed PT,
Powrie JK, Swaminathan R.
No. 13
The effectiveness of domiciliary health
visiting: a systematic review of
international studies
and a selective review of the British
literature.
By Elkan R, Kendrick D, Hewitt M,
Robinson JJA, Tolley K, Blair M, et al.
Queens Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 16
No. 14
The determinants of screening uptake
and interventions for increasing uptake:
a systematic review.
By Jepson R, Clegg A, Forbes C,
Lewis R, Sowden A, Kleijnen J.
No. 15
The effectiveness and cost-effectiveness
of prophylactic removal of wisdom
teeth.
A rapid review by Song F, OMeara S,
Wilson P, Golder S, Kleijnen J.
No. 16
Ultrasound screening in pregnancy: a
systematic review of the clinical
effectiveness, cost-effectiveness and
womens views.
By Bricker L, Garcia J, Henderson J,
Mugford M, Neilson J, Roberts T, et al.
No. 17
A rapid and systematic review of the
effectiveness and cost-effectiveness of
the taxanes used in the treatment of
advanced breast and ovarian cancer.
By Lister-Sharp D, McDonagh MS,
Khan KS, Kleijnen J.
No. 18
Liquid-based cytology in cervical
screening: a rapid and systematic review.
By Payne N, Chilcott J, McGoogan E.
No. 19
Randomised controlled trial of non-
directive counselling,
cognitivebehaviour therapy and usual
general practitioner care in the
management of depression as well as
mixed anxiety and depression in
primary care.
By King M, Sibbald B, Ward E, Bower
P, Lloyd M, Gabbay M, et al.
No. 20
Routine referral for radiography of
patients presenting with low back pain:
is patients outcome influenced by GPs
referral for plain radiography?
By Kerry S, Hilton S, Patel S, Dundas
D, Rink E, Lord J.
No. 21
Systematic reviews of wound care
management: (3) antimicrobial agents
for chronic wounds; (4) diabetic foot
ulceration.
By OMeara S, Cullum N, Majid M,
Sheldon T.
No. 22
Using routine data to complement and
enhance the results of randomised
controlled trials.
By Lewsey JD, Leyland AH,
Murray GD, Boddy FA.
No. 23
Coronary artery stents in the treatment
of ischaemic heart disease: a rapid and
systematic review.
By Meads C, Cummins C, Jolly K,
Stevens A, Burls A, Hyde C.
No. 24
Outcome measures for adult critical
care: a systematic review.
By Hayes JA, Black NA,
Jenkinson C, Young JD, Rowan KM,
Daly K, et al.
No. 25
A systematic review to evaluate the
effectiveness of interventions to
promote the initiation of
breastfeeding.
By Fairbank L, OMeara S, Renfrew
MJ, Woolridge M, Sowden AJ,
Lister-Sharp D.
No. 26
Implantable cardioverter defibrillators:
arrhythmias. A rapid and systematic
review.
By Parkes J, Bryant J, Milne R.
No. 27
Treatments for fatigue in multiple
sclerosis: a rapid and systematic
review.
By Braas P, Jordan R, Fry-Smith A,
Burls A, Hyde C.
No. 28
Early asthma prophylaxis, natural
history, skeletal development and
economy (EASE): a pilot randomised
controlled trial.
By Baxter-Jones ADG, Helms PJ,
Russell G, Grant A, Ross S, Cairns JA,
et al.
No. 29
Screening for hypercholesterolaemia
versus case finding for familial
hypercholesterolaemia: a systematic
review and cost-effectiveness analysis.
By Marks D, Wonderling D,
Thorogood M, Lambert H, Humphries
SE, Neil HAW.
No. 30
A rapid and systematic review of the
clinical effectiveness and cost-
effectiveness of glycoprotein IIb/IIIa
antagonists in the medical management
of unstable angina.
By McDonagh MS, Bachmann LM,
Golder S, Kleijnen J, ter Riet G.
No. 31
A randomised controlled trial of
prehospital intravenous fluid
replacement therapy in serious trauma.
By Turner J, Nicholl J, Webber L,
Cox H, Dixon S, Yates D.
No. 32
Intrathecal pumps for giving opioids in
chronic pain: a systematic review.
By Williams JE, Louw G, Towlerton G.
No. 33
Combination therapy (interferon alfa
and ribavirin) in the treatment of
chronic hepatitis C: a rapid and
systematic review.
By Shepherd J, Waugh N,
Hewitson P. 83
 Health Technology Assessment reports published to date
No. 34
A systematic review of comparisons of
effect sizes derived from randomised
and non-randomised studies.
By MacLehose RR, Reeves BC,
Harvey IM, Sheldon TA, Russell IT,
Black AMS.
No. 35
Intravascular ultrasound-guided
interventions in coronary artery disease:
a systematic literature review, with
decision-analytic modelling, of outcomes
and cost-effectiveness.
By Berry E, Kelly S, Hutton J,
Lindsay HSJ, Blaxill JM, Evans JA, et al.
No. 36
A randomised controlled trial to
evaluate the effectiveness and cost-
effectiveness of counselling patients with
chronic depression.
By Simpson S, Corney R, Fitzgerald P,
Beecham J.
No. 37
Systematic review of treatments for
atopic eczema.
By Hoare C, Li Wan Po A, Williams H.
No. 38
Bayesian methods in health technology
assessment: a review.
By Spiegelhalter DJ, Myles JP,
Jones DR, Abrams KR.
No. 39
The management of dyspepsia: a
systematic review.
By Delaney B, Moayyedi P, Deeks J,
Innes M, Soo S, Barton P, et al.
No. 40
A systematic review of treatments for
severe psoriasis.
By Griffiths CEM, Clark CM, Chalmers
RJG, Li Wan Po A, Williams HC.
Volume 5, 2001
No. 1
Clinical and cost-effectiveness of
donepezil, rivastigmine and
galantamine for Alzheimers disease: a
rapid and systematic review.
By Clegg A, Bryant J, Nicholson T,
McIntyre L, De Broe S, Gerard K, et al.
No. 2
The clinical effectiveness and cost-
effectiveness of riluzole for motor
neurone disease: a rapid and systematic
review.
By Stewart A, Sandercock J, Bryan S,
Hyde C, Barton PM, Fry-Smith A, et al.
No. 3
Equity and the economic evaluation of
healthcare.
By Sassi F, Archard L, Le Grand J.
No. 4
Quality-of-life measures in chronic
diseases of childhood.
84 By Eiser C, Morse R.
No. 5
Eliciting public preferences for
healthcare: a systematic review of
techniques.
By Ryan M, Scott DA, Reeves C, Bate
A, van Teijlingen ER, Russell EM, et al.
No. 6
General health status measures for
people with cognitive impairment:
learning disability and acquired brain
injury.
By Riemsma RP, Forbes CA,
Glanville JM, Eastwood AJ, Kleijnen J.
No. 7
An assessment of screening strategies for
fragile X syndrome in the UK.
By Pembrey ME, Barnicoat AJ,
Carmichael B, Bobrow M, Turner G.
No. 8
Issues in methodological research:
perspectives from researchers and
commissioners.
By Lilford RJ, Richardson A, Stevens
A, Fitzpatrick R, Edwards S, Rock F, et al.
No. 9
Systematic reviews of wound care
management: (5) beds; (6) compression;
(7) laser therapy, therapeutic
ultrasound, electrotherapy and
electromagnetic therapy.
By Cullum N, Nelson EA, Flemming
K, Sheldon T.
No. 10
Effects of educational and psychosocial
interventions for adolescents with
diabetes mellitus: a systematic review.
By Hampson SE, Skinner TC, Hart J,
Storey L, Gage H, Foxcroft D, et al.
No. 11
Effectiveness of autologous chondrocyte
transplantation for hyaline cartilage
defects in knees: a rapid and systematic
review.
By Jobanputra P, Parry D, Fry-Smith
A, Burls A.
No. 12
Statistical assessment of the learning
curves of health technologies.
By Ramsay CR, Grant AM,
Wallace SA, Garthwaite PH, Monk AF,
Russell IT.
No. 13
The effectiveness and cost-effectiveness
of temozolomide for the treatment of
recurrent malignant glioma: a rapid and
systematic review.
By Dinnes J, Cave C, Huang S,
Major K, Milne R.
No. 14
A rapid and systematic review of the
clinical effectiveness and cost-
effectiveness of debriding agents in
treating surgical wounds healing by
secondary intention.
By Lewis R, Whiting P, ter Riet G,
OMeara S, Glanville J.
No. 15
Home treatment for mental health
problems: a systematic review.
By Burns T, Knapp M,
Catty J, Healey A, Henderson J,
Watt H, et al.
No. 16
How to develop cost-conscious
guidelines.
By Eccles M, Mason J.
No. 17
The role of specialist nurses in multiple
sclerosis: a rapid and systematic review.
By De Broe S, Christopher F,
Waugh N.
No. 18
A rapid and systematic review of the
clinical effectiveness and cost-
effectiveness of orlistat in the
management of obesity.
By OMeara S, Riemsma R,
Shirran L, Mather L, ter Riet G.
No. 19
The clinical effectiveness and cost-
effectiveness of pioglitazone for type 2
diabetes mellitus: a rapid and systematic
review.
By Chilcott J, Wight J, Lloyd Jones
M, Tappenden P.
No. 20
Extended scope of nursing practice: a
multicentre randomised controlled trial
of appropriately trained nurses and
preregistration house officers in pre-
operative assessment in elective general
surgery.
By Kinley H, Czoski-Murray C,
George S, McCabe C, Primrose J,
Reilly C, et al.
No. 21
Systematic reviews of the effectiveness of
day care for people with severe mental
disorders: (1) Acute day hospital versus
admission; (2) Vocational rehabilitation;
(3) Day hospital versus outpatient
care.
By Marshall M, Crowther R, Almaraz-
Serrano A, Creed F, Sledge W,
Kluiter H, et al.
No. 22
The measurement and monitoring of
surgical adverse events.
By Bruce J, Russell EM, Mollison J,
Krukowski ZH.
No. 23
Action research: a systematic review and
guidance for assessment.
By Waterman H, Tillen D, Dickson R,
de Koning K.
No. 24
A rapid and systematic review of the
clinical effectiveness and cost-
effectiveness of gemcitabine for the
treatment of pancreatic cancer.
By Ward S, Morris E, Bansback N,
Calvert N, Crellin A, Forman D, et al.

