Technical Background for "A Precision Medicine Approach to Develop and Internally Validate Optimal Exercise and Weight Loss Treatments for Overweight and Obese Adults with Knee

01/27/2020 ∙ by Xiaotong Jiang, et al. ∙ 0

A precision medicine (PM) pipeline was developed to determine the optimal treatment regime for participants in an exercise (E), dietary weight loss (D), and D+E randomized clinical trial for knee osteoarthritis to maximize their expected outcomes. Using data from 343 participants of the Intensive Diet and Exercise for Arthritis (IDEA) trial, we applied 24 machine-learning models to develop individualized treatment rules on seven outcomes: SF-36 physical component score, weight loss, WOMAC pain/function/stiffness scores, compressive force, and IL-6. The optimal precision medicine model (PMM) was selected based on jackknife value function estimates that indicate improvement in the outcome(s) had future participants followed the estimated decision rule, which is then compared against the optimal single, fixed treatment model called zero-order model (ZOM) with a Z-test. Multiple outcome random forest was the optimal model for the WOMAC outcomes. The PMMs supported the overall findings from IDEA that the D+E intervention was optimal for most participants, but there was evidence that a subgroup of participants would likely benefit more from diet alone for two outcomes. This article provides detailed technical background for the clinical data analysis.

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