Advancing Pediatric Drug Development

Translation from adults data

Community Member kudos icon + Community member
The common approach to dose selection in pediatric population when only adults data is available is population PKPD (PBPK) modelling.

If age and weight are not identified as covariates for the model, if the flat exposure-response curve is observed in adult population, if in vitro tests and biology theory claim that there are no effects of growth and maturation on the observed levels of PD-markers (or components of the... more »

Voting

9 votes

Advancing Pediatric Drug Development

Predictability of Adult Biomarkers Across Pediatric Disease and Therapeutic Areas

While there is general recognition of the need for pediatric-specific biomarkers, sponsors and researchers are often left with adult biomarkers out of convenience or necessity. It would be helpful to have a broader understanding of the suitability of this occurrence for dose selection and/or clinical endpoint utility across pediatric disease states, therapeutic area, drug class and developmental status to drive the effort... more »

Voting

12 votes

Advancing Pediatric Drug Development

MRD as a surrogate for Overall Survival

MRD as a general measure of tumor burden has multiple potential regulatory and clinical uses as a biomarker; however, the evidence to support the clinical validity of MRD as a biomarker varies across hematologic cancer types and patient populations. In pediatric patients with relapsed/refractory AML, MRD-negative CR has not yet been established as an intermediate endpoint likely to predict overall survival. To investigate... more »

Voting

22 votes

Advancing Pediatric Drug Development

Risk of osteonecrosis and bone fractures with long-term use of proton-pump inhibitors

Is the long-term use of proton-pump inhibitors associated with an increased risk of bone fractures, osteonecrosis (or even growth delay) in children?  If so, what are the primary determinants of risk?  For example: CYP2D6 metabolizer status, concomitant use of high-dose corticosteroids, age of onset, duration of use, other disease states/comorbidities?  

 

See also: 

https://pubmed.ncbi.nlm.nih.gov/31175146/ 

https://pubmed.ncbi.nlm.nih.gov/32176276/... more »

Voting

1 vote

Advancing Pediatric Drug Development

Growth reference of pediatric cancer patients

Currently, the pediatric patients growth parameters (e.g., height, weight, BMI, and head circumference) are supposed to be reported relative to the WHO/CDC growth charts.  Since these growth charts represent the growth of healthy children without cancers, it is challenging to understand the impact of the cancer treatment on pediatric patients' growth, especially in interpreting safety data from a single-arm pediatric... more »

Voting

5 votes

Advancing Pediatric Drug Development

Rare Disease Aggregate Control Arm Data to Alleviate Pediatric Patient Burden

Placebo- and active-controlled trials are considered the "gold standard" of well-controlled trials. However, for rare pediatric diseases, this imposes a large burden on families who are desperate for new treatments that could impact the unmet needs of the disease and do not want to enroll their children in a trial in which they may not gain access to the treatment with the potential to provide greater benefit (see for... more »

Voting

9 votes

Advancing Pediatric Drug Development

Reducing or eliminating placebo burden on pediatric patients in areas of unmet need

Community Member kudos icon 34 Community member
i. With the goal of reducing or eliminating placebo burden on pediatric patients while maintaining FDA's high standards for the development of safe and effective medicines, it is recommended that FDA conduct analyses of placebo and natural history data from both successful and unsuccessful clinical trials in pediatric rare diseases. The aims of the research should be to: 1) consider published, peer-reviewed literature... more »

Voting

27 votes

Advancing Pediatric Drug Development

Data requirement to facilitate Pediatric Drug Development

How could we maximize use of all available data (e.g., existing clinical data in adults, in pediatric population in other diseases, MOA of drug, etiology of the disease, maturation of drug target, safety data in adults and pediatric patients on similar compounds, preclinical data, in vitro data etc.), to minimize data requirement from clinical trial in neonate and older pediatric population.

Voting

7 votes

Advancing Pediatric Drug Development

The quality and quantity of reports of suspected ADRs from young people

Spontaneous adverse drug reaction reports to the UK regulatory agency (MHRA) have shown a difference in both the type of drugs and reactions reported, when comparing reports about young people, and those that originated from a young person themselves (Bhoombhla 2020). The reactions that were identified by young people included serious mental health issues. This difference may also be true in clinical trials - but it would... more »

Voting

1 vote

Advancing Pediatric Drug Development

Influence of pharmacogenomics on antiemetic response and efficacy

Does CYP2D6 genotype influence ondansetron efficacy and/or toxicity?  For example, do patients with a CYP2D6 ultra-rapid metabolizer phenotype experience more treatment failure?  Do patients with intermediate or poor metabolizer phenotype experience greater toxicity (e.g., QT prolongation, headache, constipation).

https://cpicpgx.org/guidelines/guideline-for-ondansetron-and-tropisetron-and-cyp2d6-genotype/

Voting

2 votes

Advancing Pediatric Drug Development

Balancing safety risks and speed

Community Member kudos icon + Community member
What is the number of Adverse Events (AEs), serious AEs, AEs leading to discontinuation, grouped by age? Do younger children tend to have more AE's than older children?

How similar is the safety profile in children compared to that previously observed in adults?

Are pediatric trials without a preceding trial in adults more likely to be stopped for safety concerns?

Answers to these questions could help accelerate pediatric... more »

Voting

6 votes

Advancing Pediatric Drug Development

Understanding placebo response

Community Member kudos icon 1 Community member
Placebo response in pediatric clinical trials dilutes drug-placebo differences and severely hinders drug development. However, the factors that are associated with placebo effects are poorly understood, with most evidence coming from post-hoc analyses of single trial data or single indication meta-analyses. The FDA pooled pediatric clinical trial data using randomized placebo-controlled trials would afford the possibility... more »

Voting

7 votes

Advancing Pediatric Drug Development

Effect of Vitamin D Supplementation on Bone Health During Cancer Treatment

Oncology therapies (steroids, methotrexate) and supportive care medications (proton pump inhibitors?) are part of a multi-modal approach to curing pediatric acute lymphoblastic leukemia and also contribute to osteopenia/osteoporosis.  Pediatric patients are different from adult patients in the way that their bones are still maturing during oncology treatment.  

What are the rates of osteopenia/osteoporosis and/or AVN... more »

Voting

1 vote