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

MRC Biostatistics Unit, University of Cambridge, Cambridge, UK. Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK. NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Cambridge, UK. Department of Health Sciences, University of Leicester, Leicester, UK. BRC Haematology Theme and Radcliffe Department of Medicine, University of Oxford, Oxford, UK. National Health Service Blood and Transplant, Oxford, UK.

Stat Methods Med Res. 2020;:962280220920669
PICO Summary

Population

Male blood donors from the INTERVAL trial (n=20574).

Intervention

Simulation using INTERVAL trial data of five different methods of determining personalised inter-donation intervals.

Comparison

Standard inter-donation intervals for all male donors: 12 weeks, 10 weeks, and 8 weeks over two years.

Outcome

Findings were fairly consistent across the different approaches applied: when targeting the maximization of the total units of blood collected, almost all donors are assigned to the 8 weeks inter-donation interval. If aiming at minimizing the low haemoglobin deferral rates, almost all donors are assigned to donate every 12 weeks. When the goal was to maximize the utility score that "discounts" the total units of blood collected by the incidences of low haemoglobin deferrals, there was heterogeneity in the optimal inter-donation interval across donors and the optimal donor assignment strategy was highly dependent on the trade-off parameter in the utility function.
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.
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine