Accountability in Research Using…Con't

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Present Nih Clinical Center Policy

In 1986 the Clinical Center at NIH approved a new policy for the consent process in clinical research with patients who are or will become "cognitively impaired". It is certainly laudable that the Clinical Center, on its own initiative, took extra steps to afford more protection for cognitively impaired research subjects, yet several concerns remain.

Aside from obviating the current debate as to what constitutes "cognitively impaired" as opposed to "organically impaired", the policy, which was adopted in 1987, included a new effort to assure that the consent process is appropriate. This new protection was afforded by a Durable Power of Attorney (DPA). They state that their use of the DPA was modled after a Maryland State law which, they claimed, extended the use of the DPA (originally used for purposes of property management) to allow competent Maryland residents to select a surrogate in advance who could later consent to procedures in health care if that resident should become incompetent to make these decisions in the future (Clinical Center 1987; Fletcher 1985, p. 1).

Under this new Clinical Center policy (which applies only to intramural research in the Clinical Center), the Institute Clinicl Research Subpanel (ICRS) - or the CC's IRB - may give approval for a subject who is "not seriously impaired" to give informed consent to select a surrogate decision maker. The DPA is the record of the impaired subject's choice of a surrogate. That is, human subjects who are or will become cognitively impaired may appoint a surrogate to make decisions for the subject about his or her participation in medical research at the NIH. Thus, the surrogate would provide the "best substituted judgment that the subject would consent to the research if he or she were not impaired" (Clinical Center 1987, p. 2; Fletcher 1985, p. 1-3).

We have several concerns with this present Clinical Center policy. First, in 1987, when this policy was written, the Maryland State DPA statute was generally applied to the management of financial affairs only. (a) It was unclear if it could apply to health care decisions. In 1987 one Maryland attorney general stated in an opinion that the generic DPA could possibly apply to healthcare decisions if the document specified that intent. (b) It's application to medical research decisions had not really been addressed, although it could possibly have applied if executed by a competent person and so specified in the document. (c) It could only be executed by competent persons, not by never or presently incompetent persons - i.e., the category of research subjects participating in medical research at the Clinical Center. In October of 1993, a new Health Care Decisions Act will go into effect which specifically authorizes the use of the DPA for health care decision makers. But to use it for never competent persons, or persons who lack decision making capacity at the time the document is executed, would not be consistent with either the current Maryland law or the new (1993) Health Care Decisions Act (D. Hoffmann 1993).

Second, there is already a growing concern about the acceptance of the use of the concept of "substituted judgment" in many health care contexts (e.g., Case Studies 1992; Nelson 1992; King 1992; Truog 1992; Capron 1992; Santurri 1982; Dresser 1984). Third, this policy applies only to research with cognitively impaired human subjects, and does not include persons with any of the other mental illnesses that are being studied.

Fourth, one has to wonder how a subject who always has been and who is still cognitively impaired can competently give informed consent to choose a surrogate who will make such important decisions and "substituted" judgments for him/her. There ae some who would argue that:

…It may seem anomalous to say that a subject is, at the time of appointment, incapable of consenting for herself. However, it is not unusual to see situations in which a subject may be capable of understanding that someone may act for her in making a decision and of naming a trusted person to perform that function, even though the subject is not capable of understanding the risks and benefits associated with a complicated research protocol (Fletcher, 1985, p. 2).

This analgy between a subject's ability to choose who to trust, and the ability to know that that person would - or could - know if the subject would choose to participate in research if the subject were competent, would still remain an "anomaly" to many.

This rationale is similar to that used in determining the capacity of the research subject. For example, in such determinations, the assessment of a patient's actual functioning in decision-making situations is given precedence over either the outcome of a patient's decision or the patient's status (Fletcher, 1985, p. 4). The relevant issue, they claim, is whether the individual is capable of making a particular decision. However convincing this may seem to some, it is clearly very possible that there is a distinct difference between the mere ability to make a decision, and the kind of decision that one is making. Arguments about imposing other's preferences on these subjects aside, there is at least a broad area of decision making which is considered in most other contexts of life as "competent" and "rational", and past that point the kind of decision that is made is definitely relevant to the determiniation of competency (unless one is willing to entertain the notion that a person is "competent to be irrational). In the genuine concern to restore and protect the individual rights and dignity of incompetent persons, perhaps care is needed not to extend their "autonomy" so far that these persons are instead actually injured or neglected (see Shamoo and Irving, 193; Ganzini, Lee and Bloom 1993).

