Covariate Adjustment in Pragmatic Randomized Clinical Trials in Pain Research

A working document from the Pain Management Collaboratory Biostatistics/Design work group

Prepared by: Tassos C. Kyriakides, Cynthia R. Long, Brenda Fenton, Willie Hale
Version 1.0, last updated May 30, 2019

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While covariate adjustments, and the impact of variables on outcomes and conclusions, should be considered in any clinical trial, accounting for them in pragmatic clinical trials (PCTs) studying non-pharmacological approaches to pain management can be particularly complicated because pain is incredibly varied in onset, duration, severity, causation and diagnosis. Additionally, potential participants in a trial may have access to other, concurrent prevention and treatment modalities, or have had treatments or prevention programs prior to joining the current trial program. What follows in this working document is an overview of considerations for covariate-related methodological, statistical and analytical issues, and some additional considerations directly related to studying pain management options, as well background information and recommendations based on the review of published literature.