In a previous article, we examined the shortcomings of some informed consent procedures in clinical trials in the United States. In the current article, we take a look at the process known as “deferred consent,” and analyze its adherence to regulations set by the Office of Human Research Protection, part of the US Department of Health and Human Services. The code of federal regulations (CFR) for the protection of human research subjects (CFR Title 45, Part 46) was initially published in 1974 and most recently revised in 2009. Additional changes were proposed in 2011, but have not yet taken effect.
In general, the process for obtaining informed consent from a research subject involves the disclosure of the fact that the study involves research, a description of the reasonably foreseeable risks of that research (as well as any potential benefits), the disclosure of alternative courses of treatment, a description of any ways in which confidentiality will be broken, an explanation regarding any compensation orremedial treatment for incurring any risk above a “minimal” level, instruction as to points of contact for questions about the research, and an assurance that participation in the research is voluntary and may be terminated by the subject at any time. In part, the regulations state, “No investigator may involve a human being as a subject … unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative. An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate [emphasis ours].”
One apparent violation of the provision requiring sufficient opportunity for consideration of participation is the concept of “deferred consent,” advanced in a 1986 issue of JAMA. In the article “Deferred Consent: A New Approach for Resuscitation Research on Comatose Patients,” Norman Abramson, Alan Meisel, and Peter Safar argue that when performing experimental resuscitation procedures, an “emergency exception to informed consent” applies. (The CFR for the protection of human research subjects states, “Nothing in this policy is intended to limit the authority of a physician to provide emergency medical care, to the extent the physician is permitted to do so under applicable federal, state, or local law.”) Abramson et al argue that treating physician-researchers should be able to use a process of “deferred consent,” during which consent to continue treatment is sought from the patient after treatment has begun in an emergency situation.
The concept of deferred consent has gone on a long, strange journey since 1986, making a 2011 appearance in the Journal of Psychopharmacology. Framing being used as a research subject as a privilege of which incapacitated patients should not be deprived, Jamie Labuzetta, Rowan Burnstein, and John Pickard argue for broader use of deferred consent among “vulnerable patients.” The language used by Labuzetta et al is stunning in its presumption: “Many subjects cannot give fully informed consent to take part in research by virtue of age or mental capacity,” they begin, going on to assert, “However, it is unacceptable to deny these patients involvement in research by virtue of a lack of capacity to consent to such research. Further, this would hinder the advancement of medical science and technologies that might ultimately benefit these patients.”
The arguments by Labuzetta and colleagues appear to have taken hold in the research community, as shown by the use of deferred consent in a recent statin trial, proposed in a 2011 Trials article by a Canadian research team. Researchers planned to randomize 80 adults who were receiving mechanical ventilation and were suspected of having H1N1 flu into two groups: one receiving rosuvastatin, and the other receiving placebo. (Rosuvastatin is marketed by AstraZeneca as Crestor for the treatment of high cholesterol, and at the time of the proposed study, did not have a prescribing indication for flu treatment.) “We propose several approaches to informed consent,” the researchers cavalierly state, “including a priori consent from the substitute decision maker (SDM), waived, and deferred consent.” Another criterion for selection into the study was having received antiviral therapy for less than 72 hours.
Deferred consent? Is it likely that someone with suspected H1N1 infection — which could be confirmed with a simple lab test — would opt in to receive Crestor instead of continued antiviral therapy? The researchers noted that rosuvastatin was known to carry a risk of myopathy (muscle failure) and rhabdomyolysis (breakdown of skeletal muscle). They did not mention the increased risk of diabetes carried by statins, despite the publication of research to that effect in the Lancet in 2010 — not that it would have mattered for many of the research participants, as the scientists intended to enroll incapacitated individuals for whom no substitute decision maker could be located, under the process of “deferred consent.” “In the event that patients die before providing consent [emphasis ours],” they state, “we request permission from REBs [Research Ethics Boards] to include data collected during study participation.” Indeed, one would not want to waste the valuable data gathered from the use of subjects who never gave their permission. It remains to be seen whether the US Department of Health and Human Services will act to clarify the legality of deferred consent.