Ethical issues in psychiatric research

international Journal of Law and Psychratry, Printed In the U.S.A. All rtghts reserved.

Vol 4. Pp. 271.292, 1981

0160.2527/81/030271-22$02.00/O Copyright 1982 Pergamon Press Ltd

Ethical Issues in Psychiatric Research Bernard M. Dickens*

Ethical Values It is fortunate that it may appear trite and self-evident to observe that medical research’ must be conducted in accordance with ethical standards. National and international codes of medical research ethics, even predating the celebrated Nuremberg Code of 1947,? recite the basic principles of investigators’ responsibilites. Nevertheless, in considering psychiatric research it may be useful initially to state the ethical values at stake, and to try to express the limitations upon research which protection of these values may impose. The flood of recent bioethical literature, certainly in North America, has disclosed many formulations and refinements of ethical values which conscientious and sensitive investigators are expected to observe. Primary analysis may seem to centre, however, upon a small number of principles which have been so widely agreed to theoretically, as opposed to in application, that they now appear superfluous to state in terms. It is part of the fascination of psychiatric research that these basic principles may pose significant obstacles to studies which most reasonable observers would in principle agree should be pursued. A founding principle of subjects’ involvement in research is that of their autonomy, which reinforces their rights of personal inviolability. It has fallen to courts of law most authoritatively to express and assert this principle of the physician-patient relation, which is projected into the comparable (but not coextensive) relation between scientific investigator and research subjecL3 The most celebrated expression of personal inviolability, cited almost invariably in the bioethical and legal literature, contains two limitations at least one of which concerns psychiatric patients. In the 1914 case of Schloendorff v. Society ofNew York Hospital,4 Mr. Justice Cardozo confirmed basic legal doctrine that “Every human being of adult years and sound mind has a right to determine what shall

*Professor

of Law, University

‘Occasionally, physically

the

invasive.

of Toronto,

distinction

This

is

distinction

an invasion of confidentiality

may

Toronto,

“research”

be useful

to medical

>For an interesting presentation

MSS

clinicians,

but

IAI. whereas

“experimentation”

it i< not drawn

is

here, sinceethically

to a psychiatric patient.

are used Tynonymously.

31 IUTFtw4TtONAt

guidelines are more clear, concrete and far-reaching

J2l I N.Y.

Canada, noninvasive,

of German research guidelines in force from 1931 to 1945, SW 1931 German

guidelines on human experimentation, ‘SeeSlater

is

may be more damaging than taking blood, particularly

The words “research” and “experimentation”

(Sask. C.A.

Ontario,

that

drawn

v. Baker, 95 Eng. Rep. 860(1767);see.

DIWST

or H~AI TH L~C;ISI ATION 408 (1980).

than the Nuremberg e.g., Halushkav.

1965). 125 (1914).

271

The

Code.

Univ. Saskatchewan,

53 D.L.R.

(2d)436

272

BERNARD

M. DICKENS

be done with his own body.“5 This ubiquitously agreed principle leaves curiously open the status of the young and the mentally disordered, and their vulnerability to fall under the bodily disposition of others. The principle of inviolability protects the competent not only against bodily intrusion, but also against noninvasive measures affecting identity, confidentiality and personality. This reveals further dimensions of uncertainty affecting the violability of the incompetent. An instinctive response on behalf of the handicapped that their guardians should protect them is doctrinally appealing, but fails to differentiate between affording the incompetent the same protection as the competent can exercise, and affording them greater protection. It is legally unclear whether guardians must pursue only positive benefits for their charges, or whether they must merely protect them from harm, so that dependents may be submitted to harm-free but non-beneficial enterprises.6 Further, if the autonomy of the incompetent is to be maximized, and their position assimilated as closely as possible to that of the competent, guardians may have to serve not necessarily their best interests, but their perhaps conflicting but reasonable wishes insofar as they can be formulated and identified. The wish to participate in a moderate, calculable risk may ethically have to be respected. A related principle to autonomy is that of truth-telling. A potential and actual research subject should not be deceived in any regard,’ by for instance the withholding of information which may affect the decision to join or remain in a study.* Proposed subjects should be told why they have been approached to take part in a project, for instance because of their particular physical, psychiatric, genetic, social or other characteristics, or because of their “normality” if they are being invited to participate as random, matched or other controls. They must be informed not only about their relevant characteristics, but also how the proposed study may affect them or place them at risk.’ Information must also be given of what the study aims to achieve, what gap in knowledge it hopes to fill, and the particular population group it aims to assist. Information of this nature serves the purpose of subject autonomy, of course, and lies at the heart of legal concepts of informed consent,10 but the principle serves the ethical function for investigators of compelling frankness. ‘Id. at 129-30. bSee the discussion in G. ANNAS. L. GLANTZ & B. KATI, INF~KMED CONSENT TO HUMAN ESPERIM~NTATION: THE Sua.~tcrs DILEVMA 91-96 (1977) and Dickens, The Use of Children in Medical Experimentation, 43 MEDICO-LEGAL. .I. 166 (1975). ‘In restricted circumstances not involving bodily intrusion but concerning, for instance, psychological testing, where prior disclosure would bias responses, limited non-disclosure or even deception might be legitimate, provided that the study is more than ordinarily significant, and the research subject is fully informed (debriefed) as soon as possible. Further, the subject should then have the power to exclude use of data deceptively acquired, so that the investigator needs the subject’s retrospective consent before the study can profit from data so obtained. RSee generally Dickens, Information for Consent in Human Experimentation, 24 U. TORONTO L. J. 381 (1974). VZourts have held that the level of disclosure made to potential subjects of research is higher than would be required in informing patients about proposed therapy. See Halushka v. Univ. of Saskatchewan, note 3, supra, and Dickens, note 8, supra. loOn the separation of moral questions about experimentation from legal questions, see Ladd, Legalism and Medical Ethics, in J. DAVIS. B. HOFFMASTER & S. SHORTEN (eds.) CONTEMPORARYISSUES IN BIOMEDICAL ETHICS l-35 (1978).

ETHICAL

ISSUES IN PSYCHIATRIC

RESEARCH

273

The principle may interact with the underlying principle of benevolence, expressed Hippocratically as the obligation to do no harm. If frankness to potential subjects about themselves would risk causing them harm, including harm to self-esteem, this harm, even if compensated by proposed benefits, may strongly demonstrate that their involvement is ethically contraindicated. This application of the principle of benevolence intersects, however, the aim of treating with a view to curing the sick. The standard of informing is governed by the criterion of achieving not “full” disclosure, but adequate disclosure depending upon therapeutic goals. Accordingly, where giving information to the sick in a therapeutic relation would be contraindicated or countertherapeutic, there may be a “therapeutic privilege” of offering treatment upon the basis of limited nondisclosure, as the law has recognized. I1 By definition, this has no relation to a non-therapeutic setting, however, including non-therapeutic aspects of therapeutic innovation.” The principle of equality or equity has a double application. First, it requires the investigator to consider and treat a research subject as an equal collaborator in the study. For this reason, language and concepts derived from the unequal relation of physician and patient should not be employed.13 Indeed, the physician-patient relation is diametrically reversed in research, since the subject is serving the wishes and needs of the investigator. The investigator must pay the subject of research the same respect and consideration of interests and feelings which should be paid in good conscience to any other colleague. Second, the principle embodies the philosophical or jurisprudential concept of distributive justice, requiring burdens and benefits to be distributed in accordance with standards of equity. This indicates that populations at disadvantage, notably patients and particularly psychiatric patients, should not be invited to participate in research not directed specifically to the relief of their disadvantage for which non-patients could scientifically serve equally well. Those in captivity or under restraints or dependency should not be recruited when the free would be equally suitable, lest their vulnerability to pressure, including undue inducement, and the mere convenience of access to them be inequitably exploited. Where the purpose of the study is to benefit them as individuals or the medically-defined group to which they belong, however, and especially when the sound scientific design of the proposal contains a subject group in which only such persons can serve, it may be ethical to invite them to share the risks of the study. The distribution of risks and proposed benefits may then be in equilibrium. These ethical principles will be further considered and applied below. An attempt should be made, however, by way of introduction, to explain why these ethical values legitimately impose limits upon research and investigation. This is particularly the case because, under the principles of equality and autonomy, investigators enjoy entitlements to the pursuit of their disciplines. They have no “See Ci. ANNAS, L. GLANTZ & B. KATZ, note 6 supra, at 32.

