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Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis.

Publication ,  Journal Article
Quintana, M; Saville, BR; Vestrucci, M; Detry, MA; Chibnik, L; Shefner, J; Berry, JD; Chase, M; Andrews, J; Sherman, AV; Yu, H; Drake, K ...
Published in: Ann Neurol
September 2023

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.

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Published In

Ann Neurol

DOI

EISSN

1531-8249

Publication Date

September 2023

Volume

94

Issue

3

Start / End Page

547 / 560

Location

United States

Related Subject Headings

  • Time Factors
  • Neurology & Neurosurgery
  • Humans
  • Disease Progression
  • Clinical Trials as Topic
  • Bayes Theorem
  • Amyotrophic Lateral Sclerosis
  • 3209 Neurosciences
  • 3202 Clinical sciences
  • 1109 Neurosciences
 

Citation

APA
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Quintana, M., Saville, B. R., Vestrucci, M., Detry, M. A., Chibnik, L., Shefner, J., … HEALEY ALS Platform Trial Study Group, . (2023). Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis. Ann Neurol, 94(3), 547–560. https://doi.org/10.1002/ana.26714
Quintana, Melanie, Benjamin R. Saville, Matteo Vestrucci, Michelle A. Detry, Lori Chibnik, Jeremy Shefner, James D. Berry, et al. “Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis.Ann Neurol 94, no. 3 (September 2023): 547–60. https://doi.org/10.1002/ana.26714.
Quintana M, Saville BR, Vestrucci M, Detry MA, Chibnik L, Shefner J, et al. Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis. Ann Neurol. 2023 Sep;94(3):547–60.
Quintana, Melanie, et al. “Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis.Ann Neurol, vol. 94, no. 3, Sept. 2023, pp. 547–60. Pubmed, doi:10.1002/ana.26714.
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. Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis. Ann Neurol. 2023 Sep;94(3):547–560.
Journal cover image

Published In

Ann Neurol

DOI

EISSN

1531-8249

Publication Date

September 2023

Volume

94

Issue

3

Start / End Page

547 / 560

Location

United States

Related Subject Headings

  • Time Factors
  • Neurology & Neurosurgery
  • Humans
  • Disease Progression
  • Clinical Trials as Topic
  • Bayes Theorem
  • Amyotrophic Lateral Sclerosis
  • 3209 Neurosciences
  • 3202 Clinical sciences
  • 1109 Neurosciences