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Activity Number:
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140
- The Challenges and Advantages of Utilizing Bayesian Statistical Methodology in Extrapolation of Adult Use Data to Pediatric Study Designs and Evaluation
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Type:
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Invited
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Date/Time:
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Monday, July 31, 2017 : 10:30 AM to 12:20 PM
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Sponsor:
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Biopharmaceutical Section
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Abstract #322104
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Title:
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Bayesian and Frequentist Partial Extrapolation Approaches in Organ Transplantation to Support the Pediatric Plan for European Health Authorities
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Author(s):
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Steffen Ballerstedt* and Jennifer Ng
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Companies:
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Novartis Pharma AG and Novartis Pharmaceuticals Inc
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Keywords:
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Pediatric investigation plan ;
extrapolation ;
meta-analysis ;
Bayesian ;
regulatory
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Abstract:
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An extrapolation methodology was developed to bridge a recruitment gap in the planned sample size of 2 pediatric kidney and liver Tx studies for a PIP commitment. The primary efficacy endpoint was biopsy proven acute rejection, graft loss, or death. In kidney Tx, a generalized linear mixed meta-regression model was used to estimate the event rate in children and its difference to adults. Covariates accounted for treatment regimen. The extrapolation concept was then validated by checking if the predicted pediatric efficacy was in the range of observed pediatric efficacy. A Bayesian prediction approach demonstrated robustness of the result as a sensitivity analysis. Vague priors for the Bayesian approach led to similar parameter estimates than the ML approach. The Bayesian approach delivered also statements about the probability of the population difference being within a specific interval and a check for validity of asymptotic confidence intervals in the ML analysis. The analyses provided a synthesis of evidence in the rare pediatric population and in comparison to the adult population, in line with the recent EMA concept paper on extrapolation (EMA 2013).
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Authors who are presenting talks have a * after their name.
