WASHINGTON -- The FDA recently issued an updated guidance document on obtaining informed consent for clinical trials, with increased detail about how consent should be obtained.
The document, posted online last week, updates guidance on informed consent that was issued in 1998. It contains sections on basic elements of informed consent, including providing patients with a description of the trial, its risks, benefits, alternative treatments, confidentiality, and compensation in the event of injury. It also offers guidance on how investigators and institutional review boards (IRBs) can help ensure that informed consent is adequate and meets the FDA's requirements.
Rosamond Rhodes, PhD, director of bioethics education at Mount Sinai School of Medicine in New York City, said she was pleased that the revised guidance included a section urging that trial participants be told the outcome of the trial.
"This is a very good thing," she said in a phone interview. "It was never a requirement at all that people be informed what happened, so this is a big change and a very positive change."
The rest of the document, she said, "appears to be making no changes" from the earlier guidance -- "just specifying in greater detail how things should be done, in no way inconsistent with what's been done in the past."
Increased Attention to Detail
Michael Carome, MD, director of the Public Citizen Health Research Group, said he was pleased with the guidance’s increased attention to detail. “It is definitely an improvement over the 1998 informed consent information sheet,” Carome said in a phone interview. “It is much more comprehensive and detailed, and it expands a number of discussions of various elements of informed consent … and adds new elements not found in the 1998 document.”
One new element in the guidance is the requirement that researchers explain alternative treatments that participants might be able to receive if they were not involved in the research, he continued. “Putting the research in the context of other alternatives and having some amount of detail about that is very good guidance about informed consent.”
On a related note, the guidance also says it’s all right to disclose off-label uses of the drug being tested. “Perhaps the drug is already approved for another indication, and patients don’t necessarily have to enter a randomized trial to get that intervention,” Carome said.
“In the past, the FDA has been reluctant to say it’s OK to disclose off-label uses of the drug being tested. This guidance has language that essentially acknowledges that is acceptable to do. I think it’s good that the guidance allows for that.”
Some Problems Remain
Several problems from the original 1998 guidance remain, according to Rhodes. For one thing, it doesn't fully address what should be done in the case of participants who don't have the capacity to consent themselves -- such as children and people who are unconscious, who have dementia, or who are mentally ill.
"This document is full of language about a 'legal representative' [for such people], but most states have no laws designating who the legal representative is," she said.
New York state, for instance, has a law known as the Family Healthcare Decision Act allowing a patient-appointed proxy or a family member to make decisions on behalf of patients regarding their treatment, but it doesn't address decisions related to participation in research.
"A couple of states have such regulations but in most cases nobody knows about it," she said. "Some IRBs take a permissive attitude and others are very restrictive, but that remains a mess."
One recent controversy around informed consent involved the SUPPORT trial, which evaluated oxygen saturation targets in premature infants.
In 2013, the watchdog group Public Citizen alleged that the federal Office for Human Research Protections (OHRP) failed to respond appropriately when it uncovered deficiencies in the consent forms that left infants' parents uninformed about potential risks in a study.
Public Citizen said babies in the trial were subjected to an increased risk of blindness, brain injury, and death. No consent forms mentioned death as a risk. Twenty of 22 forms failed to identify brain injury as a risk.
In response to the criticisms, the Department of Health and Human Services called a day-long public hearing at which patient advocates urged federal regulators to strengthen the informed consent required in research studies and to increase oversight of the process.
Not Relevant to SUPPORT
Rhodes said she didn't see anything in the new guidance that would help prevent the problems alleged in SUPPORT. That's because blindness and death can be among "the natural complications of [standard treatment for premature infants] ... That's what the parents should have been told as part of treatment and care of their child, before they were in any way involved in the study.
"Now did the study impose any additional risk? According to the [guidance], the investigators should tell them about the risks involved in an investigation, but those risks [of blindness and death] are from the condition and treating the condition. They were only trying to find out if they could narrow the window of how much oxygen to give."
Carome said the updated guidance doesn’t really address the issues his group raised regarding the SUPPORT trial. “It’s our view that what was appropriate in context of informed consent for SUPPORT was clear at the time,” he said. “There are things in this guidance that support our position … but I don’t think a lack of guidance justifies the deficiencies that occurred in the SUPPORT study.”
“We think design of the study was flawed, so even with a perfect consent process the trial shouldn’t have been done the way it was done,” he added.
However, Carome said, to the extent that the new guidance “has a nice discussion about how you have to explain what patients would get outside of research, and [what is usual care], that is consistent with what should have occurred in the SUPPORT study and was lacking.”
Rhodes noted that the request for the updated guidance came from OHRP, which said it wanted to make it easier for scientists to conduct research. "Nothing in this document makes it any easier to do research," largely because the FDA is limited in what areas it can advise people about, she said. "They can't; they're just specifying how to do things, and what they're saying is fine."
UPDATE: This article, originally published July 22, 2014, @ 5:58 p.m., was updated with new material (July 23, 2014, at 12:00 p.m.).