Prespecification of subgroup analyses and examination of treatment-subgroup interactions in cancer individual participant data meta-analyses are suboptimal

Ya Gao, Ming Liu, Shuzhen Shi, Mingming Niu, Jiang Li, Junhua Zhang, Fujian Song, Jinhui Tian

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Objectives: This study aimed to explore the prespecification and conduct of subgroup analyses in cancer individual participant data meta-analyses (IPDMAs). Study Design and Setting: We searched PubMed,, Cochrane Library, and Web of Science to identify IPDMAs of randomized controlled trials evaluating intervention effects for cancer. We evaluated how often cancer IPDMAs prespecify subgroup analyses and statistical approaches for examining treatment-subgroup interactions and handling continuous subgroup variables. Results: We included 89 IPDMAs, of which 41 (46.1%) reported a statistically significant treatment-subgroup interaction (P < 0.05) in at least one subgroup analysis. 47 (52.8%) IPDMAs prespecified methods for conducting subgroup analyses and the remaining 42 (47.2%) did not prespecify subgroup analyses. Of the 47 IPDMAs prespecified subgroup analyses, 19 performed the planned subgroup analyses, 21 added subgroup analyses, 7 reduced subgroup analyses. Eighty IPDMAs examined treatment-subgroup interactions, but 72 IPDMAs did not provide enough information to determine whether an appropriate approach that avoided aggregation bias was used. 85 IPDMAs that used continuous variables in subgroup analyses categorized continuous variables and only 1 IPDMA examined non-linear relationships. Conclusion: Many cancer IPDMAs did not prespecify subgroup analyses, nor did they fully perform planned subgroup analyses. Lack of details for the test of treatment-subgroup interactions and examination of non-linear interactions was suboptimal.

Original languageEnglish
Pages (from-to)156-167
Number of pages12
JournalJournal of Clinical Epidemiology
Early online date26 Jun 2021
Publication statusPublished - 1 Oct 2021


  • Individual participant data meta-analysis
  • Methodology
  • Neoplasm
  • Prespecification
  • Subgroup analysis
  • Treatment-subgroup interaction

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