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van HalewijnKF, etal. BMJ Open 2024;14:e078942. doi:10.1136/bmjopen-2023-078942
Open access
Reasons for unsuccessful recruitment of
children with atopic dermatitis in
primary care in the Netherlands to a
cohort study with an embedded
pragmatic, randomised controlled open-
label trial: a survey
Karlijn F van Halewijn ,1 Arthur M Bohnen,1 Suzanne G M A Pasmans,2
Patrick J E Bindels,1 Gijs Elshout 1
To cite: van HalewijnKF,
BohnenAM, PasmansSGMA,
etal. Reasons for unsuccessful
recruitment of children with
atopic dermatitis in primary
care in the Netherlands
to a cohort study with an
embedded pragmatic,
randomised controlled open-
label trial: a survey. BMJ Open
2024;14:e078942. doi:10.1136/
bmjopen-2023-078942
►Prepublication history
and additional supplemental
material for this paper are
available online. To view these
les, please visit the journal
online (https://doi.org/10.1136/
bmjopen-2023-078942).
Received 17 August 2023
Accepted 02 May 2024
1Department of General
Practice, Erasmus MC University
Medical Center, Rotterdam, The
Netherlands
2Department of Dermatology,
Erasmus MC University
Medical Center, Rotterdam, The
Netherlands
Correspondence to
Dr Karlijn F van Halewijn;
k. vanhalewijn@ erasmusmc. nl
Original research
© Author(s) (or their
employer(s)) 2024. Re- use
permitted under CC BY- NC. No
commercial re- use. See rights
and permissions. Published by
BMJ.
ABSTRACT
Background The Rotterdam Eczema Study was an
observational cohort study with an embedded pragmatic
randomised controlled open- label trial. It was conducted in
children with atopic dermatitis (AD) in the Dutch primary
care system. The objective of the trial was to determine
whether a potent topical corticosteroid (TCS) is more
effective than a low- potency TCS.
Objective We are aiming to communicate transparently
about the poor recruitment for the trial part and to explore
the reasons why recruitment was weak.
Design We used a survey to nd out what patients in the
cohort did when they experienced a are- up.
Methods Descriptive statistics were used to present the
baseline characteristics of participants in the trial and the
results of the survey.
Results In total, 367 patients were included in the cohort.
Of these, 32 were randomly assigned to a trial treatment;
they had a median age of 4.0 years (IQR 2.0–9.8). A total
of 69 of the 86 children (80.2%) who could participate
in the survey responded. 39 (56.5%) suffered a are- up
during the follow- up (making them potentially eligible for
inclusion in the trial). 26 out of 39 (66.7%) increased their
use of an emollient and/or TCS themselves. Only 12 of the
39 (30.7%) contacted their general practitioner (GP) as
instructed in the study protocol, but 8 out of these 12 did
not meet the inclusion criteria for the trial.
Conclusion The main reason why cohort participants did
not take part in the trial was that they did not contact their
GPs when they experienced an AD are- up. Furthermore,
the majority of patients who contacted their GPs did not
match the inclusion criteria of the trial. We expect that
the lessons learnt from this study will be useful when
developing future studies of children with AD in primary
care.
INTRODUCTION
Eczema, also known as atopic dermatitis (AD),
is a persistent, intensely itchy, inflammatory
skin condition that affects many children.
In general practice, AD is among the top 10
most prevalent conditions in children aged
under 18.1 As there is no curative treatment
for AD, suppressive treatment aims to control
the condition. The majority of patients in
general practice use emollients along with
topical corticosteroids (TCS) as symptomatic,
suppressive medication for managing their
symptoms.2 3 The recommended treatment
strategy for TCS use when AD flares up differs
between guidelines.4 The Cochrane review
of TCS treatment strategies concludes that
potent and moderate TCS are probably more
effective than mild ones, primarily in cases of
moderate or severe eczema.5 However, most
of the included studies were small- scale and
had a moderate to severe risk of bias. We,
therefore, conducted a trial (the Rotterdam
Eczema Study) aiming to test the hypoth-
esis that a treatment strategy starting with
a potent TCS during a flare- up of AD leads
to faster and more efficacious results than
starting with a low- potency TCS.
