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Statistical consideration of the strategy for demonstrating clinical evidence of effectiveness—one larger vs two smaller pivotal studies
Author(s) -
Shun Zhenming,
Chi Eric,
Durrleman Sylvain,
Fisher Lloyd
Publication year - 2005
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.2015
Subject(s) - pooling , type i and type ii errors , computer science , statistical power , statistical inference , sample size determination , statistical model , inference , econometrics , population , statistical hypothesis testing , sample (material) , statistics , machine learning , artificial intelligence , mathematics , medicine , environmental health , chemistry , chromatography
As a regulatory strategy, it is nowadays not uncommon to conduct one confirmatory pivotal clinical trial, instead of two, to demonstrate efficacy and safety in drug development. This paper is intended to investigate the statistical foundation of such an approach. The one‐study approach is compared with the conventional two‐study approach in terms of power, type‐I error, and fundamental statistical assumptions. Necessary requirements for a single‐study model is provided in order to maintain equivalent evidence as that from a two‐study model. In general, one‐study model is valid only under a ‘one population’ assumption. In addition, higher data quality and more convincing and robust results need to be demonstrated in such cases. However, when ‘one‐population’ assumption is valid and appropriate methods are selected, a one‐study model can have a better power using the same sample size. The paper also investigates statistical assumptions and methods for making an overall inference when a two‐study model has been used. The methods for integrated analysis are evaluated. It is important for statisticians to select correct pooling strategy based on the project objective and statistical hypothesis. Copyright © 2004 John Wiley & Sons, Ltd.