Considerations for Issues of Regression to the Mean and Contextual Effects in Clinical Trials for Pain in Rheumatic Diseases.

Abstract

Recently, there has been growing discussion about how to best assess pain in clinical trials in rheumatic diseases. Reliable measurement of pain outcomes is essential for accurately determining the effectiveness of treatments. Although pain intensity is the most common measure of change in pain trials, other pain-related measures, such as pain interference, are also frequently assessed. Interpreting treatment effects on these outcomes can be complicated due to statistical phenomena, particularly regression to the mean and contextual effects. These issues can substantially distort clinical trial findings, potentially leading to inaccurate conclusions about the efficacy of interventions. The present article provides an overview of regression to the mean and contextual effects, emphasizing their implications for internal validity, clinical decision-making, and ethical considerations in trials. Additionally, this article highlights key study design and analysis considerations, including methodologic and statistical approaches, that researchers can implement to mitigate or better account for these challenges. Practical recommendations are offered to enhance the rigor of pain assessment, with specific attention to osteoarthritis as a representative example within rheumatic disease research. By recognizing and addressing regression to the mean and contextual effects proactively, researchers can strengthen trial outcomes, improve clinical interpretations, and support the identification of effective treatments.