Special Article Ethics in Psychiatric Research Resources for Faculty Development and Resident Education Laura Weiss Roberts, M.D., Zachary Solomon, M.D. Brian B. Roberts, M.D., Samuel J. Keith, M.D. Controversy has arisen in recent years about the participation of psychiatric patients in questionably ethical research protocols. Consequently, academic psychiatrists have been called upon to enrich their understanding of the ethical aspects of research and to teach residents more intensively about these issues in scientific methodology. Toward these ends, the authors have assembled an extensive resource listing in the area of psychiatric research ethics. Articles were identified through MEDLINE and BIOETHICS LINE computerized searches and the authors’ review of relevant literature through 1996. Emphasis was placed on those pieces with special historical value, empirical studies, and papers that provide background on the current controversies in psychiatric research ethics. The references were organized into five logical categories. Based on the resource review, the authors briefly discuss areas related to research ethics that merit greater attention in academic psychiatry. (Academic Psychiatry 1998; 22:1–20)

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he field of psychiatry has received unfortunate attention over the past several years with regard to the ethics of our research practices. Posthumous publication of patient records; questionable experimental use of placebos; scientifically necessary but dangerous “wash-out” periods in medication trials; and involvement of potentially vulnerable, decisionally “incapable” subjects have stimulated controversy, threatening the continuation of some psychiatric research activities (1–8). In response, psychiatry faculty have undertaken a process of academic inquiry and self-scrutiny with regard to the ethics of clinical research (1,,2,4,9–11). With this increasing attention, a clearer understanding of the ethics of human experimentation has become a significant mission for academic psychiatry. Translation and implementation of these important issues into the training of residents and students are the task of the ACADEMIC PSYCHIATRY

psychiatric educator. Preparing physicians to be astute, critical-thinking, and ethically minded psychiatric clinicians and investigators is not a simple undertaking. This task requires that psychiatry faculty understand the history, scientific basis, and philosophical elements of research involving human subjects. It further requires that these issues be integrated successfully into residency curricula and supervision. Academic psychiatrists should feel optimistic about these activities, however, for two reasons: 1) psychiatry residents have expressed significant Dr. L. Roberts is assistant professor and associate director, Medical Student Education; Dr. Solomon is a postgraduate year-2 resident; Dr. B.Roberts is assistant professor; and Dr. Keith is professor and chair; all in the Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, New Mexico. Address reprint requests to Dr. L. Roberts, University of New Mexico, Department of Psychiatry, 2400 Tucker NE, Albuquerque, NM 87131–5326. Copyright 䉷 1998 Academic Psychiatry.

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interest in topics related to research ethics (12), and 2) valuable resources exist that can serve to strengthen faculty knowledge and resident education in this area. It is with this latter reason in mind that we have assembled the following list of resources in psychiatric research ethics. We provide this list hoping to enrich academic psychiatrists’ understanding of the ethical aspects of research and to foster the teaching of research ethics in psychiatry residency programs. Articles included in this bibliography were identified primarily through two methods. First, MEDLINE and BIOETHICS LINE searches were conducted to find references on the topic of the ethics of human experimentation, with particular emphasis on psychiatric research. The searches used key words such as ethics, research, experimentation, clinical trial, placebo, informed consent, competence, psychiatry, and others to generate an optimally representative set of articles from 1966 to 1996. Second, the authors reviewed literature and previously published annotated bibliographies (13–16) in the areas of medical ethics and psychiatric ethics to capture historically important articles and book chapters in this area. We were able to obtain more than 90% of the relevant English-language references. We excluded “Letters to the Editor,” brief editorials, and commentaries when their content was covered more fully by other writings, when they focused on special situations in foreign countries, and when they did not relate directly to the topic of psychiatric research. As not all full articles could be included, our selection process was informed but ultimately subjective— placing emphasis on those writings with special historical value, empirical studies, and papers that provide background on the current controversies in research ethics (e.g., salient articles describing clinical aspects of informed consent and decisional capacity). The references have been organized into five logical categories. Articles related 2

