Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California, United States of America.
Department of Clinical Pharmacy, University of California San Francisco, San Francisco, California, United States of America ; Institute for Health Policy Studies, University of California San Francisco, San Francisco, California, United States of America.
PLoS Biol. 2014 Jan;12(1):e1001770. doi: 10.1371/journal.pbio.1001770. Epub 2014 Jan 21.
Industry-sponsored clinical drug studies are associated with publication of outcomes that favor the sponsor, even when controlling for potential bias in the methods used. However, the influence of sponsorship bias has not been examined in preclinical animal studies. We performed a meta-analysis of preclinical statin studies to determine whether industry sponsorship is associated with either increased effect sizes of efficacy outcomes and/or risks of bias in a cohort of published preclinical statin studies. We searched Medline (January 1966-April 2012) and identified 63 studies evaluating the effects of statins on atherosclerosis outcomes in animals. Two coders independently extracted study design criteria aimed at reducing bias, results for all relevant outcomes, sponsorship source, and investigator financial ties. The I(2) statistic was used to examine heterogeneity. We calculated the standardized mean difference (SMD) for each outcome and pooled data across studies to estimate the pooled average SMD using random effects models. In a priori subgroup analyses, we assessed statin efficacy by outcome measured, sponsorship source, presence or absence of financial conflict information, use of an optimal time window for outcome assessment, accounting for all animals, inclusion criteria, blinding, and randomization. The effect of statins was significantly larger for studies sponsored by nonindustry sources (-1.99; 95% CI -2.68, -1.31) versus studies sponsored by industry (-0.73; 95% CI -1.00, -0.47) (p value<0.001). Statin efficacy did not differ by disclosure of financial conflict information, use of an optimal time window for outcome assessment, accounting for all animals, inclusion criteria, blinding, and randomization. Possible reasons for the differences between nonindustry- and industry-sponsored studies, such as selective reporting of outcomes, require further study.
行业赞助的临床药物研究与有利于赞助商的研究结果的发表有关，即使在控制使用方法中的潜在偏倚的情况下也是如此。然而，在临床前动物研究中尚未研究过赞助偏见的影响。我们对临床前他汀类药物研究进行了荟萃分析，以确定在已发表的临床前他汀类药物研究队列中，行业赞助是否与疗效结果的效应大小增加和/或偏倚风险增加有关。我们检索了 Medline（1966 年 1 月至 2012 年 4 月），并确定了 63 项评估他汀类药物对动物动脉粥样硬化结果影响的研究。两位编目员独立提取了旨在减少偏倚的研究设计标准，所有相关结果，赞助来源和研究者财务关系的结果。使用 I(2)统计量检查异质性。我们为每个结果计算了标准化均数差（SMD），并在研究间汇总数据以使用随机效应模型估算汇总平均 SMD。在预先设定的亚组分析中，我们根据所测量的结果，赞助来源，是否存在财务冲突信息，是否使用评估结果的最佳时间窗口，是否考虑所有动物，纳入标准，盲法和随机化来评估他汀类药物的疗效。与行业赞助的研究相比（-0.73；95％CI-1.00，-0.47），非行业赞助的研究（-1.99；95％CI-2.68，-1.31）的他汀类药物的效果明显更大（p<0.001）。披露财务冲突信息，使用评估结果的最佳时间窗口，考虑所有动物，纳入标准，盲法和随机化均不影响他汀类药物的疗效。非行业赞助和行业赞助研究之间差异的可能原因，例如选择性报告结果，需要进一步研究。