No. 25
A rapid and systematic review of the
evidence for the clinical effectiveness
and cost-effectiveness of irinotecan,
oxaliplatin and raltitrexed for the
treatment of advanced colorectal cancer.
By Lloyd Jones M, Hummel S,
Bansback N, Orr B, Seymour M.
No. 26
Comparison of the effectiveness of
inhaler devices in asthma and chronic
obstructive airways disease: a systematic
review of the literature.
By Brocklebank D, Ram F, Wright J,
Barry P, Cates C, Davies L, et al.
No. 27
The cost-effectiveness of magnetic
resonance imaging for investigation of
the knee joint.
By Bryan S, Weatherburn G, Bungay
H, Hatrick C, Salas C, Parry D, et al.
No. 28
A rapid and systematic review of the
clinical effectiveness and cost-
effectiveness of topotecan for ovarian
cancer.
By Forbes C, Shirran L, Bagnall A-M,
Duffy S, ter Riet G.
No. 29
Superseded by a report published in a
later volume.
No. 30
The role of radiography in primary care
patients with low back pain of at least 6
weeks duration: a randomised
(unblinded) controlled trial.
By Kendrick D, Fielding K, Bentley E,
Miller P, Kerslake R, Pringle M.
No. 31
Design and use of questionnaires: a
review of best practice applicable to
surveys of health service staff and
patients.
By McColl E, Jacoby A, Thomas L,
Soutter J, Bamford C, Steen N, et al.
No. 32
A rapid and systematic review of the
clinical effectiveness and cost-
effectiveness of paclitaxel, docetaxel,
gemcitabine and vinorelbine in non-
small-cell lung cancer.
By Clegg A, Scott DA, Sidhu M,
Hewitson P, Waugh N.
No. 33
Subgroup analyses in randomised
controlled trials: quantifying the risks of
false-positives and false-negatives.
By Brookes ST, Whitley E,
Peters TJ, Mulheran PA, Egger M,
Davey Smith G.
No. 34
Depot antipsychotic medication in the
treatment of patients with schizophrenia:
(1) Meta-review; (2) Patient and nurse
attitudes.
By David AS, Adams C.
Queens Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 16
No. 35
A systematic review of controlled trials
of the effectiveness and cost-
effectiveness of brief psychological
treatments for depression.
By Churchill R, Hunot V, Corney R,
Knapp M, McGuire H, Tylee A, et al.
No. 36
Cost analysis of child health
surveillance.
By Sanderson D, Wright D, Acton C,
Duree D.
Volume 6, 2002
No. 1
A study of the methods used to select
review criteria for clinical audit.
By Hearnshaw H, Harker R, Cheater
F, Baker R, Grimshaw G.
No. 2
Fludarabine as second-line therapy for
B cell chronic lymphocytic leukaemia:
a technology assessment.
By Hyde C, Wake B, Bryan S, Barton
P, Fry-Smith A, Davenport C, et al.
No. 3
Rituximab as third-line treatment for
refractory or recurrent Stage III or IV
follicular non-Hodgkins lymphoma: a
systematic review and economic
evaluation.
By Wake B, Hyde C, Bryan S, Barton
P, Song F, Fry-Smith A, et al.
No. 4
A systematic review of discharge
arrangements for older people.
By Parker SG, Peet SM, McPherson A,
Cannaby AM, Baker R, Wilson A, et al.
No. 5
The clinical effectiveness and cost-
effectiveness of inhaler devices used in
the routine management of chronic
asthma in older children: a systematic
review and economic evaluation.
By Peters J, Stevenson M, Beverley C,
Lim J, Smith S.
No. 6
The clinical effectiveness and cost-
effectiveness of sibutramine in the
management of obesity: a technology
assessment.
By OMeara S, Riemsma R, Shirran
L, Mather L, ter Riet G.
No. 7
The cost-effectiveness of magnetic
resonance angiography for carotid
artery stenosis and peripheral vascular
disease: a systematic review.
By Berry E, Kelly S, Westwood ME,
Davies LM, Gough MJ, Bamford JM,
et al.
No. 8
Promoting physical activity in South
Asian Muslim women through exercise
on prescription.
By Carroll B, Ali N, Azam N.
No. 9
Zanamivir for the treatment of influenza
in adults: a systematic review and
economic evaluation.
By Burls A, Clark W, Stewart T,
Preston C, Bryan S, Jefferson T, et al.
No. 10
A review of the natural history and
epidemiology of multiple sclerosis:
implications for resource allocation and
health economic models.
By Richards RG, Sampson FC,
Beard SM, Tappenden P.
No. 11
Screening for gestational diabetes: a
systematic review and economic
evaluation.
By Scott DA, Loveman E, McIntyre L,
Waugh N.
No. 12
The clinical effectiveness and cost-
effectiveness of surgery for people with
morbid obesity: a systematic review and
economic evaluation.
By Clegg AJ, Colquitt J, Sidhu MK,
Royle P, Loveman E, Walker A.
No. 13
The clinical effectiveness of trastuzumab
for breast cancer: a systematic review.
By Lewis R, Bagnall A-M, Forbes C,
Shirran E, Duffy S, Kleijnen J, et al.
No. 14
The clinical effectiveness and cost-
effectiveness of vinorelbine for breast
cancer: a systematic review and
economic evaluation.
By Lewis R, Bagnall A-M, King S,
Woolacott N, Forbes C, Shirran L, et al.
No. 15
A systematic review of the effectiveness
and cost-effectiveness of metal-on-metal
hip resurfacing arthroplasty for
treatment of hip disease.
By Vale L, Wyness L, McCormack K,
McKenzie L, Brazzelli M, Stearns SC.
No. 16
The clinical effectiveness and cost-
effectiveness of bupropion and nicotine
replacement therapy for smoking
cessation: a systematic review and
economic evaluation.
By Woolacott NF, Jones L, Forbes CA,
Mather LC, Sowden AJ, Song FJ, et al.
No. 17
A systematic review of effectiveness and
economic evaluation of new drug
treatments for juvenile idiopathic
arthritis: etanercept.
By Cummins C, Connock M,
Fry-Smith A, Burls A.
No. 18
Clinical effectiveness and cost-
effectiveness of growth hormone in
children: a systematic review and
economic evaluation.
By Bryant J, Cave C, Mihaylova B,
Chase D, McIntyre L, Gerard K, et al. 85
 Health Technology Assessment reports published to date
No. 19
Clinical effectiveness and cost-
effectiveness of growth hormone in
adults in relation to impact on quality of
life: a systematic review and economic
evaluation.
By Bryant J, Loveman E, Chase D,
Mihaylova B, Cave C, Gerard K, et al.
No. 20
Clinical medication review by a
pharmacist of patients on repeat
prescriptions in general practice: a
randomised controlled trial.
By Zermansky AG, Petty DR, Raynor
DK, Lowe CJ, Freementle N, Vail A.
No. 21
The effectiveness of infliximab and
etanercept for the treatment of
rheumatoid arthritis: a systematic review
and economic evaluation.
By Jobanputra P, Barton P, Bryan S,
Burls A.
No. 22
A systematic review and economic
evaluation of computerised cognitive
behaviour therapy for depression and
anxiety.
By Kaltenthaler E, Shackley P, Stevens
K, Beverley C, Parry G, Chilcott J.
No. 23
A systematic review and economic
evaluation of pegylated liposomal
doxorubicin hydrochloride for ovarian
cancer.
By Forbes C, Wilby J, Richardson G,
Sculpher M, Mather L, Reimsma R.
No. 24
A systematic review of the effectiveness
of interventions based on a stages-of-
change approach to promote individual
behaviour change.
By Riemsma RP, Pattenden J, Bridle C,
Sowden AJ, Mather L, Watt IS, et al.
No. 25
A systematic review update of the
clinical effectiveness and cost-
effectiveness of glycoprotein IIb/IIIa
antagonists.
By Robinson M, Ginnelly L, Sculpher
M, Jones L, Riemsma R, Palmer S, et al.
No. 26
A systematic review of the effectiveness,
cost-effectiveness and barriers to
implementation of thrombolytic and
neuroprotective therapy for acute
ischaemic stroke in the NHS.
By Sandercock P, Berge E, Dennis M,
Forbes J, Hand P, Kwan J, et al.
No. 27
A randomised controlled crossover
trial of nurse practitioner versus
doctor-led outpatient care in a
bronchiectasis clinic.
By Caine N, Sharples LD,
Hollingworth W, French J, Keogan M,
86 Exley A, et al.
No. 28
Clinical effectiveness and cost
consequences of selective serotonin
reuptake inhibitors in the treatment of
sex offenders.
By Adi Y, Ashcroft D, Browne K,
Beech A, Fry-Smith A, Hyde C.
No. 29
Treatment of established osteoporosis:
a systematic review and costutility
analysis.
By Kanis JA, Brazier JE, Stevenson M,
Calvert NW, Lloyd Jones M.
No. 30
Which anaesthetic agents are cost-
effective in day surgery? Literature
review, national survey of practice and
randomised controlled trial.
By Elliott RA Payne K, Moore JK,
Davies LM, Harper NJN, St Leger AS,
et al.
No. 31
Screening for hepatitis C among
injecting drug users and in
genitourinary medicine clinics:
systematic reviews of effectiveness,
modelling study and national survey of
current practice.
By Stein K, Dalziel K, Walker A,
McIntyre L, Jenkins B, Horne J, et al.
No. 32
The measurement of satisfaction with
healthcare: implications for practice
from a systematic review of the
literature.
By Crow R, Gage H, Hampson S,
Hart J, Kimber A, Storey L, et al.
No. 33
The effectiveness and cost-effectiveness
of imatinib in chronic myeloid
leukaemia: a systematic review.
By Garside R, Round A, Dalziel K,
Stein K, Royle R.
No. 34
A comparative study of hypertonic
saline, daily and alternate-day
rhDNase in children with cystic
fibrosis.
By Suri R, Wallis C, Bush A,
Thompson S, Normand C, Flather M,
et al.
No. 35
A systematic review of the costs and
effectiveness of different models of
paediatric home care.
By Parker G, Bhakta P, Lovett CA,
Paisley S, Olsen R, Turner D, et al.
Volume 7, 2003
No. 1
How important are comprehensive
literature searches and the assessment of
trial quality in systematic reviews?
Empirical study.
By Egger M, Jni P, Bartlett C,
Holenstein F, Sterne J.
No. 2
Systematic review of the effectiveness
and cost-effectiveness, and economic
evaluation, of home versus hospital or
satellite unit haemodialysis for people
with end-stage renal failure.
By Mowatt G, Vale L, Perez J, Wyness
L, Fraser C, MacLeod A, et al.
No. 3
Systematic review and economic
evaluation of the effectiveness of
infliximab for the treatment of Crohns
disease.
By Clark W, Raftery J, Barton P,
Song F, Fry-Smith A, Burls A.
No. 4
A review of the clinical effectiveness and
cost-effectiveness of routine anti-D
prophylaxis for pregnant women who
are rhesus negative.
By Chilcott J, Lloyd Jones M, Wight
J, Forman K, Wray J, Beverley C, et al.
No. 5
Systematic review and evaluation of the
use of tumour markers in paediatric
oncology: Ewings sarcoma and
neuroblastoma.
By Riley RD, Burchill SA, Abrams KR,
Heney D, Lambert PC, Jones DR, et al.
No. 6
The cost-effectiveness of screening for
Helicobacter pylori to reduce mortality
and morbidity from gastric cancer and
peptic ulcer disease: a discrete-event
simulation model.
By Roderick P, Davies R, Raftery J,
Crabbe D, Pearce R, Bhandari P, et al.
No. 7
The clinical effectiveness and cost-
effectiveness of routine dental checks: a
systematic review and economic
evaluation.
By Davenport C, Elley K, Salas C,
Taylor-Weetman CL, Fry-Smith A,
Bryan S, et al.
No. 8
A multicentre randomised controlled
trial assessing the costs and benefits of
using structured information and
analysis of womens preferences in the
management of menorrhagia.
By Kennedy ADM, Sculpher MJ,
Coulter A, Dwyer N, Rees M,
Horsley S, et al.
No. 9
Clinical effectiveness and costutility of
photodynamic therapy for wet age-related
macular degeneration: a systematic review
and economic evaluation.
By Meads C, Salas C, Roberts T,
Moore D, Fry-Smith A, Hyde C.
No. 10
Evaluation of molecular tests for
prenatal diagnosis of chromosome
abnormalities.
By Grimshaw GM, Szczepura A,
Hultn M, MacDonald F, Nevin NC,
Sutton F, et al.

