Deficient Reporting and Interpretation of Non-Inferiority Randomized Clinical Trials in HIV Patients: A Systematic Review

ObjectivesNon-inferiority (NI) randomized clinical trials (RCTs) commonly evaluate efficacy of new antiretroviral (ARV) drugs in human immunodeficiency virus (HIV) patients. Their reporting and interpretation have not been systematically evaluated. We evaluated the reporting of NI RCTs in HIV patients according to the CONSORT statement and assessed the degree of misinterpretation of RCTs when NI was inconclusive or not established.DesignSystematic review.MethodsPubMed, Web of Science, and Scopus were reviewed until December 2011. Selection and extraction was performed independently by three reviewers.ResultsOf the 42 RCTs (n = 21,919; range 41–3,316) selected, 23 were in ARV-naïve and 19 in ARV-experienced patients. Twenty-seven (64%) RCTs provided information about prior RCTs of the active comparator, and 37 (88%) used 2-sided CIs. Two thirds of trials used a NI margin between 10 and 12%, although only 12 explained the method to determine it. Blinding was used in 9 studies only. The main conclusion was based on both intention-to-treat (ITT) and per protocol (PP) analyses in 5 trials, on PP analysis only in 4 studies, and on ITT only in 31 studies. Eleven of 16 studies with NI inconclusive or not established highlighted NI or equivalence, and distracted readers with positive secondary results.ConclusionsThere is poor reporting and interpretation of NI RCTs performed in HIV patients. Maximizing the reporting of the method of NI margin determination, use of blinding and both ITT and PP analyses, and interpreting negative NI according to actual primary findings will improve the understanding of results and their translation into clinical practice.

研究目的：非劣效性（Non-inferiority, NI）随机对照试验（Randomized Clinical Trials, RCTs）常被用于评估新型抗逆转录病毒（Antiretroviral, ARV）药物在人类免疫缺陷病毒（Human Immunodeficiency Virus, HIV）感染者中的疗效。目前学界尚未对这类试验的报告规范与解读情况开展系统性评估。本研究依据CONSORT声明（CONSORT Statement）评估HIV感染者相关NI RCTs的报告质量，并分析当NI结论不明确或未成立时，研究解读存在的偏误程度。
研究设计：系统性综述。
研究方法：检索PubMed、Web of Science及Scopus数据库，检索时限截至2011年12月。由3名研究者独立完成文献筛选与数据提取工作。
研究结果：最终纳入42项RCTs，共涉及21919名受试者（样本量范围41~3316），其中23项针对ARV初治感染者，19项针对ARV经治感染者。27项（64%）研究提供了阳性对照药物既往相关RCTs的信息，37项（88%）采用双侧置信区间（Confidence Intervals, CIs）。三分之二的试验设定的NI界值介于10%~12%之间，但仅12项研究说明了界值的确定方法。仅9项研究采用了盲法设计。主要结论的分析依据情况为：5项试验同时采用意向治疗（Intention-to-Treat, ITT）分析与符合方案（Per Protocol, PP）分析，4项仅采用PP分析，31项仅采用ITT分析。在16项NI结论不明确或未成立的研究中，有11项强调NI或等效性结论，并借助阳性次要结果转移读者注意力。
研究结论：HIV感染者相关NI RCTs的报告质量与结果解读均存在明显不足。优化NI界值确定方法的报告规范、采用盲法设计、同时开展ITT与PP分析，以及依据原始主要研究结果解读阴性NI结论，将有助于提升研究结果的理解度，并推动其向临床实践的转化。