Rationale for Sponsor-unblinded Phase 1 Trials: Challenging the Double-blind Paradigm

Abstract

Randomized, double-blind, phase 1 clinical trials conceal study treatment assignment from the subject, the investigator, and the sponsor while the trial is ongoing. We make a case for unwinding the sponsor because there is much to gain and little to lose at this very early phase of clinical development. Some of the advantages of unblinding include a direct assessment of treatment-related safety signals with the option to make appropriate trial design modifications and speeding up early drug development. The disadvantage includes the increased risk of the study investigator becoming inadvertently unblinded to individual subject treatment assignments on a few subjects. We make the case that on balance the benefits of sponsor unblinding outweigh the risks. Phase 1 trials for which unblinding may not be appropriate are also mentioned.