No. 11
First and second trimester antenatal
screening for Downs syndrome: the
results of the Serum, Urine and
Ultrasound Screening Study
(SURUSS).
By Wald NJ, Rodeck C,
Hackshaw AK, Walters J, Chitty L,
Mackinson AM.
No. 12
The effectiveness and cost-effectiveness
of ultrasound locating devices for
central venous access: a systematic
review and economic evaluation.
By Calvert N, Hind D, McWilliams
RG, Thomas SM, Beverley C,
Davidson A.
No. 13
A systematic review of atypical
antipsychotics in schizophrenia.
By Bagnall A-M, Jones L, Lewis R,
Ginnelly L, Glanville J, Torgerson D,
et al.
No. 14
Prostate Testing for Cancer and
Treatment (ProtecT) feasibility
study.
By Donovan J, Hamdy F, Neal D,
Peters T, Oliver S, Brindle L, et al.
No. 15
Early thrombolysis for the treatment
of acute myocardial infarction: a
systematic review and economic
evaluation.
By Boland A, Dundar Y, Bagust A,
Haycox A, Hill R, Mujica Mota R,
et al.
No. 16
Screening for fragile X syndrome:
a literature review and modelling.
By Song FJ, Barton P, Sleightholme V,
Yao GL, Fry-Smith A.
No. 17
Systematic review of endoscopic sinus
surgery for nasal polyps.
By Dalziel K, Stein K, Round A,
Garside R, Royle P.
No. 18
Towards efficient guidelines: how to
monitor guideline use in primary
care.
By Hutchinson A, McIntosh A, Cox S,
Gilbert C.
No. 19
Effectiveness and cost-effectiveness of
acute hospital-based spinal cord injuries
services: systematic review.
By Bagnall A-M, Jones L,
Richardson G, Duffy S,
Riemsma R.
No. 20
Prioritisation of health technology
assessment. The PATHS model:
methods and case studies.
By Townsend J, Buxton M,
Harper G.
Queens Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 16
No. 21
Systematic review of the clinical
effectiveness and cost-effectiveness
of tension-free vaginal tape for
treatment of urinary stress
incontinence.
By Cody J, Wyness L, Wallace S,
Glazener C, Kilonzo M, Stearns S,
et al.
No. 22
The clinical and cost-effectiveness of
patient education models for diabetes:
a systematic review and economic
evaluation.
By Loveman E, Cave C, Green C,
Royle P, Dunn N, Waugh N.
No. 23
The role of modelling in prioritising
and planning clinical trials.
By Chilcott J, Brennan A, Booth A,
Karnon J, Tappenden P.
No. 24
Costbenefit evaluation of routine
influenza immunisation in people 6574
years of age.
By Allsup S, Gosney M, Haycox A,
Regan M.
No. 25
The clinical and cost-effectiveness of
pulsatile machine perfusion versus cold
storage of kidneys for transplantation
retrieved from heart-beating and non-
heart-beating donors.
By Wight J, Chilcott J, Holmes M,
Brewer N.
No. 26
Can randomised trials rely on existing
electronic data? A feasibility study to
explore the value of routine data in
health technology assessment.
By Williams JG, Cheung WY,
Cohen DR, Hutchings HA, Longo MF,
Russell IT.
No. 27
Evaluating non-randomised intervention
studies.
By Deeks JJ, Dinnes J, DAmico R,
Sowden AJ, Sakarovitch C, Song F, et al.
No. 28
A randomised controlled trial to assess
the impact of a package comprising a
patient-orientated, evidence-based self-
help guidebook and patient-centred
consultations on disease management
and satisfaction in inflammatory bowel
disease.
By Kennedy A, Nelson E, Reeves D,
Richardson G, Roberts C, Robinson A,
et al.
No. 29
The effectiveness of diagnostic tests for
the assessment of shoulder pain due to
soft tissue disorders: a systematic review.
By Dinnes J, Loveman E, McIntyre L,
Waugh N.
No. 30
The value of digital imaging in diabetic
retinopathy.
By Sharp PF, Olson J, Strachan F,
Hipwell J, Ludbrook A, ODonnell M,
et al.
No. 31
Lowering blood pressure to prevent
myocardial infarction and stroke:
a new preventive strategy.
By Law M, Wald N, Morris J.
No. 32
Clinical and cost-effectiveness of
capecitabine and tegafur with uracil for
the treatment of metastatic colorectal
cancer: systematic review and economic
evaluation.
By Ward S, Kaltenthaler E, Cowan J,
Brewer N.
No. 33
Clinical and cost-effectiveness of new
and emerging technologies for early
localised prostate cancer: a systematic
review.
By Hummel S, Paisley S, Morgan A,
Currie E, Brewer N.
No. 34
Literature searching for clinical and
cost-effectiveness studies used in health
technology assessment reports carried
out for the National Institute for
Clinical Excellence appraisal
system.
By Royle P, Waugh N.
No. 35
Systematic review and economic
decision modelling for the prevention
and treatment of influenza
A and B.
By Turner D, Wailoo A, Nicholson K,
Cooper N, Sutton A, Abrams K.
No. 36
A randomised controlled trial to
evaluate the clinical and cost-
effectiveness of Hickman line
insertions in adult cancer patients by
nurses.
By Boland A, Haycox A, Bagust A,
Fitzsimmons L.
No. 37
Redesigning postnatal care: a
randomised controlled trial of
protocol-based midwifery-led care
focused on individual womens
physical and psychological health
needs.
By MacArthur C, Winter HR,
Bick DE, Lilford RJ, Lancashire RJ,
Knowles H, et al.
No. 38
Estimating implied rates of discount in
healthcare decision-making.
By West RR, McNabb R,
Thompson AGH, Sheldon TA,
Grimley Evans J. 87
 Health Technology Assessment reports published to date
No. 39
Systematic review of isolation policies in
the hospital management of methicillin-
resistant Staphylococcus aureus: a review of
the literature with epidemiological and
economic modelling.
By Cooper BS, Stone SP, Kibbler CC,
Cookson BD, Roberts JA, Medley GF,
et al.
No. 40
Treatments for spasticity and pain in
multiple sclerosis: a systematic review.
By Beard S, Hunn A, Wight J.
No. 41
The inclusion of reports of randomised
trials published in languages other than
English in systematic reviews.
By Moher D, Pham B, Lawson ML,
Klassen TP.
No. 42
The impact of screening on future
health-promoting behaviours and health
beliefs: a systematic review.
By Bankhead CR, Brett J, Bukach C,
Webster P, Stewart-Brown S, Munafo M,
et al.
Volume 8, 2004
No. 1
What is the best imaging strategy for
acute stroke?
By Wardlaw JM, Keir SL, Seymour J,
Lewis S, Sandercock PAG, Dennis MS,
et al.
No. 2
Systematic review and modelling of the
investigation of acute and chronic chest
pain presenting in primary care.
By Mant J, McManus RJ, Oakes RAL,
Delaney BC, Barton PM, Deeks JJ, et al.
No. 3
The effectiveness and cost-effectiveness
of microwave and thermal balloon
endometrial ablation for heavy
menstrual bleeding: a systematic review
and economic modelling.
By Garside R, Stein K, Wyatt K,
Round A, Price A.
No. 4
A systematic review of the role of
bisphosphonates in metastatic disease.
By Ross JR, Saunders Y, Edmonds PM,
Patel S, Wonderling D, Normand C, et al.
No. 5
Systematic review of the clinical
effectiveness and cost-effectiveness of
capecitabine (Xeloda ) for locally
advanced and/or metastatic breast cancer.
By Jones L, Hawkins N, Westwood M,
Wright K, Richardson G, Riemsma R.
No. 6
Effectiveness and efficiency of guideline
dissemination and implementation
strategies.
By Grimshaw JM, Thomas RE,
MacLennan G, Fraser C, Ramsay CR,
88 Vale L, et al.
No. 7
Clinical effectiveness and costs of the
Sugarbaker procedure for the treatment
of pseudomyxoma peritonei.
By Bryant J, Clegg AJ, Sidhu MK,
Brodin H, Royle P, Davidson P.
No. 8
Psychological treatment for insomnia in
the regulation of long-term hypnotic
drug use.
By Morgan K, Dixon S, Mathers N,
Thompson J, Tomeny M.
No. 9
Improving the evaluation of therapeutic
interventions in multiple sclerosis:
development of a patient-based measure
of outcome.
By Hobart JC, Riazi A, Lamping DL,
Fitzpatrick R, Thompson AJ.
No. 10
A systematic review and economic
evaluation of magnetic resonance
cholangiopancreatography compared
with diagnostic endoscopic retrograde
cholangiopancreatography.
By Kaltenthaler E, Bravo Vergel Y,
Chilcott J, Thomas S, Blakeborough T,
Walters SJ, et al.
No. 11
The use of modelling to evaluate new
drugs for patients with a chronic
condition: the case of antibodies against
tumour necrosis factor in rheumatoid
arthritis.
By Barton P, Jobanputra P, Wilson J,
Bryan S, Burls A.
No. 12
Clinical effectiveness and cost-
effectiveness of neonatal screening for
inborn errors of metabolism using
tandem mass spectrometry: a systematic
review.
By Pandor A, Eastham J, Beverley C,
Chilcott J, Paisley S.
No. 13
Clinical effectiveness and cost-
effectiveness of pioglitazone and
rosiglitazone in the treatment of
type 2 diabetes: a systematic
review and economic
evaluation.
By Czoski-Murray C, Warren E,
Chilcott J, Beverley C, Psyllaki MA,
Cowan J.
No. 14
Routine examination of the newborn:
the EMREN study. Evaluation of an
extension of the midwife role
including a randomised controlled
trial of appropriately trained midwives
and paediatric senior house
officers.
By Townsend J, Wolke D, Hayes J,
Dav S, Rogers C, Bloomfield L,
et al.
No. 15
Involving consumers in research and
development agenda setting for the
NHS: developing an evidence-based
approach.
By Oliver S, Clarke-Jones L,
Rees R, Milne R, Buchanan P,
Gabbay J, et al.
No. 16
A multi-centre randomised controlled
trial of minimally invasive direct
coronary bypass grafting versus
percutaneous transluminal coronary
angioplasty with stenting for proximal
stenosis of the left anterior descending
coronary artery.
By Reeves BC, Angelini GD, Bryan
AJ, Taylor FC, Cripps T, Spyt TJ, et al.
No. 17
Does early magnetic resonance imaging
influence management or improve
outcome in patients referred to
secondary care with low back pain?
A pragmatic randomised controlled
trial.
By Gilbert FJ, Grant AM, Gillan
MGC, Vale L, Scott NW, Campbell MK,
et al.
No. 18
The clinical and cost-effectiveness of
anakinra for the treatment of
rheumatoid arthritis in adults: a
systematic review and economic analysis.
By Clark W, Jobanputra P, Barton P,
Burls A.
No. 19
A rapid and systematic review and
economic evaluation of the clinical and
cost-effectiveness of newer drugs for
treatment of mania associated with
bipolar affective disorder.
By Bridle C, Palmer S, Bagnall A-M,
Darba J, Duffy S, Sculpher M, et al.
No. 20
Liquid-based cytology in cervical
screening: an updated rapid and
systematic review and economic
analysis.
By Karnon J, Peters J, Platt J,
Chilcott J, McGoogan E, Brewer N.
No. 21
Systematic review of the long-term
effects and economic consequences of
treatments for obesity and implications
for health improvement.
By Avenell A, Broom J, Brown TJ,
Poobalan A, Aucott L, Stearns SC, et al.
No. 22
Autoantibody testing in children with
newly diagnosed type 1 diabetes
mellitus.
By Dretzke J, Cummins C,
Sandercock J, Fry-Smith A, Barrett T,
Burls A.

