A review assessing the quality of

reporting of risk factor research in

implant dentistry using smoking,
diabetes and periodontitis and
implant loss as an outcome:
critical aspects in design and
outcome assessment
Rocchietta I, Nisand D. A review assessing the quality of reporting of risk factor
research in implant dentistry using smoking, diabetes and periodontitis and implant
loss as an outcome: Critical aspects in design and outcome assessment. J Clin
Periodontol 2012; 39 (Suppl. 12): 114121. doi: 10.1111/j.1600-051X.2011.01829.x
Abstract
Aim: To assess, using a structured review, the quality of reporting (design and
outcome assessment) of risk factor research using the STROBE statements. The
outcome was implant loss, and the risk factors assessed were smoking, diabetes
and periodontitis.
Materials and Methods: Literature search was performed individually for each of
the risk factors and the outcome using three sets of database: (a) MEDLINE, (b)
references derived from relevant reviews and (c) references derived from identied
manuscripts. Only casecontrol and cohort studies were included and assessed
using the STROBE statements.
Results: A total of 104 papers were retrieved, three of which were found to be
cohort studies (one in the diabetes and two in the periodontitis review) and none
was a casecontrol study. A total of 101 of 104 papers were case series or cross-
sectional study.
Conclusions: Risk factor research in implant dentistry is mostly comprised of case
series studies. These are used to generate hypotheses, but are the wrong tool to
test these hypotheses. In the near future, well-designed observational studies are
needed and should be reported according to the proposed checklist.
Isabella Rocchietta
1
and David
Nisand
2
1
Foundation IRCCS Ca` Granda Maggiore
Policlinico Hospital, Department of
Reconstructive Surgery Science and
Diagnostics, University of Milan, School of
Dentistry, London, UK;
2
Private practice,
Paris, France
Key words: casecontrol study; cohort study;
dental implants; diabetes; periodontitis;
review; smoke
Accepted for publication 8 November 2011
Conict of interest and source of funding statement
The author declares no personal conict of interest. This workshop was nancially
supported by the European Federation of Periodontology and by unrestricted
grants from Astra, Nobel Biocare, and Straumann.
2012 John Wiley & Sons A/S 114
J Clin Periodontol 2012; 39 (Suppl. 12): 114121 doi: 10.1111/j.1600-051X.2011.01829.x
Introduction
Risk factor research is a major topic
in implant dentistry with numerous
reports in the literature discussing
poorer outcomes in association with
a variety of conditions. Implant loss
is the most frequently assessed out-
come within the implant dentistry
eld. The most frequently and
known risk factors associated with
the outcome of implant loss are the
following exposures/diseases: diabe-
tes, periodontitis and smoking hab-
its. Unfortunately, most of the
available data regarding risk factors
in implant dentistry are extracted
from case series. The latter could be
dened as descriptive papers, where
a group of patients in which a cer-
tain treatment has been carried out
(for example, dental implant inser-
tion) are followed and observed for
a certain period of time (these may
be retrospective or prospective).
During this time, some parameters
are assessed (usually through the
patients charts, for example, smok-
ing habits) and evaluated with
respect to their inuence on the
overall outcome (implant loss).
While such study design helps in
generating hypotheses, it could not
be used to test a hypothesis (Grimes
& Schulz 2002a).
Observational studies have been
generated to conduct risk factor
research. It employs three major
designs: cross-sectional studies, case
control studies and cohort studies.
These three designs are considered to
have dierent validity, with cross-
sectional studies being at the highest
risk of bias and results of properly
designed and executed casecontrol
and cohort studies being the most
authoritative. Frequently, the three
designs are used sequentially: cross-
sectional studies are employed
initially to generate hypotheses.
Thereafter, casecontrol and cohort
studies are used to verify the hypoth-
eses and assess causality (Bradford
Hill 1965).
A casecontrol study is an obser-
vational study that selects individu-
als based on their disease or health
outcome status (e.g. implant loss).