12See infra. “The law recognizes that the physician-patient relation, like the lawyer-client relation, is unequal through the presumption that any benefit (beyond reasonable payment) flowing to the stronger party, namely the party with the power of special knowledge, has been procured by the exercise of undue influence. The benefit is accordingly voidable at the instance of the patient, or another claiming through the patient. See G. ANNAS. L. GI.ANTZ & B. KATZ, note 6 supra, at 114-117.

274

BERNARD

M. DICKENS

right, of course, to impose the risk of harm upon others, nor to compel others’ nonconsensual recruitment to their purposes. Where others appear not to be harmed or affected, however, investigators may assert their right, and indeed their duty, to undertake investigation. This claim may be reinforced in the setting of a university or teaching hospital, where the principle of academic freedom is celebrated. Researchers are all too familiar with financial constraints upon their endeavours, and these may provide a means or analogy to explain ethical constraints. However costly pursuit of medical or other knowledge may be, a community dedicated to its achievement can often pay the cost by foregoing other benefits the resources devoted to research could have purchased. The race to the moon, for instance, saw two countries of different economic systems devoting vast public resources to that objective, under twin incentives of seeking technological advance and avoiding perceived strategic disadvantage. The cost of that commitment of scarce resources was the loss of, for instance, health services or social programmes the money might have supported. In this sense, some objectives are too costly, since what would have to be foregone in their pursuit is deemed of greater value. The same is true of ethical values in medical experimentation. If the need for research is adequately compelling, it may be pursued at the sacrifice of other values. The bodies of the vulnerable and the minds of the disordered may be conscripted to the service of a transcendent cause. If values such as individual autonomy, defence of the vulnerable and protection of both individuals and communities against risk of abuse are awarded priority, however, psychiatric and other experimentation may have to be redesigned, redirected, postponed, or even foregone. In ethical values no less than monetary values, some prospective research is too expensive. This analogy is weak, of course, in that there is no obvious monopoly of ethical currency or credit in the hands of an exchequer. Researchers may question the credentials of institutional or other personnel who claim to assess costs of prospective projects in terms of ethical values. They clearly have a right to statement of the scale of priorities in accordance with which their proposals are devalued and rejected. The growth of different national patterns of institutional review boards which assess the ethical status and priority of research proposalsI shows, however, that within the discipline of medical science assessments of the ethical calibre of research proposals can be made by acceptable procedures. Further, two planes of ethical assessment may be distinguished. Traditional ethics have concentrated upon person-to-person relations, and have become described as “microethics.” Relations between groups also have an ethical dimension, however, which may be described as social ethics or “macroethics.” While both ethical focuses are governed by comparable principles, they may be applied with somewhat different effects. The unavoidably contentious issue of abortion may, for instance, be assessed at both levels of ethical concern. In person-to-person microethics, once the personhood of the fetus is presumed, 14Different (eds.)

international

practices

on review boards

are discussed

in N. HOWARD-JONES & 2. BANK~WSKI

MEDICAL EXPERIMENTATION AND THE PROTECTION OF HUMAN RIGHTS (XIIth

Conference,

1979).

CIOMS

Round

Table

ETHICAL

ISSUES

IN PSYCHIATRIC

RESEARCH

275

termination of its existence may be agonizing to justify, depending upon its condition and potential. At the macroethical plane, however, the high rate of spontaneous abortion of grossly defective fetuses indicates that early induced abortion upon grounds of severe fetal abnormality duplicates rather than defies the course of nature. Further, the contraceptive effect of childbirth where the child is seriously abnormal, or where the burdens upon an unsupported mother in rearing a child would devastate her prospects of marriage and the procreation of later children, permits a trade-off to be made between early fetal loss and the conception and birth of later children. Thus, a practice raising discomfort on the microethical plane may appear legitimate in macroethical terms. Similarly, practices ethical in themselves in microethical terms may be macroethically unacceptable. Such professionals as physicians and lawyers, for instance, may observe ethical standards fastidiously in their dealings with patients and clients. If the practitioners in a given area decline to accept as patients or clients persons whose incomes fall into the lower social brackets, however, they as members of professional groups may be in violation of macroethical responsibilities in denying the poor access to adequate services, on the delivery of which they exercise public control if not a monopoly. Medical and other research must be seen at both microethical and macroethical levels, since the undertaking of research is itself an ethical enterprise pursued for the public good. Whether in monitoring the effectiveness and safety of existing practices or in advancing new potential therapies, it accords to the highest ideals of society. A medical profession which turned its back upon research would be condemned for dereliction of its duty. At whichever plane of ethical analysis human experimentation is assessed, the importance of protecting human subjects against undue risk must be emphasized. Risk is not merely risk of destruction or of physical or psychiatric harm, but extends to risk of suffering indignity, deceit or use as an object. While the principal aim of a study may be the augmentation of the stock of human knowledge, and the advance of science, limits must be indicated, agreed or imposed beyond which harm to an individual subject will not be risked, even with the subject’s free and informed consent. This issue is of particular significance in the scientific context, since where a hypothesis is to be tested, falsification has as much scientific value as verification, and perhaps more.15 An experiment designed to test a hypothesis that a specific intervention will cure a given condition would be successful even if the intervention failed to achieve a cure, and if it injured the subject. Knowledge would have been achieved and advanced. Since each human subject of experimentation is valuable and irreplaceable, risks of destructionI and of damage have to be anticipated with a protective imagination. Psychiatric patients may already appear to their therapeutically inspired investigators to be damaged, however, and they are proposed for research in order to find cures not currently available. Accordingly, investigators may become desensitized through their therapeutic enthusiasm to the risks of harm ISSee Ladd, Ethical Issues in Human Experimentation, in 2. BANKOWSKI & J. CORVERA BERNARDELLI (eds.) MEDICAL ETHICS AND MEDICAL EDUCATION (XIVth CIOMS Round Table Conference) 26, 33 (1981). leThe self-evident proposition that human beings arc not to be tested to destruction was not self-evident to the scientists pursuing research the Nuremberg Code was expressed to condemn.

