PDF(Pubmed)
Abstract：
Biomarkers can guide precision medicine in clinical trials and practice. They can increase clinical trials\' efficiency through selection of study populations more likely to benefit from treatment, thus increasing statistical power and reducing sample size requirements or study duration. We performed a narrative synthesis to explore biomarker utilization for patient selection to guide precision medicine trials in marketing authorization dossiers of centrally approved medicines in Europe between 2018 and 2020 and analyzed in-depth those that eventually included biomarkers in the medicines\' indications. From 119 eligible products, 26 included a biomarker in the indication, of which most were oncology products (n = 15). Included biomarkers were often known from literature or from previously approved products in the European Union or the United States. Additionally, 52 dossiers mentioned one or more biomarkers for patient selection in their clinical efficacy and safety information. Although these were not always included in the medicines\' indication, they were often implicitly embedded in condition definitions adopted from clinical guidelines or practice. In 15 out of the 26 medicines with a biomarker-guided indication, only biomarker-positive populations were included in the main clinical studies supporting the marketing authorization. These studies were mostly randomized controlled trials or single-arm trials; only two products were studied for multiple indications in an innovative basket trial. Definitions of biomarkers could be subject of debate and needed adaptation after post hoc analyses requested by the assessment committee in four cases, stressing the importance of thorough justification of these definitions to include the right population for an optimal benefit-risk balance, enabling precise medicine.
摘要：
生物标志物可以指导精准医学的临床试验和实践。他们可以通过选择更有可能从治疗中受益的研究人群来提高临床试验的效率，从而提高统计能力，减少样本量要求或研究持续时间。我们进行了叙述性综合，以探索生物标志物在患者选择中的应用，以指导2018年至2020年间在欧洲集中批准的药物的上市授权档案中的精准医学试验，并深入分析了最终将生物标志物纳入药物适应症的药物。从119个合格产品中，26在适应症中包括生物标志物，其中大多数是肿瘤产品（n=15）。包括的生物标志物通常从文献或从欧盟或美国的先前批准的产品中得知。此外,52个档案在其临床疗效和安全性信息中提到了用于患者选择的一种或多种生物标志物。虽然这些并不总是包括在药物适应症中，它们通常隐含在临床指南或实践中采用的疾病定义中.在26种具有生物标志物指导适应症的药物中，有15种，仅生物标志物阳性人群被纳入支持上市许可的主要临床研究.这些研究大多是随机对照试验或单臂试验；在一项创新的篮式试验中，仅研究了两种产品的多种适应症。生物标志物的定义可能是辩论的主题，需要在评估委员会在四个案例中进行事后分析后进行调整。强调必须对这些定义进行彻底论证，以包括正确的人群，以实现最佳的利益-风险平衡，使精确的药物。