It looks back through time at
potential exposures that both groups
(cases and controls) may have
encountered (Schulz & Grimes
2002). The statistic generated to
measure association is the odds
ratio (OR), which is the ratio of the
odds of exposure in the cases to the
odds of exposure in the controls.
OR greater than 1 indicate that
those with the disease are more
likely to have been exposed,
whereas if it is close to 1, then the
exposure and disease are not likely
to be associated. The advantage of
casecontrol studies is that they are
relatively simple to conduct and less
expensive than cohort studies.
A cohort study selects individuals
based on exposure status (e.g.
tobacco, diabetes). The study sub-
jects should be at risk of the out-
come under investigation at the
beginning of the cohort study; this
usually means that they should be
disease free (e.g. no implant loss)
when the cohort study starts. The
cohort is followed through time to
assess their later outcome status
(Grimes & Schulz 2002b). The point
estimate generated is the Relative
Risk (RR), which is the probability
of disease for a person in the
exposed group, over the probability
of disease for a person in the unex-
posed group. RR greater than 1
indicates association; in such an
occasion, the conclusion is that those
with the exposure were more likely
to develop disease.
Along with a need for qualita-
tively high study designs to test
hypotheses in the eld of risk factors
research, there is also a great need
to improve the quality of reporting
of studies, as inadequate reporting
of research may hamper the assess-
ment of the strengths and weak-
nesses of the studies reported in the
literature.
In 2007, the STROBE statements
was introduced to properly assess
the quality of reporting of observa-
tional studies. The checklist stands
for Strengthening the Reporting of
Observational studies in Epidemio-
logy (http://www.strobe_statement.
org) and it is composed of 22 items
by a group of international research-
ers. It is mandatory to highlight that
the checklist presented is not an
instrument to evaluate the quality of
observational research. They serve as
guidance on how to report these
studies.
The aim of this review was to
clearly identify all casecontrol and
cohort studies published, evaluate
the quality of reporting and make
pragmatic recommendations for
future well-performed risk factor
research.
Materials and Methods
A literature search was performed
individually for each of the risk fac-
tors and the outcome using three
sets of database; (a) MEDLINE, (b)
references derived from relevant
reviews published in the last 5 years
and (c) references derived from ini-
tially identied manuscripts. The
MEDLINE search was limited to
clinical articles published in the Eng-
lish language until May 2011.
In the rst search, smoking was
dened as the suspected risk for
implant loss. As such, the following
search terms were used: smoking
OR smoking AND dental
implants OR dental AND
implants OR dental implants OR
dental AND implant OR dental
implant AND humans AND Eng-
lish.
A second search was performed
setting periodontitis as the suspected
risk. The search strategy included
the following terms: periodontitis
OR periodontitis AND dental
implants OR dental AND
implants OR dental implants OR
dental AND implant OR dental
implant AND humans AND Eng-
lish.
In the third search, diabetes was
considered as the suspected risk and
the following terms were used: dia-
betes mellitus OR diabetes AND
mellitus OR diabetes mellitus
OR diabetes OR diabetes insipi-
dus OR diabetes AND insipidus
OR diabetes insipidus AND dental
implants OR dental AND
implants OR dental implants
AND humans AND English.
Two examiners then reviewed
titles and abstracts individually. A
total of 176 titles were identied
(106 in the smoking group, 48 in the
periodontitis group and 22 in the
diabetes group) of a total of 1200
papers. The abstracts were read, and
consequently a total of 104 full text
articles were generated (71 in the
smoking group, 25 in the periodonti-
tis group and 8 in the diabetes
group). The articles were carefully
read by both authors and sorted by
study design, and only casecontrol
2012 John Wiley & Sons A/S
Quality of reporting risk factor research studies 115
and cohort studies were included to
be assessed using the STROBE state-
ments to evaluate the quality of
reporting. (Figs 13).