BERNARD

276

M. DICKENS

and human indignity they may be imposing, not least because their subjects may not demonstrate human dignity in their untreated condition. Even at that level, however, some sacrifices of communal ethical values may be too great to risk or impose. To express the point in its most agonizing form, sick people may be left without hope of relief because society decides not to mobilize the expenditure of its limited financial capital in their cause, and equally there are disordered people in need to whose possible relief communities cannot sacrifice their ethical values. Health of each individual is not the only goal of a society, nor necessarily its highest value. The Concept of Research There is a sense in which all standard medical treatments and psychotherapies present a step into the unknown. Much continues to be learned, of both beneficial and detrimental effects, from unexpected and idiosyncratic responses to routine care. Anecdotal and clinical accounts can add considerably to medical knowledge and affect treatment methods. Further, some common treatments can be shown to have unrecognized long-term side-effects when group or cohort statistical follow-up studies are done. These aspects of routine treatments are distinguishable, however, from a deliberate prospective study undertaken to test a hypothesis by way of experimental management of individuals, whether patients or lay volunteers. Experimentation may be defined as a deliberate departure from standard medical management.” This makes it obvious that treating a non-patient is experimentation, as is treating persons who happen to be patients but who are affected by conditions other than those intended to be studied. It may be noted that a number of healthy people may be in hospitals, such as when suffering from bone fractures perhaps incurred in sporting or recreational activities. Even if non-patients or unaffected patients are not actually treated, but are merely questioned, observed, weighed or for instance measured to serve as normal controls, the inspection of their bodies, minds or medical records for research will constitute medical experimentation. It departs from the inspection or monitoring they would normally receive, and affects their interests not so much in bodily integrity as in confidentiality of medical or other personal data. Even though such examination may be of advantage, in that it provides a free medical check or therapeutic monitoring not normally undertaken, and presents little risk, it still represents human research and must conform to institutional ethical approval procedures. Where patients are involved in studies designed to improve treatment of the conditions from which they are suffering, and the involvement of particular patients requires them to receive the standard treatment and nothing more or less, for instance when another group of patients is to receive the investigational treatment, patients on the standard treatment are nevertheless involved in medical experimentation. They may not be suffering any additional bodily invasions or administrations, and may not be monitored in any additional way. Use of their medical data, for instance for comparison with those of patients on the inT7.%?e

generdy

Dickens,

What Is A Medical

Experiment?

113 CAN MED. ASS’N. J. 635 (1975).

ETHICAL

ISSUES IN PSYCHIATRIC

RESEARCH

277

vestigational treatment, will constitute the critical departure from standard therapy. Because the risks to patients of such data inspection may be low, the risk-to-benefit ratio of their involvement in the study may be favourable. Their interests in confidentiality require in principle, however, that their separate consent to non-therapeutic medical file inspection be obtained, or that investigators justify non-consensual access to their medical records. The fact that hospital regulations or legislation permit research access without prior individual consent indicates only legal permission. It does not give ethical legitimacy to the breach of confidentiality involved. Investigators must make a case for non-consensual access on ethical grounds, not on legal grounds alone. This reasoning shows that even standard care of affected patients may have a research aspect. It must be recognized, however, that the concept of standard care is elastic. A form of therapy, such as a drug or psychotherapeutic technique, or a particular dosage level of a drug, may have fallen out of favour or style but remain within the ambit of legitimate patient care. The concept of standard care has dimensions of time and place, since treatment which is not or which has ceased to be standard in one location may be so in another.18 The test of standard care is whether a conscientious practitioner within the broadly defined regionly would consider it a legitimate or appropriate modality of treatment. The notional conscientious practitioner is up to date in clinical practice and in awareness of relevant literature. When a treatment is professionally discredited or superseded, it ceases to fall within the range of available standard treatment. Similarly, premature employment of a treatment, before it is established as safe and effective through adequately rigorous testing and research, may be a departure from standard care. This tends to have more visible geopolitical dimensions, since a treatment which is standard in one country may not yet be so in another. Accordingly, its use may be required to be approved by the agency conducting ethical review of experimentation. This proposition applies equally, of course, to a treatment which is standard in itself when it is proposed to be employed in a manner or for a purpose which is not standard. Using a different route of administration, such as intravenous injection of a drug routinely administered orally, may be experimentation when results are to be compared to perhaps retrospective data of patients receiving an oral application. If a particular patient is intolerant to routine administration, however, another route may be used therapeutically outside the concept of experimentation.*” Basic to the concept of experimentation as a deliberate departure” from the range of standard treatment is a means to establish standard treatment. In ethical review, as in courts of law, this usually requires recourse to the observations and assessments of medical experts. Where a patient presents with newly diagnosed symptoms, for instance, or a combination of characteristics which are ‘*Although the so-called “locality rule” applied by courts to identify the legal standard of care required of a medical practitioner is now in decline; see HOLDER, MEDICAL MALPRACTICE LAW 58-59 (1978). ‘9This may coincide with the jurisdictional area of a particular practitioner’s licensing authority or of the medical association to which the physician belongs. 2oThis may require peer review if time allows, but this for therapeutic as opposed to research purposes. 21An inadvertent departure may, of course, be legal negligence, although this may not follow regarding standard treatments with an irreducible risk of uncontrollable deviation; some surgical techniques may illustrate such risk.

278

BERNARD

M. DICKENS

unique or which render standard treatment contraindicated, no standard treatment for that patient may exist. A physician may then undertake therapeutic innovation, which in itself does not require ethical monitoring applicable to research. 12 Further, where a standard treatment has become discredited, following for instance rigorous scientific research or anecdotal evidence of extreme adverse reactions, and no alternative exists, no standard treatment may be found to exist. The same is the case where treatments in current use have not been tested for efficacy and safety in properly designed and conducted studies. Their use may actually prove upon appropriate testing to be unsafe or harmful, despite the ethical obligation binding physicians to do no harm, and if they are merely ineffective, they may delay more potentially successful treatments or spontaneous recovery. An ethical issue in psychiatric treatments and research is that so many therapeutic modalities in standard use remain unproven by scientific tests. Standard

Psychiatric

Care

It is a remarkable and perhaps medically distinguishing feature of psychiatry, including psychotherapy, that its techniques in regular use have only occasionally been proven sound by suitably designed, statistically valid, adequately executed studies. Neurology may appear to have a more secure scientific base, but psychosurgery has come under critical scrutiny and cannot easily be described as standard therapy’? in many areas where advanced or enlightened medicine is now practised. It was noted in 1964, for instance, that “of the 4,000 odd publications concerning lobotomy to date, a ridiculously small number have paid even lip service to experimental design, adequate sampling procedures, control of the variables involved and other salutary statistical cautions.“2J The problems with psychiatry do not commence with its standard treatment modalities, since its preliminary nosology, diagnostic categories and diagnostic techniques can appear imprecise, and incapable of common application among different practitioners. The validity of the commonly made diagnosis of schizophrenia, for instance, has been shown to be very questionable,25 and this must affect the credibility of studies claiming to show effects of its treatment. While electro-convulsive therapy (ECT) is in widespread use for treating schizophrenia, and appears as effective in relieving symptoms of acute schizophrenia as psychotropic drugs, 2h it is still not possible to make any definitive statements regarding the effectiveness of ECT in the treatment of schizophrenia. Many of the studies in this area suffer from serious methodologi-

z’Sec note 20 supra. Any additional use of patient data for comparative or other research purpose will, however, constitute medical research involving a human subject. *‘Treatments affecting the brain may be used, of course, not for therapy but for purposes of restraint and control. ZJEditoria/, 91 CAN. MED. ASS’N. J. 1228 (1964). 25See, e.g., Garvey & Tuason, Mania Misdiagnosedas Schizophrenia, 41 J. CI INICALP\uc-I{. 75 (1980), and Taylor & Abrams, The Prevalence of Schizophrenia: A Reassessment Using Modern Diugnoslrc Crileriu. 135 AM J. PSYCH. 945 (1978). 26See May & Thuma, A follow-up s(udv of [he results of lreuttneni o-f schizophrenia, in R. SPITZER & D. KI TIN (eds.) EVAI U~TION or THE PSYCHOI OG~CAI.TH~KAPIES (1976).

