Chow Shein-Chung, Chow Susan S, Pong Annpey
Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA.
Kansas City University, College of Osteopathic Medicine, Kansas City, Missouri, USA.
Gen Psychiatr. 2021 Oct 27;34(5):e100540. doi: 10.1136/gpsych-2021-100540. eCollection 2021.
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.
在临床开发中，通常会进行充分且严格控制的随机临床试验，以评估正在研究的试验性治疗的安全性和有效性。目的是确保对所研究的试验性治疗进行准确可靠的评估。然而，在实践中，尽管遵循了良好临床实践规范，但一些有争议的问题仍不可避免地出现。这些有争议的问题包括但不限于：（1）临床研究假设的合理性；（2）样本量所需功效计算的可行性；（3）随机化/盲法的完整性；（4）临床终点选择策略；（5）证明有效性或无效性；（6）方案修订的影响；以及（7）独立数据监测委员会的独立性。本文将对这些有争议的问题进行讨论。还将评估这些问题对正在研究的试验性治疗安全性和有效性评估的影响。只要有可能，就会针对这些问题的可能解决方案提供建议。
