Review of current controversial issues in clinical trials

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In clinical development, adequate and well-controlled randomised clinical trials are usually conducted to evaluate the safety and efficacy of test treatment under investigation. The purpose is to ensure that there is an accurate and reliable assessment of test treatment under study. In practice, however, some controversial issues inevitably appear despite the compliance of good clinical practice. These debatable issues include, but are not limited to, (1) appropriateness of hypotheses for clinical investigation, (2) feasibility of power calculation for sample size requirement, (3) integrity of randomisation/blinding, (4) strategy for clinical endpoint selection, (5) demonstrating effectiveness or ineffectiveness, (6) impact of protocol amendments and (7) independence of independent data monitoring committee. In this article, these controversial issues are discussed. The impact of these issues in evaluating the safety and efficacy of the test treatment under investigation is also assessed. Recommendations regarding possible resolutions to these issues are provided whenever possible.






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Chow, SC, SS Chow and A Pong (2021). Review of current controversial issues in clinical trials. General Psychiatry, 34(5). pp. e100540–e100540. 10.1136/gpsych-2021-100540 Retrieved from

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Shein-Chung Chow

Professor of Biostatistics & Bioinformatics

My research interest includes statistical methodology development and application in the area of biopharmaceutical/clinical statistics such as bioavailability and bioequivalence, clinical trials, bridging studies, medical devices, and translational research/medicine. Most recently, I am interested in statistical methodology development for the use of adaptive design methods in clinical trials and methodology development for assessment of biosimilarity of follow-on biologics. In addition, I am also interested in methodology development for statistical evaluation of traditional Chinese medicine (TCM) clinical trials.

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