No. 23
Clinical effectiveness and cost-
effectiveness of prehospital intravenous
fluids in trauma patients.
By Dretzke J, Sandercock J, Bayliss S,
Burls A.
No. 24
Newer hypnotic drugs for the short-
term management of insomnia: a
systematic review and economic
evaluation.
By Dndar Y, Boland A, Strobl J,
Dodd S, Haycox A, Bagust A,
et al.
No. 25
Development and validation of methods
for assessing the quality of diagnostic
accuracy studies.
By Whiting P, Rutjes AWS, Dinnes J,
Reitsma JB, Bossuyt PMM, Kleijnen J.
No. 26
EVALUATE hysterectomy trial: a
multicentre randomised trial comparing
abdominal, vaginal and laparoscopic
methods of hysterectomy.
By Garry R, Fountain J, Brown J,
Manca A, Mason S, Sculpher M, et al.
No. 27
Methods for expected value of
information analysis in complex health
economic models: developments on the
health economics of interferon- and
glatiramer acetate for multiple sclerosis.
By Tappenden P, Chilcott JB,
Eggington S, Oakley J, McCabe C.
No. 28
Effectiveness and cost-effectiveness of
imatinib for first-line treatment of
chronic myeloid leukaemia in chronic
phase: a systematic review and economic
analysis.
By Dalziel K, Round A, Stein K,
Garside R, Price A.
No. 29
VenUS I: a randomised controlled trial
of two types of bandage for treating
venous leg ulcers.
By Iglesias C, Nelson EA, Cullum NA,
Torgerson DJ on behalf of the VenUS
Team.
No. 30
Systematic review of the effectiveness
and cost-effectiveness, and economic
evaluation, of myocardial perfusion
scintigraphy for the diagnosis and
management of angina and myocardial
infarction.
By Mowatt G, Vale L, Brazzelli M,
Hernandez R, Murray A, Scott N, et al.
No. 31
A pilot study on the use of decision
theory and value of information analysis
as part of the NHS Health Technology
Assessment programme.
By Claxton
on K,
K Ginnelly L, Sculpher
M, Philips Z, Palmer S.
Queens Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 16
No. 32
The Social Support and Family Health
Study: a randomised controlled trial and
economic evaluation of two alternative
forms of postnatal support for mothers
living in disadvantaged inner-city areas.
By Wiggins M, Oakley A, Roberts I,
Turner H, Rajan L, Austerberry H, et al.
No. 33
Psychosocial aspects of genetic screening
of pregnant women and newborns:
a systematic review.
By Green JM, Hewison J, Bekker HL,
Bryant, Cuckle HS.
No. 34
Evaluation of abnormal uterine
bleeding: comparison of three
outpatient procedures within cohorts
defined by age and menopausal status.
By Critchley HOD, Warner P,
Lee AJ, Brechin S, Guise J, Graham B.
No. 35
Coronary artery stents: a rapid systematic
review and economic evaluation.
By Hill R, Bagust A, Bakhai A,
Dickson R, Dndar Y, Haycox A, et al.
No. 36
Review of guidelines for good practice
in decision-analytic modelling in health
technology assessment.
By Philips Z, Ginnelly L, Sculpher M,
Claxton K, Golder S, Riemsma R, et al.
No. 37
Rituximab (MabThera) for aggressive
non-Hodgkins lymphoma: systematic
review and economic evaluation.
By Knight C, Hind D, Brewer N,
Abbott V.
No. 38
Clinical effectiveness and cost-
effectiveness of clopidogrel and
modified-release dipyridamole in the
secondary prevention of occlusive
vascular events: a systematic review and
economic evaluation.
By Jones L, Griffin S, Palmer S, Main
C, Orton V, Sculpher M, et al.
No. 39
Pegylated interferon -2a and -2b in
combination with ribavirin in the
treatment of chronic hepatitis C: a
systematic review and economic
evaluation.
By Shepherd J, Brodin H, Cave C,
Waugh N, Price A, Gabbay J.
No. 40
Clopidogrel used in combination with
aspirin compared with aspirin alone in
the treatment of non-ST-segment-
elevation acute coronary syndromes: a
systematic review and economic
evaluation.
By Main C, Palmer S, Griffin S,
Jones L, Orton V, Sculpher M, et al.
No. 41
Provision, uptake and cost of cardiac
rehabilitation programmes: improving
services to under-represented groups.
By Beswick AD, Rees K, Griebsch I,
Taylor FC, Burke M, West RR, et al.
No. 42
Involving South Asian patients in
clinical trials.
By Hussain-Gambles M, Leese B,
Atkin K, Brown J, Mason S, Tovey P.
No. 43
Clinical and cost-effectiveness of
continuous subcutaneous insulin
infusion for diabetes.
By Colquitt JL, Green C, Sidhu MK,
Hartwell D, Waugh N.
No. 44
Identification and assessment of
ongoing trials in health technology
assessment reviews.
By Song FJ, Fry-Smith A, Davenport
C, Bayliss S, Adi Y, Wilson JS, et al.
No. 45
Systematic review and economic
evaluation of a long-acting insulin
analogue, insulin glargine
By Warren E, Weatherley-Jones E,
Chilcott J, Beverley C.
No. 46
Supplementation of a home-based
exercise programme with a class-based
programme for people with osteoarthritis
of the knees: a randomised controlled
trial and health economic analysis.
By McCarthy CJ, Mills PM,
Pullen R, Richardson G, Hawkins N,
Roberts CR, et al.
No. 47
Clinical and cost-effectiveness of once-
daily versus more frequent use of same
potency topical corticosteroids for atopic
eczema: a systematic review and
economic evaluation.
By Green C, Colquitt JL, Kirby J,
Davidson P, Payne E.
No. 48
Acupuncture of chronic headache
disorders in primary care: randomised
controlled trial and economic analysis.
By Vickers AJ, Rees RW, Zollman CE,
McCarney R, Smith CM, Ellis N, et al.
No. 49
Generalisability in economic evaluation
studies in healthcare: a review and case
studies.
By Sculpher MJ, Pang FS, Manca A,
Drummond MF, Golder S, Urdahl H,
et al.
No. 50
Virtual outreach: a randomised
controlled trial and economic evaluation
of joint teleconferenced medical
consultations.
By Wallace P, Barber J, Clayton W,
Currell R, Fleming K, Garner P, et al. 89
 Health Technology Assessment reports published to date
Volume 9, 2005
No. 1
Randomised controlled multiple
treatment comparison to provide a
cost-effectiveness rationale for the
selection of antimicrobial therapy in
acne.
By Ozolins M, Eady EA, Avery A,
Cunliffe WJ, ONeill C, Simpson NB,
et al.
No. 2
Do the findings of case series studies
vary significantly according to
methodological characteristics?
By Dalziel K, Round A, Stein K,
Garside R, Castelnuovo E, Payne L.
No. 3
Improving the referral process for
familial breast cancer genetic
counselling: findings of three
randomised controlled trials of two
interventions.
By Wilson BJ, Torrance N, Mollison J,
Wordsworth S, Gray JR, Haites NE, et al.
No. 4
Randomised evaluation of alternative
electrosurgical modalities to treat
bladder outflow obstruction in men with
benign prostatic hyperplasia.
By Fowler C, McAllister W, Plail R,
Karim O, Yang Q.
No. 5
A pragmatic randomised controlled trial
of the cost-effectiveness of palliative
therapies for patients with inoperable
oesophageal cancer.
By Shenfine J, McNamee P, Steen N,
Bond J, Griffin SM.
No. 6
Impact of computer-aided detection
prompts on the sensitivity and specificity
of screening mammography.
By Taylor P, Champness J, Given-
Wilson R, Johnston K, Potts H.
No. 7
Issues in data monitoring and interim
analysis of trials.
By Grant AM, Altman DG, Babiker
AB, Campbell MK, Clemens FJ,
Darbyshire JH, et al.
No. 8
Lay publics understanding of equipoise
and randomisation in randomised
controlled trials.
By Robinson EJ, Kerr CEP, Stevens
AJ, Lilford RJ, Braunholtz DA, Edwards
SJ, et al.
No. 9
Clinical and cost-effectiveness of
electroconvulsive therapy for depressive
illness, schizophrenia, catatonia and
mania: systematic reviews and economic
modelling studies.
By Greenhalgh J, Knight C, Hind D,
90 Beverley C, Walters S.
No. 10
Measurement of health-related quality
of life for people with dementia:
development of a new instrument
(DEMQOL) and an evaluation of
current methodology.
By Smith SC, Lamping DL,
Banerjee S, Harwood R, Foley B,
Smith P, et al.
No. 11
Clinical effectiveness and cost-
effectiveness of drotrecogin alfa
(activated) (Xigris) for the treatment of
severe sepsis in adults: a systematic
review and economic evaluation.
By Green C, Dinnes J, Takeda A,
Shepherd J, Hartwell D, Cave C,
et al.
No. 12
A methodological review of how
heterogeneity has been examined in
systematic reviews of diagnostic test
accuracy.
By Dinnes J, Deeks J, Kirby J,
Roderick P.
No. 13
Cervical screening programmes: can
automation help? Evidence from
systematic reviews, an economic analysis
and a simulation modelling exercise
applied to the UK.
By Willis BH, Barton P, Pearmain P,
Bryan S, Hyde C.
No. 14
Laparoscopic surgery for inguinal
hernia repair: systematic review of
effectiveness and economic evaluation.
By McCormack K, Wake B, Perez J,
Fraser C, Cook J, McIntosh E, et al.
No. 15
Clinical effectiveness, tolerability and
cost-effectiveness of newer drugs for
epilepsy in adults: a systematic review
and economic evaluation.
By Wilby J, Kainth A, Hawkins N,
Epstein D, McIntosh H, McDaid C, et al.
No. 16
A randomised controlled trial to
compare the cost-effectiveness of
tricyclic antidepressants, selective
serotonin reuptake inhibitors and
lofepramine.
By Peveler R, Kendrick T, Buxton M,
Longworth L, Baldwin D, Moore M,
et al.
No. 17
Clinical effectiveness and cost-
effectiveness of immediate angioplasty
for acute myocardial infarction:
systematic review and economic
evaluation.
By Hartwell D, Colquitt J, Loveman
E, Clegg AJ, Brodin H, Waugh N,
et al.
No. 18
A randomised controlled comparison of
alternative strategies in stroke care.
By Kalra L, Evans A, Perez I,
Knapp M, Swift C, Donaldson N.
No. 19
The investigation and analysis of critical
incidents and adverse events in
healthcare.
By Woloshynowych M, Rogers S,
Taylor-Adams S, Vincent C.
No. 20
Potential use of routine databases in
health technology assessment.
By Raftery J, Roderick P, Stevens A.
No. 21
Clinical and cost-effectiveness of newer
immunosuppressive regimens in renal
transplantation: a systematic review and
modelling study.
By Woodroffe R, Yao GL, Meads C,
Bayliss S, Ready A, Raftery J, et al.
No. 22
A systematic review and economic
evaluation of alendronate, etidronate,
risedronate, raloxifene and teriparatide
for the prevention and treatment of
postmenopausal osteoporosis.
By Stevenson M, Lloyd Jones M,
De Nigris E, Brewer N, Davis S,
Oakley J.
No. 23
A systematic review to examine the
impact of psycho-educational
interventions on health outcomes and
costs in adults and children with difficult
asthma.
By Smith JR, Mugford M, Holland R,
Candy B, Noble MJ, Harrison BDW, et al.
No. 24
An evaluation of the costs, effectiveness
and quality of renal replacement
therapy provision in renal satellite units
in England and Wales.
By Roderick P, Nicholson T, Armitage
A, Mehta R, Mullee M, Gerard K, et al.
No. 25
Imatinib for the treatment of patients
with unresectable and/or metastatic
gastrointestinal stromal tumours:
systematic review and economic
evaluation.
By Wilson J, Connock M, Song F, Yao
G, Fry-Smith A, Raftery J, et al.
No. 26
Indirect comparisons of competing
interventions.
By Glenny AM, Altman DG, Song F,
Sakarovitch C, Deeks JJ, DAmico R, et al.
No. 27
Cost-effectiveness of alternative
strategies for the initial medical
management of non-ST elevation acute
coronary syndrome: systematic review
and decision-analytical modelling.
By Robinson M, Palmer S, Sculpher
M, Philips Z, Ginnelly L, Bowens A, et al.

