Does random treatment assignment cause harm to research participants?

Abstract

Background: Some argue that by precluding individualized treatment, randomized clinical trials (RCTs) provide substandard medical care, while others claim that participation in clinical research is associated with improved patient outcomes. However, there are few data to assess the impact of random treatment assignment on RCT participants. We therefore performed a systematic review to quantify the differences in health outcomes between randomized trial participants and eligible non-participants.

Methods and findings: Studies were identified by searching Medline, the Web of Science citation database, and manuscript references. Studies were eligible if they documented baseline characteristics and clinical outcomes of RCT participants and eligible non-participants, and allowed non-participants access to the same interventions available to trial participants. Primary study outcomes according to patient group (randomized trial participants versus eligible non-participants) were extracted from all eligible manuscripts. For 22 of the 25 studies (88%) meeting eligibility criteria, there were no significant differences in clinical outcomes between patients who received random assignment of treatment (RCT participants) and those who received individualized treatment assignment (eligible non-participants). In addition, there was no relation between random treatment assignment and clinical outcome in 15 of the 17 studies (88%) in which randomized and nonrandomized patients had similar health status at baseline.

Conclusions: These findings suggest that randomized treatment assignment as part of a clinical trial does not harm research participants.

Figure 1. Relative Risk of Experiencing Primary Outcome According to RCT Participation

Asterisks indicate statistical significance. The relevant references for the studies listed along the x-axis are as follows: AVID [ 50, 68], EAST [ 51], Cooper [ 52], BARI [ 24], Chilvers [ 53], Bain [ 54], CASS [ 55], Link [ 57], Blichert-Toft [ 30], Henshaw [ 58], Nicolaides [ 59], SMASH [ 63], Mosekilde [ 64], Kerry [ 67], Bijker [ 25], Melchart [ 29], and Antman [ 31].