Optimal individualized decision rules from a multi-arm trial: A comparison of methods and an application to tailoring inter-donation intervals among blood donors in the UK

Yuejia Xu*, Angela M. Wood, Michael J. Sweeting, David J. Roberts, Brian D.M. Tom

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

There is a growing interest in precision medicine where individual heterogeneity is incorporated into decision-making and treatments are tailored to individuals to provide better healthcare. One important aspect of precision medicine is the estimation of the optimal individualized treatment rule (ITR) that optimizes the expected outcome. Most methods developed for this purpose are restricted to the setting with two treatments, while clinical studies with more than two treatments are common in practice. In this work, we summarize methods to estimate the optimal ITR in the multi-arm setting and compare their performance in large-scale clinical trials via simulation studies. We then illustrate their utilities with a case study using the data from the INTERVAL trial, which randomly assigned over 20,000 male blood donors from England to one of the three inter-donation intervals (12-week, 10-week, and eight-week) over two years. We estimate the optimal individualized donation strategies under three different objectives. Our findings are fairly consistent across five different approaches that are applied: when we target the maximization of the total units of blood collected, almost all donors are assigned to the eight-week inter-donation interval, whereas if we aim at minimizing the low hemoglobin deferral rates, almost all donors are assigned to donate every 12 weeks. However, when the goal is to maximize the utility score that “discounts” the total units of blood collected by the incidences of low hemoglobin deferrals, we observe some heterogeneity in the optimal inter-donation interval across donors and the optimal donor assignment strategy is highly dependent on the trade-off parameter in the utility function.

Original languageEnglish
Pages (from-to)3113-3134
Number of pages22
JournalStatistical Methods in Medical Research
Volume29
Issue number11
DOIs
Publication statusPublished - 1 Nov 2020
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank the reviewers for their helpful comments and suggestions, which led to an improved paper. In addition, we thank members of the NIHR Blood and Transplant Research Unit in Donor Health and Genomics including Dr Steven Bell, Dr Emanuele Di Angelantonio, Dr Stephen Kaptoge, Dr Lois Kim, Andrew Browne, and Tom Bolton for discussions and feedback on an earlier version of this manuscript. A complete list of the investigators and contributors to the INTERVAL trial is provided in Di Angelantonio et?al. 12 The academic coordinating center would like to thank blood donor center staffs and blood donors for participating in the INTERVAL trial.

Publisher Copyright:
© The Author(s) 2020.

Keywords

  • blood donation
  • individualized treatment rule
  • multi-arm trial
  • Precision medicine
  • utility function

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