Oregon Health & Science University and Portland Veterans Affairs Medical Center, Portland, OR 97239, USA.
Ann Intern Med. 2013 Jun 18;158(12):890-902. doi: 10.7326/0003-4819-158-12-201306180-00006.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is used as a bone graft substitute in spinal fusion, which unites (fuses) bones in the spine. The accuracy and completeness of journal publications of industry-sponsored trials on the effectiveness and harms of rhBMP-2 has been called into question.
To independently assess the effectiveness and harms of rhBMP-2 in spinal fusion and reporting bias in industry-sponsored journal publications.
Individual-patient data (IPD) from 17 industry-sponsored studies; related internal documents; and searches of MEDLINE (1996 to August 2012), other databases, and reference lists.
Randomized, controlled trials (RCTs) and cohort studies of rhBMP-2 versus any control and uncontrolled studies of harms.
Effectiveness outcomes in IPD were recalculated using consistent definitions. Study characteristics and results were abstracted by 1 investigator and confirmed by another. Two investigators independently assessed quality using predefined criteria.
Thirteen RCTs and 31 cohort studies were included. For lumbar spine fusion, rhBMP-2 and iliac crest bone graft were similar in overall success, fusion, and other effectiveness measures and in risk for any adverse event, although rates were high across interventions (77% to 93% at 24 months from surgery). For anterior lumbar interbody fusion, rhBMP-2 was associated with nonsignificantly increased risk for retrograde ejaculation and urogenital problems. For anterior cervical spine fusion, rhBMP-2 was associated with increased risk for wound complications and dysphagia. At 24 months, the cancer risk was increased with rhBMP-2 (risk ratio, 3.45 [95% CI, 1.98 to 6.00]), but event rates were low and cancer was heterogeneous. Early journal publications misrepresented the effectiveness and harms through selective reporting, duplicate publication, and underreporting.
Outcome assessment was not blinded, and ascertainment of harms in trials was poor. No trials were truly independent of industry sponsorship.
In spinal fusion, rhBMP-2 has no proven clinical advantage over bone graft and may be associated with important harms, making it difficult to identify clear indications for rhBMP-2. Earlier disclosure of all relevant data would have better informed clinicians and the public than the initial published trial reports did.
Yale University and Medtronic.
重组人骨形态发生蛋白-2（rhBMP-2）被用作脊柱融合中的骨移植替代物，可使脊柱中的骨骼融合。行业赞助的临床试验关于 rhBMP-2 的有效性和危害的期刊出版物的准确性和完整性受到了质疑。
独立评估 rhBMP-2 在脊柱融合中的有效性和危害，以及行业赞助期刊出版物中的报告偏倚。
17 项行业赞助研究的个体患者数据（IPD）；相关内部文件；以及 MEDLINE（1996 年至 2012 年 8 月）、其他数据库和参考文献列表的检索。
rhBMP-2 与任何对照的随机对照试验（RCT）和队列研究，以及危害的未对照研究。
使用一致的定义重新计算 IPD 中的有效性结果。由一名调查员提取研究特征和结果，并由另一名调查员确认。两名调查员使用预先确定的标准独立评估质量。
共纳入 13 项 RCT 和 31 项队列研究。对于腰椎融合，rhBMP-2 和髂嵴骨移植物在总体成功率、融合和其他有效性指标以及任何不良事件风险方面相似，尽管各干预措施的发生率均较高（手术 24 个月时为 77%至 93%）。对于前路腰椎椎间融合术，rhBMP-2 与逆行性射精和泌尿生殖问题的风险增加无关。对于前路颈椎融合术，rhBMP-2 与伤口并发症和吞咽困难的风险增加有关。在 24 个月时，rhBMP-2 增加了癌症风险（风险比，3.45 [95%CI，1.98 至 6.00]），但事件发生率较低，且癌症呈异质性。早期期刊出版物通过选择性报告、重复发表和漏报歪曲了有效性和危害。
结局评估未设盲，试验中危害的确定较差。没有真正独立于行业赞助的试验。
在脊柱融合中，rhBMP-2 与骨移植物相比没有明显的临床优势，并且可能与重要的危害有关，这使得难以确定 rhBMP-2 的明确适应证。与最初发表的试验报告相比，更早地披露所有相关数据将使临床医生和公众获得更好的信息。
耶鲁大学和美敦力。
