Exploring treatment by covariate interactions using subgroup analysis and meta-regression in cochrane reviews: a review of recent practice

Sarah Donegan, Lisa Williams, Sofia Dias, Catrin Tudur-Smith, Nicky Welton

Research output: Contribution to journalArticle (Academic Journal)peer-review

21 Citations (Scopus)
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BACKGROUND: Treatment by covariate interactions can be explored in reviews using interaction analyses (e.g., subgroup analysis). Such analyses can provide information on how the covariate modifies the treatment effect and is an important methodological approach for personalising medicine. Guidance exists regarding how to apply such analyses but little is known about whether authors follow the guidance.

METHODS: Using published recommendations, we developed criteria to assess how well interaction analyses were designed, applied, interpreted, and reported. The Cochrane Database of Systematic Reviews was searched (8th August 2013). We applied the criteria to the most recently published review, with an accessible protocol, for each Cochrane Review Group. We excluded review updates, diagnostic test accuracy reviews, withdrawn reviews, and overviews of reviews. Data were summarised regarding reviews, covariates, and analyses.

RESULTS: Each of the 52 included reviews planned or did interaction analyses; 51 reviews (98%) planned analyses and 33 reviews (63%) applied analyses. The type of analysis planned and the type subsequently applied (e.g., sensitivity or subgroup analysis) was discrepant in 24 reviews (46%). No review reported how or why each covariate had been chosen; 22 reviews (42%) did state each covariate a priori in the protocol but no review identified each post-hoc covariate as such. Eleven reviews (21%) mentioned five covariates or less. One review reported planning to use a method to detect interactions (i.e., interaction test) for each covariate; another review reported applying the method for each covariate. Regarding interpretation, only one review reported whether an interaction was detected for each covariate and no review discussed the importance, or plausibility, of the results, or the possibility of confounding for each covariate.

CONCLUSIONS: Interaction analyses in Cochrane Reviews can be substantially improved. The proposed criteria can be used to help guide the reporting and conduct of analyses.

Original languageEnglish
Article numbere0128804
Number of pages17
JournalPLoS ONE
Issue number6
Publication statusPublished - 1 Jun 2015

Structured keywords

  • ConDuCT-II


Dive into the research topics of 'Exploring treatment by covariate interactions using subgroup analysis and meta-regression in cochrane reviews: a review of recent practice'. Together they form a unique fingerprint.
  • ConDuCT-II

    Blazeby, J.


    Project: Research

  • Sarah Donegan MRC Fellowship

    Welton, N. J.


    Project: Research


    Welton, N. J.


    Project: Research

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