Cost-Effectiveness Research (CER) is much in the news these days. Must researchers who conduct such studies always obtain informed consent from their patients/human subjects? Two recent articles by prominent bioethicists offer different perspectives.
In the February 20 edition of the New England Journal of Medicine (subscription or payment required), Ruth Faden, Tom Beauchamp, and Nancy Kass took the position that some comparative effectiveness research may be done without the consent or even knowledge of subjects. They give the examples of “randomized studies that compare the effectiveness of sending medication reminders by text or e-mail,” or tests of “the usefulness of repeating a routine laboratory test once or twice during hospitalization when both are standard practice.” But a further example of a study that would not require obtaining the consent of, or informing, patients would be a “pragmatic” randomized trial of treatment algorithms used to assign patients to one of two or more drugs that are widely understood to have clinically equivalent effects. A further safeguard would be that the treating physician would retain the power to override the randomized choice. An example of a study that would require consent [as at present] would be a randomized study comparing two different approaches to treatment, where there might be a clinically meaningful difference in outcome. But CER could be streamlined, to the benefit of making health care entities (like hospitals) “learning” entities, by eliminating the need to tell people in a wide range of instances that they are participating in research. Deciding which studies need consent would be overseen by “ethics-oversight panels,” the membership of which would include patients.
In the same issue, Scott Kim and Franklin Miller countered that generating the knowledge sought in “pragmatic” randomized trials is already compatible with current research oversight procedures. They argued that adopting a no-consent model for some randomized studies would harm the physician-patient relationship by requiring the physician to conceal some relevant facts about the patient’s care, unjustifiably overriding a presumption of transparency in the physician’s communications with the patient. The no-consent model would wrongly bypass the patient’s agency (autonomy), assume that the patient has no interest in the choice being subjected to randomization, and gain no real benefit in any case. Instead of the no-consent model, they argue for abbreviated consent documents that could be integrated into regular practice and could be briefer precisely because the alternative treatments had previously been subjected to rigorous studies with more detailed consent processes for the participants. To be sure, the sort of “ethics-oversight panels” envisioned by Faden, Beauchamp, and Kass already exist: we call them IRBs. (And by regulation, every IRB must include at least one voting member from the general public.) Kim and Miller would require that all “pragmatic” trials in question undergo IRB review, as is currently required for all research on human subjects.
In a related article in the March 10 issue of JAMA (available for free), Miller joins with Nayak and Pearson to argue that participants in research designed to compare two clinically equivalent treatments—one cheaper and one more expensive—should be told that a major driver of doing the research in the first place is to see whether the cheaper alternative is indeed as good as the more extensive one. Case in point: a recent trial of treating age-related macular degeneration (AMD) with [expensive] ranizumab (Lucentis®) or [much cheaper] bevicuzumab (Avastin®, originally developed to treat cancer but widely used for AMD.
The issue arises in part because the Department of Health and Human Services (HHS) is in the midst of a fairly protracted exercise intended to revise the “common rule” for human subjects’ research. As part of that, HHS has considering whether all research on humans indeed requires IRB review, and it has been asking for public comment on whether some randomized studies, reviewed by the IRB, might rightly have consent waived.
Research on humans is regulated in the U.S. by the Office of Human Research Protection (OHRP) of the HHS, and by FDA. FDA does not provide for waiver of informed consent except for emergency research. However, OHRP, in the Code of Federal Regulations, 45 CFR 46.116, provides that an IRB may waive the requirement for informed consent, or alter the required elements of informed consent, for a research project if it cannot be “practicably” carried out otherwise, and it either involves public benefit or service programs, or, failing that, if the research involves no more than minimal risks to the subjects and the waiver or alteration of consent does not adversely affect the subjects’ rights or welfare. In cases of the latter (non-public-program) research, subjects “should be provided with additional pertinent information after participation,” whenever this is “appropriate.” The sort of “pragmatic” studies under discussion here would probably fall more under the OHRP regulations than FDA regulations.
Kim and Miller essentially argue for briefer, altered consent forms and processes for certain “pragmatic” research, as opposed to placing large areas of research under a no-consent veil. And the IRB can and should oversee all this. A counter argument is that leaving all this research under the purview of the IRB is too cumbersome, and that IRBs are overly conservative, especially when it comes to consent requirements. But the answer for this is better consent processes, better (including shorter, clearer, more pertinent) consent forms, and more judicious IRBs.
I’m with Miller and his colleagues on this one. I’ve served on an IRB, and I support caution in rewriting the IRB’s charge too much. Now, issues remain: for example, would CER studies done on Medicaid patients (beneficiaries of a public program) be more likely to be considered for consent waivers that might be unjustly granted? I imagine so. But it is for properly-working IRBs to act to prevent abuses.