SUBJECT:          Traumatized and Comatose Patients                                                                                               

Research involving subjects undergoing emergency care differs from clinical research in other settings because the patient's capacity to provide informed consent is often severely compromised, and decisions about participation in research may have to be made too quickly to obtain permission from the patient's legally authorized representative. The patient's altered mental status may vary from one of confusion and disorientation to coma. Altered mental status may result from an accident or emergency condition, a physiological response such as shock or infection, a psychological response (anxiety, grief, or physical pain), or the effects of drugs.

DHHS regulations (and the Federal Policy) permit the waiver of informed consent requirements only in the case of research that presents no more than minimal risk (45CFR46.116). FDA regulations, on the other hand, permit exception from the informed consent requirement for patients confronted by a life-threatening situation where there is no alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the subject's life (21CFR50.23; 45CFR).). Some legal scholars have suggested that experimental emergency treatment might be given to a patient who cannot give informed consent if, in the opinion of the physician, it is the most promising treatment available. DHHS regulations say only that "nothing in these regulations is intended to limit the authority of a physician to provide emergency medical care, to the extent the physician is permitted to do so under applicable Federal, State, or local law" [45CFR46.116(f)].

The risks and benefits of studies in emergency care may each vary from extremely high to negligible. At one extreme, where significant incapacity or death is almost certain, a new therapeutic measure may offer a reasonable chance for recovery, sustaining life, or preventing serious and permanent deficits. In other situations, the potential benefits and risks may be equally great; one may not "outweigh" the other. Drugs given in an effort to save the lives of trauma victims might do so at the risk of preserving those lives in a persistent vegetative state. Many studies involving emergency care may be almost without risk yet yield information useful in the treatment of the patient (e.g., monitoring certain physiological events by noninvasive means).

HRAC CONSIDERATIONS:

The HRAC should ensure that the risks are minimized, the confidence in the anticipated benefits is justifiable, and the risks are reasonable in relation to the anticipated benefits. According to DHHS regulations (and the Federal Policy), the HRAC may waive the informed consent requirements when the risks are no more than minimal, the research could not reasonably be carried out without waiving the requirement of informed consent, and such a waiver would not adversely affect the subject's rights or welfare [45 CFR 46.116(d); 38CFR16.116(d)]. Subjects or their legally authorized representative should be provided with pertinent information when, and if, it becomes possible and appropriate. DHHS regulations and the Federal Policy preclude research presenting more than minimal risk without the subject's legally valid consent unless it is possible to obtain the permission of the patient's legally authorized representative. The mental state of family members in the emergency situation may, however, preclude good decision making. Further, it is often not possible to locate family members in time to make the decisions necessary in emergency care. The HRAC and investigators should also note the distinction between "next-of-kin" and "legally authorized representative." Although physicians treating incompetent or comatose patients traditionally accept “consent” by next-of-kin, family members do not have clear legal authority to give such consent. 

If prior informed consent is not possible, and the HRAC has not waived the informed consent requirements (e.g., if the research involves greater than minimal risk), the patient should be excluded from the study and provided with standard care. In cases in which the requirement for emergency care is foreseeable and subjects can be identified in advance (e.g., a study to be performed after elective major surgery), informed consent might be obtained well before the surgery.

The HRAC and investigators should note that where a patient requires emergency care, DHHS regulations requiring prior HRAC review remain in effect. While the regulations do not "limit the authority of a physician to provide emergency medical care" [45 CFR 46.116(f)], they also do not permit research activities to begin as part of emergency medical care unless the research has received prior HRAC review and approval [45CFR46.103(b); "Emergency Medical Care," OPRR Reports (May 15, 1991)]. While such patients may receive emergency medical care, the patient may not be considered to be a research subject. "Such emergency care may not be claimed as research, nor may the outcome of such care be included in any report of a research activity" [OPRR Reports (May 15, 1991)].

FDA regulations permit exception from the informed consent requirements when both the investigator and a physician not otherwise involved in the research certify in writing that: (1) the subject is confronted by a life-threatening situation necessitating the use of the test article; (2) informed consent cannot be obtained from the subject because of an inability to communicate with, or obtain legally effective consent from the subject; (3) there is not sufficient time to obtain consent from the subject's legally authorized representative; and (4) there is no alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the life of the subject available [21 CFR 50.23]. Documentation of such circumstances must be submitted to an HRAC within five working days. Any subsequent use of the test article is subject to HRAC review [21CFR50.23; 21CFR56.104(c); 45CFR).]. The FDA's regulations on emergency use of test articles is discussed in greater detail in Guidebook Chapter 2, Section B, "Food and Drug Administration Regulations and Policies."