Unblinding in Randomized Controlled Trials: A Research Ethics Case

Abstract

A pregnant woman was enrolled in a double‐blind randomized controlled trial (RCT) in which participants were randomized to a placebo or a drug being tested to prevent a hypertensive complication. After completing the trial, the research participant insisted on being told which drug she received to prepare for a future pregnancy. This case highlights an element of RCT procedure that has received minimal attention—whether to unblind study participants at the end of their participation. Given that unblinding is not standard practice for nonserious adverse events, what actions are justifiable for the investigators to take? To synthesize the information about this case, we used the CASES model, created by the National Center for Ethics in Health Care to analyze ethics cases. Ethical principles that guide research emphasize communication with participants and the importance of reducing harm within the constraints of the scientific goals. Participants may value knowing which drug they received for future health care decision‐making. We review information about the benefits and harms of unblinding.

Ethical Considerations in Clinical Trials for Disorders of Consciousness

“…Withholding such information from clinicians or family members, even if the information is investigational in nature and non-conclusive, may be viewed as running contrary to the ethical principles of autonomy, transparency, reciprocity, and beneficence [ 162 , 163 , 164 , 165 , 166 ]. Arguments in favor of non-disclosure may appeal to concerns of affecting the integrity of the research study or study outcomes (e.g., if un-blinding occurs or if the results influence subsequent longitudinal data acquisition), confusing family members or clinicians, reinforcing false hope (in the case of an unduly optimistic study result), or generating false despair (in the case of a unduly pessimistic study result) [ 167 , 168 , 169 ]. To manage these concerns and mitigate risks, investigators should work closely with ethicists to develop a standardized approach to sensitively handle investigational results pertaining to the presence or absence of consciousness.…”

Unblinding at disease progression in double-blinded randomized controlled cancer drug clinical trials: A controversy requires more attention

“…The notification of treatment allocation after unblinding and the informed consent cannot be ignored. The treatment assignment must be disclosed at the patient level, especially when the subsequent care is provided by other physicians rather than the investigators ( 10 ). The risk of blinding (e.g., delaying the subsequent medical care) and the conditions of unblinding should be addressed in the written informed consent and reviewed by the ethics committee.…”

Challenges in Conducting Therapeutic Trials in Pregnancy: Emphasizing Recent Lessons Learned

“…As researchers, clinicians, and patients become aware of the potential to use pravastatin for the treatment and prevention of preeclampsia, it is likely that off‐label use will increase. An ethics committee was convened when 1 of the participants in the Obstetric‐Fetal Pharmacology Research Centers pravastatin pilot study requested unblinding to guide her decision making for her next pregnancy (the patient was ultimately informed of her assignment) 69 . As in the case of COVID‐19, health care providers may be burdened with informing patients about pravastatin use prior to obtaining data from a randomized, placebo‐controlled study to guide their counseling: the safest approach to address a potential useful therapeutic.…”