Those articles designed as case
control or cohorts were scored using
a dichotomic scoring system on the
full 22 items of the STROBE state-
ments to determine if certain items
were properly addressed. Six of the
22 items contained more than one
criterion, which are strongly con-
nected to each other. Hence, if the
paper assessed failed one of the crite-
ria, the entire item was considered to
be not properly addressed.
Results
Of the 104 articles that were read in
full text, only three were found to be
cohort while none were categorized
as casecontrols, with the vast
majority of the papers being case
series (Table 1).
The smoking risk factor research
retrieved a total of 71 papers. Of
these full text articles, none was clas-
sied as casecontrol study or
cohort.
The diabetes risk factor research
comprised of eight papers, of which
only one was a cohort study. The
rest were case series.
Lastly, a total of 25 full text
papers were assessed for the peri-
odontitis risk factor research. Two
were cohort studies and none were
casecontrols.
Table 2 reports the scoring of the
three included cohort studies using
the STROBE statements.
The cohort studies within the
periodontitis risk factor research ful-
lled more criteria of the STROBE
statements compared with the diabe-
tes risk factor paper.
All authors addressed focused
and pertinent questions that were
explained in the papers. All three
papers addressed the issue of report-
ing key results well.
The three cohort studies poorly
addressed clear denitions of out-
comes, exposures, predictors, poten-
tial confounders and eect modiers.
Also, the potential sources of bias
were poorly reported. The statistical
methods employed were found to be
the weakest points for all three
cohorts, in particular; reporting on
handling of missing data, loss to fol-
low-up and sensitivity analyses. In
addition, the translation of relative
risk data into absolute risk was
absent in all three papers.
Discussion
Only three papers in the English lit-
erature were found to be cohort
studies, whereas none was judged to
be casecontrol studies when the dia-
betes, periodontitis and smoking risk
factors were assessed for implant
loss. The fact that no casecontrol
studies were found at all within the
Arcles Reviewed arcles
Key words
Smoking and dental implant 297 53
Limits
English, Human 261 45
Title selecon 106 matching with systemac review*
Abstract Selecon 71 (Full text arcles retrieved)
Case control study 0
Cohort study 0
155/261: Reason for exclusion: dierent topic,
case reports and review.
35/106: Reason for exclusion: incorrect
outcome assessment.
71/71: Reason for exclusion: case series or cross
seconal design.
Fig. 1. Search strategy for cigarette smoking. Heitz-Mayeld and Huynh-Ba 2009,
Strietzel et al. 2007
Arcles Reviewed arcles
Key words
Periodons and dental implant 1057 187
Limits
English, Human 857 172
Title selecon 48 matching with systemac review*
Abstract selecon 25 (Full text arcles retrieved)
Case-control study 0
Cohort study 2
809/857: Reason for exclusion: dierent topic,
case reports and review.
23/48: Reason for exclusion: incorrect outcome
assessment.
23/25: Reason for exclusion: case series and
cross seconal design.
Fig. 2. Search strategy for periodontitis. Heitz-Mayeld et al. 2009, Sai et al. 2010
and Ong et al. 2008
2012 John Wiley & Sons A/S
116 Rocchietta et al.
extensive literature search made the
authors of the review look into the
strict characteristics of the study
design to understand the reason for
this lack of information. A casecon-
trol study requires a strict selection
of the control group. This was
clearly stated by Grimes & Schulz
(2002a). The matching is fundamen-
tal either on an individual basis (in a
1:1 ratio) or on a group basis, trans-
lating this into a complex and chal-
lenging methodology. Realistically,
this may be accessible for an extre-
mely large population from which to
select the appropriate controls. In
addition, the authors of casecontrol
studies are required to clearly
describe the methodology of the
matching process, specifying the con-
founding factors that are taken into
account. All the confounding vari-
ables that inevitably will not be
matched or controlled need to be
adjusted using appropriate statistical
methods. A casecontrol study
should aim at minimizing the recall
bias as well as the participation bias.
