Evidence-Based Practice Center, Kern Center for the Science of Healthcare Delivery, Mayo Clinic, 200 First ST SW, Rochester, MN, 55905, USA.
Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
BMC Med Res Methodol. 2024 Nov 1;24(1):263. doi: 10.1186/s12874-024-02388-y.
The current practice in guideline development is to use the control group event rate (CR) as a surrogate of baseline risk and to assume portability of the relative treatment effect across populations with low, moderate and high baseline risk. We sought to emulate this practice in a very large sample of meta-analyses.
We retrieved data from all meta-analyses published in the Cochrane Database of Systematic Reviews (2003-2020) that evaluated a binary outcome, reported 2 × 2 data for each individual study and included at least 4 studies. We excluded studies with no events. We conducted meta-analyses with odds ratios and relative risks and performed subgroup analyses based on tertiles of CR. In sensitivity analyses, we evaluated the use of total event rate (TR) instead of CR and using quartiles instead of tertiles.
The analysis included 2,531 systematic reviews (27,692 meta-analyses, 226,975 studies, 25,669,783 patients).The percentages of meta-analyses with statistically significant interaction (P < 0.05) based on CR tertile or quartile ranged 12-18% across various sensitivity analyses. This percentage increased as the number of studies or range of CR per meta-analysis increased, reflecting increased power of the subgroup test. The percentages of meta-analyses with statistically significant interaction (P < 0.05) with TR quantiles were lower than those with CR but remained higher than expected by chance.
This analysis suggests that when CR or TR are used as surrogates for baseline risk, relative treatment effects may not be portable across populations with varying baseline risks in many meta-analyses. Categroization of the continuous CR variable and not addressing measurement error limit inferences from such analyses and imply that CR is an undesirable source for baseline risk. Guideline developers and decision-makers should be provided with relative and absolute treatment effects that are conditioned on the baseline risk or derived from studies with similar baseline risk to their target populations.
目前，指南制定的实践是将对照组事件发生率（CR）作为基线风险的替代指标，并假定相对治疗效果在低、中、高基线风险人群中具有可转移性。我们试图在一个非常大的荟萃分析样本中模拟这种做法。
我们从 Cochrane 系统评价数据库（2003-2020 年）中检索所有发表的评估二分类结局的荟萃分析数据，报告了每个单独研究的 2×2 数据，并至少包含 4 项研究。我们排除了没有事件的研究。我们进行了荟萃分析，使用优势比和相对风险，并根据 CR 的三分位数进行了亚组分析。在敏感性分析中，我们评估了使用总事件发生率（TR）替代 CR 和使用四分位数替代三分位数的效果。
分析包括 2531 项系统评价（27692 项荟萃分析，226975 项研究，25669783 名患者）。基于 CR 三分位数或四分位数的荟萃分析中具有统计学意义交互作用（P<0.05）的百分比在各种敏感性分析中为 12-18%。随着研究数量或每荟萃分析 CR 的范围增加，亚组检验的效力增加，该百分比增加。使用 TR 分位数的荟萃分析中具有统计学意义交互作用（P<0.05）的百分比低于 CR，但仍高于预期的随机效应。
这项分析表明，当 CR 或 TR 被用作基线风险的替代指标时，在许多荟萃分析中，相对治疗效果可能不会在基线风险不同的人群中具有可转移性。连续 CR 变量的分类和未解决测量误差限制了对这些分析的推论，并暗示 CR 是基线风险的不理想来源。指南制定者和决策者应该提供基于基线风险的相对和绝对治疗效果，或者从与目标人群具有相似基线风险的研究中得出这些效果。
