The document discusses the complexities and challenges of conducting pediatric clinical trials, particularly in dermatology, highlighting the differences in drug responses between children and adults. It outlines regulatory frameworks aimed at improving pediatric research and the ethical concerns surrounding off-label prescribing and informed consent. The necessity for effective treatments for conditions like alopecia areata in children is emphasized, along with the need for innovative formulations and research methodologies tailored to this demographic.

1. Amy S. Paller, M.S., M.D.
Walter J. Hamlin Professor and Chair
Department of Dermatology
Professor of Pediatrics
Northwestern Univ. Feinberg Med. School
Chicago, Illinois USA
Grants – LEO Foundation; Abbvie; Investigator– Celgene, Astellas; Consultant with honorarium - Galderma, GSK-
Stiefel, Novartis, Pfizer/Anacor, Regeneron, Vitae Pharmaceuticals

2. Most prescribing in children is off-label
 Pediatric responses cannot be predicted from data collected in adult
studies
 Differences in size and metabolism in different ages: different efficacy and
different susceptibility to side effects
 Best Pharmaceuticals for Children Act (BPCA; 2002) gives
manufacturers voluntary incentive of additional 6 months of
marketing exclusivity (no competition from generics) if pediatric
studies are conducted
 Pediatric Research Equity Act (PREA) requires drugs to be studied in children in
certain circumstances
 Has reduced off-label prescribing overall to 50%, but still high
percentage for dermatologic drugs

3. Huge unmet need for alopecia treatment
 For alopecia areata/ totalis/ universalis, clinical trials will
move to pediatric age after adults
 Have some idea of effectiveness and safety from adult trials
 Considered ethical to do placebo controlled studies, but
recommend limiting to early studies for safety
 Excess use of placebo controlled trials, esp. in US
 Informed consent must be obtained from parent(s) or
guardian; assent from older child
Flohr, Weidinger. JID 2016;136:1930

4. What are the challenges in pediatric
trials and what can be done?

5. General challenges
 Recruitment is a greater challenge
- Parental consent and assent may take longer: greater fears
about risks vs. benefits – more complex consenting
- More intense requirements by the IRB to protect child
- Difficulty in scheduling study visits: conflicts and constraints
with school and activities/ parent work schedules
- Minimize number of visits/ missed school and work
- Worry about discomfort (blood draws, biopsies)
 Children are less cooperative than adults: more time is required
for every visit for the same procedures

6. Drug toxicity
 Cannot extrapolate to predict toxic effects in infants and
children (only efficacy extrapolation)
 Differences in drug metabolism
 Drug toxicity in developing child (e.g., immune system;
nervous system development; teeth/bones with tetracyclines
under 8 years old)
 Long-term toxicity more important in children: no 1 year
safety trial can predict an issue decades down the road

7. Blood sampling
 Keep blood studies to a minimum
 pK studies in Phase 2 trials: done in small numbers of children of
different ages: often adolescents; 6-11 y/o; 2-6 y/o
 Sometimes opportunity for extrapolation of efficacy from other
ages and population pK studies (more children) to pool data
and minimize individual sampling
 Microassays are important for younger children
 Offer topical local anesthetic/other devices (cryospray, buzzy bee)
for all blood draws

8. Formulations
 Usually need a liquid formulation for oral: taste is issue
- Cannot cut tablets or capsules easily
- Fast-dissolving drug formulations or multiple unit systems
with small sized particles better for younger children
 Injection vials of appropriate size for s.c. injection
- Minimize medication errors
 Topical products to limit risk of toxicity
- For example, effective topical JAK inhibitor highly desirable
for pediatric patients, especially with more limited
involvement

9. Outcomes measures
 SALT scoring should not be a problem for children, although
formal testing has not been performed
 CDLQI is validated quality of life score in children but
nonspecific; no validated QoL score for pediatric alopecia
 Validated pediatric tools for depression, anxiety, and social
functioning
 New stigma scale based on validate PROMIS tool being tested
for variety of pediatric disorders, including alopecia areata
through PeDRA

10. In conclusion….
 Alopecia areata/ totalis/ universalis has a huge potential impact
on the psychosocial development of children and intervention
studies in children and adolescents are needed
 Given the greater safety concerns in pediatric patients, the
availability of effective topical formulations is desirable
 Doing clinical trials in pediatric patients is challenging, given the
greater time required per patient, difficulty with recruitment,
and fewer validated outcomes measures
 Consideration must be given to minimizing invasive activities,
including blood draws and biopsies