Strategy for addressing research-site overlap in pragmatic clinical trials: lessons learned from the NIH-DOD-VA Pain Management Collaboratory (PMC).

BACKGROUND

The Pain Management Collaboratory (PMC) is a multi-site network of pragmatic clinical trials (PCTs) focused on nonpharmacological approaches to pain management, conducted in health care systems of the US Department of Defense (DoD) and Department of Veterans Affairs (VA) and co-funded by the National Institutes of Health (NIH). Concerns about potential research-site overlap prompted the PMC investigator community to consider strategies to avert this problem that could negatively affect recruitment and contaminate interventions and thus pose a threat to trial integrity.

METHODS

We developed a two-step strategy to identify and remediate research-site overlap by obtaining detailed recruitment plans across all PMC PCTs that addressed eligibility criteria, recruitment methods, trial settings, and timeframes. The first, information-gathering phase consisted of a 2-month period for data collection from PIs, stakeholders, and ClinicalTrials.gov . The second, remediation phase consisted of a series of moderated conference calls over a 1-month time period to develop plans to address overlap. Remediation efforts focused on exclusion criteria and recruitment strategies, and they involved collaboration with sponsors and stakeholder groups such as the Military Treatment Facility Engagement Committee (MTFEC). The MTFEC is comprised of collaborating DoD and university-affiliated PIs, clinicians, and educators devoted to facilitating successful pragmatic trials in DoD settings.

RESULTS

Of 61 recruitment sites for the 11 PMC PCTs, 17 (28%) overlapped. Four PCTs had five overlapping Military Treatment Facilities (MTFs), and eight PCTs had 12 overlapping VA Medical Centers (VAMCs). We developed three general strategies to avoid research-site overlap: (i) modify exclusion criteria, (ii) coordinate recruitment efforts, and/or (iii) replace or avoid any overlapping sites. Potential overlap from competing studies outside of the PMC was apparent at 26 sites, but we were not able to confirm them as true conflicts.

CONCLUSION

Proactive strategies can be used to resolve the issue of overlapping research sites in the PMC. These strategies, combined with open and impartial mediation approaches that include researchers, sponsors, and stakeholders, provide lessons learned from this large and complex pragmatic research effort.