Ethics, consent and blinding: lessons from a placebo/sham controlled CPAP crossover trial.

Introduction: Performing rigorously designed clinical trials in device-based treatments is challenging. Continuous positive airway pressure (CPAP) is the most effective device-based treatment for obstructive sleep apnoea. We performed a randomised crossover trial of CPAP versus placebo therapy and did not disclose the presence of placebo. We assessed rates of staff unblinding, the likelihood of patient unblinding and obtained patient perceptions on lack of full disclosure.

Methods: All patients (n=30) underwent a semi-structured exit interview. Prior to full disclosure patients were asked questions to ascertain whether they suspected one therapy was ineffective. The use of placebo was then disclosed and additional questions were administered to indicate the likelihood of unblinding had full disclosure occurred during consent. Staff unblinding was determined by means of a questionnaire that was completed after each patient encounter.

Results: While the lack of full disclosure prevented patient unblinding during the trial, patients revealed a clear preference for active CPAP. After disclosing the presence of placebo, 73% (n=22) felt they would have been unblinded had they known at the start of the trial. Only one patient described unease about the lack of full disclosure. Staff thought they were unblinded in 6% (n=16/282) of encounters. They correctly identified the treatment device in 69% of cases (n=11/16, p<0.001).

Conclusions: Successful patient blinding was achieved, however this was probably reliant on the lack of full disclosure. Staff unblinding occurred and highlights the difficulty with investigator blinding in device-based trials. Ethical challenges in this type of study are likely to compromise research feasibility.

Trial Registration Number: This clinical trial is registered with the Australian and New Zealand Clinical Trials Registry at http://www.anzctr.org.au (ACTRN 12605000066684).