Sample size calculation should be
undertaken a priori to ensure the
study has enough statistical power.
In light of the relatively small sample
size of all the identied studies
(ranging between 10 and 980), it
remains unlikely that the authors
could have both matched case and
controls and accounted for con-
founding variables (Schulz & Grimes
2002).
Three cohort studies were found
and assessed to extrapolate useful
information. The fact that very few
cohort studies were found highlights
the complexity of performing such
study design when the incidence of
the outcome assessed is rare. The 5-
year failure rate of implant support-
ing single crowns was reported to be
only 3.2% according to Jung et al.
(2008). Moreover, it should be kept
in mind that the main feature of a
cohort study is observation of a
Arcles Reviewed arcles
Key words
Diabetes and dental implant 112 33
Limits
English, Human 82 28
Title selecon 22 matching with systemac review*
Abstract selecon 8 (Full text arcles retrieved)
Case-control study 0
Cohort study 1
60/82: Reason for exclusion: dierent topic,
case reports and review.
14/22: Reason for exclusion: incorrect outcome
assessment.
7/8: Reason for exclusion: case series design.
Fig. 3. Search strategy for diabetes. Salvi et al. (2008) and Javed and Romanos 2009
Table 1. References assessed as full text articles according to the risk factors
Risk factors
research
Number of
retrieved articles References
Smoking 71 Cavalcanti et al. 2011, Anner et al. 2010, Arisan et al. 2010, Garc a-Bellosta et al. 2010, Gianserra
et al. 2010, Simonis et al. 2010, Vercruyssen et al. 2010, Alou et al. 2009, De Boever et al. 2009,
Koldsland et al. 2009, Alsaadi et al. 2008a, b, Anitua et al. 2008, Balshe et al. 2008, Gatti et al.
2008, Huynh-Ba et al. 2008, Machtei et al. 2008, Sverzut et al. 2008, Aykent et al. 2007, Doyle
et al. 2007, Machtei et al. 2007, Sanna et al. 2007, Strietzel et al. 2007, Sa nchez-Pe rez et al. 2007,
Schwartz-Arad et al. 2007, DeLuca et al. 2006, Ellegaard et al. 2006, Mundt et al. 2006, Levin
et al. 2006, Noguerol et al. 2006, Peleg et al. 2006, Roos-Jansa ker et al. 2006, Wagenberg &
Froum. 2006, Jansson et al. 2005, Lemmerman & Lemmerman 2005, Moheng & Feryn 2005, Moy
et al. 2005, Baelum & Ellegaard 2004, Kourtis et al. 2004, Ortorp & Jemt. 2004, van Steenberghe
et al. 2004, Karoussis et al. 2003, Rocci et al. 2003, Chuang et al. 2002, Kan et al. 2002,
Kumar A et al. 2002, Penarrocha et al. 2002, Schwartz-Arad et al. 2002, van Steenberghe et al.
2002, Eckert et al. 2001, Kronstro m et al. 2001, Widmark et al. 2001, Berge & Grnningsaeter
2000, Lambert et al. 2000, Schwartz-Arad et al. 2000, Wallace 2000, De Bruyn et al. 1999,
Grunder et al. 1999, Jones et al. 1999, Kan et al. 1999, Keller et al. 1999, Watson et al. 1999,
Wilson & Nunn1999, Minsk & Polson 1998, Watson et al. 1998, Bain 1996, Minsk et al. 1996,
Wang et al. 1996, De Bruyn & Collaert 1994, Gorman et al. 1994, Bain & Moy 1993.
Periodontitis 25 Aglietta et al. 2011, Anner et al. 2010, Garc a-Bellosta et al. 2010, Gianserra et al. 2010, Matarasso
et al. 2010, Roccuzzo et al. 2010, Simonis et al. 2010, De Boever et al. 2009, Koldsland et al.
