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Estimating Treatment-Switching Bias in a Randomized Clinical Trial of Ovarian Cancer Treatment: Combining Causal Inference with Decision-Analytic Modeling

Author

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  • Felicitas Kuehne

    (Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT–University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria)

  • Ursula Rochau

    (Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT–University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria)

  • Noman Paracha

    (Bayer Consumer Care AG, Pharmaceuticals, Oncology SBU, Basel, Basel-Stadt, Switzerland)

  • Jennifer M. Yeh

    (Department of Pediatrics, Harvard Medical School & Boston Children’s Hospital)

  • Eduardo Sabate

    (Daiichi Sankyo Inc, Oncology, Basking Ridge, NJ, USA)

  • Uwe Siebert

    (Department of Public Health, Health Services Research and Health Technology Assessment, Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT–University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria
    Division of Health Technology Assessment, ONCOTYROL-Center for Personalized Cancer Medicine, Innsbruck, Austria
    Center for Health Decision Science, Departments of Epidemiology and Health Policy & Management, Harvard T.H. Chan School of Public Health, Boston, MA, USA
    Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA)

Abstract

Background Bevacizumab is efficacious in delaying ovarian cancer progression and controlling ascites. The ICON7 trial showed a significant benefit in overall survival for bevacizumab, whereas the GOG-218 trial did not. GOG-218 allowed control group patients to switch to bevacizumab upon progression, which may have biased the results. Lack of data on switching behavior prevented the application of g-methods to adjust for switching. The objective of this study was to apply decision-analytic modeling to estimate the impact of switching bias on causal treatment-effect estimates. Methods We developed a causal decision-analytic Markov model (CDAMM) to emulate the GOG-218 trial and estimate overall survival. CDAMM input parameters were based on data from randomized clinical trials and the published literature. Overall switching proportion was based on GOG-218 trial information, whereas the proportion switching with and without ascites was estimated using calibration. We estimated the counterfactual treatment effect that would have been observed had no switching occurred by denying switching in the CDAMM. Results The survival curves generated by the CDAMM matched well with the ones reported in the GOG-218 trial. The survival curve correcting for switching showed an estimated bias such that 79% of the true treatment effect could not be observed in the GOG-218 trial. Results were most sensitive to changes in the proportion progressing with severe ascites and mortality. Limitations We used a simplified model structure and based model parameters on published data and assumptions. Robustness of the CDAMM was tested and model assumptions transparently reported. Conclusions Medical-decision science methods may be merged with empirical methods of causal inference to integrate data from other sources where empirical data are not sufficient. We recommend collecting sufficient information on switching behavior when switching cannot be avoided.

Suggested Citation

  • Felicitas Kuehne & Ursula Rochau & Noman Paracha & Jennifer M. Yeh & Eduardo Sabate & Uwe Siebert, 2022. "Estimating Treatment-Switching Bias in a Randomized Clinical Trial of Ovarian Cancer Treatment: Combining Causal Inference with Decision-Analytic Modeling," Medical Decision Making, , vol. 42(2), pages 194-207, February.
    • Handle: RePEc:sae:medema:v:42:y:2022:i:2:p:194-207
    DOI: 10.1177/0272989X211026288
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    References listed on IDEAS

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    1. J.Robert Beck & Stephen G. Pauker, 1983. "The Markov Process in Medical Prognosis," Medical Decision Making, , vol. 3(4), pages 419-458, December.
    2. Uwe Siebert, 2003. "When should decision-analytic modeling be used in the economic evaluation of health care?," The European Journal of Health Economics, Springer;Deutsche Gesellschaft für Gesundheitsökonomie (DGGÖ), vol. 4(3), pages 143-150, September.
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