Open AccessFrequentist rules for regulatory approval of subgroups in phase III trials: A fresh look at an old problem
Author(s) -
Kate Edgar,
Dan Jackson,
Kirsty Rhodes,
Thomas P. Duffy,
Burman Cf,
Linda D. Sharples
Publication year - 2021
Publication title -
statistical methods in medical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.952
H-Index - 85
eISSN - 1477-0334
pISSN - 0962-2802
DOI - 10.1177/09622802211017574
Subject(s) - frequentist inference , subgroup analysis , sample size determination , type i and type ii errors , multiple comparisons problem , econometrics , statistics , covariate , medicine , population , statistical power , meta analysis , mathematics , actuarial science , bayesian probability , bayesian inference , economics , environmental health
The number of Phase III trials that include a biomarker in design and analysis has increased due to interest in personalised medicine. For genetic mutations and other predictive biomarkers, the trial sample comprises two subgroups, one of which, say B + is known or suspected to achieve a larger treatment effect than the other B - . Despite treatment effect heterogeneity, trials often draw patients from both subgroups, since the lower responding B - subgroup may also gain benefit from the intervention. In this case, regulators/commissioners must decide what constitutes sufficient evidence to approve the drug in the B - population.