Can keeping clinical trial participants blind to their study treatment adversely affect subsequent care?

Abstract

Subjects in controlled clinical trials obtain experience with study-provided treatment that could inform their further therapy by awareness of the efficacy or inefficacy of the study treatment they received. However, patients in blinded trials typically do not learn right after their participation what treatment they actually received during the study, even though it is possible to do so while maintaining the necessary blinding of investigators. Keeping investigators and subjects blind to treatment assignment throughout a trial is a key element of clinical research methodology, but the value of keeping participants and their medical providers blinded after participation is less certain and may pose risks that include delay in the receipt of efficacious care, exacerbation of symptoms, or prolonged exposure to superfluous or toxic treatment. The significance of these risks is likely to vary with the specific disease and the time course of its response to available therapies. Currently, it seems appropriate for investigators a) to evaluate the risks of keeping subjects blind after participation, b) to justify doing so in relation to serious, identifiable risks to the study's validity and apprise prospective subjects clearly that information about their response to specific treatment during the trial will not be available to guide their post-study care, and c) to consider methods for debriefing subjects before their resumption of open treatment that preserve the integrity of investigator blinding. In the long-run, research on the impact that keeping subjects uninformed about study treatment has on post-study patient outcomes and on study integrity can foster the development of procedures that optimally balance both.

Reporting and Interpretation of Randomized Controlled Trials With Statistically Nonsignificant Results for Primary Outcomes

“…For this purpose, in a first step, we reviewed the literature published on this topic. 3,6,[13][14][15][16][17][18][19][20][21][22] We also contacted by e-mail all the members of the Cochrane Statistical Method Group and invited them to send us any examples of published RCTs with spin, in any medical field, and with any publication date. Lastly, we reviewed a sample of trials with statistically nonsignificant results published in general medical journals with high impact factors or in specialist journals.…”

Blinding in Clinical Trials: Seeing the Big Picture

“…Additionally, blinding inherently deviates from real-world experience, making it a hallmark feature of trials which aim to maximize the likelihood of establishing the efficacy of an intervention by testing it in an ideal setting (i.e., “explanatory trials”), but potentially less relevant for trials which aim to generate situations that are as close to routine practice as possible (i.e., “pragmatic trials”) [ 51 ]. Blinding has also been suggested to potentially adversely impact subsequent care after the conclusion of a clinical trial [ 52 ].…”

Unblinding in Randomized Controlled Trials: A Research Ethics Case

“…The principles described in The Belmont Report laid a foundation for regulations regarding the ethics of human subjects research in the United States 22 . Among other effects, these principles obligate biomedical researchers to maximize benefits to the participants, within the constraints of the scientific aims of the study, while minimizing harm 23 . In relation to the case on which we are focused, the issue is whether avoidable harm was being done by not disclosing the study intervention postparticipation.…”

“…They could reveal their treatment to the study investigators, which could bias the ongoing study. Study investigators may consciously or unconsciously view data, analyze outcomes, or report results differently 29 . Studies in which subjects become aware of their randomized assignment during the RCT due to inadequate blinding procedures have larger treatment effect sizes, which may not be valid 30 …”

“…Unblinding participants so they can make an informed decision about further treatment may be advisable for several reasons 34 . Participants who knew the aggregate results of a trial but not their own treatment allocation reported being frustrated with the situation 35 .…”