Feasibility of placebo-controlled trial designs for new CFTR modulator evaluation.

BACKGROUND: New CFTR modulators are in development that sponsors anticipate will be comparable or superior to approved modulators. Testing these agents for efficacy will require either placebo-controlled or active-comparator trials.

METHODS: We surveyed US CF physicians and their patients eligible to receive approved modulators or their families for willingness to participate in placebo-controlled modulator trials of varying duration.

RESULTS: Interest in placebo-controlled trials of short duration (2-4weeks) was greatest, with few respondents, particularly among patient respondents, willing to consider 6month studies. Patients/families with access to approved modulators were consistently less interested in placebo-controlled modulator trials of any duration.

CONCLUSIONS: Sample size and interpretability advantages of placebo-controlled trials outweigh alternative active-comparator trials, but must consider physician and patient thresholds for forgoing treatment with approved modulators. Enrollment will be most feasible for short-duration trials and those conducted among populations without access to approved modulators.