ETHICAL

ISSUES

IN PSYCHIATRIC

RESEARCH

279

cal inadequacies such as the lack of a control group, non-random assignment of subjects to treatment groups, failure to equate groups on important pretreatment variables, use of multiple treatments within groups, lack of blind rating procedures and systematic, standardized outcome assessments, and, when appropriate, lack of sufficient follow-up data. It has been observed that “It is regrettable that at this period of controversy in psychiatry, there is not one well controlled study to determine the validity of various positive and negative claims made for ECT.“*’ Accordingly, its status as a standard treatment of therapeutic effect remains unestablished. Beyond the surgical, physical and pharmaceutical treatments of mental disorder, the noninvasive psychotherapies appear affected by the same problems of objective diagnosis and, for instance, scientific measurement of treatment effectiveness. There are many different forms of psychotherapy, which adds to uncertainty about their effects the uncertainty of which type of psychotherapy was used in a retrospective study and is proposed to be used clinically or in a prospective study. Further, a number of psychotherapies may be applied following drug administrations, in compound techniques such as narcoanalysis.** In a 1980 survey of the field of endeavour, it was noted that “modest evidence now supports the claim that psychotherapy is capable of producing some beneficial changes - but the negative results still outnumber the positive findings, and both of these are exceeded by reports that are beyond interpretation.“29 This is perhaps inevitable, since the goals of the therapist and patient may encompass many variables, including their individual definitions of treatment success and failure. More certainty might be expected where goals are influenced by factors external to the therapeutic relation, notably where the patient has been convicted and incarcerated because of crime associated with a mental disorder. Dr. Seymour Halleck has noted, however, that “It must be admitted that there are even less objective data to prove the effectiveness of psychotherapy with offenders than there are with the [non-offending] mentally ill.“30 He explains the problem of evaluating psychotherapy in correctional settings as involving imprecision in changes sought, and lack of care in determining what interactions are psychotherapeutic. The same imprecision affects what may variously be described as behaviour therapy, behaviour modification and conditioning therapy, undertaken with the institutionalized mentally disordered. Accordingly, while it may be possible to state the treatments which are standardly applied to psychiatric disorders, there is a dearth of evidence of adequately established effectiveness, and a number of standard treatments may appear discredited, or indeed never to have achieved scientific credibility. Studies to monitor the effectiveness and side-effects of routinely used treatments may therefore appear justifiable, and proposals to try a new modality of treatment

2’Turek & Hanlon,

The Effectiveness

and Safety of Electroconvulsive

Therapy (ECT),

164 J. NERVOUS&

MENTAL DISEASES419, 420 (1977). 28See, e.g. Sharoff, Nurcotherupy,

in A. FREEDMAN& H. KAPLAN (eds.) COMPREHENSIVE TEXTBOOKOF

PSYCHIATRY1277 (1967). 2%. RACHMAN& G. WILSON, THE EFFECTSOF PSYCHOLOGICAL THERAPY259 (1980). 3%. HALLECK. PSYCHIATRYAND THE DILEMMASOF CRIME: A STUDY OF CAUSES, PUNISHMENTAND TREATMENT.338-39

(1971).

280

BERNARD

M. DICKENS

may appear to fall into the category of therapeutic innovation rather than of which consists in deliberate departure from an pure experimentation, acknowledged and effective orthodoxy. The middle ground between pure therapy and pure experimentation has been heavily contested by analysts who tackle the ethical, legal and philosophical status of innovation undertaken with therapeutic intent. “Therapeutic ex” “treatment research” and comparable expressions have been apperimentation, plied, and subtle distinctions have been proposed and refined to describe different types of management and their ethical incidents. The phrase “therapeutic innovation” adopted here identifies both a departure from discredited standard care and the taking of action where no standard medical response is indicated, and has two implications. The first is that the treatment would be legitimate as pure therapy, so that in itself it would not be dependent upon ethical approval by an experimentation institutional review board. The second is that, in addition to its therapeutic aspects, there may be a separate element which is not compelled by its therapeutic goal. The research element which may be isolated may concern additional use of data for research analysis, or, for instance, for comparison with data acquired from other patients similarly treated. The pursuit of data gathering and use not necessary for the individual patient’s therapy will constitute the separable research component of patient management in therapeutic innovation which requires ethical review as experimentation. The advantages to investigators in presenting their proposals for new managements of patients whose specific conditions they propose to relieve as therapeutic innovation are that such patients are not being deprived of effective standard therapy, since the efficacy of standard treatment is unestablished, and that the only experimental part of the treatment proposed may involve patients’ confidentiality in comparative use of resulting data. The treatment itself ranks as justifiable, even if new, therapy. Further, since therapy is involved, the therapeutic privilege of selective non-disclosure of data may apply, where giving information would be countertherapeutic or otherwise dysfunctional, without violation of legal duties to obtain the patient’s adequately informed consent. Courts have recognized that the range of privilege from disclosure in psychiatry is wider than in ordinary physician-patient relations.3’ The purpose of giving material information to patients is to assist their rational choice,“’ but psychiatric patients’ perceived elevated liability to irrationality may justify nondisclosure of information which non-psychiatric patients would be expected to be given. Nevertheless, the privilege attaches only to information pertinent to therapy, and does not apply regarding experimental aspects of treatment such as additional data collection and distribution. If a patient cannot be given material information in this area for therapeutic reasons, the patient may not be able to participate in the experimental aspects of the new treatment. Psychiatrists proposing to present a research protocol as therapeutic innovation rather than pure experimentation face particular problems. They must show that standard treatments of the patients they intend to treat and study are of un“SW,

e.g., Grosslight

“This

does not render their irrational

autonomy.

v. Superior Court of Los Angeles County, choice less effective,

140 Cal. Rptr. 278 (Cal. (‘.A.,

however,

as an exprersion

1977).

of their legitimate

ETHICAL

ISSUES IN PSYCHIATRIC

RESEARCH

281

proven and even doubtful therapeutic effect. They must also show that their proposal is likely to offer either advantages not currently available, or comparable positive results to those currently available without the adverse effects known to attach to standard treatments. The innovative treatment must also be shown to be appropriate to attempt in the opinion of independent peer review. Further, investigators must show the methodological soundness of their research design and that informed consent is to be obtained regarding the non-therapeutic aspects of proposed treatment.33 Location of particular proposals within the general area of therapeutic innovation does not relieve investigators of their duties to give adequate information for the proposed subjects’ consent. The therapeutic privilege of nondisclosure is an exception to this rule which cannot be used to evade the rule itself. Further, it cannot be supposed that psychiatric patients are per se incapable of giving autonomous consent, even when their detention in a psychiatric facility is involuntary. Courts are increasingly coming to recognize that subjection to involuntary detention should not axiomatically include liability to involuntary treatment. 34The judicial approach has been influenced by the growing realization of the unproven nature of many psychiatric treatments and their risks of causing untoward side-effects. This presents prospective investigators with a dilemma, since the unfavourable assessments of standard treatments they may invoke to justify their proposals as therapeutic innovation may disclose reasons why a particularly high level of informed consent should be obtained, and why patients incapable of absorbing or applying material information should not be placed at risk upon the consent of a surrogate. Where a standard treatment is claimed to be effective, furthermore, the level of information to accompany a proposal to a patient that it be withheld, altered or replaced by an investigational treatment is even greater. The initial presumption that a psychiatric patient, whether of voluntary or involuntary status, is competent to give or withhold autonomous consent regarding treatment has legal and ethical authority. 35It is reinforced regarding the mentally retarded, whose conditions may be of mild, borderline or moderate retardation, and who may live relatively independent lives notwithstanding their institutionalization. Accordingly, whether standard therapy, therapeutic innovation or pure experimentation is concerned, those who propose to treat or research such patients must address the problems of giving them information for consent, and thereby of obtaining their own informed consent. The problems extend beyond informed consent, furthermore, since consent must also be freely given. Free Consent The issue of free consent is particularly pressing when a prospective research subject is a patient of the prospective investigator’s or a patient in the investigator’s facility. It has been seen that, notwithstanding the physician’s zeal to j3They must also have proper consent to therapeutic aspects of proposed treatment, of course, but it is not the responsibility of ethical vetting by an experimentation institutional review board to address this issue. j4See Rogers v. Okin, 634 F. 2d. 650, (C.A. 1st Cir., 1980), appeal pending to the Supreme Court. 3sFor consent when the patient is not competent, see The Role of Third Parties, infru.

