Recruitment and retention for chronic pain clinical trials: a narrative review

Opioid misuse is at a crisis level. In response to this epidemic, the National Institutes of Health has funded $945 million in research through the Helping to End Addiction Long-term (HEAL) Pain Management Initiative, including funding to the Vanderbilt Recruitment Innovation Center (RIC) to strategize methods to catalyze participant recruitment. The RIC, recognizing the challenges presented to clinical researchers in recruiting individuals experiencing pain, conducted a review of evidence in the literature on successful participant recruitment methods for chronic pain trials, in preparation for supporting the HEAL Pain trials. Study design as it affects recruitment was reviewed, with issues such as sufficient sample size, impact of placebo, pain symptom instability, and cohort characterization being identified as problems. Potential solutions found in the literature include targeted electronic health record phenotyping, use of alternative study designs, and greater clinician education and involvement. For retention, the literature reports successful strategies that include maintaining a supportive staff, allowing virtual study visits, and providing treatment flexibility within the trial. Community input on study design to identify potential obstacles to recruitment and retention was found to help investigators avoid pitfalls and enhance trust, especially when recruiting underrepresented minority populations. Our report concludes with a description of generalizable resources the RIC has developed or adapted to enhance recruitment and retention in the HEAL Pain studies. These resources include, among others, a Recruitment and Retention Plan Template, a Competing Trials Tool, and MyCap, a mobile research application that interfaces with Research Electronic Data Capture (REDCap).