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Estimating causal effects of treatment in a randomized trials when some participants only partially adhere

Shrier, Ian MD, PhD; Platt, Robert W. PhD; Steele, Russell J. PhD; Schnitzer, Mireille PhD
doi: 10.1097/EDE.0000000000000771
Original Article: PDF Only

The intention-to-treat analysis evaluates the causal effect of treatment assignment in a randomized controlled trial; however, participants do not always adhere to assigned treatment and the intention to treat effect may differ from the effect of treatment receipt. Although more recent adherence-based methods assess a well-defined causal effect of receiving treatment, adherence is assumed to be dichotomized as all or none. This approach can lack precision in the real world because adherence is a complex and heterogeneous phenomenon. In this paper, we illustrate a simple method that provides estimates of bounds on the causal effect of full adherence to treatment in the presence of partial adherence. We first define three types of partial adherence (delayed, partial-dose, post-treatment). We then use casual diagrams to show that categorizing partial adherence as non-adherence in a sensitivity analysis can lead to a violation of the exclusion restriction principle. Finally, we apply recently published sensitivity analyses related to principal stratification that allow for creating bound estimates around the causal effect of treatment in the presence of partial adherence.

Data and Programming Code for Replication: The data are simulated and code is available from the author upon request.

Funding Support: This specific work did not receive any funding support.

Conflict of Interest: The authors have no conflicts of interest to declare

Acknowledgements: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Shrier is supported by the Lady Davis Institute, Jewish General Hospital, McGill University. Dr. Platt holds the Albert Boehringer I Chair in Pharmacoepidemiology at McGill University and is supported by a Chercheur-national award from the Fonds de Recherche du Québec – Santé, and is supported by the Research Institute of the McGill University Health Centre and the Lady Davis Institute, Jewish General Hospital, McGill University. Dr. Steele is supported by the Lady Davis Institute, Jewish General Hospital, and the Department of Mathematics and Statistics, McGill University. Dr. Schnitzer is supported by the Canadian Institutes of Health Research New Investigator Award.

Corresponding Author: Ian Shrier MD, PhD, Centre for Clinical Epidemiology, Jewish General Hospital, 3755 Cote Sainte-Catherine Road, Montreal, QC H3T 1E2, Canada

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