282

BERNARD

M. DICKENS

aid patients, the research relation reverses the traditional physician-patient relation. The patient’s participation as a subject represents a service requested by and rendered to the physician. Many physicians strongly resent theimplication that they might abuse the power and influence they have over patients for whom they have a therapeutic responsibility. Their conscientious dedication to their patient’s protection and welfare may be double-edged, however, in that it provides the strongest personal safeguard against wilful abuse, but alsoinspires theconcern to find out moreabout the conditions affecting the patients and to undertake research to improve therapy. In law, unequal relations such as exist between physicians and patients, lawyers and clients and, for instance, priests and penitents are subject to fiduciary duties binding the party with the power of knowledge.36 That party is accordingly under equitable duties to act in the utmost good faith, with a high level of disclosure and with no undue personal benefit. Any exceptional material or other advantage flowing to the stronger party is presumed in law to have been procured by the exercise of undue influence. The presumption may be rebutted by the more powerful party discharging the burden of proving that the weaker or dependent party had access or recourse to independent counsel before making the exceptional commitment. Thus, when sick patients dedicate themselves to the research interests of their attending physicians, or of other physicians closely identified with authority figures in the patient’s immediate life, this creates an inherently questionable transaction. Evidence shows, indeed, that reversal of the traditional physician-patient relation may have occurred unrecognized not only by the patient/subject, but also by the physician/investigator. Further, patients may feel not simply a dependency upon their physicians, but also an authentic gratitude. They may therefore be prepared to submit themselves to purposes and risks at their hands to which they would not submit themselves upon the request of an unfamiliar person. Some physicians pride themselves on the dedication, allegiance and confidence they inspire in their patients, and this is not to be discredited or diminished. It may inadvertently be abused, however, and many institutions prefer research to be proposed to patients in a more objective light. Unfamiliar and ostensibly uninfluential personnel may be required to introduce patients to the prospect of their participation in research and to invite patients’ commitment. In principle, physicians should not ask their own patients to take research risks, or suffer inconveniences or for instance losses of confidentiality, when scientifically suitable patients of other physicians have not been invited to participate, or when upon invitation they have declined involvement. Research should accordingly be directed to another physician’s patients in preference to one’s own, lest a relationship of dependency and gratitude be abused. In some cases, of course, where all of the patients with a given condition in an area are treated by a physician or medical team which proposes the research or therapeutic innovation regarding that condition, it may be appropriate under adequate safeguards to permit physicians to have their own patients take part in their research. This would serve macroethical interests in the pursuit of new therapies, but care must be applied to prevent abuse and to prevent contrivance 36See Natanson

v. Kline, 35 P.2d

1093 (Kan. SC.,

1960). per Schroeder,

J. at 1101.

ETHICAL

ISSUES

IN PSYCHIATRIC

RESEARCH

283

of a false separation between the roles of physician and of investigator which gives an appearance of the physician not acting as defacto investigator regarding his or her own patients. Informing and free consent-testing strategies may have to be developed to maximize patient autonomy. It is obvious that when potential subjects are involuntarily detained, as mental health patients or criminal offenders, they exist in conditions of some coercion. Similarly, legal minors such as adolescents committed to mental health institutions at the instance of parents or other adult guardians may feel under pressure to comply with proposals made to them.” The disturbing history of drug experimentation in United States prisons3* need not be invoked by way of illustration. Consent from those who do not perceive themselves as free, of which their objective physical or psychological captivity may be a compelling indication, is unavoidably suspect. The unfree should not be approached when scientifically suitable free persons decline involvement. Investigators whose research is critically dependent upon recruitment of such subjects bear an exceptional duty of justification and must offer a risk-to-benefit ratio or a macroethical justification in their protocols which accommodates the risk of exploitation of those unable freely to consent to participation. The awful history of exploitation of involuntarily detained persons such as criminal prisoners and the “dangerous” mentally disturbed as subjects of experimentation3” may almost justify ethical if not legislated prohibition of their future recruitment, by way of legitimate protection and macroethical compensation. Indeed, the only convincing argument in favour of permitting competent unfree persons to be involved in non-therapeutic studies may lie in the principle that nothing should be taken from them which it is not essential to take for their safe and secure custody as imposed by law. Accordingly, their rights of voluntary informed participation must be respected. It must be ensured, however, that they are not disproportionately invited to take the risks of experimentation as against scientifically suitable free persons. While an individual protocol may not disclose any disproportion in medical recourse to the unfree, ethical review agencies must be vigilant to enquire about proportionate approaches to the free and the unfree, and require particularly compelling grounds to seek research recruits among the latter. Information

for Decision

There is a spate of modern literature, produced by psychiatrists, lawyers, psychologists, ethicists, sociologists and others, on special problems of informed decision-making which arise in the psychiatric setting.40 This is reinforced and fed particularly in the United States by a series of judicial decisions concerning treatment of psychiatric patients and the retarded; indeed, a new series of United 37See generally Dickens, The Modern Function and Limits of Parental Rights, 97 L. Q. REV. 462, 477-80 (1981). ‘aSee P. MEYER, DRUG EXPERIMENTS ON PRISONERS:ETHICAL,ECONOMICOR EXPLOITATIVE?(1976). 39See G. ANNAS. L. GLANTZ & B. KATZ, note 6 supra, chs. 4 and 5. 40The expression “informed decision-making” may be preferred to the more usual “informed consent,” since the latter presupposes that the decision will be to consent rather than to refuse consent, and that a patient’s or subject’s refusal need not be informed and may be a sign of ignorance.

BERNARD

284

M. DICKENS

States law reports, The Mental Disability Law Reporter? is now published to bring these cases together and to discuss their implications. Doctrine and detail on informed consent emerge from various sources beyond the courts, which themselves address the legal issue in routine malpractice litigation and in, for instance, constitutional litigation on the right to the offer of treatmenP2 and the right to refuse treatment.43 Express legislation may address the issue of informed consent to medical treatments by specifying what information must be given and by saying what is deemed not to be covered by the giving of c0nsent.j” Government departments may also specify information required to be given before particular procedures may be undertaken, such as in the regulations issued in the United States by the federal Department of Health and Human Services to govern informed consent to research participation. Regulations may also come from other governmental or nongovernmental agencies, such as those responsible for hospital accreditation. Whatever the source of guidance or direction on information for decision-making may be, it must be noted that courts of law require a higher level of disclosure for research than they do for therapy.j’ A person incapable of absorbing and applying that level of disclosure must be omitted from research, rather than recruited upon the basis of inadequate disclosure. The mass of legal and administrative provisions defies simple or brief attempts to pull it together in a helpful synthesis, or even to describe its contours in a way applicable to more than a single jurisdiction. Nevertheless, application of the undifferentiated concept of informed consent46 can be considered regarding psychiatric treatment in general, and regarding particular categories of patients. Underlying most considerations of obtaining legally effective and ethically acceptable decisions from patients is their capacity to reach decisions. A number of tests of competency to consent to psychiatric treatment have been proposed,47 outcome of choice, choice but whether they focus upon choice, “reasonable” based on “rational” reasons, ability to understand, or actual understanding, they suppose a level of cognitive and affective functioning which a psychiatric patient may lack. Their reliance upon levels or types of brain function discloses the paradox of their dependence upon the very organ or mechanism which may be dysfunctional in the psychiatric patient.@ -“A publication ?*See Wyatt 1305 (5th Cir. Ji.r,,

of the American

v. Stickney.

Commission

Ala,

on the Mentally

1972), uffdsub

no~7.

Disabled.

