Supplementary materials: Increasing transparency in indirect treatment comparisons: is selecting effect modifiers the missing part of the puzzle? A review of methodological approaches and critical considerations

These are peer-reviewed supplementary materials for the article 'Increasing transparency in indirect treatment comparisons: is selecting effect modifiers the missing part of the puzzle? A review of methodological approaches and critical considerations' published in the Journal of Comparative Effectiveness Research.Supplementary Table 1: Combined Embase and MEDLINE Search (via Ovid)Supplementary Table 2: Health Technology Assessment Submission Search StrategySupplementary Table 3: Included Published Indirect Treatment ComparisonsFailure to adjust for effect modifiers (EMs) in indirect treatment comparisons (ITCs) can produce biased and uncertain effect estimates. This is particularly important for health technology assessments (HTAs), where the availability of new treatments is based on comparative effectiveness results. Much emphasis has been placed on advancing ITC methods to adjust for EMs, yet whether EMs are appropriately identified for the conduct of ITCs in the first place is unclear. To understand the extent of guidance and requirements for the selection of EMs for ITCs currently available and if and how this guidance is applied in practice, a series of pragmatic reviews of guidance documents from HTA and non-payer organizations, primary published ITC analyses, and prior HTA submissions in two indications (non-small cell lung cancer and psoriasis) was conducted. The reviews showed that current ITC guidance mainly focused on developing analytical methods to adjust for EMs. Some organizations, such as HTA bodies in the UK, France and Germany, recommended the use of literature reviews, expert opinion and statistical methods to identify EMs. No detailed guidance on the selection process or the appropriate literature review approach was found. Similar trends were identified through the database search and review of prior HTA submissions; only few published ITCs and submissions included information on the EM selection process which was either based on findings from the literature, trial subgroup analyses, or clinical input. No reference to a systematic selection approach was found. There is an urgent need to fill the guidance gap identified across the reviews by including a step in ITC guidelines on how EMs should be identified through systematic reviews, formal expert elicitation, and a quantitative assessment of the EM distribution. Researchers and manufacturers are also encouraged to improve transparent reporting and justification of their selection of EMs to allow for an independent review of the set of factors being considered for adjustment. Both will

此为发表于《比较疗效研究杂志》的论文《提高间接治疗比较的透明度：选择效应修饰因子是否是拼图缺失的一环？方法学途径及批判性思考》的同行评审补充材料。补充表1：通过Ovid检索的Embase和MEDLINE联合搜索；补充表2：健康技术评估提交搜索策略；补充表3：纳入的已发表间接治疗比较。在间接治疗比较（ITC）中未能调整效应修饰因子（EMs）可能导致偏差和不确定的效果估计。这对于健康技术评估（HTAs）尤为重要，因为新治疗方法的可用性基于比较疗效的结果。大量研究着重于推进ITC方法以调整EMs，然而，是否能够适当地识别EMs以进行ITC尚不明确。为了理解目前关于选择ITC中EMs的指导和要求的范围，以及这些指导在实际中的应用情况，本研究对来自HTA和非付费组织的指导文件、已发表的ITC分析和两个适应症（非小细胞肺癌和银屑病）的先前HTA提交进行了一系列实用性的回顾。回顾结果显示，当前的ITC指导主要集中于发展调整EMs的分析方法。一些组织，如英国、法国和德国的HTA机构，建议使用文献综述、专家意见和统计方法来识别EMs。未找到关于选择过程或适当文献综述方法的详细指导。通过数据库搜索和先前HTA提交的回顾也发现了类似趋势；只有少数发表的ITC和提交包含了关于EM选择过程的信息，这些信息或基于文献发现、试验亚组分析，或临床输入。未发现关于系统性选择方法的参考。迫切需要通过在ITC指南中增加一个步骤，关于如何通过系统综述、正式专家征询和EM分布的定量评估来识别EMs，来填补回顾中发现的指导差距。同时，鼓励研究人员和制造商提高其对EMs选择的透明度报告和论证，以允许对考虑调整的因素集进行独立审查。双方都将