The Rotterdam Eczema Study was an obser-
vational cohort study with an embedded
pragmatic, randomised controlled open-
label trial. It was conducted in children being
STRENGTHS AND LIMITATIONS OF THIS STUDY
⇒When it transpired that inclusion for the cohort was
running behind schedule, we started recruiting pa-
tients through social media.
⇒A limitation of the trial was an excessively narrow
set of inclusion criteria.
⇒A limitation of the survey is that we did not explore
in depth why participants did not contact their gen-
eral practitioners.
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Open access
treated by Dutch general practices.6 A cohort study with
an embedded trial design was chosen as it can be chal-
lenging to recruit and randomise the selection of chil-
dren in primary care. This lets us follow- up and monitor
the AD- affected children participating in the cohort and
include them quickly in the trial in the event of a flare- up.
The aim of the cohort was to determine the frequency and
determinants of flare- ups of AD during a 1- year follow- up.
Recruiting patients for randomised controlled trials
(RCTs) in primary care is challenging in many ways.7 8
Two interventions where the evidence gave a high degree
of certainty that they could improve recruitment were
identified by the Cochrane review about strategies for
improving recruitment to randomised trials.8 These strat-
egies are an open- trial design and telephone reminders
for people who do not respond to a postal invitation. We
incorporated the first of these strategies and participants
received a reminder in the weekly digital questionnaire
to contact their general practitioner (GP) if their AD
worsened.
Nevertheless, we failed to enrol a sufficient number of
patients in the trial part of the study . This article aims to
communicate transparently about the failure to enrol a
sufficient number of patients in our trial and to present
descriptive data about the patients whom we did include
in the trial. In addition, we want to determine why recruit-
ment for the trial was unsuccessful and thereby provide
information for researchers who may be considering
cohort studies with an embedded RCT in future research.
METHODS
Study setting
Data were used from the Rotterdam Eczema Study. A
detailed description of the study design for the Rotterdam
Eczema Study has already been given.6 Eligible children
were recruited using two strategies. In the ‘General Practi-
tioner (GP) strategy’, children were eligible for inclusion
if they were aged between 3 months and 18 years, had
AD diagnosed by a GP, and had received an AD- related
consultation or prescription within the previous 12
months. All parents of children aged ≤16 and patients
aged ≥12 gave informed consent. Follow- up of the cohort
was for 12 months, during which patients received weekly
questionnaires. Patients were also visited at baseline,
after 6 months and after 12 months for objective assess-
ment of the severity of AD using the Eczema Area and
Severity Index (EASI). Inclusion for the cohort using
this strategy turned out to be slower than expected, so in
January 2020, we additionally started a strategy of ‘open
recruitment’ through social media and newspapers. The
same inclusion criteria were applied here as in the ‘GP
strategy’. However, children being treated by a specialist
at the time of inclusion (eg, a dermatologist, paedia-
trician or allergist) were also included. The children
recruited by open recruitment received the same weekly
questionnaires. However, they were only visited at base-
line, after 6 months and after 12 months if they lived near
Rotterdam. Because of the inherent logistical challenges,
patients recruited through social media were not able to
participate in the trial part.
If a patient in the cohort recruited via their GP experi-
enced a flare- up during the follow- up period, they were
instructed to visit their GP to check their eligibility for the
trial. The GP examined the AD severity and checked the
other inclusion and exclusion criteria (see online supple-
mental table 1). In brief, inclusion criteria for the trial
were participation in the cohort, flare- up (ie, the need
to intensify topical treatment) from the child’s and/or
parents’ point of view, and a Three- Item Severity (TIS)
score between 3 and 5. Patients were excluded from
the trial if they had used a TCS in the 2 weeks before
inclusion in the trial, had AD on their eyelids, had >50%
of the body affected by AD, had other skin disorders
hampering proper assessment of AD, were pregnant or
breast feeding or had untreated skin infections based
on clinical signs and symptoms (bacterial, viral, fungal
or parasitic). If the patient was eligible for the trial, they
were assigned randomly to either the intervention group
(potent TCS, fluticasone propionate, once daily)) or the
control group (moderately potent TCS, hydrocortisone,
once daily). After 1 week, 4 weeks and 24 weeks, the chil-
dren received a home visit from a researcher for inter alia
an objective assessment of the AD severity using the EASI.
