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On controversial statistical issues in clinical research

Authors Chow S, Song F

Received 17 January 2015

Accepted for publication 25 February 2015

Published 2 May 2015 Volume 2015:7 Pages 43—51


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Greg Martin

Shein-Chung Chow,1 Fuyu Song2

1Duke University School of Medicine, Durham, NC, USA; 2Peking University Clinical Research Institute, Peking University Health Science Center, Beijing, People's Republic of China

Abstract: In clinical development of a test treatment under investigation, clinical trials are often conducted for evaluation of safety and efficacy of the test treatment. To provide an accurate and reliable assessment, adequate and well-controlled clinical trials using valid study designs are necessarily conducted for obtaining substantial evidence of safety and efficacy of the test treatment under investigation. In practice, however, some debatable issues are commonly encountered regardless compliance with good statistics practice and good clinical practice. These issues include, but are not limited to: 1) appropriateness of statistical hypotheses for clinical investigation; 2) correctness of power analysis assumptions; 3) integrity of randomization and blinding; 4) post hoc endpoint selection; 5) impact of protocol amendments on the characteristics of the trial population; 6) multiplicity in clinical trials; 7) missing data imputation; 8) adaptive design methods; and 9) independence of a data monitoring committee. In this article, these issues are briefly described. The impact of these issues on the evaluation of the safety and efficacy of the test treatment under investigation are discussed with examples whenever applicable. Some recommendations regarding possible resolutions of these issues are also provided.

Keywords: data safety monitoring committee, endpoint selection, integrity of blinding, missing data imputation, multiplicity, protocol amendment, two-stage adaptive designs

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