The US Food and Drug Administration is reviewing the limited circumstances under which emergency research may be conducted on patients without their informed consent.
Ten years after the waiver from informed consent requirements was codified as 21 CFR 50.24, the FDA is “taking a close look” at how the regulation operates in practice to ensure emergency research “is being carried out in a scientifically sound and ethical manner,” the agency says. Recently the unease felt in some quarters over the introduction of Section 50.24 has resurfaced in widely publicised concerns about ‘no-consent’ testing of the blood substitute PolyHeme in trauma patients.
The review of emergency research is part of the Human Subject Protection and Bioresearch Monitoring (HSP/BIMO) Initiative announced by the FDA in June. The HSP/BIMO programme, which centres largely on data quality and oversight of institutional review boards, falls under the wider umbrella of the FDA’s Critical Path initiative. Current HSP/BIMO projects include tighter rules on reporting clinical trial fraud and guidance on adverse event reporting to IRBs.
The two main elements of the review are a public meeting on emergency research, to be held on 11 October, and draft guidance for IRBs, clinical investigators and trial sponsors on the development and conduct of emergency research, including the permitted exceptions from informed-consent requirements.
Clarifying the terminology
The FDA is asking for written comments on the draft guidance, which expands on a previous guidance document to define more explicitly the roles of IRBs, investigators and sponsors, broaden discussion of community consultation and public disclosure in these cases, and to clarify some of the regulatory terminology around emergency research.
Since 1996, the agency has received a “sizeable number of requests” to conduct clinical studies under Section 50.24, it notes. While acknowledging the concerns expressed by investigators, ethicists and other interested parties about the regulation, the FDA stands by the principle behind the waiver. “Unless the medical community can conduct studies in these life-threatening emergency situations, we may not truly have scientifically validated solutions to benefit patients in these extremely difficult circumstances,” said Deputy Commissioner for Operations, Dr Janet Woodcock.
Section 50.24 sets out the restricted context in which patients with life-threatening conditions, such as head trauma, cardiac arrest or stroke, may be enrolled in studies for emergency treatments without granting informed consent. This may occur before the patient is admitted to hospital or in a hospital emergency room, where the patient is unable to give informed consent due to his/her medical condition and a legally authorised representative (eg. family member) cannot be reached in time.
Earlier this year, the clause came under scrutiny amid criticism of a Phase III trial in which trauma patients were being randomised to either PolyHeme or regular blood transfusions when they arrived at hospital. The trial sponsor, Northfield Laboratories, has also come under flak for allegedly trying to bury negative results from an earlier PolyHeme study in which 10 of 81 patients receiving the blood substitute suffered heart attacks, two of them dying.
In an open letter published on the website of the American Journal of Bioethics in March, three medical researchers condemned the current trial as ethically compromised because patients were in no position to opt for donated blood with proven benefits. Following a wave of coverage in the mainstream media, Senate Finance Committee chairman Charles Grassley asked the FDA to address publicly the ethics of the PolyHeme study. By Peter Mansell