The conceptual framework of pragmatism in clinical trials is explored using the American Society of Clinical Oncology's pragmatic, non-randomized, phase II, multi-center basket clinical trial, the Targeted Agent and Profiling Utilization Registry Study (NCT02693535) as a model. The Targeted Agent and Profiling Utilization Registry Study aims to identify signals of drug activity when Food and Drug Administration approved drugs are matched to pre-specified genomic targets in patients with advanced cancer outside of their approved indication(s). The objectives of the study are to generate evidence of potential signals of activity in targeted therapies prescribed in an off-label setting as well as to expose and educate community cancer centers to genomic testing and precision medicine through the study protocol. The principles of pragmatic trial design can be applied across a broad spectrum of evidence-generation strategies, from explanatory trials to real-world evidence studies, and are briefly discussed. American Society of Clinical Oncology's Targeted Agent and Profiling Utilization Registry Study falls closer to the pragmatic end of this spectrum as it seeks to assess the efficacy of Food and Drug Administration approved drugs used outside their approved indications under usual care conditions, yielding results generalizable to the population that would likely receive the intervention in practice, while still adhering to rigorous data quality standards. The Targeted Agent and Profiling Utilization Registry Study's pragmatic objectives, characteristics, strengths, and limitations in its implementation are discussed and demonstrate that a large, multi-center, precision medicine basket trial can be mounted in the context of community practice and can generate clinically useful information with minimal burden to patients and clinical trial sites.

中文翻译：

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靶向药物和分析利用登记研究：一项实用的临床试验。

以美国临床肿瘤学会的实用性、非随机、II 期、多中心篮子临床试验、靶向药物和分析利用登记研究 (NCT02693535) 作为模型，探讨了临床试验中实用主义的概念框架。靶向药物和分析利用登记研究旨在当美国食品和药物管理局批准的药物与批准适应症之外的晚期癌症患者的预先指定的基因组靶标相匹配时，识别药物活性信号。该研究的目的是生成在标签外环境中规定的靶向治疗的潜在活性信号的证据，并通过研究方案向社区癌症中心公开和教育基因组测试和精准医学。实用试验设计的原则可以应用于广泛的证据生成策略，从解释性试验到现实世界的证据研究，并对此进行了简要讨论。美国临床肿瘤学会的靶向药物和分析利用登记研究更接近这一范围的务实一端，因为它旨在评估食品和药物管理局批准的药物在常规护理条件下在其批准的适应症之外使用的疗效，产生的结果可推广到可能在实践中接受干预的人群，同时仍然遵守严格的数据质量标准。讨论了靶向药物和分析利用登记研究的务实目标、特点、优势和实施中的局限性，并证明大型、多中心、精准药物篮试验可以在社区实践的背景下进行，并可以产生临床上有用的结果信息对患者和临床试验地点的负担最小。