Another determination that is used is that, except as noted, individuals should be assumed to possess decisional capacity unless otherwise demonstrated; incapacity should be found to exist only when the individual lacks the ability to make decisions that promote his/her well-being in conformity with his/her own previously expressed values and preferences. However, it is not unusual for an incompetent person to appear to be competent when they are not; many learn how to play that game. In addition, it does not follow that if a person's expressed values are to slam his head against the floor every five minutes, and that therefore if he expresses that he now desires not to do so, that that person is incompetent. These diectives as to the determination of competency or incompetency need to be seriously addressed by as large a body of responsible experts as possible.

Fifth, of equal concern is the provision in the Clinical Center policy that when the subject is so seriousy impaired as to be incapable of understanding the intent or meaning of the DPA process, then a next-of-kin surrogate may be chosen by the physician, with an additional consultation with the bioethicist from the CC Bioethics Program - who may delegate this responsibility to other consultants approved by the Director of the Clinical Center. This includes participation in therapeutic research. This NIH practice would probably not be consonant with most past or present state laws in this area which provide definite ranking of family members for the use of substituted consent. Under the current substituted consent law in Maryland (Health Gen. Sec. 20-107) family members in a certain order could make health care treatment decisions for an incapacitated patint, but it is "highly unlikely that medical research would be considered such treatment under the statute". The law will be repealed in October 1993; and the new Health Care Decisions Act would not likely be interpreted to allow an agent, including famiy members, to consent to the use of incapacitated patients in medical research unless the patients were competent at the time the document was executed and unless specified explicitly in the document. For never or presently incompetent patients, even famly members probably could not consent for such purposes. In any event, under most state laws, the choice of who the surrogate would be would not depend on the physician, or the CC bioethicist, or the Director of the Clinical Center, etc. - but on the family ranking as already specified in the law. (D. Hoffmann 1993). Certainly some clear rationale openingly discussed and accessible to the public should preceed a policy which would use institutionalized seriously cognitively impaired human subjects in any kind of medical research.

It would appear that what has transpired up to the present, then, is a constant shifting of the accountability involved in the use of persons with mental illness in research. No Federal Regulations have incorporated the earlier calls for special protections for this vulnerable group. And even the purported protections afforded by an IRB have now been transfered in part to surrogate decision-makers under the "legal protection" of a dubiously valid DPA - a surrogate who may be appointed by a cognitively impaired person, or his/her physician to participate in medical research, with the approval of the CC bioethicist, who may delegate this authority to "other consultants". Who, then, is clearly legally responsible and accountablefor any harm which the research subject sustains as a result of the experiment? And who is responsible, now, for the "welfare" and the "protection" of the research subject?

The Present Federal Regulations (1991)

In 1991 the Federal Regulations were amened to incorporate the relevant provisions required in the Common Rule (1991). These present regulations make no changes in reference to any special protections for persons with mental illness, other than, as before, an IRB. However, there is a subtle chnge in the language concerning IRB membership when the use of vulnerable subjects are to be considered:

…If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects. (Code of Federal Regulations 45 CFR 46, 1991, p. 7) (emphasis added)

Our concern is the shift from the language "shall include one or more individuals who are primarily concerned with the welfare of these subjects" as used in the 1981-1989 Federal Regulations, to "the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects."

The primary goal, as stipulated in a long series of recommendations and regulations, is the respect, protection, and welfare of these vulnerable human subjects. Such protection may not necessarily be afforded if the IRB member is now simply someone who is "knowledgeable about and experienced with these subjects." Clearly, if this role is now played by a physician researcher, for example, who has personal interests in the outcome of the experiment, there is a serious concern for a conflict of interests.

So the question is not only why were persons with mental illness dropped as a special category of vulnerable subjects in the Federal Regulations, but also who is accountable for these vulnerable patients, and who is protecting them and truly looking out for their welfare? At present, no regulations cover research subjects with mental illness who are not institutionalized; those who are institutionalized are only covered by an IRB, with a board member who only has to be "knowledgeable about and experienced with" these kinds of human subjects; only an IRB policy at the NIH Clinical Center covers in more detail such protections, but those protections apply only to research subjects who are cognitively impaire, involves the use of a dubious DPA which has been authorized by a cognitively impaired subject, and if they are severely impaired may be authorized by the physician researcher himself.