Wyatt \. Aderholt,

503 F. 2d

1974).

Rogers v. Okin,

J4The Mental regarding

Bar Association’s

344 F. Supp. 373 (M.D.

Health

an involuntary

note 34 supra. Act of Ontario,

for instance,

provides

that no consent to treatment

given by or

patient shall include or be deemed to include consent to psychosurgery;

see S. 3 la,

subsections (3) and (5). “SSee Halushka

v. Univ.

*6The Nuremberg voluntariness

Saskatchewan,

and knowledge.

case of Kaimowitz

note 3 supra.

Code may be found to have described the elements of informed Rudimentary

v. Dept. of Mental

and unrefined

Health,

Civ. No. 73

IO, 1973); the case is fully discussed in G. ANNAS. L. GI j’See,

e.g., Roth, Meisel & Lidz,

conrent a\ competency,

as these criteria may be, they were applied in the 19434

.%NT/

&

AW (Cir. Ct. Wayne Counry,

Mich. July

B. KATI. note 6 s~pru.

Tesl.7 of Con1peienc.v lo Consenl to Treaimeni,

l34:3

A~I. .I. PSYCH 279

that

severely

(1977). ‘*There psychiatric not expose Psychiatric

are some

recent

preliminary

patients evaluate participation themselves

findings

in a rather

small

scale study

disturbed

in research in a manner similar to that of medical patient,

to high risks to a greater

Patients as Research Participants:

degree.

A Population

See Stanley

pi al.,

Preliminary

and do

Findings

at Risk? I38 AM. J. PSYCt<. 669 (1981).

on

ETHICAL

ISSUES

IN PSYCHIATRIC

RESEARCH

285

Of less special significance is the patient’s potential failure of recollection. Not only psychiatric patients may subsequently forget or deny that they gave consent to run risks in medical treatment. This may be especially so when the risks have materialized in injuries or other impairments. Defective memory is clearly a matter to be taken into serious account in patient management, but it should not serve to concentrate disproportionate attention upon the moment when the patient gives initial consent to therapy, or when the subject consents to participate in a research project. Consent is not given once for the duration of therapy or research. Rather, consent is a quality which arises in interpersonal relations between the patient or subject and the physician and health team, or the investigator and research associates. Its enduring presence remains the precondition of involvement of the patient or subject. Consent forms in experimentation usually express the subject’s right of withdrawal without explanation, but even when that term is not made explicit, it remains implicit in both research and therapeutic relations. Clearly, withdrawal from a course of therapy or of research may not terminate the effect of previous therapy, drug administrations or other forms of management, but it will prevent subsequent treatment. Informed consent is therefore an ongoing condition of both therapy and research, and the patient or subject who has forgotten that consent was once given remains as free to withdraw from unpleasant treatment as the patient of perfect recollection. On the other hand, since the means to recall the acceptance of risk are less, particular care must be taken to ensure that the patient remains willing to take that risk, whether in therapy or research. It therefore serves physicians and investigators well to ensure that patients and subjects have appropriate means to recall their commitment. Ideally, information serving as the basis of initial involvement should be expressed in writing and a copy left with the patient or subject to assist memory. It is less clear that the patient or subject should retain a copy of consent bearing his or her own signature, since this may inhibit withdrawal by seeming more binding than it actually is. Further, since informed consent is the continuing precondition of therapeutic or experimental management, the information should be appropriately updated. Any new information which may be material to the patient’s or subject’s decision to remain in the course of therapy or the research should be disclosed. Mounting uncertainty about the efficacy of a treatment or, for instance, the safety of an experimental technique should be disclosed even before scientific resolution of the uncertainty where it affects the overall foreseeable risks of the treatment, including the statistical prospects of its therapeutic ineffectiveness and the risk-tobenefit ratio of experimentation. The governing principle is that updated information must be given of matters which make inapplicable the data initially presented, upon the basis of which initial and therefore continuing consent has been given. This is part of the therapist’s or investigator’s fiduciary duty of acting frankly and in good faith, and it respects the equal partnership with the patient or research subject. When patient or subject management is on the threshhold of passing beyond the express or implied limits of the consent initially given, therefore, informed consent must be renewed or extended. Fresh information may properly express its uncertain status and lack of scientific verification. It may say, for instance, that while a research subject has been allocated to a treatment group whose

288

BERNARD

M. DICKENS

results to date are significantly adverse in contrast to results of an alternative group, longer term results may prove the subject’s group to be favourable. The information has to be given, however, in order to maintain the patient’s or subject’s informed consent in good repair. The patient’s or subject’s potential failure of recollection is accordingly not a special problem in psychiatric treatments, since the need to maintain and renew informed consent must be addressed in all physician-patient and investigatorsubject relations. More problematic in certain psychiatric conditions, however, may be changes in patients’ perceptions as their treatment evolves, affecting their understanding of the procedures directed towards them.4” The central focus must nevertheless rest upon what information to give, at whatever time. This is governed by the form of therapy or research proposed, alternative methods of management, and the goals, effectiveness and risks including side-effects of the treatment in issue. Regarding therapeutic innovation, of course, the only experimental aspect may consist in extra use of data for comparative analysis, and information beyond that required in the therapeutic setting may be confined to the confidentiality issues involved. For pure research, the regulations of the United States Department of Health and Human Services’ regulations, effective from late July 198 1, require in principle that eight issues be included in information to potential subjects, namely: (a) (b) (c) (d)

the purpose, duration and procedures of the project; the foreseeable risks and discomforts that could affect the subject; the benefits expected from the research; alternative procedures that could be more advantageous to the subiect; confidentiality safeguards; if more than minimal risk is involved, possible compensation and/or medical treatments available to the subject; (8) persons to contact for answers to questions about the research or about difficulties that could arise during its conduct; and a (W statement that refusal to participate or a decision to discontinue participation will not prejudice the subject in any way or deprive the subject of any benefits due.

I:

Information must be given in both positive and negative forms, so that if no benefit will result to the subject under item (c), or no compensation is payable under item (f), this must be stated. Information should be in written form to be retained by the subject, as should updated information of amendments to data in the initial document. It must be emphasized that, whatever the source of guidance or direction on information for decision-making, the aim is to achieve adequately informed decisions. The pursuit offully informed decisions is illusory, not least because of a lack of consensus on what full information means and how it may be achieved. It is not an acceptable explanation for withholding data, however, that the very research in issue is compelled by the need to fill gaps in knowledge. Information must be given not only of material facts which are known, but also of material 49See Sacks, Carpenter&Strauss, pretation of Research Procedures,

Recovery From Delusions: Three Phases Documented 30 ARCH. GEN. PSYCH. 117 (1974).

by Patient’s Inter-

ETHICAL

ISSUES

IN PSYCHIATRIC

RESEARCH

287

information which is unavailable or uncertain. Investigators must disclose the lack of knowledge in their discipline. In the purely therapeutic relation, physicians may justify nondisclosure of uncertainty and the unknown elements of practice by invoking their “therapeutic privilege,” and may avail themselves of the same privilege regarding nonresearch aspects of therapeutic innovation. This may be offensively paternalistic and reflect therapists’ needs to appear omniscient before their patients, but it is an ethical, legal and sociological issue pertinent to therapy as opposed to experimentation. In research, appropriate information of professional uncertainty and ignorance must in principle be given. An otherwise competent person who cannot understand or cope with that information, and, for instance, a patient for whom it would be countertherapeutic, should not be invited to participate in the research. Particular forms of treatment pose their particular problems of identifying material information for decision-making, such as ECT,50 and treatment of antipsychotic5r and, for instance, neuroleptic drugs.52 Comparable problems attach to the proposed withholding of such treatments standardly given, for instance in a randomized clinical trial contrasting treatment with non-treatment or placebo treatment. The special difficulty presented by having to communicate information to psychiatric patients may centre, however, upon their own characteristics and disorders. A patient’s denial of illness presents an obvious obstacle to informing the patient of therapeutic means and alternatives. The severe depression of a patient to whom ECT may be offered raises questions about capacity to consent, and indeed to refuse to consent.s3 This may confound a randomized trial of ECT and an alternative method of management. Evidence that up to half of schizophrenic outpatients who have consented to antipsychotic drug treatments do not take the prescribed medications4 raises questions about genuineness of consent and capacity for compliance. Potential research subjects who are not pathologically disturbed but who are mentally retarded, or who have the psychological and affective conditions associated with advanced age, raise similar clinical problems regarding receiving information upon which to reach decision .55It would oppose the thrust of evolving ethical sensitivities regarding the retarded and the elderly to presume their incapacity to comprehend, and to relegate them to or to retain them in a dependent status. They are vulnerable to abuse, of course, but an excess of protections against their exercise of autonomy where no serious risk is at stake, whether high risk of minor disadvantage or small risk of significant disadvantage, may itself

