Centre for Reviews and Dissemination, University of York, UK.
BMJ. 2013 Jun 20;346:f3981. doi: 10.1136/bmj.f3981.
To investigate whether published results of industry funded trials of recombinant human bone morphogenetic protein 2 (rhBMP-2) in spinal fusion match underlying trial data by comparing three different data sources: individual participant data, internal industry reports, and publicly available journal publications and conference abstracts.
The manufacturer of rhBMP-2 products (Medtronic; Minneapolis, MN) provided complete individual participant data and internal reports for all its studies of rhMBP-2 in spinal fusion. We identified publications and conference abstracts through comprehensive literature searches. We compared outcomes provided in the individual participant data against outcomes reported in publications. For effectiveness outcomes, we compared meta-analyses of randomised controlled trials based on each of the three data sources. For adverse events, meta-analysis of the published aggregate data was not possible and we compared the number and type of adverse events reported between data sources.
32 publications reported outcomes from 11 of the 17 existing manufacturer sponsored studies. For individual randomised controlled trials, 56% (9/16) to 88% (15/17) of effectiveness outcomes known to have been collected were reported in the published literature. Meta-analyses of effectiveness data were almost identical for pain outcomes and similar for fusion across the three data sources. A minority of adverse event data known to have been collected were reported in the published literature. Several journal articles reported only "serious," "related," or "unanticipated" adverse events, without defining these terms. Others reported a small proportion of the collected adverse event categories. Around 23% (533/2302) of the total adverse events collected in published randomised controlled trials have been reported in the literature, with randomised controlled trials evaluating the licensed preparation (Infuse) reporting around 11% (122/1108) of collected adverse events.
The published literature only partially represents the total data known to have been collected on the effects of rhBMP-2. This did not lead to substantially different results for meta-analysis of effectiveness outcomes. In contrast, reporting of adverse event data in trial publications was inadequate and inconsistent to the extent that any systematic review based solely on the publicly available data would not be able to properly evaluate the safety of rhBMP-2. Analysis of individual participant data enabled the most complete, detailed, and in-depth analysis and was not more resource intensive than extracting, collating, and analysing aggregate data from multiple trial publications and conference abstracts. Confidential internal reports presented considerably more adverse event data than publications, and in the absence of individual participant data access to these reports would support more accurate and reliable investigation, with less time and effort than relying on incomplete published data.
通过比较三种不同的数据来源：个体参与者数据、内部行业报告以及公开的期刊出版物和会议摘要，来研究产业资助的重组人骨形态发生蛋白 2（rhBMP-2）临床试验的已发表结果是否与基础试验数据相符。
rhBMP-2 产品的制造商（美敦力公司；明尼苏达州明尼阿波利斯）提供了其所有 rhMBP-2 脊柱融合研究的完整个体参与者数据和内部报告。我们通过全面的文献检索确定了出版物和会议摘要。我们将个体参与者数据中提供的结果与出版物中报告的结果进行比较。对于有效性结果，我们比较了基于这三个数据来源的随机对照试验的荟萃分析。对于不良事件，不可能对已发表的汇总数据进行荟萃分析，因此我们比较了数据来源之间报告的不良事件的数量和类型。
32 篇出版物报告了 17 项现有制造商赞助研究中的 11 项研究的结果。对于个体随机对照试验，已知已收集的有效性结果中有 56%（16/29）至 88%（17/19）在已发表的文献中报告。疼痛结果的有效性数据荟萃分析在三个数据来源中几乎相同，融合结果也相似。在已发表的文献中报告了已知已收集的少数不良事件数据。一些期刊文章仅报告了“严重”、“相关”或“意外”的不良事件，而没有定义这些术语。其他文章则报告了一小部分收集的不良事件类别。已发表的随机对照试验中，约有 23%（533/2302）的总不良事件已在文献中报告，评估许可制剂（Infuse）的随机对照试验报告了约 11%（122/1108）的已收集不良事件。
已发表的文献仅部分代表了已知已收集的 rhBMP-2 对疗效的全部数据。这并没有导致对有效性结果的荟萃分析产生显著不同的结果。相比之下，试验出版物中不良事件数据的报告不足且不一致，以至于任何仅基于公开数据的系统评价都无法正确评估 rhBMP-2 的安全性。个体参与者数据的分析能够进行最完整、详细和深入的分析，而且并不比从多个试验出版物和会议摘要中提取、整理和分析汇总数据更耗费资源。机密的内部报告提供了比出版物更多的不良事件数据，而且在没有个体参与者数据的情况下，访问这些报告将比依赖不完整的已发表数据更能支持更准确和可靠的调查，所需的时间和精力也更少。