No. 28
Outcomes of electrically stimulated
gracilis neosphincter surgery.
By Tillin T, Chambers M, Feldman R.
No. 29
The effectiveness and cost-effectiveness
of pimecrolimus and tacrolimus for
atopic eczema: a systematic review and
economic evaluation.
By Garside R, Stein K, Castelnuovo E,
Pitt M, Ashcroft D, Dimmock P, et al.
No. 30
Systematic review on urine albumin
testing for early detection of diabetic
complications.
By Newman DJ, Mattock MB, Dawnay
ABS, Kerry S, McGuire A, Yaqoob M, et al.
No. 31
Randomised controlled trial of the cost-
effectiveness of water-based therapy for
lower limb osteoarthritis.
By Cochrane T, Davey RC,
Matthes Edwards SM.
No. 32
Longer term clinical and economic
benefits of offering acupuncture care to
patients with chronic low back pain.
By Thomas KJ, MacPherson H,
Ratcliffe J, Thorpe L, Brazier J,
Campbell M, et al.
No. 33
Cost-effectiveness and safety of epidural
steroids in the management of sciatica.
By Price C, Arden N, Coglan L,
Rogers P.
No. 34
The British Rheumatoid Outcome Study
Group (BROSG) randomised controlled
trial to compare the effectiveness and
cost-effectiveness of aggressive versus
symptomatic therapy in established
rheumatoid arthritis.
By Symmons D, Tricker K, Roberts C,
Davies L, Dawes P, Scott DL.
No. 35
Conceptual framework and systematic
review of the effects of participants and
professionals preferences in randomised
controlled trials.
By King M, Nazareth I, Lampe F,
Bower P, Chandler M, Morou M, et al.
No. 36
The clinical and cost-effectiveness of
implantable cardioverter defibrillators:
a systematic review.
By Bryant J, Brodin H, Loveman E,
Payne E, Clegg A.
No. 37
A trial of problem-solving by community
mental health nurses for anxiety,
depression and life difficulties among
general practice patients. The CPN-GP
study.
By Kendrick T, Simons L,
Mynors-Wallis L, Gray A, Lathlean J,
Pickering R, et al.
Queens Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 16
No. 38
The causes and effects of socio-
demographic exclusions from clinical
trials.
By Bartlett C, Doyal L, Ebrahim S,
Davey P, Bachmann M, Egger M,
et al.
No. 39
Is hydrotherapy cost-effective? A
randomised controlled trial of combined
hydrotherapy programmes compared
with physiotherapy land techniques in
children with juvenile idiopathic
arthritis.
By Epps H, Ginnelly L, Utley M,
Southwood T, Gallivan S, Sculpher M,
et al.
No. 40
A randomised controlled trial and cost-
effectiveness study of systematic
screening (targeted and total population
screening) versus routine practice for
the detection of atrial fibrillation in
people aged 65 and over. The SAFE
study.
By Hobbs FDR, Fitzmaurice DA,
Mant J, Murray E, Jowett S, Bryan S,
et al.
No. 41
Displaced intracapsular hip fractures
in fit, older people: a randomised
comparison of reduction and fixation,
bipolar hemiarthroplasty and total hip
arthroplasty.
By Keating JF, Grant A, Masson M,
Scott NW, Forbes JF.
No. 42
Long-term outcome of cognitive
behaviour therapy clinical trials in
central Scotland.
By Durham RC, Chambers JA,
Power KG, Sharp DM, Macdonald RR,
Major KA, et al.
No. 43
The effectiveness and cost-effectiveness
of dual-chamber pacemakers compared
with single-chamber pacemakers for
bradycardia due to atrioventricular
block or sick sinus syndrome:
systematic review and economic
evaluation.
By Castelnuovo E, Stein K, Pitt M,
Garside R, Payne E.
No. 44
Newborn screening for congenital heart
defects: a systematic review and
cost-effectiveness analysis.
By Knowles R, Griebsch I, Dezateux
C, Brown J, Bull C, Wren C.
No. 45
The clinical and cost-effectiveness of left
ventricular assist devices for end-stage
heart failure: a systematic review and
economic evaluation.
By Clegg AJ, Scott DA, Loveman E,
Colquitt J, Hutchinson J, Royle P,
et al.
No. 46
The effectiveness of the Heidelberg
Retina Tomograph and laser diagnostic
glaucoma scanning system (GDx) in
detecting and monitoring glaucoma.
By Kwartz AJ, Henson DB,
Harper RA, Spencer AF,
McLeod D.
No. 47
Clinical and cost-effectiveness of
autologous chondrocyte implantation
for cartilage defects in knee joints:
systematic review and economic
evaluation.
By Clar C, Cummins E, McIntyre L,
Thomas S, Lamb J, Bain L, et al.
No. 48
Systematic review of effectiveness of
different treatments for childhood
retinoblastoma.
By McDaid C, Hartley S,
Bagnall A-M, Ritchie G, Light K,
Riemsma R.
No. 49
Towards evidence-based guidelines
for the prevention of venous
thromboembolism: systematic
reviews of mechanical methods, oral
anticoagulation, dextran and regional
anaesthesia as thromboprophylaxis.
By Roderick P, Ferris G, Wilson K,
Halls H, Jackson D, Collins R,
et al.
No. 50
The effectiveness and cost-effectiveness
of parent training/education
programmes for the treatment of
conduct disorder, including oppositional
defiant disorder, in children.
By Dretzke J, Frew E, Davenport C,
Barlow J, Stewart-Brown S,
Sandercock J, et al.
Volume 10, 2006
No. 1
The clinical and cost-effectiveness of
donepezil, rivastigmine, galantamine
and memantine for Alzheimers
disease.
By Loveman E, Green C, Kirby J,
Takeda A, Picot J, Payne E,
et al.
No. 2
FOOD: a multicentre randomised trial
evaluating feeding policies in patients
admitted to hospital with a recent
stroke.
By Dennis M, Lewis S, Cranswick G,
Forbes J.
No. 3
The clinical effectiveness and cost-
effectiveness of computed tomography
screening for lung cancer: systematic
reviews.
By Black C, Bagust A, Boland A,
Walker S, McLeod C, De Verteuil R,
et al. 91
 Health Technology Assessment reports published to date
No. 4
A systematic review of the effectiveness
and cost-effectiveness of neuroimaging
assessments used to visualise the
seizure focus in people with refractory
epilepsy being considered for
surgery.
By Whiting P, Gupta R, Burch J,
Mujica Mota RE, Wright K, Marson A,
et al.
No. 5
Comparison of conference abstracts
and presentations with full-text
articles in the health technology
assessments of rapidly evolving
technologies.
By Dundar Y, Dodd S, Dickson R,
Walley T, Haycox A, Williamson PR.
No. 6
Systematic review and evaluation of
methods of assessing urinary
incontinence.
By Martin JL, Williams KS, Abrams
KR, Turner DA, Sutton AJ, Chapple C,
et al.
No. 7
The clinical effectiveness and
cost-effectiveness of newer drugs for
children with epilepsy. A systematic
review.
By Connock M, Frew E, Evans B-W,
Bryan S, Cummins C, Fry-Smith A,
et al.
92
No. 8
Surveillance of Barretts oesophagus:
exploring the uncertainty through
systematic review, expert workshop and
economic modelling.
By Garside R, Pitt M, Somerville M,
Stein K, Price A, Gilbert N.
No. 9
Topotecan, pegylated liposomal
doxorubicin hydrochloride and
paclitaxel for second-line or subsequent
treatment of advanced ovarian cancer: a
systematic review and economic
evaluation.
By Main C, Bojke L, Griffin S,
Norman G, Barbieri M, Mather L,
et al.
No. 10
Evaluation of molecular techniques in
prediction and diagnosis of
cytomegalovirus disease in
immunocompromised patients.
By Szczepura A, Westmoreland D,
Vinogradova Y, Fox J, Clark M.
No. 11
Screening for thrombophilia in high-risk
situations: systematic review and cost-
effectiveness analysis. The Thrombosis:
Risk and Economic Assessment of
Thrombophilia Screening (TREATS)
study.
By Wu O, Robertson L, Twaddle S,
Lowe GDO, Clark P, Greaves M,
et al.
No. 12
A series of systematic reviews to inform
a decision analysis for sampling and
treating infected diabetic foot ulcers.
By Nelson EA, OMeara S, Craig D,
Iglesias C, Golder S, Dalton J, et al.
No. 13
Randomised clinical trial, observational
study and assessment of cost-effectiveness
of the treatment of varicose veins
(REACTIV trial).
By Michaels JA, Campbell WB,
Brazier JE, MacIntyre JB, Palfreyman SJ,
Ratcliffe J, et al.
No. 14
The cost-effectiveness of screening for
oral cancer in primary care.
By Speight PM, Palmer S, Moles DR,
Downer MC, Smith DH,
Henriksson M et al.
No. 15
Measurement of the clinical and cost-
effectiveness of non-invasive diagnostic
testing strategies for deep vein
thrombosis.
By Goodacre S, Sampson F, Stevenson
M, Wailoo A, Sutton A, Thomas S, et al.
No. 16
Systematic review of the effectiveness
and cost-effectiveness of HealOzone
for the treatment of occlusal pit/fissure
caries and root caries.
By Brazzelli M, McKenzie L, Fielding
S, Fraser C, Clarkson J, Kilonzo M, et al.