They received a weekly online questionnaire for 24 weeks.
See figure 1 for a flowchart of the study.
The weekly online questionnaire was the same for
cohort and trial participants; the only difference was
home visits at 1, 4 and 24 weeks during the trial follow- up
whereas cohort participants visited the practice at 6 and
12 months.
To prevent patients from using any TCS they had at
home if their AD worsened, they had to hand in any TCS
if they were not using it at the time of the baseline visit,
Figure 1 Flowchart of intended inclusion in the Rotterdam
Eczema Study. AD, atopic dermatitis; GP, general practitioner.
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and repeat prescriptions were stopped in the patient file.
Throughout the follow- up period of the cohort, partici-
pants received a weekly questionnaire, with a reminder
to contact their GP if their AD worsened. The above
measures were taken to ensure that cohort participants
would contact their GPs in the event of a flare- up so that
suitability for the trial could be assessed. The inclusion
and exclusion criteria for the trial can be found in online
supplemental table 1. To determine the severity of AD for
the inclusion criteria, the TIS score was used as recom-
mended in the Dutch GP guideline.9 10 The primary trial
outcome was determined as the change in disease severity
over 24 weeks of follow- up in the trial, as measured by the
average score of the Patient- Oriented Eczema Measure
(POEM; range of score: 0–28). POEM is a patient- reported
outcome based on symptoms over the previous week that
can be self- completed by the child’s parent, the child or
both together and it is part of the core outcomes for trials
as determined by the Harmonising Outcome Measure for
Eczema (HOME) initiative.11
During the study period, we noticed that inclusion rates
for the trial were low. We wanted to identify the reasons
for this inclusion problem. We designed a survey to find
out what patients did when they had a flare- up (online
supplemental file survey). The survey was designed and
administered 1.5 years after the start of inclusion and
was administered to patients participating in the cohort
at that time and who were eligible for participating in
the trial (n=86). We asked questions about four different
topics: whether they had ever experienced flare- ups
during the follow- up, what they did when they experi-
enced a flare- up, what their GP did after being contacted
and whether it was clear to them what they should do
when they experienced flare- ups.
Patient and public involvement
It was neither appropriate nor possible to involve patients
or the public in the design, conduct, reporting or dissem-
ination plans of our research. The outcome measures of
our study are based on the recommendations stated by
the HOME initiative.11 Patients were intensively involved
during the development of the core outcome set and
its measurement tools by this initiative. The results of
our research will be disseminated to study participants
through newsletters and infographics.
Statistical methods
The calculated power for the trial, including secondary
analyses and an assumed drop- out rate of 15%, gave a
recommended sample size of 72 children per treatment
arm (a total of 144). Descriptive statistics have been
used to present baseline characteristics and the primary
outcome, the POEM, for the 32 patients who participated
in the trial. The response to the survey is also presented
using descriptive statistics. Missing data were not included
in the analyses.
