|Title||Identifying optimal dosage regimes under safety constraints: An application to long term opioid treatment of chronic pain.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Laber, Eric B., Fan Wu, Catherine Munera, Ilya Lipkovich, Salvatore Colucci, and Steve Ripa|
|Date Published||2018 Apr 30|
|Keywords||Analgesics, Opioid, Chronic Pain, Drug Dosage Calculations, Humans, Long-Term Care, Models, Statistical, Precision Medicine, Statistics as Topic, Statistics, Nonparametric|
There is growing interest and investment in precision medicine as a means to provide the best possible health care. A treatment regime formalizes precision medicine as a sequence of decision rules, one per clinical intervention period, that specify if, when and how current treatment should be adjusted in response to a patient's evolving health status. It is standard to define a regime as optimal if, when applied to a population of interest, it maximizes the mean of some desirable clinical outcome, such as efficacy. However, in many clinical settings, a high-quality treatment regime must balance multiple competing outcomes; eg, when a high dose is associated with substantial symptom reduction but a greater risk of an adverse event. We consider the problem of estimating the most efficacious treatment regime subject to constraints on the risk of adverse events. We combine nonparametric Q-learning with policy-search to estimate a high-quality yet parsimonious treatment regime. This estimator applies to both observational and randomized data, as well as settings with variable, outcome-dependent follow-up, mixed treatment types, and multiple time points. This work is motivated by and framed in the context of dosing for chronic pain; however, the proposed framework can be applied generally to estimate a treatment regime which maximizes the mean of one primary outcome subject to constraints on one or more secondary outcomes. We illustrate the proposed method using data pooled from 5 open-label flexible dosing clinical trials for chronic pain.
|Alternate Journal||Stat Med|
|Original Publication||Identifying optimal dosage regimes under safety constraints: An application to long term opioid treatment of chronic pain.|
|PubMed Central ID||PMC6293986|
|Grant List||P01 CA142538 / CA / NCI NIH HHS / United States |
R01 DE024984 / DE / NIDCR NIH HHS / United States
Identifying optimal dosage regimes under safety constraints: An application to long term opioid treatment of chronic pain.