Advancing Pediatric Drug Development

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

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 »

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27 votes

Advancing Pediatric Drug Development

MRD as a surrogate for Overall Survival trending idea

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 »

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22 votes

Advancing Pediatric Drug Development

Predictability of Adult Biomarkers Across Pediatric Disease and Therapeutic Areas trending idea

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 »

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12 votes

Advancing Pediatric Drug Development

Translation from adults data trending idea

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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 »

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9 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 »

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9 votes

Advancing Pediatric Drug Development

Data requirement to facilitate Pediatric Drug Development trending idea

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.

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7 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 »

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7 votes

Advancing Pediatric Drug Development

Balancing safety risks and speed

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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 »

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6 votes

Advancing Pediatric Drug Development

Diversity and Inclusion

Community Member kudos icon 1 Community member
Diversity in clinical trials is imperative to better understand the safety and efficacy profile of novel pediatric therapies and to reduce disparities and advance equal access and opportunities. Yet, the extent to which individuals from minority racial and ethnic groups, across different educational backgrounds, and those with intellectual disabilities and other cognitive impairments are represented in pediatric clinical... more »

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6 votes

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 »

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5 votes

Advancing Pediatric Drug Development

Pediatric biomarkers

There is extreme interest in identifying pediatric specific biomarkers for multiple disease states including NAFLD, heart failure, chronic kidney disease (CKD).

• Biomarkers may serve as alternatives to invasive diagnostic techniques (e.g. Liver biopsy in NAFLD), early indicators of disease progression, and predictors of treatment efficacy. Does the pooled database support this?

• Specifically, what is the utility of... more »

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4 votes

Advancing Pediatric Drug Development

Steroid-resistant acute graft-versus-host disease in pediatric populations

In steroid-resistant graft versus host disease, what are the expected distributions of main characteristics (age, underlying disease, aGvHD grade and organs affected, source of the graft, graft compatibility, type of conditioning regimen, distribution of steroid-resistance ... ) ? Which ones differ importantly from the adult population ?

Some characteristics are known to differ between age groups in aGvHD, such as the... more »

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3 votes

Advancing Pediatric Drug Development

Longitudinal natural history of pediatric disease

Can the pooled databases be used to better understand the longitudinal natural history of pediatric disease states such as Nonalcoholic fatty liver disease (NAFLD), including differences between pediatric and adult onset, pathophysiology, mechanism and disease progression/long term sequelae?

• Considering the recently published paper on the long term complications observed in the TODAY study, long term cardiovascular... more »

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3 votes