Clinically-Integrated Randomized Trial of Radical Prostatectomy

描述（由申请人提供）：最近出现的大量证据表明，不同外科医生的癌症手术结果差异很大。外科医生之间的结果差异的大小通常与我们对辅助化疗等治疗的期望相当。外科医生之间的结果差异很可能至少部分归因于手术技术的可识别方面。这表明比较不同手术技术的随机试验是有价值的；然而，这类试验缺乏。这与实施有充分动力的研究所面临的严峻实际挑战有关。在这一建议中，我们提出了一种新的方法——“临床综合随机试验”——用于外科研究。这是通过系统地识别与手术试验相关的问题而发展起来的。核心原则是，无论随机化与否，病人、医生和其他医院工作人员的经历实际上是无法区分的。特别是，由于结果数据直接从患者电子病历中获得，因此不需要繁琐的问卷调查、表格或其他程序。临床综合随机试验的其他关键方面包括：最低资格标准；将每个患者随机化，作为临床护理的常规部分；使用单一的“主”协议；析因设计可以同时评估手术技术的几种修改。我们建议试点一项临床综合随机试验，在单一机构测试根治性前列腺切除术的三种修改。这将提供“原则性证据”，证明可以以低成本进行高应计率的癌症手术试验。该提案得到了主办机构外科领导的热情支持，外科主席担任该资助的主要研究者和IRB方案的共同发起人。公共卫生相关性：大量证据表明，不同外科医生的癌症手术结果差异很大，可能是由于手术技术的差异。然而，目前还缺乏比较不同癌症手术技术的随机试验。我们提出了一种新的外科研究方法，通过系统地识别与手术试验相关的实际问题。我们打算在一项比较前列腺根治术的试验中试点这种方法。

DESCRIPTION (provided by applicant): Copious evidence has recently emerged to suggest that the outcomes of cancer surgery vary importantly between different surgeons. The magnitude of the difference in outcome between surgeons is often comparable to that we expect from treatments such as adjuvant chemotherapy. It is likely that differences in outcome between surgeons are attributable, at least in part, to identifiable aspects of surgical technique. This suggests that randomized trials to compare different surgical techniques would be of value; there is, however, a dearth of such trials. This is related to the serious practical challenges associated with implementing adequately powered studies. In this proposal, we propose a novel methodology - the "clinically-integrated randomized trial" - for surgery research. This has been developed by systematic identification of the problems associated with surgery trials. The core principle is that the experience of the patient, doctor and other hospital staff is virtually indistinguishable irrespective of randomization. In particular, because outcome data are obtained directly from the patient electronic medical record, there is no requirement for burdensome questionnaires, forms or other procedures. Other key aspects of the clinically-integrated randomized trial include: minimal eligibility criteria; randomization of every patient as a routine part of clinical care; the use of a single "master" protocol; factorial design such that several modifications to surgical technique can be evaluated simultaneously. We propose to pilot a clinically-integrated randomized trial testing three modifications to radical prostatectomy at a single institution. This would provide "proof of principle" that trials on cancer surgery with high accrual rates can be conducted at low cost. The proposal has the enthusiastic support from the surgical leadership at the host institution, with the Chair of Surgery acting as key investigator of this grant and co-PI of the IRB protocol. PUBLIC HEALTH RELEVANCE: This is copious evidence that the outcomes of cancer surgery vary importantly between surgeons, likely due to differences in surgical technique. Yet there is dearth of randomized trials comparing different techniques of cancer surgery. We propose a novel methodology for surgery research developed by systematic identification of the practical problems associated with surgery trials. We intend to pilot this methodology in a trial comparing modifications to radical prostatectomy.