Ma Christopher, Panaccione Remo, Fedorak Richard N, Parker Claire E, Khanna Reena, Levesque Barrett G, Sandborn William J, Feagan Brian G, Jairath Vipul
Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.
Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
BMJ Open. 2017 Jun 9;7(6):e016146. doi: 10.1136/bmjopen-2017-016146.
Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel disease (IBD), are chronic, progressive and disabling disorders of the gastrointestinal tract. Although data from randomised controlled trials (RCTs) provide the foundation of evidence that validates medical therapy for IBD, considerable heterogeneity exists in the measured outcomes used in these studies. Furthermore, in recent years, there has been a paradigm shift in IBD treatment targets, moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance, inflammatory biomarkers and histological and radiographic end points. The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development. Accordingly, there exists a need to harmonise measures used in clinical trials through the development of a core outcome set (COS).
The development of an IBD-specific COS includes four steps. First, a systematic literature review is performed to identify outcomes previously used in IBD RCTs. Second, semistructured qualitative interviews are conducted with key stakeholders, including patients, clinicians, researchers, pharmaceutical industry representatives, healthcare payers and regulators to identify additional outcomes of importance. Using the outcomes generated from literature review and stakeholder interviews, an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials.
Given that over 30 novel therapeutic compounds are in development for IBD treatment, the design of robust clinical trials measuring relevant and standardised outcomes is crucial. Standardising outcomes through a COS will reduce heterogeneity in trial reporting, facilitate valid comparisons of new therapies and improve clinical trial quality.
克罗恩病（CD）和溃疡性结肠炎（UC）是炎症性肠病（IBD）的主要形式，是胃肠道的慢性、进行性和致残性疾病。尽管随机对照试验（RCT）的数据为验证IBD药物治疗的证据提供了基础，但这些研究中所使用的测量结果存在相当大的异质性。此外，近年来，IBD治疗目标发生了范式转变，从基于症状的评分转向炎症客观指标的改善或正常化，如内镜表现、炎症生物标志物以及组织学和影像学终点。新治疗选择的丰富和不断演变的终点给参与药物研发的所有利益相关者带来了机遇和挑战。因此，有必要通过制定核心结局集（COS）来统一临床试验中使用的测量指标。
特定于IBD的COS的制定包括四个步骤。首先，进行系统的文献综述，以确定先前在IBD RCT中使用的结局。其次，与关键利益相关者进行半结构化定性访谈，这些利益相关者包括患者、临床医生、研究人员、制药行业代表、医疗保健支付方和监管机构，以确定其他重要结局。利用文献综述和利益相关者访谈产生的结局，进行两轮国际德尔菲调查，以确定纳入COS的结局的优先级。最后，召开共识会议，批准COS并传播研究结果，以便在未来的IBD试验中应用。
鉴于有30多种新型治疗化合物正在研发用于IBD治疗，设计测量相关且标准化结局的稳健临床试验至关重要。通过COS使结局标准化将减少试验报告中的异质性，促进新疗法的有效比较并提高临床试验质量。
