Eugene Laska1, Carole Siegel2, Ziqiang Lin3. 1. Department of Psychiatry, New York University Grossman School of Medicine, One Park Avenue, New York, NY 10016, USA; Department of Population Health, Division of Biostatistics, NYU Grossman School of Medicine, 180 Madison Avenue, New York, NY 10016, USA. Electronic address: eugene.laska@nyumc.org. 2. Department of Psychiatry, New York University Grossman School of Medicine, One Park Avenue, New York, NY 10016, USA; Department of Population Health, Division of Biostatistics, NYU Grossman School of Medicine, 180 Madison Avenue, New York, NY 10016, USA. Electronic address: carole.siegel@nyumc.org. 3. Department of Psychiatry, New York University Grossman School of Medicine, One Park Avenue, New York, NY 10016, USA. Electronic address: ziqiang.lin@nyumc.org.
Abstract
OBJECTIVE: To further the precision medicine goal of tailoring medical treatment to individual patient characteristics by providing a method of analysis of the effect of test treatment, T, compared to a reference treatment, R, in participants in a RCT who are likely responders to T. METHODS: Likely responders to T are individuals whose expected response at baseline exceeds a prespecified minimum. A prognostic score, the expected response predicted as a function of baseline covariates, is obtained at trial completion. It is a balancing score that can be used to match likely responders randomized to T with those randomized to R; the result is comparable treatment groups that have a common covariance distribution. Treatments are compared based on observed outcomes in this enriched sample. The approach is illustrated in a RCT comparing two treatments for opioid use disorder. RESULTS: A standard statistical analysis of the opioid use disorder RCT found no treatment difference in the total sample. However, a subset of likely responders to T were identified and in this group, T was statistically superior to R. CONCLUSION: The causal treatment effect of T relative to R among likely responders may be more important than the effect in the whole target population. The prognostic score function provides quantitative information to support patient specific treatment decisions regarding T furthering the goal of precision medicine.
OBJECTIVE: To further the precision medicine goal of tailoring medical treatment to individual patient characteristics by providing a method of analysis of the effect of test treatment, T, compared to a reference treatment, R, in participants in a RCT who are likely responders to T. METHODS: Likely responders to T are individuals whose expected response at baseline exceeds a prespecified minimum. A prognostic score, the expected response predicted as a function of baseline covariates, is obtained at trial completion. It is a balancing score that can be used to match likely responders randomized to T with those randomized to R; the result is comparable treatment groups that have a common covariance distribution. Treatments are compared based on observed outcomes in this enriched sample. The approach is illustrated in a RCT comparing two treatments for opioid use disorder. RESULTS: A standard statistical analysis of the opioid use disorder RCT found no treatment difference in the total sample. However, a subset of likely responders to T were identified and in this group, T was statistically superior to R. CONCLUSION: The causal treatment effect of T relative to R among likely responders may be more important than the effect in the whole target population. The prognostic score function provides quantitative information to support patient specific treatment decisions regarding T furthering the goal of precision medicine.
Authors: Richard Wyss; Ben B Hansen; Alan R Ellis; Joshua J Gagne; Rishi J Desai; Robert J Glynn; Til Stürmer Journal: Am J Epidemiol Date: 2017-05-01 Impact factor: 4.897
Authors: Andrea Lamont; Michael D Lyons; Thomas Jaki; Elizabeth Stuart; Daniel J Feaster; Kukatharmini Tharmaratnam; Daniel Oberski; Hemant Ishwaran; Dawn K Wilson; M Lee Van Horn Journal: Stat Methods Med Res Date: 2016-03-17 Impact factor: 3.021