Abstract Number:
1207
Submission Type:
Invited Paper Session
Participants:
Margaret Gamalo (1), Kristine Broglio (3), Kristine Broglio (3), Ran Liao (2), Jingjing Ye (4), Benjamin Saville (5), Joseph Marion (6), James Travis (7)
Institutions:
(1) Pfizer, N/A, (2) Eli Lilly, N/A, (3) AstraZeneca, N/A, (4) BeiGene, N/A, (5) Berry Consultants, N/A, (6) Berry Consultants, LLC, N/A, (7) FDA, N/A
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Session Description:
Pediatric clinical trials have become a breeding ground for statistical innovation in order to address the unique challenges and ethical considerations associated with studying new therapies in children. These innovations aim to improve trial design, analysis, and interpretation to ensure that pediatric patients receive safe and effective treatments in a timely and resource efficient manner. Extrapolation from adult to pediatric populations has been one successful strategy. Other notable statistical innovations in pediatric clinical trials include:
• Adaptive Trial Designs: These designs can be particularly useful in pediatric trials to optimize sample size, dosing, and treatment regimens, while minimizing the exposure of children to potentially ineffective or unsafe treatments.
• Bayesian Methods: Bayesian statistical approaches allow for the incorporation of prior knowledge, such as data from adult trials or other related data sources, into the analysis of pediatric trials.
• External control arms: Using existing sources of data including RWD, registries, or previous clinical trials to either benchmark safety and efficacy or as a formal comparator can allow for efficient single-arm trials of new therapies.
• Modeling and Simulation: Pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation help predict drug behavior in pediatric populations. Population PK-PD models can guide dosing strategies, inform trial design, and aid in dose individualization for children of different ages.
• Surrogate Endpoints: Surrogates can accelerate trials by providing earlier outcomes, such as biomarkers or physiological measures.
However, each of these approaches has challenges and potential pitfalls such as:
• Regulatory and Ethical Hurdles: By definition, there is a lack of experience with novel trial designs and statistical approaches. Innovative ideas may encounter regulatory resistance or ethical concerns, especially if they involve more complex statistical methods and alternatives to gold-standard randomized comparisons.
• Data Quality and Interpretation: Sophisticated analyses may rely on unverifiable assumptions and the use of data outside of a randomized comparison may introduce bias. This creates difficulties in interpretation and decision-making.
• Resource Intensiveness: While the statistical innovations are introduced to make the trial resource efficient in terms of sample size and time, they may require higher levels of expertise, infrastructure, and stakeholder interaction, making them less feasible for all research settings.
Balancing the potential benefits and challenges of innovative methodologies is crucial to ensure the successful execution of pediatric clinical trials. We will examine root causes around why some approaches were successful while others were not and how future challenges can be mitigated or avoided. The panel is composed of expert pediatric drug developers who are key opinion leaders in this area of drug development.
Speakers:
1. Jingjing Ye (Beigene): Recent Use of Pediatric Extrapolation in Pediatric Drug Development in US
2. Ben Saville (Berry): Borrowing across pediatric indications: A pediatric epilepsy trial within the FDA CID
3. Joe Marion: Complex Problems Demand Complex Solutions: Innovating Clinical Trial Designs in Pediatric Neurodevelopmental Disorders
4. James Travis: Perspectives on informative Bayesian methods in pediatrics
Discussant: Kristine Broglio
Sponsors:
Biopharmaceutical Section 1
Health Policy Statistics Section 2
International Society for Clinical Biostatistics 3
Theme:
Statistics and Data Science: Informing Policy and Countering Misinformation
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Applied
Yes
Estimated Audience Size
Small (<80)
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I understand and have communicated to my proposed speakers that JSM participants must register and pay the appropriate registration fee by June 1, 2024. The registration fee is nonrefundable.
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