Gewandter Jennifer S, McDermott Michael P, McKeown Andrew, Hoang Kim, Iwan Katarzyna, Kralovic Sarah, Rothstein Daniel, Gilron Ian, Katz Nathaniel P, Raja Srinivasa N, Senn Stephen, Smith Shannon M, Turk Dennis C, Dworkin Robert H
Department of Anesthesiology University of Rochester, Rochester, NY, USA.
Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA.
Pain. 2016 Nov;157(11):2544-2551. doi: 10.1097/j.pain.0000000000000673.
Cross-over trials are typically more efficient than parallel group trials in that the sample size required to yield a desired power is substantially smaller. It is important, however, to consider some issues specific to cross-over trials when designing and reporting them, and when evaluating the published results of such trials. This systematic review evaluated the quality of reporting and its evolution over time in articles of cross-over clinical trials of pharmacologic treatments for chronic pain published between 1993 and 2013. Seventy-six (61%) articles reported a within-subject primary analysis, or if no primary analysis was identified, reported at least 1 within-subject analysis, which is required to achieve the gain in power associated with the cross-over design. For 39 (31%) articles, it was unclear whether analyses conducted were within-subject or between-group. Only 36 (29%) articles reported a method to accommodate missing data (eg, last observation carried forward, n = 29), and of those, just 14 included subjects in the analysis who provided data from only 1 period. Of the articles that identified a within-subject primary analysis, 21 (51%) provided sufficient information for the results to be included in a meta-analysis (ie, estimates of the within-subject treatment effect and variability). These results and others presented in this article demonstrate deficiencies in reporting of cross-over trials for analgesic treatments. Clearer reporting in future trials could improve readers' ability to critically evaluate the results, use these data in meta-analyses, and plan future trials. Recommendations for proper reporting of cross-over trials that apply to any condition are provided.
交叉试验通常比平行组试验更有效，因为产生所需检验效能所需的样本量要小得多。然而，在设计和报告交叉试验以及评估此类试验的已发表结果时，考虑一些特定于交叉试验的问题很重要。本系统评价评估了1993年至2013年间发表的关于慢性疼痛药物治疗的交叉临床试验文章的报告质量及其随时间的演变。76篇（61%）文章报告了受试者内的主要分析，或者如果未确定主要分析，则报告了至少1项受试者内分析，这是实现与交叉设计相关的检验效能提高所必需的。对于39篇（31%）文章，不清楚所进行的分析是受试者内分析还是组间分析。只有36篇（29%）文章报告了处理缺失数据的方法（例如，末次观察结转，n = 29），其中只有14篇在分析中纳入了仅提供1个时期数据的受试者。在确定了受试者内主要分析的文章中，21篇（51%）提供了足够的信息，其结果可纳入荟萃分析（即受试者内治疗效应和变异性的估计）。本文呈现的这些结果及其他结果表明，镇痛治疗交叉试验的报告存在缺陷。未来试验中更清晰的报告可以提高读者批判性评估结果、在荟萃分析中使用这些数据以及规划未来试验的能力。本文提供了适用于任何情况的交叉试验正确报告的建议。
