Resistance to a Novel Clinical Trial Design for Multicancer Detection Tests: Experimental Investigation of Ambiguity Aversion.

BACKGROUND: Randomized controlled trials (RCTs) are needed to evaluate multicancer detection (MCD) tests. A novel "intended-effect" RCT design in which control group participants receive MCD testing but results remain undisclosed can increase statistical efficiency. Prospective participants may find this design unacceptable due to ambiguity aversion introduced by the existence of undisclosed but theoretically knowable test results. We evaluated this effect and tested if reducing ambiguity by ensuring the unknowability of test results mitigates this bias. METHODS: US adults aged 45 to 70 y (N = 1,576) were randomized to read about 1 of 4 RCT designs evaluating MCD testing: 1) RCT with a conventional control group (no testing), 2) RCT with a standard intended-effect control group (ie, control gets testing but not the results), 3) modified intended-effect RCT emphasizing disclosure safeguards to ensure the unknowability of control group test results to participants and researchers, and 4) modified intended-effect RCT with time-delayed testing on control group blood samples after trial completion. Outcomes were study interest (5-point scale, with higher values indicating more interest) and intention to participate (yes/no). Analyses of variance, chi-square tests, and regression-based analyses examined the main effects and potential mediating roles of the perceived net benefit of participating in the study and trust in study researchers. RESULTS: Intention to participate was similar across all conditions (range: 14%-21%). Study interest was higher in the conventional control (M = 3.73) vs the 3 intended-effect designs (P < 0.05), which did not differ (Ms = 3.36-3.45). The negative influence of intended-effect designs on study interest was partially mediated by perceived net benefit. CONCLUSION: Intended-effect RCT designs lower interest in MCD trial participation, in part by reducing prospective participants' perceptions of benefiting from the trial. Strategies to reduce ambiguity do not mitigate this effect.