Lessons learned conducting a multi-center trial with a military population: The Tinnitus Retraining Therapy Trial

摘要

Background The Tinnitus Retraining Therapy Trial (TRTT), a randomized, placebo-controlled, multi-center trial, evaluated the efficacy of tinnitus retraining therapy and its individual components, tinnitus-specific educational counseling and sound therapy versus the standard of care, in military practice to improve study participants’ quality of life. The trial was conducted at six US military hospitals to take advantage of the greater prevalence of tinnitus in the military population. Methods During the trial, various challenges arose that were uniquely related to the military setting. To convey these challenges to investigators planning future multi-center trials in military hospitals, we itemized various challenges that arose during the trial, interviewed clinic directors and coordinators to elicit their viewpoints, and then collated and organized their responses, together with those challenges presented while conducting the Tinnitus Retraining Therapy Trial. Results We encountered challenges in site selection, the approval process, administrative issues, study personnel training and retention, participant recruitment methods and issues, adherence to protocol, reimbursement issues, and military security. Site selection involved visiting 20 military hospitals to identify six sites that enrolled and followed study participants. We found that commitment for the trial must be obtained from the full military chain of command, but with ongoing changes in staff or military priorities, initial commitments were insufficient to sustain support throughout the entire trial. More time is required to obtain necessary administrative approvals by various military authorities and institutional review boards than is typically experienced in civilian settings. Recruitment strategies must be flexible due to changing military regulations regarding display of materials. Protracted periods of inactivity were due to sequestration and delays in institutional review board approval of required study personnel or protocol amendments. While mostly adherent to the protocol, study staff had difficulties in integrating study visits into the military clinical schedule. Unexpected study expenses revolved around hiring civilian study staff and obtaining associated security clearance while maintaining a consistent flow of funds to each site. The added expense negated cost savings realized by conducting the National Institutes of Health–funded trial at federal institutions, whose personnel could not be reimbursed for their efforts. Military security concerns impacted the use of web-based data systems and led to increased time and effort required for site visits. Conclusion Overall, US military hospitals provide a unique setting to conduct multi-center trials. Challenges arise mainly due to ever-changing authority personnel and military priorities. Pre-planning and flexibility are keys in overcoming these challenges. Multi-center trials conducted in the military will likely take longer to initiate and complete than those in the civilian sector due to multiple levels of command and administrative approvals.