Community Consultation for Emergency Exception to Informed Consent: How Much is Enough?

Minimizing Uncertainty 

Several medical and research groups, though, believe they have now made advances in removing at least some of that uncertainty by formally recommending a graduated scale of consultation based on the degree of risk posed to patients in the study. Clinical investigators and medical bioethicists generally agree that longstanding dilemmas may be reduced by these new recommendations for institutional review boards regarding the Food and Drug Administration (FDA) rules. Last fall, the American College of Emergency Physicians (ACEP) and the Society for Academic Emergency Medicine endorsed American Heart Association (AHA) recommendations for implementing new guidelines for consulting with communities and making public disclosures under the FDA’s so-called Final Rule, the requirement for exceptions from informed consent for emergency research.

The FDA (and concurrently, the US Department of Health and Human Services) rule left the extent and appropriateness of community consultation up to each institutional review board (IRB). The result is that the regulation can be interpreted and applied in varied—and, critics say, uneven—ways.

“Current regulations do allow studies to be performed with exception to informed consent, but ambiguities in implementing studies under current regulations can be onerous for IRBs and investigators and may discourage research to evaluate promising interventions for Americans,” the AHA report concluded. It stated that the proposed template guide would be “an appropriate balance between protecting eligible patients and preserving the public good.”

A Graduated Scale 

The AHA recommendations call for a stratified approach to satisfying the requirement. Simply put, they say that the greater the potential for harm to the study patient, the more community consultation and disclosure is needed for the study.

“Instead of paying heed only to the inherent risk of the underlying disease, which is present whether the patient is enrolled in the study or not, we recommend evaluating the incremental risk from participating in the proposed study,” the AHA report stated. “That evaluation can then be used to determine the degree of community consultation and public disclosure appropriate for the proposed study.”

Research comparing an approved therapy with another approved therapy, to determine which may be better for emergency patients, was cited as an example. Even though the patient might have a life-threatening condition, the additional risk posed by the study would be relatively low. Therefore, minimal community consultation would be needed. For high-risk studies, the guidelines call for comprehensive approaches—meetings with key community groups and leaders, media and public disclosure campaigns, and other significant measures to ensure maximum awareness and input for the study.

“Our point is that although all emergency research that is not minimal risk requires some level of public disclosure and community consultation, emergency research studies that have less incremental risk and are not politically and culturally controversial may be performed ethically with lesser degrees of community consultation and public disclosure than would be needed for high-risk or controversial studies,” the AHA recommendations stated.

A Logical Solution 

Robert Silbergleit, MD, an associate professor of emergency medicine and clinical investigator at the University of Michigan, lauded the recommendations as a logical extension of the FDA intentions on informed consent.

“Community consultation is one of the more important, and one of the more challenging, aspects of exception from informed consent research,” Silbergleit said. “A lot of the regulators, IRBs and investigators sort of struggle with the notion of how much effort is enough.” Several factors make it difficult to determine the appropriate degree of community consultation, he said, “but one of the things is that more should be required for studies that are more risky, and less should be required for things that are more routine—that makes a lot of sense.”

Silbergleit emphasized that the recommendations are not intended to remove requirements to make the communities aware of the studies; they would merely guide investigators on the extent of the efforts needed according to the potential harm posed by studies. “There’s always a floor on that,” he said. “Even if things are very low risk, we are talking about doing research where people could get enrolled in the program without knowing about it ahead of time. So there’s always going to be some level of community consultation and public notification, even for the lowest risk trials … We’re not talking about getting rid of those things.”

When ACEP presented its position for the FDA public hearing on the issue in 2006, it also stressed balance between the interests of research and patient safety. The statement was submitted on behalf of ACEP by Edward P. Sloan, MD, and Charles B. Cairns, MD.

“Any revisions to current regulations should serve to expand the ability to perform the highest quality emergency research and to enhance patient protections through fairness, openness, and use of all media that provide explicit detail regarding the research,” the ACEP statement said. “Burdens should not be placed upon researchers in a way that is disproportionate to the inherent risks and need to advance emergency care through the conduct of quality emergency research utilizing the exception to informed consent.”

In terms of absolutes, the issue would outwardly appear to put emergency medicine research at odds with bioethical considerations.

Can a Community Consent? 

George Annas, MD, chair of the Department of Health Law, Bioethics and Human Rights at Boston University, Boston, MA, said he was troubled that the FDA and medical groups are “revisiting” requirements for informed consent waivers. “My own bias is to just figure ways to get consent, not to figure out ways not to get consent.”

He said his “main point is that it is always problematic to do research without consent, so everybody wants to try to get a substitute for consent. Obviously that makes sense.”