to ethical aspects of the conduct, design, and publication of human research are presented first, followed by a series of articles that emphasize special ethical considerations in psychiatric investigation. The third section focuses on informed consent, decisional capacity, and research involving vulnerable populations. The fourth section, and the most interesting and compelling to us, provides a set of empirical studies on the ethical aspects of research. Brief annotations accompany all of about 75 references in these 4 sections. The fifth section (Appendix) gives titles of 25 additional resources, including ethical codes, other bibliographies, and related texts. These groupings may at times seem artificial, as articles may naturally span two or more of our defined categories (e.g., empirical articles focusing on informed consent or articles considering scientific design and placebo use in psychiatric research). It is hoped, nevertheless, that the resource listing will be intuitive and helpful in the endeavors of psychiatric faculty and trainees. I. ETHICAL ASPECTS OF THE CONDUCT, DESIGN, AND PUBLICATION OF HUMAN RESEARCH Beecher HK: Ethics and clinical research. N Engl J Med 1966; 274:1354–1360 This short report describing 22 unethical or questionably ethical clinical studies is considered by many to be the most important paper written about the ethics of clinical research. Beecher identified a series of studies in which patients were placed in serious or unnecessary jeopardy, often without their knowledge or consent, “for the sake of science.” The author concludes with four imperatives for researchers: they must strive for the sometimes difficult goal of obtaining informed consent; they must be conscientious and compassionate in all of their experimental work; they must not exploit patients by placing them at risk without the possibility of commensurate gain; and they VOLUME 22 • NUMBER 1 • SPRING 1998

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must document their conduct. Without question, this simple, relevant, and influential article should be read by every clinician, human researcher, and trainee in medicine. Bok S: The ethics of giving placebos. Sci Am 1974; 231:17–23 This early essay describes the deception, the harms, and the costs of placebo use in experimentation and treatment. It is a carefully reasoned and well-written piece. Engler RL, Covell JW, Friedman PJ, et al: Misrepresentation and responsibility in medical research. N Engl J Med 1987; 317:1383–1389 Triggered by the case of a researcher who published 12 decidedly fraudulent and 48 questionably fraudulent papers in 7 years, this article addresses the problem of intentional misrepresentation in scientific research and publication. The authors discuss how personal motivations (e.g., career advancement) may lead some researchers to compromise their scientific integrity. Stating that “sophisticated dishonesty can escape detection,” the authors offer suggestions to help the scientific community minimize fraudulent research without discouraging innovative investigation. Feinstein AR: Clinical biostatistics: XXVI Medical ethics and the architecture of clinical research. Clin Pharmacol Ther 1974; 15:316–334 A balanced analysis of the relationship between research ethics, scientific methodology, and clinical practice is offered. The author discusses the ethical ramifications of research “architecture,” such as clinical trials with placebo control subjects, and considers case examples. Grisso T, Baldwin E, Blanck PD, et al: Standards in research: APA’s mechanism for monitoring the challenges. Am Psychol 1991; 46:758–766 This document was developed by the American Psychological Association’s Committee on Standards in Research and articulates several recent developments in ACADEMIC PSYCHIATRY

