Prevalence of Multiplicity and Appropriate Adjustments Among Cardiovascular Randomized Clinical Trials Published in Major Medical Journals
Prevalence of Multiplicity and Appropriate Adjustments Among Cardiovascular Randomized Clinical Trials Published in Major Medical Journals
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DOI：
10.1001/jamanetworkopen.2020.3082
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发表时间：
2020-04-17
影响因子：
13.8
通讯作者：
Kalra, Ankur
中科院分区：
文献类型：
--
作者：
Khan, Muhammad Shahzeb;Khan, Maaz Shah;Kalra, Ankur
重要性临床试验中的多项分析可能会增加得出不准确结论的可能性，即存在统计学显著性治疗效果。然而，到目前为止，尚不清楚有多少随机临床试验（RCT）对多重比较进行了调整，缺乏这种调整可能会导致错误的结果。目的评估6种高影响因子医学期刊发表的心血管RCT中多重性的发生率以及是否进行了适当的多重性调整。设计、设置和参与者在这项横断面研究中，心血管RCT选自世界各地，包括北美、西欧、多地区和世界其他地区。数据收集自2015年8月1日至2018年7月31日期间发表的3种心血管期刊（《循环》、《欧洲心脏杂志》和《美国心脏病学会杂志》）和3种全科医学期刊（《JAMA》、《柳叶刀》和《新英格兰医学杂志》）的既往期刊，这些期刊具有高影响因子。还检索了每个纳入RCT的补充和试验方案的多重性。数据分析于2018年12月20日至27日进行。来自所选RCT的数据由2名研究人员使用结构化数据工具独立提取和验证。如有分歧，则由第三位审评员协助达成共识。如果RCT有2个以上的治疗组，则认为该RCT有多个治疗组;多个结局定义为有1个以上的主要结局，多项分析定义为以多种方式分析同一结局变量。仅在主要终点分析中检查多重性。主要结局和测量关注的结局是对主要终点进行多重校正的主要分析的百分比。结果在纳入的511项心血管RCT中，300项（58.7%）具有某种形式的多重性;在这300项中，只有85项（28.3%）进行了多重性调整。干预类型和资金来源与多重风险调整报告无统计学显著相关性。评估死亡与非死亡结局的试验在其主要分析中更可能包含多重风险（66.3% [177/267] vs 50.4% [123/244]; P < .001），大型试验与小型试验相比，不太可能对多重性进行任何调整（35.6% [52/146] vs 21.4% [33/154]; P = .001）。结论和相关性本研究的结果表明，在医学期刊上发表的具有高影响因子的心血管RCT很少进行调整，以纠正主要终点的多重比较。这些参数可以通过更标准化的报告得到改善。这项横断面研究评估了多重性的患病率，以及在6种具有高影响因子的医学期刊上发表的心血管随机临床试验中是否进行了适当的多重性调整。问题在6种具有高影响因子的医学期刊上发表的心血管随机临床试验中多重性的患病率是多少，在这些试验中进行多重性调整的频率如何？在这项横断面研究中，数据收集自2015年8月1日至2018年7月31日期间发表的6种影响因子高的期刊的过去几期。在纳入本分析的511项心血管随机临床试验中，300项具有某种形式的多重性;在这300项试验中，只有85项调整了多重性。意义在当代心血管随机临床试验中，多重性调整似乎很少报告。
Importance Multiple analyses in a clinical trial can increase the probability of inaccurately concluding that there is a statistically significant treatment effect. However, to date, it is unknown how many randomized clinical trials (RCTs) perform adjustments for multiple comparisons, the lack of which could lead to erroneous findings. Objectives To assess the prevalence of multiplicity and whether appropriate multiplicity adjustments were performed among cardiovascular RCTs published in 6 medical journals with a high impact factor. Design, Setting, and Participants In this cross-sectional study, cardiovascular RCTs were selected from all over the world, characterized as North America, Western Europe, multiregional, and rest of the world. Data were collected from past issues of 3 cardiovascular journals (Circulation, European Heart Journal, and Journal of the American College of Cardiology) and 3 general medicine journals (JAMA, The Lancet, and The New England Journal of Medicine) with high impact factors published between August 1, 2015, and July 31, 2018. Supplements and trial protocols of each of the included RCTs were also searched for multiplicity. Data were analyzed December 20 to 27, 2018. Exposures Data from the selected RCTs were extracted and verified independently by 2 researchers using a structured data instrument. In case of disagreement, a third reviewer helped to achieve consensus. An RCT was considered to have multiple treatment groups if it had more than 2 arms; multiple outcomes were defined as having more than 1 primary outcome, and multiple analyses were defined as analysis of the same outcome variable in multiple ways. Multiplicity was examined only for the analysis of the primary end point. Main Outcomes and Measures Outcomes of interest were percentages of primary analyses that performed multiplicity adjustment of primary end points. Results Of 511 cardiovascular RCTs included in this analysis, 300 (58.7%) had some form of multiplicity; of these 300, only 85 (28.3%) adjusted for multiplicity. Intervention type and funding source had no statistically significant association with the reporting of multiplicity risk adjustment. Trials that assessed mortality vs nonmortality outcomes were more likely to contain a multiplicity risk in their primary analysis (66.3% [177 of 267] vs 50.4% [123 of 244]; P < .001), and larger trials vs smaller trials were less likely to make any adjustments for multiplicity (35.6% [52 of 146] vs 21.4% [33 of 154]; P = .001). Conclusions and Relevance Findings from this study suggest that cardiovascular RCTs published in medical journals with high impact factors demonstrate infrequent adjustments to correct for multiple comparisons in the primary end point. These parameters may be improved by more standardized reporting.This cross-sectional study assesses the prevalence of multiplicity and whether appropriate multiplicity adjustments were performed among cardiovascular randomized clinical trials published in 6 medical journals with a high impact factor.Questions What is the prevalence of multiplicity among cardiovascular randomized clinical trials published in 6 medical journals with a high impact factor, and how frequently are multiplicity adjustments made in these trials? Findings In this cross-sectional study, data were collected from the past issues of 6 journals with high impact factors published between August 1, 2015, and July 31, 2018. Of 511 cardiovascular randomized clinical trials included in this analysis, 300 had some form of multiplicity; of these 300, only 85 adjusted for multiplicity. Meaning Among contemporary cardiovascular randomized clinical trials, it appears that multiplicity adjustments are infrequently reported.