It is time, we think, for a full reexamination of several of the concepts and rationales which have guided the use of persons with mental illness in both therapeutic and experimental research for many years. Such a reexamination should include at least such questions as:

  1. Are vulnerable groups of human subects, e.g. persons with mental illness, really being exploited because of: their institutionalization; the impaired status of their ability to give true informed consent; sometimes the absence of any family members to protect them, e.g., the homeless, elderly; undue pressure from other members of families with vulnerable subjects to "eradicate" the illness for future generations; bench or physician researchers who benefit professionally from the research, etc.?
  2. What should be the criteria by which to determine if a patient is "competent" or "incompetent"; and who should determine these criteria? Who should be allowed to make the determination that a particular patient is competent or incompetent? How accountable should they be for their diagnoss?
  3. How should diseases which afflict persons with mental illness be classified, and who should decide? How accountable should they be for their classifications?
  4. Is it true that persons with mental illness must be used in therapeutic research for their class of illnesses because such information is "unprocurable by other means"? Is "unprocurable by other means" an absolute societal value; or are there possibly some sorts of experiments that shouldn't be done or information which must remain "unprocured" simply because to obtain it would involve the unethical or illegal use of human subjects?
  5. Should persons with mental illness be allowed to participate in medical research which is: only for their direct benefit, and/or for the benefit for classes of individuals with that same disease, and/or for the benefit of purely scientific knowledge and the greater good of society? Who decides these issues? Who is accountable for these conceptual decisions?
  6. Is it medically, ethically or legally accurate or realistic to claim that persons with mental illness are competent to choose a surrogate to make a "substituted judgment" as to whether or not they [the patients] would freely participate in therapeutic or experimental research if they [the patients] were competent?
  7. Should the appropriate "third party" role be to give a substituted judgment about what the surrogate thinks the patient would want to do, or to give an informed judgment about the best interests of these subjects?
  8. Can a Maryland DPA law, based on the protection of the property of a citizen, and now even questionably applicable to only presently competent persons to choose a surrogate to make health care decisions after they have become incompetent, be appealed to and be the jusification for the on-going practice at the Clinical Center of allowing cognitively impaired patients to choose someone to make a substituted judgment for them to participate in medical research?
  9. Precisely who is legally responsible for injuries sustained not only during the course of experiments, but for symptoms which may appear some time afterwards (the entire IRB, the CC Director, the researcher, the attending physician, the surrogate holding the DPA, the next-of-kin, the "other consultants" appointed by the CC bioethicist)?
  10. Should the role of some one who is knowledgeable about these vulnerable patients be separated from the role of some one who is concerned about the welfare of these patients? Perhaps there should be both kinds of members represented on the IRB boards.


  1. Public and academic comment should begin again on many of the issues surrounding the use of persons with mental illness in therapeutic and experimental research.
  2. We strongly urge the NIH OPRR to immediately enforce and monitor compliance by placing individuals concerned with the welfare of persons with mental illness on all IRB committees dealing with research using these vulnerable subjects. Moreover, all such individual IRB guidelines should immediately reflect this change. NAMI members should be tapped for this function. This could include the use of NAMI members as "consent auditors", as monitors of the experiments themselves, and as possibly legally approved surrogates to advocate for the wefare and best interests of persons with mental illness who have no reliable family members, next of kin or friends.
  3. NIH should immediately incorporate the relevant recommendations of the National Commission with its original language into all of its intramural and extramural research programs.
  4. The Common Rule of the Federal Regulations (45 CFR 46) should be ammended to include the recommendations of the National Commission. We further recommend that the rules be applied to all persons with menta illness - without separating them into institutionalized and non-institutionalized groups. Both groups are vulnerable and need protection - whether in an institution, a regular health care facility, an out-patient clinic or a physician's office.

The authors strongly support most research efforts, and especially research that improves the treatment of persons with mental illness. Our call for recognizing them as a vulnerable group requiring special protection from potential abuse in no way diminishes that support, nor is it incompatible with our strong support for research in general. But we all have a moral obligation to ourselves and to our society to ensure proper, ethical and humane treatment for persons with mental illness when they are used as sujects in any kind of research.


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* Center for Biomedical Ethics, and the Department of Biological Chemistry, School of Medicine, University of Maryland, Baltimore, Maryland 21201

** Department of Philosophy, De Sales School of Theology, Washington, D.C. 20017

*** This paper is an outgrowth of Dr. Shamoo's report written on the subject on request of the National Alliance of the Mentally Ill [NAMI], Science Review Committee. Dr. Shamoo is a member of the Committee. The authors gratefully acknowledge comments on this paper by Benedict Ashley, Jaes Burtchaell, Arthur Caplan, John Fletcher, Diane Hoffmann, Jay Katz, Eric Meslin, Alan Stone, David Thomasma, and Robert Veatch.

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