The implementation of accurate pain reporting (APR) and placebo response reduction (PRR) training in clinical trials

Abstract

Purpose: APR and PRR was developed in response to effective treatments failing to separate from placebo in phase II and III clinical trials. Training patients to report their symptoms more accurately has been shown to reduce variability in reporting as well as placebo response, thus increasing the difference in efficacy between arms. The objective of this study was to characterize how APR and PRR have been effectively implemented in clinical trials to date, with a specific focus on osteoarthritis studies. Methods: Components and the development of the APR and PRR training program were described methodically. Descriptive statistics were performed on clinical trials utilizing the training programs, such as indications, languages, subjects, and countries in which the training was successfully implemented. Results: The APR and PRR training programs were developed methodically using patient input, feedback, and cognitive debriefing studies, with the objective to provide information and train subjects and study staff about the importance of accurate pain reporting and to neutralize expectations in study. APR and PRR have been implemented in over 25 studies, 2,000 study sites, 34 countries, and 32 languages or dialects. The trainings have been utilized for 11 different indications with osteoarthritis being the most common with a total of 11 clinical trials. Conclusions: Training patients to accurately report their symptoms and to neutralize expectations has been found to reduce the placebo response and increase assay sensitivity. APR and PRR were systematically developed, tested, and have been adopted and viewed by many regulatory agencies and IRB committees worldwide.