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Bayesian Meta-analysis of Multiple Continuous Treatments with Individual Participant-Level Data: An Application to Antipsychotic Drugs

Author

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  • Jacob Spertus

    (Department of Health Care Policy, Harvard Medical School, Boston, MA, USA)

  • Marcela Horvitz-Lennon

    (Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA
    RAND Corporation, Santa Monica, CA, USA)

  • Sharon-Lise T. Normand

    (Department of Health Care Policy, Harvard Medical School, Boston, MA, USA
    Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA)

Abstract

Modeling dose-response relationships of drugs is essential to understanding their safety effects on patients under realistic circumstances. While intention-to-treat analyses of clinical trials provide the effect of assignment to a particular drug and dose, they do not capture observed exposure after factoring in nonadherence and dropout. We develop a Bayesian method to flexibly model the dose-response relationships of binary outcomes with continuous treatment, permitting multiple evidence sources, treatment effect heterogeneity, and nonlinear dose-response curves. In an application, we examine the risk of excessive weight gain for patients with schizophrenia treated with the second-generation antipsychotics paliperidone, risperidone, or olanzapine in 14 clinical trials. We define exposure as total cumulative dose (daily dose × duration) and convert to units equivalent to 100 mg of olanzapine (OLZ doses). Averaging over the sample population of 5891 subjects, the median dose ranged from 0 (placebo randomized participants) to 6.4 OLZ doses (paliperidone randomized participants). We found paliperidone to be least likely to cause excessive weight gain across a range of doses. Compared with 0 OLZ doses, at 5.0 OLZ doses, olanzapine subjects had a 15.6% (95% credible interval: 6.7, 27.1) excess risk of weight gain; corresponding estimates for paliperidone and risperidone were 3.2% (1.5, 5.2) and 14.9% (0.0, 38.7), respectively. Moreover, compared with nonblack participants, black participants had a 6.8% (1.0, 12.4) greater risk of excessive weight gain at 10.0 OLZ doses of paliperidone. Nevertheless, our findings suggest that paliperidone is safer in terms of weight gain risk than risperidone or olanzapine for all participants at low to moderate cumulative OLZ doses.

Suggested Citation

  • Jacob Spertus & Marcela Horvitz-Lennon & Sharon-Lise T. Normand, 2019. "Bayesian Meta-analysis of Multiple Continuous Treatments with Individual Participant-Level Data: An Application to Antipsychotic Drugs," Medical Decision Making, , vol. 39(5), pages 583-592, July.
    • Handle: RePEc:sae:medema:v:39:y:2019:i:5:p:583-592
    DOI: 10.1177/0272989X19856884
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    References listed on IDEAS

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    1. Kosuke Imai & David A. van Dyk, 2004. "Causal Inference With General Treatment Regimes: Generalizing the Propensity Score," Journal of the American Statistical Association, American Statistical Association, vol. 99, pages 854-866, January.
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