Researchers have shown, in an animal model, that alterations in the technique of cardiopulmonary resuscitation improve blood flow to vital organs and increase survival of animals in cardiac arrest.
The investigators would like to determine whether this technique will have similar effects on humans.
The hospital Institutional Review Board (IRB) (Human Subjects Committee), using National Institutes of Health (NIH) guidelines, rejects the investigator’s proposal because of the impossibility of obtaining the patient’s informed consent.
Does this mean that the research can never proceed and that lives will be lost because this potentially valuable medical procedure cannot be used on humans? What guidelines could investigators and IRBs use in judging these research projects?
This case demonstrates how devotion to the principle of informed consent can be excessive, in the sense of being contrary to the interests of identifiable patients, as well as certain classes of patients and society as a whole.
I will argue, first, that informed consent from human subjects of research is neither a necessary nor a sufficient criterion for conducting such research; second, that the IRB has seriously misunderstood the federal rules on this subject; and third, that the IRB suggest guidelines for reviewing this project and others which raise similar issues.
CONSENT SHOULD NOT BE A NECESSARY CONDITION FOR RESEARCH
The idea and practice of free and informed consent is intended to serve two important ethical functions: first, to protect patients from harm, and second, to respect autonomy by allowing patients to make choices based on their own values.
It is important to remember that the practice is only a means, not an end. If it fails to achieve the end or interferes with such achievement, it should be reconsidered or modified.
While the Nuremberg Code insisted on consent from the actual subject of research, subsequent analysis and rules have recognized the desirability of a less rigid position.
In the case of therapeutic research on incompetent patients, particularly for diseases which have no effective treatment but for which a new treatment offers reasonable promise, a strict requirement for consent may be contrary to the patient’s physical well-being (that is, may not protect him), and contrary to his personal values.
Consider, for example, the first application of external cardiac massage during a human cardiac arrest.
Prior to the development of cardiopulmonary resuscitation (CPR), a diagnosis of cardiac arrest was tantamount to pronouncing death. The most widely attempted remedy was to incise the chest, under nonsterile conditions, and squeeze the heart directly.
The benefit of this procedure was remote, and the cost high in terms of distress to onlookers and those concerned with “death with dignity.”
Assuming the patient had an otherwise good prognosis and wanted to go on living, external cardiac massage would have a favorable benefit-risk ratio.
For many patients, a strict requirement for consent would not have offered “protection” in the sense of preventing injury and maximizing health and would not have been consistent with their most strongly held values.
The conflict between consent, on the one hand, and protection and autonomy, on the other, arises in other settings besides the emergency room.
A strict requirement for informed consent from research subjects would prohibit therapeutic research on children and the chronically mentally retarded.
Diseases which affect those classes exclusively, such as disorders of prematurity and metabolic diseases which cause death in childhood, would remain therapeutic orphans.
Such a policy would not protect such persons from harm. Whether it would respect autonomy is somewhat more complicated and requires a brief consideration of the justification for nonexperimental therapeutic interventions on incompetent patients.
No one would push the concept of consent so far as to require consent from an incompetent patient for a treatment of proven benefit, with minimal risk, in a clinical situation where nontreatment is likely to cause serious harm, for example, an appendectomy for appendicitis in a three-year-old.
The obvious reason is that the protection function would not be well-served by such a requirement.
But protection alone is not sufficient to justify intervention, since reasonable people disagree on the relative value of treatment versus nontreatment.
A policy of allowing Jehovah’s Witnesses, for example, to refuse lifesaving transfusions does not, from the perspective of the majority, seem to offer protection, but we regularly allow such refusals because the respect for autonomy is considered more important. But how is the autonomy of an incompetent to be respected?
In my view, it makes little sense to talk about the autonomy of an incompetent patient, particularly if the patient has always been incompetent to a degree that his wishes are unknown.
A newborn can be autonomous, in the sense of acting on his own, but he will die without proper care, an outcome which will usually seem inconsistent with respecting him as a person.
The closest we can come to what is at the root of autonomy, when an incompetent patient is involved, is to resort to a notion of substituted judgment; that is, to ask, “What would the patient likely say if fully informed and competent to make an assessment?”
The answer would include consideration of the patient’s unique circumstances, including the prospects of continuing life in an incompetent state.
It might be, for example, that a vegetatively retarded person would refuse a treatment which would be accepted by most persons of normal intelligence, because the benefit of continued existence is so small.
Therapeutic interventions without consent, according to this view, can be perceived as consistent with respect for the person, if not autonomy, if there is a supportable argument that treatment is what the patient would likely want if fully informed and free to choose.
Similarly, therapeutic research in some situations can be justified if there are data to support the claim that the patient almost surely would have consented if competent to do so.
This view of permitting interventions on incompetent subjects without their consent still recognizes two ethically important objectives: first, to protect the patient from clear harms (that is, intrusions which would violate almost anyone’s notion of protection), and second, to make the best estimate of what the patient would want, given his idiosyncratic condition and future prospects.
In summary, consent from the patient should not be a necessary condition for therapeutic interventions on incompetent subjects.
The same arguments that justify interventions of proven benefits and risks would justify some experimental interventions.
Proxy decisions in both cases require attention to the conditions for legitimate or ideal proxy decision making.
