Background: Achieving evidence-based practice change in surgery has always been challenging, with many aspects of common clinical practice evolving through lower-level studies that are susceptible to bias and confounding rather than high-quality evidence. This challenge is even more pronounced in the setting of low-volume, high-complexity surgical oncology. Additionally, when the costs of interventions or technologies are high, designing and developing such studies within financially constrained national healthcare systems becomes even more complicated, potentially widening perceived healthcare inequalities between private and publicly funded systems. However, this is precisely the area where a lack of evidence can either hinder the development of significant new clinical advances or lead to the adoption of expensive and ineffective treatments. Here, we describe the novel approaches adopted in the design, development, and implementation of the ELECTRA trial, a randomised, controlled, double-blinded feasibility study with a planned extension to a late-phase trial.Methods: The Cancer Research UK ELECTRA (NCT05877352) trial is a three-armed randomised, controlled clinical trial designed to evaluate the incremental benefit of adding intraoperative electron beam radiotherapy (IOERT) to pelvic exenteration surgery for locally advanced and locally recurrent rectal cancer. ELECTRA is double-blinded, with patients, surgeons, and oncologists unaware of whether IOERT is administered or not. The primary feasibility outcome focuses on the ability to successfully recruit and randomise participants, while the subsequent primary outcome assesses IOERT field local control.Results: We describe the collaborative process involved in developing the trial, including national and international consultations to determine the best study design and the most optimal outcome measures to evaluate. We outline the extensive patient participation and input into the study design. Given the complexity and evolving nature of the field, with no clear international standardisations, we outline the processes used to address internationally agreed definitions, radiological standardisation, surgical learning curves, quality assurance, and pathological standardisation, as well as the broader impact and benefits of these activities. Finally, we describe the novel design utilised to facilitate the involvement of national and international units with varying levels of equipoise regarding IOERT.Conclusions: Historically, randomised clinical trials have not been the standard approach for evaluating surgical interventions due to their practical and methodological challenges, particularly in high-complexity, low-volume settings. Despite these difficulties, they remain the gold standard for evidence-based practice. The ELECTRA trial exemplifies a complex, innovative trial design that addresses an unmet need in a specialised area of high-complexity surgery. Using ELECTRA as an example, we highlight the genuine challenges in designing such complex trials and provide recommendations to facilitate the conduct of future well-designed surgical studies.
背景：在外科领域实现循证实践变革始终充满挑战，许多常见临床实践往往基于易受偏倚和混杂因素影响的低级别研究，而非高质量证据。这一挑战在低手术量、高复杂性的肿瘤外科领域尤为突出。此外，当干预措施或技术成本高昂时，在财政受限的国家医疗体系内设计和开展此类研究更为复杂，可能加剧私立与公立医疗体系间的医疗不平等。然而，正是在这一领域，证据的缺乏可能阻碍重大临床进展，或导致昂贵无效疗法的应用。本文阐述ELECTRA试验在设计、开发和实施过程中采用的新方法，该试验是一项随机对照双盲可行性研究，并计划扩展为后期阶段试验。 方法：英国癌症研究院ELECTRA试验（NCT05877352）是一项三臂随机对照临床试验，旨在评估术中电子束放疗（IOERT）联合盆腔廓清术治疗局部晚期及局部复发性直肠癌的增量效益。试验采用双盲设计，患者、外科医生和肿瘤科医生均不知晓是否实施IOERT。主要可行性终点聚焦于成功招募和随机化受试者的能力，后续主要终点则评估IOERT照射野的局部控制情况。 结果：我们详细描述了试验开发过程中的协作机制，包括通过国内外专家咨询确定最优研究设计和评估指标。概述了患者对研究设计的深度参与和贡献。鉴于该领域的高度复杂性、快速演进特性及国际标准缺失的现状，我们系统阐述了达成国际共识定义、影像学标准化、外科学习曲线管理、质量保证和病理学标准化的具体流程，以及这些工作的广泛影响与效益。最后，介绍了为促进国内外对IOERT持不同平衡观点的机构参与而采用的创新设计。 结论：历史上，由于实践和方法学上的挑战，随机临床试验并非评估外科干预措施的常规方法，在高复杂性、低手术量的领域尤其如此。尽管存在这些困难，它仍是循证实践的金标准。ELECTRA试验展示了针对高复杂性外科专科领域未满足需求的复杂创新试验设计范例。通过该案例，我们揭示了设计此类复杂试验面临的实际挑战，并为未来开展高质量外科研究提出可行性建议。
肿瘤(癌症)患者之家