2009, Fardal and Linden 2008, Gatti et al. 2008, Mengel et al. 2007, Roos-Jansa ker et al. 2006,
Wagenberg & Froum 2006, Cordaro et al. 2005, Mengel & Flores-de-Jacoby 2005, Evian et al.
2004, Rosenberg et al. 2004, Karoussis et al. 2003, Hardt et al. 2002, Quirynen et al. 2001,
Brocard et al. 2000, Watson et al. 1999, Cune & de Putter C.A 1996, Rosenquist & Grenthe 1996
Diabetes 8 Anner et al. 2010, Alsaadi G et al. 2008a, b, Tawil et al. 2008, Alsaadi et al. 2007, Moy et al.
2005, van Steenberghe et al. 2002, Morris et al. 2000
2012 John Wiley & Sons A/S
Quality of reporting risk factor research studies 117
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2012 John Wiley & Sons A/S
118 Rocchietta et al.
large sample that is representative of
a population over a long period of
time. Comparison is done on inci-
dence rates in groups that dier in
exposure levels. Finally, even if a ret-
rospective design could theoretically
be considered for a cohort study,
the latter would not be suitable in
the eld of risk factors research, as
the measurements of the exposure
will be unreliable due to the nature
of its acquirement post factum.
Few cohort studies were found,
whereas none were casecontrols.
This may be related to the fact that
cohort studies have many benets
over casecontrol studies. The RR is
a more powerful eect measure than
the OR, as the OR is just an estima-
tion of the RR, and because true
incidence cannot be calculated in a
casecontrol study where subjects
are selected based on disease status.
Temporality can be established in a
prospective study as the cohort, and
confounders are more easily con-
trolled for. Recall bias is less of a
concern than is the casecontrol
study as conrmed by Grimes &
Schulz (2002a). Nevertheless, they
are more costly, and there is a
greater chance of losing subjects to
follow-up based on the long-time
period over which the cohort is fol-
lowed.
The three cohort studies included
in our review fullled most of the
STROBE statements, with meticu-
lous attention to clearly stating the
scope of the study and reporting key
results. However, they were lacking
some of the above mentioned critical
aspects. The statistical methods
employed were found to be the
weakest points for all three cohorts,
in particular; reporting on handling
of missing data, loss to follow-up
and sensitivity analyses . In addition,
the translation of relative risk data
into absolute risk was absent in all
three papers. Likewise, Langan et al.
(2010) have recently assessed the
quality of reporting in observational
studies in dermatology. The authors
selected casecontrol, cohort and
cross-sectional studies published
from 2005 to 2007 in the ve major
dermatology journals. The authors
assessed the quality of reporting of
the studies using the STROBE state-
ments. A total of 138 articles were
included and analysed, and the
authors reported that the quality T
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2012 John Wiley & Sons A/S
Quality of reporting risk factor research studies 119
was very mixed. Key areas that were
infrequently reported included sam-
ple size calculations, missing data,
losses to follow-up, and statistical
methods. Only 13 studies (9%)
explained the role of funders in the
research. This was consistent with
the ndings derived from this review.
Smoking as a risk factor for
implant loss accounted for zero case
control studies or cohort studies.
The most likely explanation for this
phenomenon is that in the vast
majority of these studies, smoking
was only a secondary outcome vari-
able (Balshe et al. 2008), and thus,
matching these patients becomes
impossible, hence precluding them
from casecontrol studies. Also, the
incidence of smoking in the popula-
tion coupled with the low incidence
of implant loss would require a
cohort study of several thousand
patients over many years to have
enough statistical power to deter-
mine the eect. None of the 71 stud-
ies that were evaluated included
sample size greater than 980, which
then accounts for the lack of cohort
studies on this issue.
Studying the eect of cigarette
smoking in health science has many
drawbacks. Inaccuracy of assessment
of exposure was found in all the
retrieved case series. All the papers
divided the patient population into
smokers or non-smokers according
to self-reported questionnaires or by
reviewing the patients charts. Not a
single study reported on biochemical
markers, which indeed is a realistic
and pragmatic measurement of the
levels of nicotine. Patrick et al.
