Effectiveness and efficiency of an add-on active outreach strategy on research enrollments in a drug intervention trial

Abstract

Background and objectives: Adding an active outreach strategy for patients who do not respond to mail invitations may enhance clinical research recruitment; however, the effectiveness of this approach has yet to be formally tested in drug intervention trials. Using the enrollment data from the Management of Cardiovascular disease in chronic Kidney disease (MaCK) randomized trial, we aimed to evaluate the effectiveness and efficiency of the add-on active outreach compared to the mail invitation-based passive enrollment strategy.

Study design and settings: We conducted a retrospective analysis of enrollment data from August 2019 to June 2021 for the MaCK trial. We used an electronic health records (EHRs) query to derive the source cohort of Veterans with chronic kidney disease. We mailed them an invitation to participate in the study, with a brief study description and a request for a call-back within 2 weeks, irrespective of their interest in participation. Invitees not responding within 2 weeks were proactively contacted under a limited Health Insurance Portability and Accountability Act waiver. The effectiveness, defined as the rates of successful enrollments, and the efficiency, defined as the effort per enrollment, were the coprimary outcomes. The effectiveness and efficiency of successful approaches and randomizations were the secondary outcomes.

Results: Among the 747 patients sampled from the electronic database for the mail invitation-based passive outreach, 258 remained eligible for proactive contact by research staff under the active outreach strategy. Compared to the passive mail invitation-based outreach, the add-on active outreach strategy was more effective, with higher approach success rates (77.1% vs 7.1%; P < .001), enrollment rates (15.5% vs 1.7%, P < .001), and randomization rates (7.4% vs 1.34%, P < .001). Compared to the passive outreach, the active outreach strategy was also more efficient, with lower staff effort required for making a successful approach (14.8 ± 0.4 vs 2.7 ± 0.2 minutes, P < .0001), study enrollment (66.1 ± 1.6 vs 13.4 ± 0.9 minutes, P < .0001), and randomization (85.9 ± 2.1 vs 28.3 ± 1.8 minutes, P < .0001).

Conclusion: An add-on active outreach strategy is 4- to 10-fold more effective and efficient in achieving research recruitments than a passive outreach strategy for more-than-minimal-risk studies. These findings strongly argue for a greater use of these strategies for conventional research studies involving drug or device interventions.

Plain language summary: Actively reaching out to people who were mail-invited for research studies but did not respond may allow more people the opportunity for research participation and increase clinical research recruitments; however, the effectiveness of such an approach has not been formally tested for research studies outside the population and behavioral health. This retrospective analysis of a randomized drug intervention clinical trial shows that employing such an active outreach strategy increases the research participation and efficiency by 5- to 10-fold. The analysis further shows that establishing a successful contact with the potential research participant is the major determinant of overall enrollments, irrespective of the recruitment strategy. At the same time, the study did not identify any major concerns for safety or privacy among potential participants contacted. These findings suggest that incorporating the active outreach strategy for the device or drug intervention trials may allow more interested people to participate and, as such, may improve equity in research participation.

Keywords: Add-on active enrollment strategy; Drug-intervention trial; Opt-out enrollments; Passive enrollment strategy; Research methods.