BETHESDA, MD. _ Federal rules governing informed consent inemergency research are unclear and, in some cases, contradictory,according to medical researchers who testified here this week at aforum sponsored by the FDA and the National Institutes of Health(NIH). More than 400 clinical investigators gathered to tellregulators that the inconsistencies are hampering research.
Regulations governing informed consent in emergency settings muststrike a balance between patients' rights and the advancement ofmedical care. The debate touches upon complex legal and ethicalissues and was the subject of a Congressional hearing last May atwhich researchers made similar complaints about governmentpolicies.
Emergency medical research, a relatively small subset of clinicalresearch, involves administering experimental therapies andprocedures to acutely ill patients who are unable to sign informedconsent documents. Examples of such patients would include peoplesuffering from cardiac arrest, severe head injury, drug overdose,stroke or other catastrophic medical events.
Normally, any patient enrolled in an experimental drug or devicetrial would be informed of potential risks and benefits and wouldformally agree to participate. When a patient is unconscious orunable to give consent, a relative or legal guardian (if one can belocated) can give consent. The government has also definedexemptions _ conditions governing the waiver of informed consent.The problem is, both the FDA and the Department of Health andHuman Services (HHS) have their own set of rules.
Under current federal policy, local hospitals' institutional reviewboards (IRBs) are mandated to protect human subjects in clinicalresearch. But IRBs look to federal regulations for guidance on theissue of waiving informed consent. Researchers complained at thisweek's meeting that IRBs don't' know what to make of thegovernment's rules, especially because the rules don't account forthe realities of the emergency research setting.
For example, HHS has four criteria for waiving informed consent,including the requirement that the research "involve no more thanminimal risk to the subjects." However, the HHS definition of"minimal risk" requires that experiments must pose no more risks"than those ordinarily encountered in daily life." This waiver criteriahas little relevance to a critically ill or injured patient, researchersargued.
The FDA also sets out four criteria, one of which states that "thehuman subject [must be] confronted by a life-threatening situationnecessitating use of the test article." However, this requirementappears to prohibit use of a placebo control, because a placebocannot be considered necessary for a patient's survival. Yet placebocontrols are necessary for a randomized, controlled trial of anemergency intervention to yield meaningful results. (patients whoreceive placebo would also receive the standard treatment, if oneexists, for their condition.)
Despite the inconsistencies, federal policies were conceived in aneffort to protect the rights of research subjects. Gary Ellis, director ofthe NIH's Office of Protection from Research Risks, pointed out thateven dying patients have rights. "I caution you not to make facileassumptions," he warned, noting that some experimental therapiesprove to be unexpectedly harmful.
A coalition of acute resuscitation and critical care researchersprepared a consensus statement last October that formed the basis fordiscussion at the FDA/NIH forum on Monday and Tuesday. Thatgroup included 25 researchers representing professional medicalsocieties (including the American Heart Association, the Society ofCritical Care Medicine and the American College of Cardiology),universities, medical ethics associations and hospitals.
"We believe the public desires advances in acute emergency andcritical care and understands that research is required to improvemedical care," stated the coalition's consensus paper. "The risk ofnot doing emergency research is denying promising new treatmentsto individual patients with conditions that currently have no effectivetherapy, or to future patients with the same devastating condition."
The coalition made several recommendations in its Octoberstatement that received the support of other groups and individualresearchers this week. Those recommendations included thefollowing:
* Federal regulations should explicitly address the investigation ofemergency therapies for patients unable to give informed consent.These patients should be considered uniquely "vulnerable" and begranted specific safeguards that protect them from research riskswithout excluding them from research benefits.
* FDA and HHS regulations should be complete and compatible,giving IRBs clear guidance for consistent interpretation andapplication of the rules.
* A new risk category, termed "Appropriate Incremental Risk"(AIR), should be defined for studies that propose to forgo informedconsent altogether in emergency research. Incremental risk would bedefined as "the increased risk of participating in the researchprotocol relative to the natural consequences of the medicalcondition." AIR would represent the "amount of incremental riskthat is acceptable to the vast majority of patients."
Christopher Doherty, Washington director of the New EnglandBiomedical Research Coalition (a group that counts 11biotechnology companies _ in addition to hospitals, universities,patient advocacy groups and research institutes _ among itsmembers), said his organization backs the coalition'srecommendations. He also warned that federal regulators need tomove quickly.
"At last May's hearing, agency representatives assured Congressthey would seek consensus soon to resolve differences andomissions. Much emergency research has been put on hold and somecontinues under great uncertainty and possibly in violation of theregulations," said Doherty. "Unless there is some action to clarify theregulation on informed consent in emergency research, it will beincumbent upon the research community to actively pursue alegislative solution to this problem."
FDA and HHS officials will consider the comments of researchers aspresented here and could incorporate them into new guidancedocuments or a change in regulations, according to agency officials.No timetable for action was given. n
-- Lisa Piercey Washington Editor
(c) 1997 American Health Consultants. All rights reserved.