Faculty Collaboration Database

Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis. Ann Neurol 2023 Sep;94(3):547-560

Date

05/28/2023

Pubmed ID

37245090

DOI

10.1002/ana.26714

Scopus ID

2-s2.0-85163197066 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

Platform trials allow efficient evaluation of multiple interventions for a specific disease. The HEALEY ALS Platform Trial is testing multiple investigational products in parallel and sequentially in persons with amyotrophic lateral sclerosis (ALS) with the goal of rapidly identifying novel treatments to slow disease progression. Platform trials have considerable operational and statistical efficiencies compared with typical randomized controlled trials due to their use of shared infrastructure and shared control data. We describe the statistical approaches required to achieve the objectives of a platform trial in the context of ALS. This includes following regulatory guidance for the disease area of interest and accounting for potential differences in outcomes of participants within the shared control (potentially due to differences in time of randomization, mode of administration, and eligibility criteria). Within the HEALEY ALS Platform Trial, the complex statistical objectives are met using a Bayesian shared parameter analysis of function and survival. This analysis serves to provide a common integrated estimate of treatment benefit, overall slowing in disease progression, as measured by function and survival while accounting for potential differences in the shared control group using Bayesian hierarchical modeling. Clinical trial simulation is used to provide a better understanding of this novel analysis method and complex design. ANN NEUROL 2023;94:547-560.

Author List

Quintana M, Saville BR, Vestrucci M, Detry MA, Chibnik L, Shefner J, Berry JD, Chase M, Andrews J, Sherman AV, Yu H, Drake K, Cudkowicz M, Paganoni S, Macklin EA, HEALEY ALS Platform Trial Study Group

Author

Dominic B. Fee MD Vice Chair, Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amyotrophic Lateral Sclerosis
Bayes Theorem
Clinical Trials as Topic
Disease Progression
Humans
Time Factors