临床试验亚组分析结果可靠性评价及监管决策影响

Credibility evaluation of subgroup analysis in clinical trials and its impact on regulatory decision

精准医学是全球医学科技发展的前沿方向,根据内外因素将患者分成不同亚组开展针对性的亚组分析,以评价不同特征人群处理效应差异,在临床研究中越来越常见。根据不同目的,亚组分析可以分为确证性亚组分析、支持性亚组分析和探索性亚组分析3种类型。亚组分析结果已成为监管部门决策适应证能否批准及批准范围的重要依据,也是申办方制定临床开发策略的参考依据。本研究将结合肿瘤免疫抑制剂2个确证性研究案例,系统比较临床试验3种亚组分析类型的特点和要求、亚组分析结果可靠性评价体系及其对监管适应证批准范围的决策影响,最后给出确证性亚组、随机化分层亚组设置等建议。研究结果可为研究者、申办方等利益相关者提供临床试验亚组设计、结果解读方面的重要参考。

Precision medicine is the frontier of the global medical technology research.It is becoming increasingly common to divide patients into different subgroups based on internal and external factors and carry out targeted analysis to evaluate treatment effect heterogeneity between different populations for a specific medical intervention.Subgroup analysis,according to different purposes,are subdivided into confirmatory,supportive and exploratory types.It has now become an important basis for both the regulatory authorities in licensing drugs and deciding the scope of indications as well as pharmaceutical company in devising clinical development strategy.Combined with two confirmatory research cases of tumor immunosuppression agents,this study compared three different types of clinical subgroup analysis regarding their characteristics and requirements systematically,showed the reliability evaluation system of subgroup analysis results,and discussed its influence on the regulatory decision on approving the scope of indication.Some critical suggestions regarding to confirmative subgroup and randomized stratified subgroup were highlighted in the end.This study can provide scientific reference for researchers,sponsors,and other stakeholders on overall considerations about design and result interpretation of subgroup analysis in clinical trials.