Since the benefits and risks of experimental intrusions are less clear than the benefits and risks of standard treatment, the likelihood of consent is generally less, and the procedural requirements for proxy decision making should be more strict.
CONSENT IS NOT A SUFFICIENT CONDITION FOR RESEARCH ON HUMAN SUBJECTS
I have argued that consent is not necessary for therapeutic research on incompetent subjects. I would also make the point that it is not a sufficient reason for doing research on a competent patient.
The case under discussion does not involve competent subjects who might consent, so this argument will not be presented in detail. I only present it as further argument for avoiding a slavish devotion to consent as the critical issue in research.
Consent alone would not justify interventions which might be outrageous on other grounds.
Consider, for example, experiments which might be illegal, such as those conducted by unauthorized persons, or using illegally obtained or unauthorized materials, or which violate criminal laws, such as those prohibiting murder or mayhem.
There are sufficient public policy interests in such prohibitions as to allow, at least, a balancing of public interests against the interest of a subject to consent to anything he wishes.
Insofar as there is no fundamental right to experimental treatment, the patient’s right to consent to this treatment would be less than his right to consent to standard treatment.
One could also argue that the protection and autonomy functions do not call for an absolute dependence on consent as the justification for research. The reality of consent is that it often does not protect patients well.
For the same reasons, it does not maximize autonomy, because the misguided patient may make decisions which are contrary to his chosen ends.
Consider, for example, the competent patient who, because of trust in the therapist, consents to quack cancer therapy but who insists his primary value is to live as long as possible.
Assuming there is a known effective and safe cure for the condition, allowing consent alone to determine the course of treatment would not only fail to protect the patient from harm but would also thwart the attainment of his most strongly held goals.
FEDERAL RULES DO NOT REQUIRE CONSENT
The case report does not mention which section of the “NIH guidelines” led the IRB to deny approval, based on the failure to obtain consent.
Assuming the IRB is relying on the Department of Health and Human Services rules which govern NIH-funded research, it is difficult to know what section they think prohibits this study.
The regulations clearly allow for therapeutic research from incompetent subjects, anticipating studies in which consent cannot be obtained from the patient.
It is possible that the IRB misconstrued this as nontherapeutic research, but that would seem to have been an error, given the statement that the investigators wish to determine whether the technique will increase survival.
While there may be other ethical and / or legal grounds for disapproving the research, the inability to obtain consent from the subjects does not seem to be a violation, per se, of federal rules.
GUIDELINES FOR CPR RESEARCH
Based on the discussion above, it should be clear that therapeutic research on human subjects who cannot consent should be ethically warranted in some circumstances. Emergencies constitute one example in which consent often cannot be obtained.
The ethical bases for approving such research are: (a) failure to do so would, in some cases, not protect the health needs of potential patient-subjects; and (b) failure to do so would be to act contrary to the wishes and values of some patients and thereby fail to respect them as persons, in the same sense as denying standard treatment would constitute such a failure.
I would not appeal to societal interests in allowing such research or agree with the claim that such patients have a duty to participate in such research, although one could imagine a national crisis in which the social utility of doing such a project would be so great that such considerations would be relevant.
The federal rules allow for even nontherapeutic research in such a crisis, with special procedural rules, including review at a national level.
Because it is preferable for new ideas to be tried on persons with clear ability to consent, research on the incompetent patient should be considered only after initial studies on competent patients justify expanding the study population.
It is not clear from the information provided whether or why the study was not initially tried on competent patients.
For example, the modality being studied (a drug? body position? tourniquets?) could be tried in other clinical settings where competent patients could be invited to participate.
Patients could be recruited from a class at risk for cardiac arrest, prior to becoming incompetent, such as patients about to undergo heart surgery with high risk of postoperative cardiac arrest.
Assuming such options were not available, it should still be possible to do the research on incompetent patients, assuming the following conditions are met:
The person’s wishes, if known, prior to becoming incompetent should be respected. This would include casual conversations with trusted relatives or a personal physician. It would not require a formal, informed declaration.
The animal data are impressive to persons competent to review it, so that the prospects for human success are reasonable. This should include, for example, publication in a reputable journal or expert opinion in some other form.
It is not possible to study the intervention in competent patients, or there is some compelling ethical argument for not doing so.
Rather than conducting the study in the emergency department, it should be done on patients already hospitalized. The reasons for this are that such patients and their families will be better known to the medical staff, and their values and wishes can be more reasonably assessed, than will patients in the emergency department who are more likely to be strangers. In addition, the ethical questions surrounding the decision of whether even to proceed with CPR will be more informed in the inpatient setting. I assume this requirement will not substantially reduce the opportunity to enroll patients, given the high rate of cardiac arrest in a large hospital.
The procedures for proxy consent should make a reasonable attempt to emulate the criteria for an “ideal proxy”. This could include convening of a surrogate panel made up of persons who approximate the prospective subjects in pertinent demographic and psychosocial characteristics.
Assuming the surrogate group approves the research, there should still be an effort to inform and, within reason, to ask consent of the next of kin who are available at the time of the CPR. The reason for this is that close relatives are more likely to know the patient’s wishes than are others available at the time the decision must be made. Even though such consent would not be highly informed, such wishes should be respected.
Notwithstanding the apparent misinterpretation of federal rules, the approval of the IRB should obviously still be required, including appeal processes within the institution or to NIH.