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Emulation of a target trial with sustained treatment strategies: an application to prostate cancer using both inverse probability weighting and the g-formula

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Abstract

As with many chronic illnesses, recurrent prostate cancer generally requires sustained treatment to prolong survival. However, initiating treatment immediately after recurrence may negatively impact quality of life without any survival gains. Therefore, we consider sustained strategies for initiating treatment based on specific characteristics of prostate-specific antigen (PSA), which can indicate disease progression. We define the protocol for a target trial comparing treatment strategies based on PSA doubling time, in which androgen deprivation therapy is initiated only after doubling time decreases below a certain threshold. Such a treatment strategy means the timing of treatment initiation (if ever) is not known at baseline, and the target trial protocol must explicitly specify the frequency of PSA monitoring until the threshold is met, as well as the duration of treatment. We describe these and other components of a target trial that need to be specified in order for such a trial to be emulated in observational data. We then use the parametric g-formula and inverse-probability weighted dynamic marginal structural models to emulate our target trial in a cohort of prostate cancer patients from clinics across the United States.

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Funding

The authors declare that no funds, grants, or other support directly supported the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA

    Louisa H. Smith, Xabier García-Albéniz & Miguel A. Hernán

  2. Roux Institute at Northeastern University, 100 Fore St, Portland, ME, 04101, USA

    Louisa H. Smith

  3. RTI Health Solutions, Barcelona, Spain

    Xabier García-Albéniz

  4. Department of Epidemiology & Biostatistics, University of California, San Francisco, CA, USA

    June M. Chan & Matthew R. Cooperberg

  5. Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA

    June M. Chan, Shoujun Zhao, Janet E. Cowan, Jeanette M. Broering, Matthew R. Cooperberg & Peter R. Carroll

  6. Department of Surgery, University of California, San Francisco, CA, USA

    Jeanette M. Broering

  7. CAUSALab, Harvard TH Chan School of Public Health, Boston, MA, USA

    Miguel A. Hernán

  8. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Miguel A. Hernán

Authors
  1. Louisa H. Smith
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  2. Xabier García-Albéniz
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  3. June M. Chan
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  4. Shoujun Zhao
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  5. Janet E. Cowan
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  6. Jeanette M. Broering
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  7. Matthew R. Cooperberg
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  8. Peter R. Carroll
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  9. Miguel A. Hernán
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Correspondence to Louisa H. Smith.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was approved by the Harvard Longwood Campus Insitutional Review Board (IRB13-2919).

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Informed consent was obtained from all CaPSURE participants.

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Smith, L.H., García-Albéniz, X., Chan, J.M. et al. Emulation of a target trial with sustained treatment strategies: an application to prostate cancer using both inverse probability weighting and the g-formula. Eur J Epidemiol 37, 1205–1213 (2022). https://doi.org/10.1007/s10654-022-00929-7

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  • DOI: https://doi.org/10.1007/s10654-022-00929-7

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