Annas said that with children, parents would be the logical choice to get that consent. And guardians would be the ones to provide the consent for mentally incompetent patients. “But with someone who is just picked up in an automobile accident, it is really hard to think of what a substitute is,” Annas said. Even with rigorous community consultation and disclosure, “A ‘community’ can’t consent on your behalf at any time,” he said.

There are obvious obstacles—some of them very difficult—in obtaining informed consent in emergency medicine studies, Annas said. “But very, very difficult does not mean impossible; it doesn’t mean you don’t have to try.” Intense efforts should be made to get that consent from relatives or others close to the patient. If it can be proven that the research is impossible without consent waivers, then the study itself should be closely examined to ensure that it is important enough to warrant an exception to consent, he said.

“But if the study entails significant risk (to a patient), I don’t think you can do it. There is no ethical basis to draft people for experimentation without their consent,” Annas concluded. (He noted that he had not yet examined the AHA recommendations.)

Life-Saving Research at an Impasse 

Countering that are emergency investigators who point out that the consent issues may delay or stall critical clinical trials, posing greater risks to future patients than the absence of a consent form.

“In the meantime, millions of American families will have a tragic and needless loss of their loved ones because of the impasse,” Paul E. Pepe, MD, said in a summary to the FDA in 2006. Pepe is professor of Surgery, Medicine, Public Health and Riggs Family Chair in Emergency Medicine at the University of Texas Southwestern Medical Center and the Parkland Health and Hospital System in Dallas, Dallas, TX, and he is the City of Dallas director of Medical Emergency Services.

He said that “only a handful of clinical trials have been conducted in the preoperative resuscitative phase of care” that could positively affect outcomes among the “tens of thousands” of severe traumatic injury victims annually. “More striking is the fact that, among those very small numbers of trials that have been conducted, several actually demonstrated not only the ineffectiveness, but often the detriment of what had been empiric (yet widely accepted) standards of care.”

In assessing reasons for the barriers in approving studies, Pepe referred to a lingering legacy of unauthorized experimentations in both the US and Nazi Germany. “The gridlock has been largely due to political pressures that have emanated, understandably, from concerns over the protection of an individual’s right to consent to treatment along with unfaded memories of secretive human experimentation, ranging from Dachau to Tuskegee.”

The AHA recommendations also cite delays in study approvals and the resulting impacts on patients with life-threatening conditions.

“Standardization of community consultation and public disclosure is necessary because there has been uncertainty and hesitation by investigators and IRBs in the interpretation of current procedures for implementing research,” the AHA report said. It described the variations among IRBs as significant in both trying to fulfill the FDA requirements for consultation, and “what constitutes the proper venue for the community to provide feedback.”

Bogged Down by the IRBs 

As an example, the AHA report cited a large trial on public access defibrillation, which relied on devices approved by the FDA and used as they were originally intended. The research used 24 sites with diverse means of complying with the consultation and disclosure requirements—press releases, letters, brochures, public meetings, newsletters, print and electronic media, ads, notices, and other communications.

The effort drew more than 1,000 comments, with only 1 percent of them negative. Despite the overwhelming acceptance, IRBs averaged 108 days to approve the process for emergency exceptions to the consent rule. Waits ranged up to 404 days for that approval, and took up to 7 submissions by investigators, the AHA report stated.

With mortality rates ranging to 90% or higher for cardiac arrest, research that could achieve a mortality reduction of even 10% would potentially save more than 20,000 lives a year, the AHA report said.

It recommends categorizing studies into 4 areas: minimal, low, intermediate and high incremental risk. Public disclosure and community consultation requirements would be adjusted upward depending on the category of the proposed research.

Investigators who were interviewed said the recommendations resulted from cooperative efforts with bioethicists. One of those disputing the notion of conflicting interests over consent was Jill Baren, MD, who has perspectives from both bioethics and emergency medicine research. At the University of Pennsylvania, Philadelphia, PA, she is involved in clinical trials, and she is an associate professor of emergency medicine and pediatrics, and an associate professor in the Department of Medical Ethics at the Center for Bioethics.

Baren described the AHA recommendations as a collaborative effort, rather than compromise, for the researchers and bioethicists.

About the FDA rules, she said, “I can tell you what I’ve heard is that, on both sides of the fence, people have different opinions. In both groups are people who believe that these regulations are necessarily difficult to implement, and necessarily strong and stringent because they protect patients.”

“I would say it is kind of hard to group them as polar opposites, but rather people who have maybe different opinions about the usefulness of community consultation. The AHA was likely trying to address those differences to account for the varying beliefs about the usefulness of the community consultation, and the difficulties in implementing that rule,” Baren said.