(1994) performed a meta-analysis to
identify circumstances in which bio-
chemical assessments of smoking
produce systematically higher or
lower estimates of smoking than
self-reports. They reported sensitivity
values that ranged from 6% to
100% and specicity data that ran-
ged from 33% to 100%. The authors
suggested to improve accuracy, and
biochemical assessment, preferably
with plasma cotinine, should be con-
sidered in intervention studies. In
addition, Curtis et al. (1993) stated,
problems of validity arise when
study techniques do not represent
accurately actual behaviours. This is
particularly likely when the behav-
iour being investigated is socially
sensitive. Curtis et al. (1993) further
added, in addition to the problem
of validity, the variability of behav-
iours causes diculties in investiga-
tions designed to identify
associations between behaviours and
health. McKay (1999) critically
evaluated the methodologies to study
relapse in substance abusers. They
concluded that retrospective reports
can perhaps provide the most
detailed accounts of circumstances
and experiences, but are also more
likely to be inaccurate due to the
limitations of memory.
The vast majority of the papers
when risk factors are associated to
implant loss are represented by case
series. The results of these studies
show how many people develop a
disease or condition over time (e.g.
implant loss), describe the character-
istics of the disease and those
aected and generate hypotheses
about the cause of the disease. An
important caveat (often forgotten or
intentionally ignored) is that descrip-
tive studies, which do not have a
comparison group, do not allow
assessment of associations. Only
comparative studies (both analytical
and experimental) enable assessment
of possible causal associations
(Grimes & Schulz 2002a). These may
still be informative depending on the
study objective. If it was not for the
case series of Bra nemark et al.
(1983) and the Adell et al. (1981), it
might be very much that implant
dentistry would have not come of
age and be a useful armamentarium
in dentistry as it is today.
Most of the papers that claimed
to be a casecontrol or cohort study
stated the study design in the title or
abstract. Nevertheless, these were
found to be case series. On the other
hand, if the study fulls the correct
guidelines and recommendations, the
study design should be reported
clearly in the title or abstract. Ubri-
ani et al. (2007) reported the per-
centages of papers in three major
dermatology journals, where the
study design was cited in the titles
and/or in the abstracts. They con-
cluded that most articles in the three
journals did not report the study
design used in the title or abstract.
A consistent and clear indication of
the design used in studies may better
enable editors, reviewers and readers
to assess critically articles published
in scientic journals.
With the above in mind, careful
planning of future studies is likely to
result in much more casecontrol
and cohort studies. For the design of
casecontrol studies, matching
should be in the heart of its design.
Every eort should be made to
match for the most important non-
confounding factors. Adequate
statistical compensation should be
executed solely for the confounding
factors that are impossible to match.
For the future design of cohort
studies, a special emphasis should be
placed on the prospective design,
and on the correct measurement of
the exposure over a large group of
patients representative of a sample
population and assessed over a long
period of time. All things considered,
such studies that account for the
various confounding variables and
the relative rarity of the outcome
will probably require thousands and
even tens of thousands of partici-
pants. Thus, such an undertaking
could only be accomplished by a
joint eort from many centres and
even a global mission.
In conclusion, the extremely low
number of risk factor comparative
research studies found in this review
does not allow drawing any denite
conclusions. However, these have
served as a basis to highlight the
critical issues to be addressed for
future recommendations in designing
casecontrol and cohort studies. This
will not only improve the research
overall, but it will give the clinician
reliable tools to extract data from
and treat patients with evidence-
based therapies.
Acknowledgement
The authors acknowledge Prof. E.E.
Machtei for his outstanding advice
during the manuscript preparation.
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Address:
I. Rocchietta
28 Queensdale Road
W11 4QB London
UK
E-mail: isabella.rocchietta@gmail.com
2012 John Wiley & Sons A/S
Quality of reporting risk factor research studies 121