title: Effect of Unblinding on Participants' Perceptions of Risk and Confidence in a Large Double-Blind Clinical Trial of Chemotherapy for Breast Cancer.
abstract: OBJECTIVE
  Blinding patients to treatment regimen is an important component of high-quality randomized clinical trials, although concern exists about how receipt of a placebo will affect participants' views, particularly among patients with cancer.
  
  
  OBJECTIVE
  To determine whether unblinding of random assignment to placebo vs experimental agent in a large adjuvant breast cancer chemotherapy randomized clinical trial was associated with perception of greater chance of cancer recurrence and lower confidence in the decision to participate in the trial in participants who were randomized to placebo compared with those randomized to experimental therapy.
  
  
  METHODS
  Serial telephone-based prospective survey substudy of all Eastern Cooperative Oncology Group Protocol 5103 (ECOG5103) participants enrolling between January 5 and June 8, 2010. In ECOG5103, patients were randomized to receive standard adjuvant chemotherapy for breast cancer with either placebo or bevacizumab for either approximately 6 or approximately 12 months. Treatment assignment was unblinded by 24 weeks, and then patients were surveyed.
  
  
  METHODS
  Trial participants' self-reported perceived risk of recurrence and confidence in study participation.
  
  
  RESULTS
  Of 571 patients in this substudy who started protocol therapy, 550 were still in the study at unblinding and 492 (89%) responded to the unblinding survey. At unblinding, 336 of 477 (70%) believed that they had at most a small risk of breast cancer recurrence, and 342 of 480 (71%) reported perceiving at most a small risk of serious problem with therapy; most reported feeling very informed (421 of 483 [87%]) and having high levels of confidence in their study participation (420 of 483 [87%]). The 102 participants who learned that they had been randomized to placebo did not have greater perception of chance of recurrence (P = .48) or fear of recurrence (P = .69), feel less informed (P = .86), or have lower confidence in trial participation (P = .31) compared with the 390 participants who had been randomized to experimental therapy. Patients who learned that they had been randomized to bevacizumab perceived higher risk of having a serious problem caused by treatment (P = .01).
  
  
  CONCLUSIONS
  In a placebo-controlled, double-blind randomized clinical trial of chemotherapy for breast cancer, unblinding to randomization allocation did not significantly affect most participants' views except for chance of a serious problem from experimental treatment, regardless of receipt of placebo or experimental anticancer therapy along with standard chemotherapy.
authors.forename: Ann H
authors.initials: AH
authors.lastname: Partridge
authors.forename: Karen
authors.initials: K
authors.lastname: Sepucha
authors.forename: Anne
authors.initials: A
authors.lastname: O'Neill
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
authors.forename: Christine
authors.initials: C
authors.lastname: Motley
authors.forename: Ramona F
authors.initials: RF
authors.lastname: Swaby
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Schneider
authors.forename: Chau T
authors.initials: CT
authors.lastname: Dang
authors.forename: Donald W
authors.initials: DW
authors.lastname: Northfelt
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D005260:Female; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D007258:Informed Consent; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010465:Perception; D010919:Placebos; D012107:Research Design; D035842:Research Subjects / Q000523:psychology*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D020533:Angiogenesis Inhibitors; D010919:Placebos; D000068258:Bevacizumab