Schnurman Zane, Smith Michael L, Kondziolka Douglas
Department of Neurosurgery, NYU Langone Medical Center, New York, New York.
J Neurosurg Spine. 2016 Sep;25(3):406-14. doi: 10.3171/2016.1.SPINE151192. Epub 2016 Apr 22.
OBJECTIVE Off-label therapies are widely used in clinical practice by spinal surgeons. Some patients and practitioners have advocated for increased regulation of their use, and payers have increasingly questioned reimbursment for off-label therapies. In this study, the authors applied a model that quantifies publication data to analyze the developmental process from initial on-label use to off-label innovation, using as an example recombinant human bone morphogenetic protein 2 (rhBMP-2) because of its wide off-label use. METHODS As a case study of off-label innovation, the developmental patterns of rhBMP-2 from FDA-approved use for anterior lumbar interbody fusion to several of its off-label uses, including posterolateral lumbar fusion, anterior cervical discectomy and fusion, and posterior lumbar interbody fusion/transforaminal lumbar interbody fusion, were evaluated using the "progressive scholarly acceptance" (PSA) model. In this model, PSA is used as an end point indicating acceptance of a therapy or procedure by the relevant scientific community and is reached when the total number of peer-reviewed studies devoted to refinement or improvement of a therapy surpasses the total number assessing initial efficacy. Report characteristics, including the number of patients studied and study design, were assessed in addition to the time to and pattern of community acceptance, and results compared with previous developmental study findings. Disclosures and reported conflicts of interest for all articles were reviewed, and these data were also used in the analysis. RESULTS Publication data indicated that the acceptance of rhBMP-2 off-label therapies occurred more rapidly and with less evidence than previously studied on-label therapies. Additionally, the community appeared to respond more robustly (by rapidly changing publication patterns) to reports of adverse events than to new questions of efficacy. CONCLUSIONS The development of off-label therapies, including the influence of investigative methods, regulation, and changing perspectives, can be characterized on the basis of publication patterns. The approach and findings in this report could inform future off-label development of therapies and procedures as well as attempts to regulate off-label use.
目的 脊柱外科医生在临床实践中广泛使用未获批准的疗法。一些患者和从业者主张加强对其使用的监管，而支付方也越来越质疑未获批准疗法的报销问题。在本研究中，作者应用了一种对发表数据进行量化的模型，以分析从最初的获批使用到未获批准的创新这一发展过程，以重组人骨形态发生蛋白2（rhBMP-2）为例，因其广泛的未获批准使用情况。方法 作为未获批准创新的案例研究，使用“渐进学术接受”（PSA）模型评估了rhBMP-2从美国食品药品监督管理局（FDA）批准用于腰椎前路椎间融合术到其几种未获批准用途（包括腰椎后外侧融合、颈椎前路椎间盘切除融合术以及腰椎后路椎间融合/经椎间孔腰椎椎间融合术）的发展模式。在该模型中，PSA被用作一个终点指标，表明相关科学界对一种疗法或手术的接受程度，当致力于改进或完善一种疗法的同行评审研究总数超过评估初始疗效的研究总数时即达到该终点。除了社区接受的时间和模式外，还评估了报告特征，包括研究的患者数量和研究设计，并将结果与先前的发展研究结果进行比较。审查了所有文章的披露情况和报告的利益冲突，这些数据也用于分析。结果 发表数据表明，rhBMP-2未获批准疗法的接受速度比先前研究的获批疗法更快，且证据更少。此外，与新的疗效问题相比，社区似乎对不良事件报告的反应更为强烈（通过迅速改变发表模式）。结论 未获批准疗法的发展，包括研究方法、监管和观念变化的影响，可以根据发表模式来描述。本报告中的方法和发现可为未来疗法和手术的未获批准发展以及规范未获批准使用的尝试提供参考。