Health Technology Assessment
Members
Chair,
Professor Tom Walley,
Director, NHS HTA Programme,
Department of Pharmacology &
Therapeutics,
University of Liverpool
Members
Programme Director,
Professor Tom Walley,
Director, NHS HTA Programme,
Department of Pharmacology &
Therapeutics,
University of Liverpool
Chair,
Professor Jon Nicholl,
Director, Medical Care Research
Unit, University of Sheffield,
School of Health and Related
Research
Deputy Chair,
Professor Jenny Hewison,
Professor of Health Care
Psychology, Academic Unit of
Psychiatry and Behavioural
Sciences, University of Leeds
School of Medicine
Dr Jeffrey Aronson
Reader in Clinical
Pharmacology, Department of
Clinical Pharmacology,
Radcliffe Infirmary, Oxford
Professor Deborah Ashby,
Professor of Medical Statistics,
Department of Environmental
and Preventative Medicine,
Queen Mary University of
London
Current and past membership details of all HTA committees are available from the HTA website (www.hta.ac.uk)
Queens Printer and Controller of HMSO 2006. All rights reserved.
Programme
Director,
Professor Tom Walley,
Director, NHS HTA Programme,
Department of Pharmacology &
Therapeutics,
University of Liverpool
Prioritisation Strategy Group
Professor Bruce Campbell,
Consultant Vascular & General
Surgeon, Royal Devon & Exeter
Hospital
Dr Edmund Jessop, Medical
Advisor, National Specialist,
Commissioning Advisory Group
(NSCAG), Department of
Health, London
HTA Commissioning Board
Professor Ann Bowling,
Professor of Health Services
Research, Primary Care and
Population Studies,
University College London
Dr Andrew Briggs, Public
Health Career Scientist, Health
Economics Research Centre,
University of Oxford
Professor John Cairns, Professor
of Health Economics, Public
Health Policy, London School of
Hygiene and Tropical Medicine,
London
Professor Nicky Cullum,
Director of Centre for Evidence
Based Nursing, Department of
Health Sciences, University of
York
Mr Jonathan Deeks,
Senior Medical Statistician,
Centre for Statistics in
Medicine, University of Oxford
Dr Andrew Farmer, Senior
Lecturer in General Practice,
Department of Primary
Health Care,
University of Oxford
Health Technology Assessment 2006; Vol. 10: No. 16
Deputy Director,
Professor Jon Nicholl,
Director, Medical Care Research
Unit, University of Sheffield,
School of Health and Related
Research
Professor Jon Nicholl, Director,
Medical Care Research Unit,
University of Sheffield, School
of Health and Related Research
Dr John Reynolds, Clinical
Director, Acute General
Medicine SDU, Radcliffe
Hospital, Oxford
Professor Fiona J Gilbert,
Professor of Radiology,
Department of Radiology,
University of Aberdeen
Professor Adrian Grant,
Director, Health Services
Research Unit, University of
Aberdeen
Professor F D Richard Hobbs,
Professor of Primary Care &
General Practice, Department of
Primary Care & General
Practice, University of
Birmingham
Professor Peter Jones, Head of
Department, University
Department of Psychiatry,
University of Cambridge
Professor Sallie Lamb,
Professor of Rehabilitation,
Centre for Primary Health Care,
University of Warwick
Professor Stuart Logan,
Director of Health & Social
Care Research, The
Peninsula Medical School,
Universities of Exeter &
Plymouth
Dr Ron Zimmern, Director,
Public Health Genetics Unit,
Strangeways Research
Laboratories, Cambridge
Dr Linda Patterson,
Consultant Physician,
Department of Medicine,
Burnley General Hospital
Professor Ian Roberts, Professor
of Epidemiology & Public
Health, Intervention Research
Unit, London School of
Hygiene and Tropical Medicine
Professor Mark Sculpher,
Professor of Health Economics,
Centre for Health Economics,
Institute for Research in the
Social Services, University of York
Dr Jonathan Shapiro, Senior
Fellow, Health Services
Management Centre,
Birmingham
Ms Kate Thomas,
Deputy Director,
Medical Care Research Unit,
University of Sheffield
Ms Sue Ziebland,
Research Director, DIPEx,
Department of Primary Health
Care, University of Oxford,
Institute of Health Sciences
93
 Health Technology Assessment Programme

