Reporting of heterogeneity of treatment effect in cohort studies: a review of the literature

BACKGROUND This article corresponds to a literature review and analyze how heterogeneity of treatment (HTE) is reported and addressed in cohort studies and to evaluate the use of the different measures to HTE analysis. METHODS prospective cohort studies, in English language, measuring the effect of a treatment (pharmacological, interventional, or other) published among 119 core clinical journals (defined by the National Library of Medicine) in the last 16 years were selected in the following data source: Medline. One reviewer randomly sampled journal articles with 1: 1 stratification by journal type: high impact journals (the New England Journal of Medicine, JAMA, LANCET, Annals of Internal Medicine, BMJ and Plos Medicine) and low impact journal (the remaining journals) to identify 150 eligible studies. Two reviewers independently and in duplicate used standardized piloted forms to screen study reports for eligibility and to extract data. They also used explicit criteria to determine whether a cohort study reported HTE analysis. Logistic regression was used to examine the association of prespecified study characteristics with reporting versus not reporting of heterogeneity of treatment effect. RESULTS One hundred fifty cohort studies were included of which 88 (58%) reported HTE analysis. High impact journals (Odds Ratio: 3.5, 95% CI: 1.78-7.5; P < 0.001), pharmacological studies (Odds Ratio: 0.26, 95% CI: 0.13-0.51; P < 0.001) and studies published after 2014 (Odds Ratio: 0.5, 95% CI: 0.25-0.97; P = 0.004) were associated with more frequent reporting of HTE. 27 (31%) studies which reported HTE used an interaction test. CONCLUSION More than half cohort studies report some measure of heterogeneity of treatment effect. Prospective cohort studies published in high impact journals, with large sample size, or studying a pharmacological treatment are associated with more frequent HTE reporting. The source of funding was not associated with HTE reporting. There is a need for guidelines on how to perform HTE analyses in cohort studies.