OHRP issues draft guidance on standard of care research
Guidance issued in response to Support study controversy
A year after its public meeting on the Support study, the Office of Human Research Protections (OHRP) issued a draft guidance to clarify its thinking on the disclosure of reasonably foreseeable risks in standard of care research.
The guidance, titled "Draft Guidance on Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care," was released by the organization in late October. OHRP developed the draft guidance following a public comment and meeting in August 2013 after the fallout from the 2010 Surfactant, Positive Pressure, and Oxygenation Randomized Trial (Support).
The National Institutes of Health (NIH)-funded study included 23 research institutions under the coordination of the University of Alabama Birmingham and tested oxygen levels for nearly 1,300 premature infants. The study intended to find the optimal oxygen concentration for the premature infants. The infants receiving higher levels of oxygen developed retinopathy and other eye disease twice as much as the infants in lower oxygen levels. Those receiving lower oxygen levels had higher rates of brain damage and mortality.
Standard of care debate
In March of 2013, OHRP sent UAB a determination letter stating that the oxygen saturation levels portion of the study was in violation of informed consent requirements and that researchers did not fully explain the risks involved in the study. OHRP required corrective action, which touched off a debate in the research ethics world. The August 2013 public meeting brought comments on both sides of the issue, with researchers and bioethics leaders speaking in support of UAB and others who supported OHRP’s determination. (For more information on the Support study and the public debate, see "Informed consent, standard of care debated at OHRP meeting" in the October 2013 issue of IRB Advisor, page 109.)
According to the draft guidance, the public debate "raised a number of questions, including: (1) what risks to subjects are presented by clinical trials studying interventions that are standard of care in the clinical treatment context, such that an IRB must evaluate those risks in relation to the anticipated benefits of the research; and (2) how an IRB should assess whether those risks are reasonably foreseeable such that the risks must be described to subjects in the informed consent process."
The draft guidance gives clarity to IRBs and researchers on how to apply regulations 45 CFR Part 46 when evaluating studies with multiple standards of care. "It explains OHRP’s position that in general the reasonably foreseeable risks of research in a study include the already identified risks of the standards of care being evaluated as a purpose of the research when the risks being evaluated are different from the risks some of the subjects would be exposed to outside of the study," the document states. "Reasonably foreseeable risks must be described to prospective subjects when seeking their informed consent in accordance with 45 CFR 46.116(a)(2)."
Defining standards, risks
The guidance addresses the following questions.
What are "standards of care"?
OHRP uses "standard of care" to refer to medically recognized standards of care: treatments and procedures accepted and typically used by healthcare professionals to treat certain conditions or diseases.
What are "risks of research" in studies evaluating risks associated with standards of care?
The risks of a standard of care are considered risks of research if, "(1) a standard of care that at least some of the individual subjects will be assigned to receive will be different from the standard of care that they would have received if they were not participating in the study, and (2) there might be different risks associated with those standards of care," according to the guidance.
It is often the case that the risks associated with one standard of care are different from the risks of another standard, the guidance states, and do not include the risks associated with the subject’s condition or other standard of care treatments he or she may be receiving.
When is evaluating a risk in a research study considered to be a "purpose" of the research study?
According to OHRP, "research should be limited to evaluating those risks that are sufficiently important to justify the conduct of the study," the guidance reads. "The purposes of such studies should not be construed as necessarily including each and every one of the outcomes that may be measured as part of the study, but that are not part of the fundamental reasons for conducting the study." The evaluation of a risk is considered a purpose of research only if the study is designed to investigate a particular risk, it states.
Are the risks of research associated with the purposes of studies of standards of care "reasonably foreseeable risks" that must be disclosed to prospective subjects in the informed consent process?
Reasonably foreseeable risks must be disclosed to subjects in order for them to make an informed decision as to whether to participate in research, regulations state. As far as standard of care studies, "if the rationale for evaluating a risk associated with a standard of care is sufficient to warrant conducting the research, then OHRP’s view is that, in general, the research risk being evaluated has been recognized as a sufficiently possible outcome so as to make it a reasonably foreseeable’ risk, and the regulatory provision applies.
If researchers design and conduct a study for the purpose of evaluating a particular risk, then that risk is significant enough that it should be disclosed to the prospective subjects who are actually exposed to it," the guidance reads.
Public comment
OHRP is currently receiving public comment on the draft guidance. The comment period for the guidance ends on December 23, 2014. The full document can be found at http://www.hhs.gov/ohrp/newsroom/rfc/comstdofcare.html.