Cooperation More Than Compromise 

Silbergleit also balked at declaring the recommendations to be a compromise. “I think it is more of a cooperative effort to try to figure out what is most appropriate,” he said. “I don’t really think there are 2 sides in tension with each other.”

Baren called the community consultation component “one of the strongholds” of the regulations. They were issued by the FDA in 1996. Even with draft guidance by the agency later, “it still leaves quite a bit of ambiguity and guesswork on the part of investigators. So I think that’s why the different specialty groups have stepped in, in an attempt to provide some rational thought processes,” Baren said.

Action on the public disclosure and community consultation components follows some controversies over studies. They centered primarily on the phase III trials on PolyHeme, a red blood cell substitute designed to replace donated blood or saline solution for emergency patients.

Critics and some news media reports accused investigators and the FDA of failing to disclose in community consultations that earlier studies involving PolyHeme had resulted in an abnormal number of heart attacks in aneurysm repair procedures. PolyHeme maker Northfield Laboratories (Evanston, IL) argued that the heart attacks could be attributed to some personnel who inadvertently did not follow protocol when they administered both PolyHeme and donated blood. The issue prompted critical coverage in the Wall Street Journal, the “20/20” ABC news series and other publications. US Senator Charles Grassley of Iowa assailed the FDA for what he called a lapse of the community consultation and disclosure rule.

The Problem With Polyheme 

“That’s what started it (the FDA review),” said bioethicist Annas. He said one problem was the general issue over an absence of informed consent for patients, who received PolyHeme at the scene or during the ambulance ride, but at least in the out-of-hospital environment there was no standard of care option of giving blood. The bigger problem was that doctors were keeping patients on the substitute for up to 12 hours after arriving at a hospital where blood, the standard of care, was readily available.

“There is not a doctor in the United States, with the probable exception of the doctor that owns the (PolyHeme) company, that thinks that was a reasonable thing to do.” Administering the substitute when no blood is available “is one thing; it is another thing to use substitute blood when blood is available,” Annas said.

Northfield reported that thousands of opt-out bracelets had been distributed for the PolyHeme trials, although Annas and investigators who were interviewed hardly view that as a viable solution to the consent issues.

“If there is one person out there who is really interested, learns all about it and doesn’t want to be a participant, it is reasonable to create something for that one person,” Silbergleit said. “But that’s more of an ‘ornament’ than something that really makes the difference in most people’s lives.”

He explained that even the best-funded, most rigorous efforts at alerting a community cannot be expected to connect in meaningful detail with mass audiences. Silbergleit cited the example of Macy’s department stores devoting significant budgets to attract readers with advertisements on sale prices on pants.

“And yet, if you polled people on the street, most of them wouldn’t know how much those slacks were selling for at Macy’s this weekend,” Silbergleit said. “You can’t really run a few ads and expect most people to hear about your work, pay attention to it, make a decision and opt in or opt out. If we could, that would be great … But most of the people are not going to know or care about your research.”

Annas said the public actually is largely supportive of medical research studies. “The amazing thing is how many people volunteer for experiments, rather than how many people don’t. People have a lot of faith in medicine, a lot of faith in research. Even if the media tried to encourage everybody to wear their (op-out) bracelets, I think it would be real hard to get anybody to wear them.”

Guiding information, they indicated, might be best in one key area—providing a clear reason for why the community consultation is required by regulators.

Silbergleit said bioethicists and investigators generally agree on what studies need more consultation and disclosure, and which need less, “but we really don’t how much is enough because we don’t know why we are doing it.”

The FDA states the purpose as providing the opportunity for discussions and receiving opinions from the affected communities. Goals are to explain the nature, risks and benefits of the research, advise them that informed consent will not be sought, and explain the opt-out process.

A Unique Challenge 

In nonbinding recommendations issued in August 2006, the FDA noted that “the conduct of emergency research poses the unique challenges of dealing with a maximally vulnerable population, ie, a population with no control over what happens to them and no capacity to consent,” and no opportunity for investigators to get consent from relatives.

Silbergleit said that one of the prevailing beliefs is that the consultation is basically to get the community, through its leaders, to approve the project. Despite that, the FDA rule only says it is to give them the opportunity to discuss it—there is no provision for acceptance or rejection.

“I think the main thing about community consultation is that it is a sort of inherently humanizing, respectful activity,” he said. Silbergleit said the one-on-one or intimate group interactions can enable investigators to meet the people who may be enrolled in the study, and sensitize study personnel and show they respect them and their views.

“People are experts on themselves,” he said. “(They) can tell you things about themselves that might impact the way you should do your research, or how you should do your research,” he said.