title: Ethics, consent and blinding: lessons from a placebo/sham controlled CPAP crossover trial.
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  This clinical trial is registered with the Australian and New Zealand Clinical Trials Registry at http://www.anzctr.org.au (ACTRN 12605000066684).
authors.affiliation: NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Djavadkhani
authors.affiliation: NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia Sydney Nursing School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Marshall
authors.affiliation: NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia Sydney Local Health District, Sydney, New South Wales, Australia.
authors.forename: Angela L
authors.initials: AL
authors.lastname: D'Rozario
authors.affiliation: NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia Sleep Disorder Services and Research Center, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Crawford
authors.affiliation: NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Yee
authors.affiliation: NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Grunstein
authors.affiliation: NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Phillips
mesh_terms: D045422:Continuous Positive Airway Pressure; D018592:Cross-Over Studies; D030881:Disclosure / Q000941:ethics*; D004311:Double-Blind Method; D006801:Humans; D007258:Informed Consent / Q000941:ethics*; D007407:Interviews as Topic; D010349:Patient Compliance; D057240:Patient Preference; D010465:Perception; D010919:Placebos; D012108:Research Personnel; D020181:Sleep Apnea, Obstructive / Q000628:therapy*; D011795:Surveys and Questionnaires
chemical_list: D010919:Placebos
keywords: Sleep apnoea