“Standard of care” research (also known as “comparative effectiveness” research) is a design that compares two therapies in routine use to determine which has greater benefits or fewer risks.
All institutions that perform this research, including Albert Einstein College of Medicine and its University Hospital, Montefiore Medical Center, face questions about how to handle patient consent. This blog post represents my opinions on the issues, not the official position of Einstein and/or Montefiore.
This type of research has spurred an ongoing controversy following the SUPPORT trial, a study to determine the best oxygen saturation level in extremely premature infants in order to prevent “retinopathy of prematurity,” a condition that can cause blindness. The Office of Human Research Protections (OHRP) of the Department of Health and Human Services imposed sanctions on the lead research institution conducting the study for what the agency said were inadequate informed consent documents.
Criticism over Consent Forms
There followed a spate of editorials and articles in the New England Journal of Medicine (NEJM) and, under what appeared to be pressure from officials at the National Institutes of Health (the sponsor of the SUPPORT study), OHRP withdrew the sanctions but reiterated its criticism of the study’s consent forms. Critics of the OHRP action contended that consent forms for “standard of care” research need not list the risks of any interventions that patients would undergo if not enrolled in the research. One NEJM article stated, “Some of the options for conducting such research take advantage of the fact that there is no additional risk to being randomly assigned to one or another equally well-supported treatment option that falls within the standard range of care in clinical practice.” Those who defend OHRP’s action maintained that the risks even of standard interventions should be disclosed on the consent forms. In late October 2014, OHRP issued “Draft Guidance on Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care,” inviting public comment up to December 23. This guidance reignited the controversy, resulting once again in an editorial in the NEJM and other articles critical of the draft guidance. Among the arguments put forth in NEJM then was that “…the nature of consent, when needed, for research within the standard of care should be fundamentally different from that for research into novel treatments with unknown risks, since standard-of-care research does not expose participants to risk beyond the risk they might be exposed to outside the study.”
The draft guidance says: “OHRP’s general position is that in research studies designed to evaluate the risks of standards of care: (1) the risks of standards of care that at least some subjects would be exposed to by participating in a research study that are different from the risks of therapies the subjects would be exposed to outside the study are risks of the research that the IRB [institutional review board] must consider when evaluating the research; and, (2) the identified risks the research proposes to evaluate as one of the purposes of the study are reasonably foreseeable risks that generally must be disclosed to prospective subjects when seeking their informed consent.” In other words, in a randomized, controlled trial studying two “standard of care” interventions, although some participants may receive the treatment they would get outside the study, others will not. An example is a clinical trial to compare a commonly used medical intervention with a standard surgical treatment for the same condition.
IOM Workshop: Pros and Cons
On December 2 and 3, 2014, the Institute of Medicine (IOM) of the National Academies convened a workshop to address the OHRP guidance. Invited speakers and some members of the audience were among the combatants in the ongoing controversy and included authors of the articles published in the NEJM on both sides of the controversy.
I was one of the invited speakers, having been the lead author of one of the published articles. Along with two co-authors and other colleagues, I had argued that the consent documents in the SUPPORT study were flawed by failing to state a number of known risks. My general view of the matter is that consent forms for this type of research must list the risks of interventions, even if those risks are the ones some participants would receive as part of their routine treatment.
At the IOM meeting, I took the role of a hypothetical patient, providing examples of what a prospective research subject would want to know when deciding to enroll in “standard of care” research. I agree with the position OHRP outlined in its draft guidance, in opposition to critics who maintained—in the complete absence of evidence—that the need to disclose the reasonably foreseeable risks of “standard of care” interventions would cause this important type of research to grind to a halt.
The IOM has announced that it will soon make available on its website all the presentations at the December workshop, so readers can evaluate the controversy for themselves.