RESULTS
Rotterdam Eczema Study
Inclusion took place from January 2018 to September
2020 through 53 general practices in the Netherlands and
through open recruitment. A total of 367 patients were
included in the cohort; 209 were recruited via general
practices and 158 through social media (online supple-
mental figure 1). The 209 children recruited via general
practices were eligible for the trial. Of these, 32 patients
were eventually included in the trial and randomly
assigned to a treatment. They had a mean age of 5.5 years
(SD 4.8) and 40.6% were girls. In total, 15 patients were
randomly assigned for treatment with hydrocortisone and
17 patients were randomly assigned to the fluticasone
propionate group. For the baseline characteristics of the
cohort, variables are reported as the mean (SD) and trial
variables that were not normally distributed are reported
Table 1 Baseline characteristics
Baseline, cohort, n=367 (100%)
Baseline, cohort recruited via GP/
potentially eligible for trial, n=209
(100%)
Baseline, trial,
n=32 (100%)
Age in years, mean (SD)/median (IQR) 5.7 (5.0) 6.4 (5.2) 4.0 (2.0–9.8)
Sex, female, n (%) 200 (54.5%) 116 (55.5%) 13 (40.6%)
POEM, mean (SD)/median (IQR) 10.3 (6.1) 8.2 (5.6) 10.0 (6.0–15.8)
Randomised treatment, n (%)
Hydrocortisone – – 15 (46.9%)
Fluticasone propionate – –
17 (53.1%)
GP, general practitioner; POEM, Patient- Oriented Eczema Measure.
Table 2 POEM score of trial participants
Randomised treatment
Fluticasone
propionate (n=17)
Hydrocortisone
(n=15)
Baseline, n=32 7.0 (5.5–14.5) 11.0 (8.0–16.0)
Variables are reported as median (IQR).
POEM, Patient- Oriented Eczema Measure.
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as the median (IQR). At the trial baseline, the median
POEM score was 10.5 (7.0–13.8) for the intervention
group and 12.0 (8.0–17.5) for the control group (tables 1
and 2).
Survey
In total, 86 participants in the cohort who had been
recruited via their GP and who were still in follow- up were
invited in November 2020 to complete the survey. The
other 123 patients had already finished follow- up of the
cohort or had already taken part in the trial. The response
rate was 80.2%; a total of 69 participants answered the
survey. Of these 69 participants, 39 (56.5%) of them had
suffered a flare- up during the follow- up period and only
12 of those 39 (30.7%) contacted their GPs as stated in the
study protocol. Most of them started using TCS that had
been prescribed before the inclusion in our study (n=20,
51.3%) or increased their use of an emollient (n=19,
48.7%). The majority of patients who contacted the GP
(n=12) did not meet the inclusion criteria for the trial
because their AD was mild or severe rather than moderate
(n=8). Other reasons for not participating (free text) were
‘we were unable to visit the GP because of COVID’, ‘the
eczema was too bad’ and ‘the eczema was on the eyelids’
(the two latter situations were exclusion criteria). Overall,
most patients (or their parents) answered that they knew
what they had to do in the event of an exacerbation of the
eczema in order to participate in the trial (n=65, 92.8%).
Patients’ responses to this question (free text) included
‘it was clear, but the doctor did not act properly’, ‘I didn’t
understand this properly’ and ‘we’ve had no contact with
the GP’s assistant since the start of the study’ (table 3).
DISCUSSION
Summary
A total of 367 patients were included in the cohort of
the Rotterdam Eczema Study, of whom 209 patients were
recruited throughout GP practices and were potentially
Table 3 Survey and results for the 69 respondents
Question Answer options Total, n=69 (100%)
1a. In the period during which my child or I participated
in the study, the eczema worsened one or more times (=a
are- up).
Yes 39 (56.5)
No 30 (43.5)
1b. If yes, what did you do when the eczema got worse?
(multiple answers possible)
Did nothing, the AD was not so severe 5
Increased the use of emollients 19
Started TCS ointment ourselves 20
Contacted the GP 12
Other, namely: (free text) 0
1c. When I contacted the GP, I mentioned that my child/I
was participating in the Rotterdam Eczema Study.
Yes 12
No 0
1d. If you contacted the GP, they: (multiple answers
possible)
Thought the eczema was mild and started
treatment
4
Thought the eczema was severe and started
treatment
4
Was not available, I could not make an
appointment
0
Issued a repeat prescription 4
Suggested enrolling in Part 2 of the study
(the trial), which I did not want to do
because: (free text)
0
Other, namely: (free text) 4 answers*
2a. It was clear to me what I had to do in the event of an
exacerbation of the eczema in order to participate in Part 2
of the study (the trial):
Yes 64 (92.8%)
No 5 (7.2%)
2b. If no, what was unclear? Other, namely: (free text)5 answers**
1b, 1c, 1d were y- out questions that appeared if the answer to 1a was ‘yes’. 2b was a y- out question that appeared if the answer to 2a was
‘no’.
