Flacco Maria Elena, Manzoli Lamberto, Boccia Stefania, Capasso Lorenzo, Aleksovska Katina, Rosso Annalisa, Scaioli Giacomo, De Vito Corrado, Siliquini Roberta, Villari Paolo, Ioannidis John P A
Department of Medicine and Aging Sciences, University of Chieti, Via dei Vestini 5, 66013 Chieti, Italy; Regional Healthcare Agency of the Abruzzo Region, Via Attilio Monti 9, 65127 Pescara, Italy.
Department of Medicine and Aging Sciences, University of Chieti, Via dei Vestini 5, 66013 Chieti, Italy; Regional Healthcare Agency of the Abruzzo Region, Via Attilio Monti 9, 65127 Pescara, Italy; CEsI Biotech, Foundation "Università G. d'Annunzio" of Chieti, Via dei Vestini 31, 66013 Chieti, Italy.
J Clin Epidemiol. 2015 Jul;68(7):811-20. doi: 10.1016/j.jclinepi.2014.12.016. Epub 2015 Feb 7.
To map the current status of head-to-head comparative randomized evidence and to assess whether funding may impact on trial design and results.
From a 50% random sample of the randomized controlled trials (RCTs) published in journals indexed in PubMed during 2011, we selected the trials with ≥ 100 participants, evaluating the efficacy and safety of drugs, biologics, and medical devices through a head-to-head comparison.
We analyzed 319 trials. Overall, 238,386 of the 289,718 randomized subjects (82.3%) were included in the 182 trials funded by companies. Of the 182 industry-sponsored trials, only 23 had two industry sponsors and only three involved truly antagonistic comparisons. Industry-sponsored trials were larger, more commonly registered, used more frequently noninferiority/equivalence designs, had higher citation impact, and were more likely to have "favorable" results (superiority or noninferiority/equivalence for the experimental treatment) than nonindustry-sponsored trials. Industry funding [odds ratio (OR) 2.8; 95% confidence interval (CI): 1.6, 4.7] and noninferiority/equivalence designs (OR 3.2; 95% CI: 1.5, 6.6), but not sample size, were strongly associated with "favorable" findings. Fifty-five of the 57 (96.5%) industry-funded noninferiority/equivalence trials got desirable "favorable" results.
The literature of head-to-head RCTs is dominated by the industry. Industry-sponsored comparative assessments systematically yield favorable results for the sponsors, even more so when noninferiority designs are involved.
梳理直接比较的随机对照证据的现状，并评估资金资助是否会影响试验设计和结果。
从2011年发表在PubMed索引期刊上的随机对照试验（RCT）中抽取50%的随机样本，我们选择了受试者≥100名的试验，通过直接比较来评估药物、生物制品和医疗器械的疗效和安全性。
我们分析了319项试验。总体而言，289,718名随机受试者中的238,386名（82.3%）纳入了由公司资助的182项试验。在182项由行业资助的试验中，只有23项有两个行业赞助商，只有三项涉及真正的对抗性比较。与非行业资助的试验相比，行业资助的试验规模更大，更常进行注册，更频繁地使用非劣效性/等效性设计，具有更高的引用影响力，并且更有可能获得“有利”结果（试验治疗的优越性或非劣效性/等效性）。行业资助[优势比（OR）2.8；95%置信区间（CI）：1.6, 4.7]和非劣效性/等效性设计（OR 3.2；95%CI：1.5, 6.6），而非样本量，与“有利”结果密切相关。57项由行业资助的非劣效性/等效性试验中的55项（96.5%）获得了理想的“有利”结果。
直接比较的随机对照试验文献以行业为主导。行业资助的比较评估系统地为赞助商产生有利结果，在涉及非劣效性设计时更是如此。