the conduct of human research. Future challenges for standards in research are defined, including publication, use and archiving of videotaped data, research with vulnerable populations, scientific misconduct, and financial conflicts of interest. Howard-Jones N: Human experimentation in historical and ethical perspectives. Soc Sci Med 1982; 16:1429–1448 This extensive report was prepared as a background document for the World Health Organization and the Council for International Organizations of Medical Sciences in an effort to establish international ethical guidelines for human research. It is a comprehensive, well-written narrative, most valuable for its description of remarkable events in the history of human experimentation. Such events include the early “autoexperiments” (e.g., cholera ingestion, anesthetic use, and, incredibly, cardiac catheterization); controversial experimental practices (e.g., use of fetal tissue); and both disastrous and successful drug trials over the past several decades. The author reviews in detail the Nuremberg trials and Nuremberg code, the Declaration of Helsinki, and other efforts to clarify the ethics of human research. Jonas H: Philosophical reflections on experimenting with human subjects. Daedalus 1969; 98:219–247 This essay provides a philosophical overview of the issues “peculiar” to human experimentation, ranging from subject recruitment, societal vs. individual good, coercion and “conscription” of consent, medical progress, inclusion of the sick and suffering, and other topics. The article presents a valuable, early humanist perspective on research ethics. Joyce CRB: “To please or not to please.” Eur J Pharmacol 1980; 17:157–159 This is a short, pleasantly written commentary on the use of placebos in human experimentation. Unlike other pieces, the article emphasizes the issue of rigorous study design and does not dwell on the is3

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sues of deception and potential exploitation. The author quotes D.L. Sackett, who wrote, “A poorly designed human experiment is unethical by definition. . .because it exposes humans to the risks of the experimental manoeuvre without providing a valid scientific answer to the hypothesis under consideration.” Katz J: The education of the physicianinvestigator, in Experimentation with Human Subjects, edited by Freund PA. New York, George Braziller Press, 1970, pp. 293– 314 The author, a preeminent scholar and mentor in the field of reseach ethics, describes the importance of teaching physicians about the ethics of medical experimentation. He then generously and personably describes his own teaching approach—a rarity in this literature. Leber P: The placebo control in clinical trials (a view from the FDA). Psychopharmacol Bull 1986; 22:30–32 The author, in support of the Food and Drug Administration’s (FDA) position often requiring placebo-controlled trials in pharmacological research, presents an interesting analysis of the scientific advantages and the logistical problems of placebo use in clinical investigation. He concludes that placebo controls “are our surest protection against fads and fashions. . ., and most important, against our own mistaken beliefs and prejudices.” Levine RJ: The use of placebos in randomized clinical trials. Institutional Review Board 1985; 7:1–6 The author explains that placebo use in clinical trials should “be regarded as a nontherapeutic procedure that presents more than minimal risk.” He provides several examples of published research in which placebo administration essentially resulted in the withholding of needed treatment for serious illnesses, with troubling medical and ethical implications. Levine RJ: Clinical trials and physi4

cians as double agents. Yale J Biol Med 1992; 65:65–74 This is an excellent, nicely written discussion of the ethical problems that may arise when a patient’s personal physician also conducts research and wishes to enroll the patient in a scientific protocol. The author explains that such situations represent a conflict of interest if what is best for the patient and what is best for the physicianinvestigator do not fully coincide. The dual role of physician-researcher is usually ethically permissible, the author suggests, but certain factors may increase the likelihood of a serious conflict of interest. When present, these factors should prompt Institutional Review Boards to insist upon special procedures that safeguard patients. Levine RJ, Lebacqz K: Ethical considerations in clinical trials. Clin Pharmacol Ther 1979; 25:728–746 This is a comprehensive discussion of the ethics of clinical trials, each focusing on the specific example of research conducted at the Veterans Administration (VA) hospitals. The article is particularly helpful in that important ethical and scientific principles, such as beneficence, justice, rigorous research design, and informed consent, are first explained and then concretely applied to the example of research conducted at VA hospitals. This piece will be of particular interest to many academic faculty and trainees who are familiar with the VA hospital system as a setting for clinical and research activities. Macklin R, Friedland G: AIDS research: the ethics of clinical trials. Law, Medicine, and Health Care 1986; 14:273– 280 The authors discuss the dilemma of AIDS research: “Can the demands of rigorous scientific research design be met without violating the rights or harming the interests of research subjects?” An exemplary analysis, this piece presents the scientific picture of AIDS research at the time, ethical principles governing human reVOLUME 22 • NUMBER 1 • SPRING 1998

