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. 2020 Nov;29(11):3113-3134.
doi: 10.1177/0962280220920669. Epub 2020 May 8.

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  1 , Angela M Wood  2   3 , Michael J Sweeting  2   4 , David J Roberts  5   6 , Brian Dm Tom  1
Affiliations

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 et al. Stat Methods Med Res. 2020 Nov.

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.

Keywords: Precision medicine; blood donation; individualized treatment rule; multi-arm trial; utility function.

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Figures

Figure 1.
Figure 1.
Plots of the mean and 95% confidence intervals for ITR effects of the optimal ITR estimated using various methods as the trade-off parameter b in the utility function varies from 1 to 5 at an increment of 1. Optimal ITRs are estimated using data from male donors in the INTERVAL trial assuming the target is to maximize the utility. Methods to estimate the optimal ITR include l1-penalized least squares with hierarchical group LASSO variable selection (l1-PLS-HGL), l1-penalized least squares with group LASSO variable selection (l1-PLS-GL), adaptive contrast weighted learning (ACWL), and direct learning (D-learning). ITR effects on the (a) donation, (b) deferral, and (c) utility outcomes are presented. A larger ITR effect on donation/utility and a smaller ITR effect on deferral are more desirable.
Figure 2.
Figure 2.
Density plots of ITR effects on utility when (a) b = 1 (b) b = 2 (c) b = 3 (d) b = 4 (e) b = 5 for five donor assignment rules: recommend all male donors to (i) donate every eight weeks, (ii) donate every 10 weeks, (iii) donate every 12 weeks, (iv) donate according to the BART ITR, and (v) donate according to the optimized ITR (non-achievable in practice). The trade-off parameter b in the utility function varies from 1 to 5 at an increment of 1. A larger ITR effect on utility is more desirable.
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