Diagnostic Technologies & Screening Panel

Members

Chair,
Dr Ron Zimmern, Director of
the Public Health Genetics Unit,
Strangeways Research
Laboratories, Cambridge
Ms Norma Armston,
Lay Member, Bolton
Professor Max Bachmann
Professor of Health
Care Interfaces,
Department of Health
Policy and Practice,
University of East Anglia
Professor Rudy Bilous
Professor of Clinical Medicine &
Consultant Physician,
The Academic Centre,
South Tees Hospitals NHS Trust
Dr Paul Cockcroft,
Consultant Medical
Microbiologist and Clinical
Director of Pathology,
Department of Clinical
Microbiology, St Mary's
Hospital, Portsmouth
Professor Adrian K Dixon,
Professor of Radiology,
University Department of
Radiology, University of
Cambridge Clinical School
Dr David Elliman,
Consultant Paediatrician/
Hon. Senior Lecturer,
Population Health Unit,
Great Ormond St. Hospital,
London
Professor Glyn Elwyn,
Primary Medical Care
Research Group,
Swansea Clinical School,
University of Wales Swansea
Mr Tam Fry, Honorary
Chairman, Child Growth
Foundation, London
Dr Jennifer J Kurinczuk,
Consultant Clinical
Epidemiologist,
National Perinatal
Epidemiology Unit, Oxford
Dr Susanne M Ludgate, Medical Professor Lindsay Wilson
Director, Medicines & Turnbull, Scientific Director,
Healthcare Products Regulatory Centre for MR Investigations &
Agency, London YCR Professor of Radiology,
University of Hull
Professor William Rosenberg,
Professor of Hepatology, Liver Professor Martin J Whittle,
Research Group, University of
Associate Dean for Education,
Southampton Head of Department of
Obstetrics and Gynaecology,
Dr Susan Schonfield, Consultant
University of Birmingham
in Public Health, Specialised
Services Commissioning North
Dr Dennis Wright,
West London, Hillingdon
Consultant Biochemist &
Primary Care Trust
Clinical Director,
Dr Phil Shackley, Senior Pathology & The Kennedy
Lecturer in Health Economics, Galton Centre,
School of Population and Northwick Park & St Marks
Health Sciences, University of Hospitals, Harrow
Newcastle upon Tyne
Dr Margaret Somerville, PMS
Public Health Lead, Peninsula
Medical School, University of
Plymouth
Dr Graham Taylor, Scientific
Director & Senior Lecturer,
Regional DNA Laboratory, The
Leeds Teaching Hospitals

Pharmaceuticals Panel
Members

Chair,
Dr John Reynolds, Chair
Division A, The John Radcliffe
Hospital, Oxford Radcliffe
Hospitals NHS Trust
Professor Tony Avery,
Head of Division of Primary
Care, School of Community
Health Services, Division of
General Practice, University of
Nottingham
Ms Anne Baileff, Consultant
Nurse in First Contact Care,
Southampton City Primary Care
Trust, University of
Southampton
Professor Stirling Bryan,
Professor of Health Economics,
Health Services
Management Centre,
University of Birmingham
Mr Peter Cardy, Chief
Executive, Macmillan Cancer
Relief, London
Professor Imti Choonara,
Professor in Child Health,
Academic Division of Child
Health, University of
Nottingham
Dr Robin Ferner, Consultant
Physician and Director, West
Midlands Centre for Adverse
Drug Reactions, City Hospital
NHS Trust, Birmingham
Dr Karen A Fitzgerald,
Consultant in Pharmaceutical
Public Health, National Public
Health Service for Wales,
Cardiff
Mrs Sharon Hart, Head of
DTB Publications, Drug &
Therapeutics Bulletin, London
Dr Christine Hine, Consultant in
Public Health Medicine, South
Gloucestershire Primary Care
Trust
Professor Stan Kaye,
Cancer Research UK
Professor of Medical Oncology,
Section of Medicine,
The Royal Marsden Hospital,
Sutton
Ms Barbara Meredith,
Lay Member, Epsom
Dr Andrew Prentice, Senior
Lecturer and Consultant
Obstetrician & Gynaecologist,
Department of Obstetrics &
Gynaecology, University of
Cambridge
Dr Frances Rotblat, CPMP
Delegate, Medicines &
Healthcare Products Regulatory
Agency, London
Professor Jan Scott, Professor
of Psychological Treatments,
Institute of Psychiatry,
University of London
Mrs Katrina Simister, Assistant
Director New Medicines,
National Prescribing Centre,
Liverpool
Dr Richard Tiner, Medical
Director, Medical Department,
Association of the British
Pharmaceutical Industry,
London
Dr Helen Williams,
Consultant Microbiologist,
Norfolk & Norwich University
Hospital NHS Trust

