The concept of risk for human research subjects has traditionally emphasized the probability that study involvement can harm a person relative to the likelihood of harm in ordinary life. For certain progressive conditions such as dementia or diabetes, where potential benefits of treatment decrease with time or the likelihood of end-organ damage increases over time, risks of withholding knowledge of subjects' study treatment for a number of months could be appreciable if doing so prolongs the latency to effective therapy. In most cases, though, keeping individual subjects blinded is unlikely to leave them worse off than not being in the study at all. Persisting with a treatment after its futility is first detectable is hardly uncommon in clinical care. Likewise, starting or continuing therapy when no treatment or alternate treatment could produce equal or better results is practically an intrinsic element of routine care.
Besides this general concept of research risk, another approach is to consider if withholding treatment allocation information does not comport with recognized ethical obligations researchers have toward subject. The Helsinki Declaration ([24
], paragraph 30) codifies the researchers' obligation to provide subjects, after analyzing the trial's data, with access to the treatment that the study indicated was optimal. In the period between the individual subject's participation and promulgation of the study's findings, offering a supervised open trial for those still ill or facilitating subjects' transfer back to clinical care is generally felt to fulfill this obligation. Emerging standards of good clinical practice in clinical trials require somewhat less, only that adverse effects be addressed by the investigator when subjects finish a trial [25
]. Because these guidelines do not enjoin researchers to seek the immediate optimization of subjects' post-trial care, they do not oblige the disclosure of study treatment information which might serve that purpose.
It seems, rather, that the pertinent ethical issue concerns the appropriateness of withholding a benefit that would otherwise accrue to study participants. Given that knowledge of actual treatment during the study could improve decisions about further therapy, should that information be routinely available when participants end their study involvement?
From this perspective, the principal ethical benchmarks for biomedical research seem to suggest that maintaining the subject's blinding after their participation requires very strong scientific justification. The Belmont Report [26
], largely embodied in current U.S. regulations [27
], obligates biomedical research to minimize the harm to subjects while maximizing benefits. The Belmont Report also addresses directly instances when complete disclosure to subjects about the study can compromise its validity. Incomplete disclosure may be ethically permissible when 1) it “is truly necessary to accomplish the goals of the research”, 2) undisclosed risks are no more than minimal, and 3) subjects will eventually be debriefed, when appropriate. The Declaration of Helsinki [24
], paragraph 5, asserts that a consideration of the subject's welfare “should take precedence over the interests of science and society”.
Extending these principles to informing subjects about their study allocation would place an obligation on the researcher who plans to maintain subject blinding beyond his or her involvement in the controlled trial 1) to assess and minimize the risks of continued concealment of actual study treatment, including early debriefing when appropriate, 2) when these are tolerable for a specific disease to justify why doing so is essential to the study's integrity, and 3) to inform subjects about assignment and the study outcome as soon as practicable when the trial is completed.