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Patient-reported outcome measures to assess acceptability of

medicines within a paediatric population


Punam Mistry1, Hannah Batchelor1, Heather Stirling2 and Claire Callens3
1Pharmacy

and Therapeutics, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, B15 2TT, UK
2University Hospitals Coventry and Warwickshire NHS Trust, University Hospital, Clifford Bridge Road, Coventry, CV2 2DX, UK
3West Midlands NIHR Clinical Research Network (CRN), Institute of Research and Development, Vincent Drive, Birmingham, B15 2SQ

INTRODUCTION
Oral administration of medicines is the most common route of drug delivery for the
paediatric population. However, palatability of these medicines is a recognised
challenge, especially when considering liquid medicines. Patient acceptability of
medicinal products can have a significant impact on the compliance and adherence to
treatment regimens.
Acceptability has been previously defined as the overall ability at which both the
patient and provider of care can use a medicinal product as intended (Kozarewicz,
2014). The EMA have acknowledged that an internationally harmonised method to
assess acceptability has yet to be developed, therefore there is a growing need to
identify age-appropriate tools to assess acceptability.
Figure 2. Comparison of PRO scores (VAS vs hedonic scales) for taste assessment

Improving pharmaceutical design of paediatric medicines is a key factor to improve


acceptability and paediatric patient outcomes. However, before any improvements can
be implemented, we need to identify which paediatric medicines are most problematic.
ACCEPT is an ethically approved study that aims to use patient-reported outcomes
(PRO) to understand which existing oral liquid medicines are perceived as acceptable
when considering taste alone, to paediatric inpatients aged 2-16 years. The tools used
include: an age-appropriate 5-point facial hedonic scale (Chen et al., 1996); a 10mm
VAS scale with age appropriate anchor phrases and researcher observations. The output
of the ACCEPT study will be used to identify the most appropriate tool to assess taste of
medicines for children as well as identify products that are currently acceptable and
unacceptable to children.

Figure 2 shows agreement between hedonic scale and VAS reports for acceptability
in 94% of cases. A score of >5 in VAS and negative face on the hedonic scale
represent unacceptable medicines. The areas highlighted with red boxes show the
incidences where there is disagreement in the reporting by hedonic vs VAS.
Additional analysis is required to better understand the cause of these differences;
the age of the patient and their ability to understand these scales is considered to be
the primary cause for discrepancy.
The correlation between researcher observations and PRO assessment tools is
shown in Figure 3. In some cases the medicine was observed to be acceptable by
researcher observations yet the PRO reported unacceptable.
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This study was granted ethical approval from both the University of Birmingham and
NRES (REC Ref 15/LO/1253). Patient and parent/carer information leaflets were
designed, and distributed to any individuals admitted to paediatric inpatient wards.
Children requiring any oral liquid medicine during their stay within the paediatric ward
were eligible to take part. Parent/guardian consent was required for participation
alongside verbal assent from participants.
Researcher Observations
Upon administration of an oral liquid medicine, researcher observations of any facial
expression made by the participant before, during and post administration were
manually recorded. A 12-point tick chart was used based on the behavioural scale
developed by Kellerman and Siegel (1980) where a score >4 represents an unacceptable
medicine.
Patient- Reported Outcome Measures
Figure 1 shows the assessment tools used for the ACCEPT study, which consisted of a 5point hedonic scale and a 10mm VAS with age-appropriate anchor phrases. These scales
were selected in conjunction with children and young persons groups to ensure that
they were meaningful and age appropriate (groups involved were from Think Tank
Science Museum Birmingham, Young Persons Steering Group: West Midlands, Colmers
School and Sixth Form College, Birmingham). Participants completed both assessment
tools immediately after medicine administration.

VAS or hedonic score


(note: hedonic score was doubled for direct
comparison)

MATERIALS AND METHODS

9
8
7
6
5
VAS

4
3

Hedonic

2
1
0
0

3
4
5
6
7
8
9
Researcher observations (0= acceptable; a score of >4 was unacceptable)

10

11

12

Figure 3. Comparison of PRO with researcher observations for taste assessment

The level of agreement in classifying acceptability of medicines was 87.5% between


hedonic scale PRO and researcher observation and 88.3% when considering VAS with
researcher observation. Further analysis of data may help to understand why there is
discrepancy in the information collected. The area highlighted in figure 3 shows
variation in hedonic scale PRO and VAS with researcher observations.
Comments reported within structured interviews for unacceptable tasting medicines
included; I dont like the taste of the medicine, but I know I have to take it to make
me better,. In some cases, the medicine was mixed into fruit flavoured squash to
take away the taste because it is horrible .

CONCLUSIONS
Paediatric participants gave clear opinions of the taste of the medicine administered
to them whilst on the inpatient ward. Collectively, the data shows agreement with
PRO and researcher observations, however further analysis is required to understand
the cause behind data inconsistency.
Figure 1. Assessment tools used to measure acceptability of oral liquid medicines.
In cases where the participant reported disliking the taste of their medicine (negative
facial expression on hedonic scale and/or VAS score >5), a structured interview was
conducted by the researcher. This structured interview involved six questions to identify
why they didnt like the medicine and whether this would affect their compliance.

RESULTS
274 participants aged 2-16 years have been recruited from 12 sites within the UK to this
study; 128 were 2-5 years; 98 were 6-11 years and 48 were 12-16 years of age.
15 recruits had incomplete data sets therefore subsequent analysis is based on 259
recruits.
Specific medicines reported to be unacceptable to children include clarithromycin,
Movicol and prednisolone whereas analgesic medicines such as ibuprofen and
paracetamol are typically well accepted.

This is the first study to evaluate which tool is the best in determining medicines
acceptability in children and current data suggests that simple PRO measures are
effective.

ACKNOWLEDGEMENTS
This work was conducted as part of the SPaeDD-UK project
(Smart Paediatric Drug Development UK, accelerating paediatric formulation
development http://www.paediatricscienceuk.com).
The authors would like to thank all participants and hospitals for their participation in this
study.

REFERENCES
Chen, A. W., Resurreccion, A. V. A. & Paguio, L. P. 1996. Age appropriate hedonic scales to measure food preferences of young children.
Journal of sensory studies, 11, 141-163
Kozarewicz P. 2014. Regulatory perspectives on acceptability testing of dosage forms in children. International Journal of Pharmaceutics.
469(2):245-8. Epub 2014/04/08
Zeinstra, G. G., Koelen, M. A., Colindres, D., Kok, F. J. & De Graaf, C. 2009. Facial expressions in school-aged children are a good indicator of
dislikes, but not of likes. Food Quality and Preference, 20, 620-624