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Emulating a Target Trial in Perinatal Pharmacoepidemiology: Challenges and Methodological Approaches

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Abstract

Purpose of Review

The objective of this review is to examine the application of target trial emulation in perinatal pharmacoepidemiology research. Given that randomized clinical trials—the gold standard for causal inference—are often not feasible or ethical for studying medication safety during pregnancy, alternative methodologies are critically needed. This paper delves into the challenges and potential mitigation strategies of using target trial emulation in the specific context of perinatal pharmacoepidemiology research.

Recent Findings

Our review of identified studies (n = 9) reveals several unique considerations when leveraging target trial emulation for perinatal pharmacoepidemiology research. These include the alignment of the research question with the clinically relevant outcomes, identification of etiologically relevant time windows, defining relevant treatment strategies, and anchoring of exposure, eligibility criteria, and the start of follow-up. Despite these challenges, the methodology shows promise in bridging the gap between randomized clinical trials and observational research through the employment of a transparent and well-defined approach.

Summary

Target trial emulation serves as a valuable tool in perinatal pharmacoepidemiology, allowing researchers to generate more reliable evidence concerning medication safety during pregnancy. Although the approach comes with specific challenges, strategies can be implemented to mitigate these difficulties. Overall, the adoption of target trial emulation has the potential to substantially enhance evidence quality, inform clinical decisions, and ultimately improve health outcomes for birthing people and their infants.

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Data Availability

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Author information

Authors and Affiliations

  1. Division Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

    Sabrina Chiodo, Lauren Tailor & Sonia M. Grandi

  2. Child Health Evaluative Sciences, The Hospital for Sick Children, 686 Bay Street, Toronto, Ontario, Canada

    Sabrina Chiodo, Lauren Tailor & Sonia M. Grandi

  3. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada

    Robert W. Platt

  4. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada

    Robert W. Platt

  5. Department of Pediatrics, McGill University, Montreal, QC, Canada

    Robert W. Platt

  6. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA

    Mollie E. Wood

Authors
  1. Sabrina Chiodo
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  2. Lauren Tailor
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  3. Robert W. Platt
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  4. Mollie E. Wood
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Contributions

S.C. and S.M.G. conceived the study idea in consultation with all other co-authors. S.C, L.T., and S.M.G. drafted the manuscript, and all other authors (R.W.P. and M.E.W.) reviewed the manuscript for intellectual content and approved the submitted manuscript.

Corresponding author

Correspondence to Sonia M. Grandi.

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Conflict of Interest

MW is a member of the Center for Pharmacoepidemiology (CPE) at UNC, which receives funding from industry partners (AbbVie, Boehringer Ingleheim, GSK, Takeda, UCB, Sarepta, Astellas). They do not receive salary support from the CPE; funds are used to support student stipends and related expenses. They received a starter grant from the PhRMA Foundation to study the treatment of chronic hypertension in pregnancy. They are a co-I on grants from the CDC, NIH, and the Kuni Foundation, unrelated to the current work.

RWP holds the Albert Boehringer I Chair in Pharmacoepidemiology and has received personal fees from Amgen, Analysis Group, Biogen, Boehringer Ingelheim, Merck, Nant Pharma, and Pfizer, all outside of the submitted work.

SMG holds a grant as nominated principal investigator from the Canadian Institutes of Health Research (CIHR) and is a co-I on grants from the CIHR, University of Toronto Data Sciences Institute, and the Ontario Ministry of Health, unrelated to this work. She also received start-up funds from the Hospital for Sick Children, unrelated to this work.

All other authors have no conflicts of interest to disclose.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Chiodo, S., Tailor, L., Platt, R.W. et al. Emulating a Target Trial in Perinatal Pharmacoepidemiology: Challenges and Methodological Approaches. Curr Epidemiol Rep 10, 275–285 (2023). https://doi.org/10.1007/s40471-023-00339-7

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