Comparison of interaction and subgroup effects in observational studies and randomized clinical trials: Three empirical examples

Amand F. Schmidt, Maroeska M. Rovers, Olaf H. Klungel, Arno W. Hoes, Mirjam J. Knol, Mirjam Nielen, Antonius De Boer, Rolf H.H. Groenwold

    Research output: Contribution to journalMeeting AbstractOther research output

    Abstract

    Background: Compared to RCTs, observational (nonrandomized) studies often comprise larger sample sizes, which gives adequate power to study interaction. Observational studies, however, are prone to confounding. Objectives: To determine the validity of subgroup and interaction effects (differences between subgroups) for different study designs. Methods: We compared effects of medical interventions based on observational studies, RCTs, and Individual Patient Data Meta-Analysis of RCTs (IPDMAs; reference) on three different clinical topics: (1) mammography screening effects on breast cancer mortality; (2) CABG and all-cause mortality; (3) statins and the incidence of major coronary events. Main, subgroup, and interaction effects were compared. Results: Main and subgroup effects were comparable with respect to the direction of effects for IPDMAs, RCTs, and observational studies. Small differences in the magnitude of subgroup effects in observational studies yielded different interactions compared to IPDMA. In the mammography example the Ratio of Risk Ratio's (RRR) (i.e., interaction effect) among observational studies was 1.46 (95% CI 1.09;1.96) compared to an IPDMA effect of 110 (95% CI 0.89;1.37). For the CABG studies the observational RRR was 1.03 (95% CI 0.84;1.26), whereas in the IPDMA this was 1.40 (95% CI 1.08;11.81). Finally, in the statin example the RRR was 1.35 (95% CI 113;1.61) for observational studies, in the IPDMA this was 0.90 (95% CI 0.84;0.97). Conclusions: Main and subgroup effects based on observational data are in line with main and subgroup effects in IPDMAs based on RCTs, yet interactions may differ substantially.
    Original languageEnglish
    Article number270
    Pages (from-to)127
    Number of pages1
    JournalPharmacoepidemiology and Drug Safety
    Volume21
    Issue numberS3
    DOIs
    Publication statusPublished - 1 Aug 2012

    Bibliographical note

    Abstracts of the 28th International Conference on Pharmacoepidemiology & Therapeutic Risk Management, 23-26 August 2012, Barcelona, Spain

    Keywords

    • statin (protein)
    • hydroxymethylglutaryl coenzyme A reductase inhibitor
    • clinical trial (topic)
    • pharmacoepidemiology
    • risk management
    • observational study
    • mammography
    • meta analysis (topic)
    • study design
    • breast cancer
    • validity
    • meta analysis
    • mortality
    • sample size
    • screening
    • cancer mortality
    • risk
    • patient coding

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