Department of Orthopaedics, Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, Bronx, NY 10457, USA.
J Bone Joint Surg Am. 2013 Aug 21;95(16):1450-6. doi: 10.2106/JBJS.L.00251.
Recent articles in the lay press and literature have raised concerns about the ability to report honest adverse event data from industry-sponsored spine surgery studies. To address this, clinical trials may utilize an independent Clinical Events Committee (CEC) to review adverse events and readjudicate the severity and relatedness accordingly. We are aware of no prior study that has quantified either the degree to which investigator bias is present in adverse event reporting or the effect that an independent CEC has on mitigating this potential bias.
The coflex Investigational Device Exemption study is a prospective randomized controlled trial comparing coflex (Paradigm Spine) stabilization with lumbar spinal fusion to treat spinal stenosis and spondylolisthesis. Investigators classified the severity of adverse events (mild, moderate, or severe) and their relationship to the surgery and device (unrelated, unlikely, possibly, probably, or definitely). An independent CEC, composed of three spine surgeons without affiliation to the study sponsor, reviewed and reclassified all adverse event reports submitted by the investigators.
The CEC reclassified the level of severity, relation to the surgery, and/or relation to the device in 394 (37.3%) of 1055 reported adverse events. The proportion of adverse events that underwent reclassification was similar in the coflex and fusion groups (37.9% compared with 36.0%, p = 0.56). The CEC was 5.3 (95% confidence interval [CI], 2.6 to 10.7) times more likely to upgrade than downgrade the adverse event. The CEC was 7.3 (95% CI, 5.1 to 10.6) times more likely to upgrade than downgrade the relationship to the surgery and 11.6 (95% CI, 7.5 to 18.8) times more likely to upgrade than downgrade the relationship to the device. The status of the investigator's financial interest in the company had little effect on the reclassification of adverse events.
Thirty-seven percent of adverse events were reclassified by the CEC; the large majority of the reclassifications were an upgrade in the level of severity or a designation of greater relatedness to the surgery or device.
An independent CEC can identify and mitigate potential inherent investigator bias and facilitate an accurate assessment of the safety profile of an investigational device, and a CEC should be considered a requisite component of future clinical trials.
最近在大众媒体和文献中出现的一些文章对产业赞助的脊柱外科研究报告如实不良事件数据的能力提出了担忧。为了解决这个问题，临床试验可以利用独立的临床事件委员会（CEC）来审查不良事件，并据此重新评估严重程度和相关性。我们不知道以前有哪项研究量化了研究人员在不良事件报告中的偏见程度，也不知道独立的 CEC 对减轻这种潜在偏见有何影响。
Coflex 研究设备豁免试验是一项前瞻性随机对照试验，比较了 Coflex（Paradigm Spine）稳定与腰椎融合术治疗椎管狭窄和脊椎滑脱。研究人员将不良事件的严重程度（轻度、中度或重度）及其与手术和设备的关系（无关、不太可能、可能、很可能或肯定）进行分类。一个由三位与研究赞助商没有关系的脊柱外科医生组成的独立 CEC 审查并重新分类了所有由研究人员提交的不良事件报告。
CEC 重新分类了 1055 例报告的不良事件中的 394 例（37.3%）的严重程度、与手术的关系和/或与设备的关系。在 Coflex 和融合组中，需要重新分类的不良事件比例相似（37.9%与 36.0%，p=0.56）。CEC 将不良事件升级的可能性是降级的 5.3 倍（95%置信区间[CI]，2.6 至 10.7）。CEC 将手术关系升级的可能性是降级的 7.3 倍（95%CI，5.1 至 10.6），将设备关系升级的可能性是降级的 11.6 倍（95%CI，7.5 至 18.8）。研究人员在公司的财务利益状况对不良事件的重新分类影响不大。
37%的不良事件被 CEC 重新分类；大多数重新分类是严重程度的升级，或者是手术或设备相关性的更明确指定。
独立的 CEC 可以识别和减轻潜在的固有研究人员偏见，并有助于准确评估研究设备的安全性概况，CEC 应该被视为未来临床试验的必要组成部分。