* ‘eczema was too bad’, ‘we were unable to visit the GP because of COVID’, ‘eczema was on the eyelids’ and ‘eczema was mild’
** ‘it was clear, but the doctor did not act properly’, ‘I only take part in the cohort study, not in the trial’, ‘I guess I didn't understand this
properly’, ‘we’ve had no contact with the GP’s assistant since the start of the study’ and ‘I was especially confused by the informational e-
mail we received about participating in the trial’
AD, atopic dermatitis; GP, general practitioner; TCS, topical corticosteroid.
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eligible for the trial. Only 32 patients were ultimately
selected for the trial and randomly assigned to a treat-
ment arm. It was not possible to enrol enough participants
despite reminders and additional information about the
study procedure throughout the follow- up. Most of the
participants did know what to do when they had a flare- up
(92.8%). The majority of the patients in the cohort who
completed the survey experienced a flare- up (56.5%); the
main reason for failure to enrol a sufficient number of
patients in the trial was that cohort participants did not
contact their GPs when they had an AD flare- up. When
participants did contact their GPs, most of them did not
meet all the inclusion criteria for participation in the
trial. The majority of the patients treated the flare- up
themselves.
Strengths and limitations
A strength of the survey was that it gave us an under-
standing of the patients’ behaviour when they expe-
rienced a flare- up. These findings have let us make
suggestions that may lead to better and more effective
ways of recruiting trial participants in future studies in
primary care. The low rates of trial participation may be
attributed to selection bias, as patients with an under-
standing of their condition and who were more proactive
in starting treatment were more likely to be enrolled in
the cohort and therefore did not join the trial. A limita-
tion of the survey is that we did not ask in depth why
participants did not contact their GP. This makes it more
difficult to comprehend the main reason for the trial’s
failure fully.
Comparison with existing literature
Recruiting patients for RCTs in primary care is known to
be difficult in a variety of ways.7 8 One of the interven-
tions suggested by the Cochrane evaluation of methods
to increase recruitment to randomised trials is using an
open- trial design; this was also part of our study design.8
Furthermore, the Cochrane review suggests telephone
follow- ups for those who do not reply to a postal invita-
tion but our participants got a reminder in the weekly
online survey to call their GP if their AD got worse. In
retrospect, telephone reminders would probably have
been more effective for our study. A recent study by
Knapp et al found that multimedia information only (eg,
animations and videos) increased the trial recruitment
rate in children and young people compared with partic-
ipant information sheets for trial recruitment.12 We used
printed participant information only. However, the chil-
dren in our study were already participating in a cohort
study but maybe would have been more able and more
willing to participate in the trial if multimedia informa-
tion had been given.
We used a case- finding method in our study to recruit
patients through general practices. When it turned out
that inclusion for the cohort was behind schedule, we
started recruitment through social media and a news-
paper.6 Research by van der Worp et al showed largely
comparable samples for recruitment throughout the
media versus case- finding.13 That study was carried out
in a comparable setting in Dutch general practice. Baker
et al found that paid and unpaid social media recruit-
ment could be an efficient tool that can potentially
assist recruitment to clinical trials in AD.14 One solution
could be to recruit solely through social media and at
the same time increase the sample size of the cohort so
that it would finally include more patients in the trial.
However, to get a comparable patient selection, inclusion
and exclusion criteria should be properly decided. To
ensure that selection bias is minimised, it should be veri-
fied that the patient characteristics in primary care and
open recruitment are identical. It should also be possible
to overcome the logistical issue with medical supervision.
When patients are recruited via their own GPs, the GP
must have confirmed their willingness to take part in the
research, and is responsible for the patient’s treatment
and management. The GP can provide prescriptions and
is the point of contact if the treatment is not effective.
When patients are recruited through social media, that
responsibility needs to be transferred to a physician in the
research team.
