Bayesian adaptive design for clinical trials in Duchenne muscular dystrophy

A Bayesian adaptive design is proposed for a clinical trial in Duchenne muscular dystrophy. The trial was designed to demonstrate treatment efficacy on an ambulatory‐based clinical endpoint and to identify early success on a biomarker (dystrophin protein levels) that can serve as a basis for accelerated approval in the United States. The trial incorporates placebo augmentation using placebo data from past clinical trials. A thorough simulation study was conducted to understand the operating characteristics of the trial. This trial design was selected for the US FDA Complex Innovative Trial Design Pilot Meeting Program and the experience in that program is summarized.

• Publication year

  2021

• Venue

  Statistics in Medicine

• Publication date

  2021-05-07

• Fields of study

  Medicine

• Identifiers
  DOI 10.1002/sim.9021PMID 33960507
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Bayesian Frameworks for Rare Disease Clinical Development Programs

  2020cited by this paper
• Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

  2020cited by this paper
• A multi‐source adaptive platform design for testing sequential combinatorial therapeutic strategies

  2018cited by this paper
• A novel cognitive disease progression model for clinical trials in autosomal‐dominant Alzheimer's disease

  2018cited by this paper
• Bayesian model of disease progression in GNE myopathy

  2018cited by this paper
• A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy

  2017cited by this paper
• Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

  2017cited by this paper
• Individualized Prediction of Changes in 6-Minute Walk Distance for Patients with Duchenne Muscular Dystrophy

  2016cited by this paper
• Guideline on the clinical investigation of medicinal products for the treatment of Duchenne and Becker muscular dystrophy

  2016cited by this paper
• Corticosteroid Treatments in Males With Duchenne Muscular Dystrophy

  2015cited by this paper
• Not Too Big, Not Too Small: A Goldilocks Approach To Sample Size Selection

  2014cited by this paper
• A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy

  2014cited by this paper
• Evidence‐based path to newborn screening for duchenne muscular dystrophy

  2012cited by this paper
• Development of a functional assessment scale for ambulatory boys with Duchenne muscular dystrophy.

  2012cited by this paper
• Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management.

  2010cited by this paper
• Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care.

  2010cited by this paper
• Philosophy and the practice of Bayesian statistics.

  2010cited by this paper
• Bayesian meta-analysis of multiple treatment comparisons: an introduction to mixed treatment comparisons.

  2008cited by this paper
• Managing Duchenne muscular dystrophy--the additive effect of spinal surgery and home nocturnal ventilation in improving survival.

  2007cited by this paper
• Bayesian methods in meta-analysis and evidence synthesis.

  2001cited by this paper
• Bayesian approaches to random-effects meta-analysis: a comparative study.

  1995cited by this paper
• Population frequencies of inherited neuromuscular diseases--a world survey.

  1991cited by this paper
• The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein.

  1988cited by this paper
• Dystrophin: the protein product of the Duchenne muscular dystrophy locus.

  1987cited by this paper
• The combination of randomized and historical controls in clinical trials.

  1976cited by this paper

• Control of Unconditional Type I Error in Clinical Trials With External Control Borrowing—A Two‐Stage Adaptive Design Perspective

  2025influential citation
• Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis

  2023cites this paper
• Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia

  2023cites this paper
• Bayesian Design of Superiority Trials: Methods and Applications

  2022cites this paper
• Regulatory Framework for Drug Development in Rare Diseases

  2022cites this paper
• Bayesian Strategies in Rare Diseases

  2022cites this paper
• Augmenting Randomized Clinical Trial Data with Historical Control Data: Precision Medicine Applications.

  2022cites this paper
• Real-world and natural history data for drug evaluation in Duchenne muscular dystrophy: suitability of the North Star Ambulatory Assessment for comparisons with external controls.

  2022cites this paper
• Application of Bayesian methods to accelerate rare disease drug development: scopes and hurdles

  2022cites this paper
• Lessons Learned From Translational Research in Neuromuscular Diseases: Impact on Study Design, Outcome Measures and Managing Expectation

  2021cites this paper
• Adaptive Platform Trials to Transform Amyotrophic Lateral Sclerosis Therapy Development

  2021cites this paper