94
Current and past membership details of all HTA committees are available from the HTA website (www.hta.ac.uk)

Members
Chair,
Professor Bruce Campbell,
Consultant Vascular and
General Surgeon, Department
of Surgery, Royal Devon &
Exeter Hospital
Dr Aileen Clarke,
Reader in Health Services
Research, Public Health &
Policy Research Unit, Barts &
the London School of Medicine
& Dentistry, London
Dr Matthew Cooke, Reader in
A&E/Department of Health
Advisor in A&E, Warwick
Emergency Care and
Rehabilitation, University of
Warwick
Current and past membership details of all HTA committees are available from the HTA website (www.hta.ac.uk)
Therapeutic Procedures Panel
Dr Carl E Counsell, Clinical
Senior Lecturer in Neurology,
Department of Medicine and
Therapeutics, University of
Aberdeen
Ms Amelia Curwen, Executive
Director of Policy, Services and
Research, Asthma UK, London
Professor Gene Feder, Professor
of Primary Care R&D,
Department of General Practice
and Primary Care, Barts & the
London, Queen Marys School
of Medicine and Dentistry,
London
Professor Paul Gregg,
Professor of Orthopaedic
Surgical Science, Department of
General Practice and Primary
Care, South Tees Hospital NHS
Trust, Middlesbrough
Ms Bec Hanley, Co-Director,
TwoCan Associates,
Hurstpierpoint
Health Technology Assessment 2006; Vol. 10: No. 16
Ms Maryann L Hardy,
Lecturer, Division of
Radiography, University of
Bradford
Professor Alan Horwich,
Director of Clinical R&D,
Academic Department of
Radiology, The Institute of
Cancer Research,
London
Dr Simon de Lusignan,
Senior Lecturer,
Primary Care Informatics,
Department of Community
Health Sciences,
St Georges Hospital Medical
School, London
Professor Neil McIntosh,
Edward Clark Professor of
Child Life & Health,
Department of Child Life &
Health, University of
Edinburgh
Professor James Neilson,
Professor of Obstetrics and
Gynaecology, Department of
Obstetrics and Gynaecology,
University of Liverpool
Dr John C Pounsford,
Consultant Physician,
Directorate of Medical Services,
North Bristol NHS Trust
Karen Roberts, Nurse
Consultant, Queen Elizabeth
Hospital, Gateshead
Dr Vimal Sharma, Consultant
Psychiatrist/Hon. Senior Lecturer,
Mental Health Resource Centre,
Cheshire and Wirral Partnership
NHS Trust, Wallasey
Dr L David Smith, Consultant
Cardiologist, Royal Devon &
Exeter Hospital
Professor Norman Waugh,
Professor of Public Health,
Department of Public Health,
University of Aberdeen
95
 Health Technology Assessment Programme
Members
Professor Douglas Altman,
Director of CSM & Cancer
Research UK Med Stat Gp,
Centre for Statistics in
Medicine, University of Oxford,
Institute of Health Sciences,
Headington, Oxford
Professor John Bond,
Director, Centre for Health
Services Research, University of
Newcastle upon Tyne, School of
Population & Health Sciences,
Newcastle upon Tyne
Mr Shaun Brogan,
Chief Executive, Ridgeway
Primary Care Group, Aylesbury
Mrs Stella Burnside OBE,
Chief Executive, Office of the
Chief Executive. Trust
Headquarters, Altnagelvin
Hospitals Health & Social
Services Trust, Altnagelvin Area
Hospital, Londonderry
Ms Tracy Bury,
Project Manager, World
Confederation for Physical
Therapy, London
Professor Iain T Cameron,
Professor of Obstetrics and
Gynaecology and Head of the
School of Medicine,
University of Southampton
Dr Christine Clark,
Medical Writer & Consultant
Pharmacist, Rossendale
Professor Collette Clifford,
Professor of Nursing & Head of
Research, School of Health
Sciences, University of
Birmingham, Edgbaston,
Birmingham
Professor Barry Cookson,
Director, Laboratory of
Healthcare Associated Infection,
Health Protection Agency,
London
Professor Howard Cuckle,
Professor of Reproductive
Epidemiology, Department of
Paediatrics, Obstetrics &
Gynaecology, University of
Leeds
Dr Katherine Darton,
Information Unit, MIND
The Mental Health Charity,
London
Professor Carol Dezateux,
Professor of Paediatric
Epidemiology, London
96
Current and past membership details of all HTA committees are available from the HTA website (www.hta.ac.uk)
Expert Advisory Network
Mr John Dunning,
Consultant Cardiothoracic
Surgeon, Cardiothoracic
Surgical Unit, Papworth
Hospital NHS Trust, Cambridge
Mr Jonothan Earnshaw,
Consultant Vascular Surgeon,
Gloucestershire Royal Hospital,
Gloucester
Professor Martin Eccles,
Professor of Clinical
Effectiveness, Centre for Health
Services Research, University of
Newcastle upon Tyne
Professor Pam Enderby,
Professor of Community
Rehabilitation, Institute of
General Practice and Primary
Care, University of Sheffield
Mr Leonard R Fenwick,
Chief Executive, Newcastle
upon Tyne Hospitals NHS Trust
Professor David Field,
Professor of Neonatal Medicine,
Child Health, The Leicester
Royal Infirmary NHS Trust
Mrs Gillian Fletcher,
Antenatal Teacher & Tutor and
President, National Childbirth
Trust, Henfield
Professor Jayne Franklyn,
Professor of Medicine,
Department of Medicine,
University of Birmingham,
Queen Elizabeth Hospital,
Edgbaston, Birmingham
Ms Grace Gibbs,
Deputy Chief Executive,
Director for Nursing, Midwifery
& Clinical Support Services,
West Middlesex University
Hospital, Isleworth
Dr Neville Goodman,
Consultant Anaesthetist,
Southmead Hospital, Bristol
Professor Alastair Gray,
Professor of Health Economics,
Department of Public Health,
University of Oxford
Professor Robert E Hawkins,
CRC Professor and Director of
Medical Oncology, Christie CRC
Research Centre, Christie
Hospital NHS Trust, Manchester
Professor Allen Hutchinson,
Director of Public Health &
Deputy Dean of ScHARR,
Department of Public Health,
University of Sheffield
Dr Duncan Keeley, Professor Chris Price,
General Practitioner (Dr Burch Visiting Chair Oxford, Clinical
& Ptnrs), The Health Centre, Research, Bayer Diagnostics
Thame Europe, Cirencester
Dr Donna Lamping, Professor Peter Sandercock,
Research Degrees Programme Professor of Medical Neurology,
Director & Reader in Psychology, Department of Clinical
Health Services Research Unit, Neurosciences, University of
London School of Hygiene and Edinburgh
Tropical Medicine, London
Dr Eamonn Sheridan,
Mr George Levvy, Consultant in Clinical Genetics,
Chief Executive, Motor Genetics Department,
Neurone Disease Association, St Jamess University Hospital,
Northampton Leeds
Professor James Lindesay, Dr Ken Stein,
Professor of Psychiatry for the Senior Clinical Lecturer in
Elderly, University of Leicester, Public Health, Director,
Leicester General Hospital Peninsula Technology
Assessment Group,
Professor Julian Little, University of Exeter
Professor of Human Genome
Epidemiology, Department of Professor Sarah Stewart-Brown,
Epidemiology & Community Professor of Public Health,
Medicine, University of Ottawa University of Warwick,
Division of Health in the
Professor Rajan Madhok, Community Warwick Medical
Medical Director & Director of School, LWMS, Coventry
Public Health, Directorate of
Clinical Strategy & Public Professor Ala Szczepura,
Health, North & East Yorkshire Professor of Health Service
& Northern Lincolnshire Health Research, Centre for Health
Authority, York Services Studies, University of
Warwick
Professor David Mant,
Professor of General Practice, Dr Ross Taylor,
Department of Primary Care, Senior Lecturer, Department of
University of Oxford General Practice and Primary
Care, University of Aberdeen
Professor Alexander Markham,
Director, Molecular Medicine Mrs Joan Webster,
Unit, St Jamess University Consumer member, HTA
Hospital, Leeds Expert Advisory Network
Dr Chris McCall,
General Practitioner, The
Hadleigh Practice, Castle Mullen
Professor Alistair McGuire,
Professor of Health Economics,
London School of Economics
Dr Peter Moore,
Freelance Science Writer, Ashtead
Dr Sue Moss, Associate Director,
Cancer Screening Evaluation
Unit, Institute of Cancer
Research, Sutton
Mrs Julietta Patnick,
Director, NHS Cancer Screening
Programmes, Sheffield
Professor Tim Peters,
Professor of Primary Care
Health Services Research,
Academic Unit of Primary
Health Care, University of
Bristol
 HTA

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 Health Technology Assessment 2006; Vol. 10: No. 16
Health Technology Assessment 2006; Vol. 10: No. 16

Systematic review of the effectiveness

and cost-effectiveness of HealOzone
for the treatment of occlusal pit/fissure
caries and root caries

HealOzone for the treatment of occlusal pit/fissure caries and root caries
M Brazzelli, L McKenzie, S Fielding, C Fraser,
J Clarkson, M Kilonzo and N Waugh
Feedback
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May 2006

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Health Technology Assessment
NHS R&D HTA Programme HTA
http://www.hta.ac.uk ISSN 1366-5278