50See Kaufmann & Roth, Psychiatric Evaluation of Patient Decision-Making: Informed Consent to ECT, 16 SOC. PSYCH. 11 (1981). 5’See Soskis & Jaffe, Communicating With Patients About Anti-psychotic Drugs, 20 COMPREHENSIVE PSYCH. 126 (1979). 52See Deveaugh-Geiss, Informed Consent for Neuroleptic Therapy, 136 AM J. PSYCH. 959 (1979). 53See Culver, Ferrell & Green, ECT and Special Problems of Informed Consent, 137 AM. J. PSYCH. 586 (1980). 54See Soskis & Jaffe, note 51 supra, at 126. Van Putten has recorded that up to 63 percent of schizophrenic out-patients take less antipsychotic drug than the amount prescribed; see Why Do Schizophrenic Patients Refuse to Take Their Drugs? 31 ARCH. GEN. PSYCH. 67 (1974). “See Berkowitz, Informed Consent, Research, and the Elderly, 18 THE GERONTOLOGIST237 (1978).

BERNARD

288

M. DICKENS

be an abuse. UnJustified paternalism56 directed to the interests of the apparently handicapped may exist not only among physicians, but also among those who would give protection against, for instance, research involvement of the handicapped. The Role of Third

Parties

In the face of a patient’s or other potential research subject’s demonstrable incapacity, the issue must be addressed of what role a third party may play.5’ Whether the third party is a legal guardian defined by legislation or judicially appointed, or the next of kin or close friend to whom physicians may reasonably turn when he or she shows genuine concern for a patient’s well-being, the underlying issue has comparable elements. Since the first principle of patient treatment is patient autonomy, which is incapable of reliable expression by the incompetent patient, the role of the third party is to serve the patient’s autonomy. That means service to the patient’s authentic wishes.‘x Those wishes may have been clearly expressed in the patient’s competent past, in relation to specific treatment or types of treatments, or in analogous ways. Failing such expression, it may have been implicit in or capable of inference from the patient’s lifestyle, philosophy and personal history, with which the third party is expected to be familiar. The quest is for an expression of the patient’s authentic identity and a decision in character with the patient’s established personality.i’j The patient’s interpretable wishes may differ from the patient’s apparent interests, and the third party’s role is to distill and express wishes in preference to interests. Ideally, of course, wishes and interests coincide, since people will normally wish that their best interests will be achieved, but where a conflict is found between the patient’s apparent wishes and the patient’s best interests as perceived by others such as physicians and the third party, it is the patient’s wish which should prevail. The individual right to autonomy is not lost upon the loss of legal competence. A confounding element in this reasoning is that the patient’s expressed wishes may have been indicators of psychiatric disorder. A distinction may be drawn, however, based upon the time of the onset of disorder, since prior wishes will be authentic while subsequent wishes may not be genuine expressions of the patient’s true personality. This distinction has an unavoidably blurred edge but should serve in principle to locate the patient’s character from which preferences may be inferred. If the patient has suffered chronic psychiatric disorder or never generated a character relevant to the decision which has to be reached, the patient’s authenticity may be impossible to establish. In that case, since wishes can‘6Not all paternalism is unjustified; see Gert & Culver, Pa/erna/istic Behavior, 6 PHII & PCIHIIC AI I %IKS 45 (1976), and The Justification of Puternalism, 89 E rti[Cs 199 (1979). 57The approach here will be confined to adult patients; the role of parents or other adult guardians of the young is a Eeparate even if related issue. which space does not permit to be considered; see Dickens, note 37 .SL,,ui-cr. ‘*Court-appointed guardians, however, may be appointed in order to achieve a specific objective which may have been determined upon the basis of the apparent best interests of the incompetent person, as oppoced to the person’s actual wishes. “‘See Miller, Aurono~77_v and the Rqfusul oflifesuving Trearmenl, I l(4) HASTINCAC. R. 22 (1981).

ETHICAL

ISSUES

IN PSYCHIATRIC

RESEARCH

299

not be found, the third party must fall back upon the objective and less personal basis of serving the patient’s apparent and reasonable interests. There is an ethical duty, however, not to suppose too easily that the patient’s wishes at variance with apparent interests are pathological or not authentic. Although information is designed to contribute to rational decision-making, there is an inherent personal right to irrational and sentimental decision-making from which no adverse inference should be drawn. Many of the most important human decisions made, such as who one wishes to marry, may not satisfy rational or reasonable criteria. A third party may accordingly conclude that an incompetent person’s past natural personality was such as to indicate that the person would want to participate in a research proposal and to take its risks. For the reliability of this conclusion, an ethical review body must itself monitor or require investigators in good faith to monitor appropriately the association between the incompetent person and the third party. The purpose is to ensure as far as possible that it is based upon affinity and genuine caring for the incompetent person’s welfare. Mere links of blood or marriage can degenerate into antipathy or indifference, but where guardians are identified by legislated formulae, reflecting general expectations but not specific realities, legal authority may be given to those who do not welcome it and who want to discharge their responsiblities with maximum convenience, or perhaps economy, to themselves. Although they may so acquire significant legal powers of disposition over incompetents, their legal authority may be ethically unacceptable. In cases of uncertainty, their legal authority should be confined to the taking of therapeutic decisions and not be allowed to run to offering their charges for even the slightest risks of experimentation. Further, in any event, the risks to which an incompetent person may be exposed for the purposes of research upon the information of a third party must be limited to risks of a low order; it may be questioned whether treatment as invasive as venepuncture should be permitted. If it is, it should be only upon clear demonstration by the investigator that no competent person is scientifically suitable to serve the research protocol, and that blood is not obtainable by, for instance, using a surplus or running of a small extra volume upon diagnostic or therapeutic blood-taking. Similarly, small skin biopsies may be allowed from the body surface as an outer limit of invasive testing undertaken purely for research. Standard therapy variations may be allowed for those in need of therapy, including well controlled brief episodes of withholding standard therapy. Use of investigational drugs may be permitted, however, only as therapeutic innovation, or perhaps when the incompetent person may benefit as an individual. If a macroethical justification can be established, furthermore, such drug or therapy may be allowed when benefit is reasonably liable to result to patients affected by a condition shared with the incompetent person. In every case, however, it must be shown that there is no competent person or group capable of serving the scientific design of the protocol, that no alternative design would offer prospects of comparably reliable data, and that the alternative to recruitment of the incompetent person would be abandonment of the study or a severe reduction in its value. It must not be supposed that a third party can alone give legally effective consent to non-therapeutic treatment of an incompetent person, unless clearly so authorized by legislation or, for instance, specific court order. Language sug-

