Effect of opt-in versus opt-out framing on trial recruitment: a study within a trial of the GAMEPAD randomized trial

Directly contacting eligible participants with an offer to join a randomized clinical trial (RCT) is an efficient recruitment method, but the effect of different outreach strategies on enrollment fraction and completion of the trial protocol is uncertain. In a study within a trial (SWAT) of an RCT testing a physical activity intervention in patients with peripheral artery disease, eligible patients were randomized to receive an email with an invitation to join the study and a link to the trial's online platform ("opt-in") or to receive an email framing participation as part of the standard of care followed by telephone outreach from a study coordinator ("opt-out"). Among 5176 participants contacted by unsolicited email (3909 opt-in, 1267 opt-out), enrollment fraction was 1.0% in the opt-in arm (n = 39) versus 3.6% in the opt-out arm (n = 45) (OR 3.65, 95% CI 2.37-5.64); there were no significant differences between opt-in and opt-out participants in the rate of completion of trial protocol steps. This SWAT of recruitment strategies demonstrates the potential for opt-out framing and active outreach to increase enrollment fraction without compromising protocol completion in direct-to-participant RCTs.