A good example is the Panoramic trial of Butler et al.
This was a nationwide, multicentre, primary care, open-
label, multigroup, prospective, platform adaptive trial of
early treatments for COVID- 19 in the UK. They success-
fully included more than 10 000 patients.15 They included
patients not only via the central trial team but also via
hubs; these included GP Sites, Community Trusts and
other health service providers, including government
agencies for example, the UK Health Security Agency. A
medically qualified professional, research nurse, nurse
prescriber or prescribing pharmacist from the hub was
able to complete all recruitment procedures, screening,
baseline, informed consent and eligibility reviews.
Furthermore, they also could provide the patient with the
medication being studied. Although this trial had a larger
budget and studied a potentially deadly disease with a
high impact, it could be an interesting option to use the
structure of hubs with medically qualified professionals to
recruit patients for trials nationwide.
In our study, participants were told what to do in
the event of an exacerbation of the AD in order to be
included in the trial (92.8%), but a substantial number of
patients did not contact their GPs when they experienced
a flare- up (69.2%). Most of them started treating the
flare- up themselves. This meant that participants did have
a TCS at home, whereas the protocol stated that partici-
pants had to hand in any TCS they had at home during
the cohort baseline visit if they did not use a TCS at base-
line. They did not have to hand in the medication if they
were doing maintenance therapy or treating a flare- up.
Based on our baseline data, 49% of the children used a
TCS at baseline, so this substantial group of participants
probably had a TCS at home.16 One of the reasons for not
contacting their GPs could be that if patients experienced
a flare- up, it was probably more convenient to start a TCS
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they had at home than schedule a consultation with the
GP. Or maybe they reconsidered participation when a
flare- up of the AD occurred. In addition, an increase in
AD symptoms might not have been noticed as a flare- up
by parents/patients because it was assumed to be typical
fluctuation of a well- known disease.
Furthermore, our window of inclusion covered the
beginning of the COVID- 19 pandemic. It is known that the
number of consultations declined substantially compared
with pre- pandemic levels.17 It was stated in the survey that
COVID- 19 was one reason why patients could not visit the
GP when experiencing a flare- up. It is likely that patients
did not want to burden the healthcare system unneces-
sarily during the pandemic or that the appointment was
scheduled after too many days. This could have led to
higher rates of patients who started treating the flare- up
themselves.
Also, the high burden for trial participants could be a
reason for failure to enrol.18 The burden of participating
in our trial consisted of a consultation with the GP and
three home visits.6 Patients had to contact the practice
themselves to arrange an appointment with their GP.
They might have had to wait 1 or 2 days before they could
arrange an appointment, especially during the COVID- 19
period. Additionally, the multicentre design resulted in
one or only a few patients from each participating GP
practice. This could have led to less awareness among
the GPs and/or GP assistants about what to do when a
participant was experiencing a flare- up. This was also
mentioned in the survey. Moreover, the consultation with
the GP was needed for going through the inclusion and
exclusion criteria of the trial and objectively assessing the
severity of the AD; this could also be one of the barriers
that hampered contact with the GP during a flare- up. This
barrier could be resolved by transferring those respon-
sibilities to the research team and making them also
available during out- of- office hours. In addition, digital
photographs could be used to remotely assess the severity
of AD. Studies with these methods are promising.19 20
Because their AD was mild or severe rather than
moderate, the majority of patients who contacted their GP
did not satisfy the trial’s inclusion criteria. One reason for
this could be that our eligibility criteria were too narrowly
defined. Narrow eligibility criteria and an overestimation
of prevalence are known reasons for unsuccessful recruit-
ment.18 21 We selected children with moderate eczema
because we did not want to overtreat or undertreat them
with the intervention and control treatments. Another
reason for poor recruitment could be that we overes-
timated the prevalence of moderate AD in children.
However, the baseline data of the cohort showed that
mean AD severity was moderate on the POEM scale, so
this does not seem to have been the problem. The survey
showed that 56.6% of the participants in the cohort expe-
rienced a flare- up. If we had been able to recruit the
cohort sample size through the GP practices, it would
have been feasible to reach the desired trial sample size
given the numbers and severity of AD cases in the cohort.