BERNARD

290

M. DICKENS

gesting that the third party is “consenting” is misleading, since the consent power is employable only for the purpose of achieving the welfare of the incompetent person. Within the limits and under the conditions discussed above, it may be argued that welfare includes the taking of minimum risks for a philanthropic cause, compatibly with the incompetent person’s earlier expressed authentic wishes. This argument is so obviously open to abuse, however, not just by the malicious guardian but particularly by the indifferent guardian and the guardian who through caring comes to adopt unrealistic hopes for the incompetent person’s relief and restoration, that it must be held under rigorous control. Discarding descriptions of “third party consent,” “surrogate consent” and, for instance, “substituted consent,” investigators must recognize that they are dealing with the incompetent person outside the therapeutic setting upon a nonconsensual basis and can justify themselves only upon the third party’s claim that, had the incompetent person preserved competence, that person’s consent would have been given. This may provide a microethical or macroethical justification for non-consensual research, depending upon the nature and significance of the particular study. At best, however, it is a fragile basis for imposing otherwise unjustifiable risks upon an incompetent person, and investigators should avail themselves of it only under maximum safeguards and within strict limits. It comes uncomfortably close to the type of experimentation which may be ethically too expensive. Research Design It need scarcely be stated that ethical research proposals must address a valid issue, since trivial, valueless or premature enquiries involving risks to individuals, including the risks of abusing their good will, are unjustifiable. Similarly, the appropriate pre-testing of equipment, safe grounding of electronic devices, animal testing of drugs, and guarding, for instance, against flashing light being liable to trigger an epileptic attack must be shown to have been undertaken. Of particular concern to scientific proposalshO is sound and reliable methodology, including recourse during design preparation to a statistician or biostatistician, lest results be scientifically flawed and consequently of no significance. It is trite that bad science is bad ethics, and in terms of the ethical risk-to-benefit ratio, no risk is permissible where no benefit may result due to design flaws in a proposal; thus, even when prior scientific review has approved study design, this remains an issue for possible discussion at ethical review. Within limits, minor risks may be justified in bona fide preliminary studies or pilot projects, but “pilot project” has now become a semi-humorous euphemism for an inadequately designed study, and an expost facto explanation in order to rescue a publishing potential from the wreckage of a study that failed to produce valid results because of design weaknesses. It has been seen above, however, that a remarkable proportion of research studies in psychiatry are marked by design inadequacies. In part, this may be explained by particular vulnerability to insuperable design obstacles. Control groups may not be found for a controlled trial of ECT, for instance, in the same b0As opposed

to descriptive,

clinical

or anecdotal

studies,

for example.

ETHICAL

ISSUES IN PSYCHIATRIC

RESEARCH

291

way as they might be for a drug trial .61For a valid ECT trial, the control group would have to receive exactly the same treatment as the treated group except the shock. The controls would therefore have to receive the anesthetic, muscle relaxant and oxygen, and all the care and attention given for the treatment group. It is probably ethically impermissible to so use normal controls, even if useful results could come of it, and difficult to justify withholding full treatment from a distressed patient for whom it is clinically indicated in accordance with prevailing understanding.h2 Similarly, the control of variables may be difficult in a cohort of patients whose past personal histories may have contributed to their disorders and whose unique experiences and perceptions may condition their responses, particularly in individual and group psychotherapies. Thus, statistical comparisons among them may be of little significance, although purely biological data may be of comparative value. Indeed, a recent study has suggested that a high proportion of psychiatric patients suffers from conditions caused or aggravated by medical conditions.63 An objection in principle to experimentation arises when it may deliberately cause or risk irreversible harm. There is a sense, of course, in which any and every experience in life may cause irreversible change, and deliberately inducing significant irreversible change solely for purposes of experimentation may be as objectionable as risking harm. The essence of the principle in application is that no irreversible effects should be deliberately caused or risked, subject to the nature of human physiology and psychology. The method of measuring clearance times of drugs through the half-life may bear the theoretical implication that traces of the drug never finally leave the body, but this provides a model for concluding that when the significance of an effect deliberately induced nontherapeutically will substantially terminate within a reasonable and measurable time period, the effect may be allowed to be achieved. Clearly, however, extremes such as experimental psychosurgery and experimental sex-change operations would be impermissible. If justifiable at all, these would demand strong therapeutic justifications. Subjective aspects among psychiatrists of psychiatric classifications, diagnosis and assessment of patients, determination of treatment goals, treatments favoured and applied (especially psychotherapy), and measurements of results achieved present major problems in establishing the scientific validity and replicable character of psychiatric studies. These problems may be overcome with perception and appropriate strategies and methodologies, but these may require consultation with experienced professional peers or seniors and perhaps recourse to a significant number of research subjects. Numbers present problems of their own, since ethically as few subjects as possible should be exposed to risk, including the risk of lost confidentiality, inconvenience and over-exposure to research modalities. When a minimum number of subjects has been determined from whom data must be acquired in order to achieve statistical significance, it must be remembered that some may 6’See Clare, Therapeutic and Ethical Aspects of Electra-Convulsive Therapy: A British Perspective, 1 INT. J. L. & PSYCH. 237 (1978). 6ZClare discusses how the obstacles to having a suitable control group were tackled; see id. at 241-2. 63.See Undiagnosed Illness Raises Ethical, Legal Issues, 16(3) PSYCH. NEWS 28 (1981).

292

BERNARD

M. DICKENS

fail to complete the study, because they fall within predetermined criteria of post-commencement exclusion, because of inadvertent inability to continue, or, for instance, because they decide to exercise their right freely to withdraw consent. Thus, the minimum number for statistical significance is the end number, and the investigator must add the numbers of those who may reasonably be anticipated to withdraw. It is ethically important that an investigator should not feel pressure, perhaps to preserve the study and the doctoral thesis dependent on it, to keep as a subject any recruit wishing to leave. Statistical collapse of the study would waste not only the investigator’s resources of time, materials and energy, of course, but also the commitment and voluntary (and possibly involuntary) submission to risks of the subjects. Accordingly, while recruitment in a proposed study of only the statistically required, say, 30 subjects may be ethically unacceptable, recruitment to the identical study of up to 50 subjects may be approved. The issue of ethical methodology includes consideration of the proposed subject population and the method of recruiting subjects, which have been touched on above. In many cases, psychiatric research follows the method of the social sciences rather than of medical or biological science, but this renders it no less liable to requirements of structural and statistical rigor and of safety. Risks to safety arise from endangering confidentiality and, for instance, causing loss of self-esteem through inducing uninvited self-awareness. Answers to questions and questionnaires may also disclose evidence of crime, child abuse and future danger to others. Many jurisdictions have compulsory child abuse reporting legislation,64 and obligations may arise under general law to warn identifiable prospective victims of patients’ dangerous potential,65 so that legal limits exist beyond which confidentiality cannot be preserved. Further, confessions of crime may not be protectable against subpoena, unless local legislation provides for testimonial privilege. 6h The informing process conducted before prospective subjects commit themselves to make responses to questions must take account of these factors. The option of selective non-response may not entirely meet objections to particular patterns of questioning, since a specific refusal to answer may create an adverse inference. The fact that psychiatric research ranges from the biological and medical to the psychological and sociological makes it a microcosm of the world of human research and the systematic pursuit of knowledge from individual human beings. It also explains why the ethical assessment of this research can draw upon a rich historical and modern experience of studies, and why it presents a special fascination, education and reward.

64See Dickens, Legal Responses to Child Abuse, 12 FAM. L.Q. 1, 12-19 (1978). bSSee Tarasoff v. Regents of Univ. California, 551 P. 2d 334 (Cal. S.C., 1976), and the vast literature case has generated. 6bSee Dickens, Legal Protection of Psychiatric Confiden/iality, 1 INT. J. L. & PSYCH. 255 (1978).

the