Effectiveness and Efficiency of an Add-on Active Outreach Strategy on Research Enrollments in a Drug Intervention Trial

Abstract

Background: 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 for drug intervention trials.

Objective: 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 secondary analysis of the enrollment data between August 2019 and June 2021 from the Management of Cardiovascular disease in chronic Kidney disease (MaCK) randomized trial. We used an electronic health records (EHR) 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 two weeks, irrespective of their interest in participation. Invitees not responding within two weeks were proactively contacted under a limited Health Insurance Portability and Accountability Act waiver.

Outcomes: The effectiveness, defined as the rates of successful enrollments, and the efficiency, defined as the effort per enrollment, were the co-primary outcomes. The effectiveness and efficiency of successful approaches and randomizations were the secondary outcomes.

Results: Among 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<0.001), enrollment rates (15.5% vs. 1.7%, P<0.001), and randomization rates (7.4% vs. 1.34%, P<0.001). 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<0.0001), 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).

Conclusions and relevance: An add-on, active outreach strategy is 4-10-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.

Keywords: Add-on Active Enrollment Strategy; Drug-Intervention Trial; Opt-out Enrollments; Passive Enrollment Strategy; Research Methods.