Effect of Unblinding on Participants' Perceptions of Risk and Confidence in a Large Double-blind Clinical Trial of Chemotherapy for Breast Cancer.

Author(s): Partridge AH(1), Sepucha K(2), O'Neill A(1), Miller KD(3), Motley C(1), Swaby RF(4), Schneider BP(3), Dang CT(5), Northfelt DW(6), Sledge GW Jr(7).

Affiliation(s): Author information: (1)Dana Farber Cancer Institute, Boston, Massachusetts. (2)Massachusetts General Hospital, Boston, Massachusetts. (3)Indiana University Cancer Center, Indianapolis, Indiana. (4)Merck, North Wales, Pennsylvania (current location), Fox Chase Cancer Center, Philadelphia, Pennsylvania (former location). (5)Memorial Sloan Kettering Cancer Center, New York, New York. (6)Mayo Clinic, Scottsdale, Arizona. (7)Stanford University, Stanford, California (current location), Indiana University Cancer Center, Indianapolis, Indiana (former location).

Publication date & source: 2015, JAMA Oncol. , 1(3):369-374

IMPORTANCE: Blinding patients to treatment regimen is an important component of high quality randomized clinical trials (RCT) although concern exists about how receipt of a placebo will impact participants' views, particularly among patients with cancer. OBJECTIVE: To determine if unblinding of random assignment to placebo vs. experimental agent in a large adjuvant breast cancer chemotherapy randomized controlled 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 to those randomized to experimental therapy. DESIGN: Serial telephone based prospective surveys. SETTING: In ECOG5103, patients were randomized to receive standard adjuvant chemotherapy for breast cancer with either placebo or bevacizumab for either ~6 or ~12 months. Treatment assignment was unblinded by 24 weeks. PARTICIPANTS: All patients enrolling in E5103 between 1/5-6/8/10 were included in this sub-study. Patients were surveyed after unblinding of their randomization allocation. MAIN OUTCOME AND MEASURE: Survey items including perceived risk of recurrence and confidence in study participation. RESULTS: 571 patients on this sub-study started protocol therapy, 550 were still on study at unblinding and 492 responded to the unblinding survey. At unblinding, most respondents, 70% (336/477), felt they had at most a small risk of breast cancer recurrence, 71% (342/480) reported perceiving at most a small risk of serious problem with therapy; the vast majority reported feeling very informed and having high levels of confidence in their study participation (87% for both (421/483 and 420/483 respectively)). Participants who learned they had been randomized to placebo did not have greater perception of chance of recurrence (p=0.48) or fear of recurrence (p=0.69), feel less informed (p=0.86) or have lower confidence in trial participation (p=0.31) compared to those who had been randomized to experimental therapy. Patients who learned they had been randomized to bevacizumab perceived higher risk of having a serious problem caused by treatment (p=0.01). CONCLUSIONS AND RELEVANCE: In a placebo-controlled, double-blinded RCT, 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 anti-cancer therapy along with standard chemotherapy. PARENT TRIAL REGISTRATION: NCT00433511.