Implications for future research
We would like to present some suggestions for an improved
design and a more successful way to answer the important
research question of whether starting with a potent TCS
during a flare- up of AD is more efficacious than starting
with a low- potency TCS in children in primary care. See
the summary in box 1.
First, responsibility for the patients’ AD should be trans-
ferred from their own GP through hubs to a physician in
the research team or to a medically qualified professional
such as a research nurse, as shown by Butler et al.15 Second,
we consider the recruitment method. As discussed above,
our own study and the literature show social media recruit-
ment to be an effective way of including patients.13 14
Third, we suggest assessing the severity of AD digitally;
the literature has shown that this is a promising alterna-
tive.19 20 Finally, we recommend implementing a direct
medication delivery service to patients to eliminate the
need for pharmacy visits. However, the GP or study team
should verify the inclusion and exclusion criteria before
randomisation. Eliminating the need for the patient to
schedule an appointment with their doctor and visit the
pharmacy makes it possible to reduce the time between
the onset of the flare- up and the start of the randomised
treatment. However, these recommendations are not abso-
lute and depend on several factors, including the avail-
able budget, the condition being studied and the target
patient group. We advise conducting a feasibility study to
test a design that incorporates these modifications.
CONCLUSION
Although the cohort part of the Rotterdam Eczema Study
successfully included 367 children with AD, we were
unable to reach the target for the trial. We hope that the
lessons learnt from this study will be useful in developing
future studies in young patients with AD who are being
treated in primary care.
Contributors KFvH, GE and AMB conceived the study and initial study design in
collaboration with PJEB and SGMAP. KFvH and AMB conducted the analyses. All the
authors contributed to the drafting of this paper, led by KFvH and approved the nal
manuscript. KFvH is the guarantor and accepts full responsibillity for this work. The
corresponding author attests that all listed authorsmeet authorship criteria and that
no others meeting the criteria have been omitted.
Box 1 Summary of recommendations for future research
in children in general practice with AD
Recommendations for future research
Conduct a feasibility study
Choose inclusion criteria carefully
Responsible physician/nurse should be in the research team to super-
vise the treatment
Assess severity of AD digitally (via photos)
Deliver randomised medication to the home
Patient recruitment through social media or mobile research team
Telephone reminders for cohort patients
on May 17, 2024 by guest. Protected by copyright.http://bmjopen.bmj.com/BMJ Open: first published as 10.1136/bmjopen-2023-078942 on 15 May 2024. Downloaded from
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van HalewijnKF, etal. BMJ Open 2024;14:e078942. doi:10.1136/bmjopen-2023-078942
Open access
Funding The authors have not declared a specic grant for this research from any
funding agency in the public, commercial or not- for- prot sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in
the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not applicable.
Ethics approval This study involves human participants and was approved by
The Medical Ethics Committee (MEC) of the Erasmus Medical Center Rotterdam
approved the protocol (MEC- 2017- 328). Participants gave informed consent to
participate in the study before taking part.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.
Consent was not obtained from participants for data sharing. Authors will consider
reasonable request to make relevant anonymised participant level data available.
Supplemental material This content has been supplied by the author(s). It has
not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been
peer- reviewed. Any opinions or recommendations discussed are solely those
of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and
responsibility arising from any reliance placed on the content. Where the content
includes any translated material, BMJ does not warrant the accuracy and reliability
of the translations (including but not limited to local regulations, clinical guidelines,
terminology, drug names and drug dosages), and is not responsible for any error
and/or omissions arising from translation and adaptation or otherwise.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY- NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non- commercially,
and license their derivative works on different terms, provided the original work is
properly cited, appropriate credit is given, any changes made indicated, and the use
is non- commercial. See:http://creativecommons.org/licenses/by-nc/4.0/.
ORCID iDs
Karlijn Fvan Halewijn http://orcid.org/0000-0002-9516-8193
GijsElshout http://orcid.org/0000-0002-6988-0179
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