Department of Clinical Pharmacy, Institute for Health Policy Studies, University of California, San Francisco, 3333 California St, Suite 420, San Francisco, CA 94118, USA.
BMJ. 2012 Jan 3;344:d7202. doi: 10.1136/bmj.d7202.
To investigate the effect of including unpublished trial outcome data obtained from the Food and Drug Administration (FDA) on the results of meta-analyses of drug trials.
Reanalysis of meta-analyses.
Drug trials with unpublished outcome data for new molecular entities that were approved by the FDA between 2001 and 2002 were identified. For each drug, eligible systematic reviews containing at least one meta-analysis were identified by searches of Medline, Embase, and the Cochrane Library in November 2010. Selection criteria Eligible systematic reviews were done after FDA approval of the drug, were published in English, and had outcomes and comparators that were the same as those of the trials with unpublished FDA trial outcomes, and the characteristics of participants in the systematic reviews were consistent with the FDA approved indication for the drug. Clinical guidelines, conference proceedings, duplicate systematic reviews, and systematic reviews in which included trials were not referenced or that combined trials across multiple drug classes were excluded. Systematic reviews using non-standard meta-analytic techniques (such as Bayesian or network meta-analyses) and those that used inappropriate or invalid methods for calculation of summary statistics (such as unweighted pooled analyses) were also excluded.
Two authors independently extracted data from both the published systematic reviews and the FDA's medical and statistical reviews of the trials submitted to FDA.
Summary statistics (risk ratios, odds ratios, or weighted mean differences) for relevant outcomes with and without unpublished FDA trial data.
42 meta-analyses (41 efficacy outcomes, one harm outcome) for nine drugs across six drug classes were reanalysed. Overall, addition of unpublished FDA trial data caused 46% (19/41) of the summary estimates from the meta-analyses to show lower efficacy of the drug, 7% (3/41) to show identical efficacy, and 46% (19/41) to show greater efficacy. The summary estimate of the single harm outcome showed more harm from the drug after inclusion of unpublished FDA trial data.
The effect of including unpublished FDA trial outcome data varies by drug and outcome. Unpublished FDA trial outcome data should be available and included in meta-analysis. Making these data easily accessible is particularly important because the effects of including unpublished data vary.
研究纳入来自食品和药物管理局（FDA）的未发表试验结局数据对药物试验荟萃分析结果的影响。
荟萃分析再分析。
2001 年至 2002 年间 FDA 批准的新型分子实体药物的未发表结局数据的试验。在 2010 年 11 月，通过对 Medline、Embase 和 Cochrane Library 的检索，确定了每个药物的合格系统评价，这些评价至少包含一项荟萃分析。每个药物的入选标准是：在药物获得 FDA 批准后进行的合格系统评价、以英文发表、结局和对照与未发表的 FDA 试验结局的试验相同，并且系统评价中参与者的特征与 FDA 批准的药物适应证一致。排除临床试验指南、会议论文集、重复系统评价、以及未引用纳入试验或合并多个药物类别的系统评价。排除使用非标准荟萃分析技术（如贝叶斯或网络荟萃分析）和不适当或无效的汇总统计计算方法（如未加权的合并分析）的系统评价。
两位作者独立地从已发表的系统评价和 FDA 对提交给 FDA 的试验的医学和统计学评价中提取数据。
纳入和不纳入未发表的 FDA 试验数据时相关结局的汇总统计数据（风险比、优势比或加权均数差）。
再分析了 9 种药物 6 个药物类别的 42 项荟萃分析（41 项疗效结局，1 项不良结局）。总体而言，纳入未发表的 FDA 试验数据后，41 项荟萃分析的汇总估计值中有 46%（19/41）显示药物的疗效降低，7%（3/41）显示疗效相同，46%（19/41）显示疗效增加。纳入未发表的 FDA 试验数据后，单一不良结局的汇总估计值显示药物的不良事件更多。
纳入未发表的 FDA 试验结局数据的效果因药物和结局而异。未发表的 FDA 试验结局数据应可用并纳入荟萃分析。使这些数据易于获取尤其重要，因为纳入未发表数据的效果不同。