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search, and salient issues in AIDS investigation, ranging from the “argument from hope” to issues of respect and justice. The authors conclude that “the obligation to both present and future patients is to produce more good than harm.” National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research: The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, DC, Government Printing Office, 1979 The Belmont Report presents three major principles governing ethical research involving human subjects: 1) respect for persons, promoting the dignity and autonomy of research subjects and at times excluding vulnerable individuals such as children or people who are institutionalized or cognitively impaired from participation; 2) beneficence, insisting that research design be scientifically sound and cause minimal harm and maximal good at the level of the individual; and 3) justice, ensuring that the segment of the population that bears the largest burden and risk in scientific inquiry also benefits from it. This report derived from the national commission’s efforts (1974–1978) to examine ethics of human research and, with several companion reports, is the basis for subsequent federal regulations surrounding present research activities such as the establishment of required Institutional Review Boards. The report is a key document in American medicine Petersdorf RG: The pathogenesis of fraud in medical science. Ann Intern Med 1986; 104:252–254 The author argues that patterns of cheating early during professional development, the immensity of the enterprise of research, tremendous competition for grant monies, and other factors contribute to fraudulent practices in medical science (“too competitive, too big, too entrepreneurial, and too much bent on winning”). ACADEMIC PSYCHIATRY

Each investigator must make an individual commitment to truth, Petersdorf argues, and scientific institutions should create an environment to ensure that truth will prevail. Relman AS: Lessons from the Darsee affair. N Engl J Med 1983; 308:1415–1417 Violations of trust by a scientific researcher are discussed. Supervision in academic settings, peer review, and establishing standards of scientific integrity are helpful but do not offer absolute protection from fraud by a “clever cheat.” Coauthorship requires that all involved parties assume responsibility for the integrity of the study. Rothman KJ, Michels KB: The continuing unethical use of placebo controls. N Engl J Med 1994; 331:394–398 In the spirit of Henry Beecher’s early report, the authors describe several published clinical trials in which placebos were used unethically, that is, placebos were used in protracted experiments when effective treatments are known to exist and could serve as more appropriate comparisons. The authors take issue with the FDA’s apparent view of placebo trials as the “gold standard” in making drug-approval decisions. The scientific rationales and ethical counterarguments are then reviewed. Schaefer A: The ethics of the randomized clinical trial. N Engl J Med 1982; 307: 719–725 This commentary identifies five problems inherent to the randomized clinical trial: 1) the clinical investigators’ conflict of obligations as a personal physician and a researcher; 2) the need to sacrifice treatment approaches that have been tailored individually for each patient; 3) the difficulties of informed consent when the therapy to be received has been “randomly” selected; 4) the bind that exists when clinicians believe the treatments offered in one arm of a clinical trial to be clearly preferable to its alternatives (i.e., a violation of the “null” hypothesis); and 5) the question of when to 5

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withdraw patients from experimentation. The author concludes that randomized clinical trials are ethically permissible under well-defined circumstances. He states, however, that patients must certainly be informed of the random treatment-selection process and that efforts to maintain trust in the doctor-patient relationship should be pursued. Shapiro MF, Charrow RP: Scientific misconduct in investigational drug trials. N Engl J Med 1985; 312:731–736 The authors present a detailed analysis of data gathered by the FDA in the course of audits of investigational drug trials (1977–1985), including audits of trials that were disqualified or restricted because of investigator deficiencies or misconduct. Five drug trials are described in which a range of misconduct occurred. Interestingly, in routine FDA audits, 11.5% were found to contain serious deficiencies. The authors endorse tight monitoring of pharmacological research, stating that “any scientific misconduct is of considerable concern.” Spiro HM: Mammon and medicine: the rewards of clinical trials. JAMA 1986; 255:1174–1175 This is a disarmingly engaging and personal commentary about the motives and dilemmas experienced by clinicians who enroll patients in research protocols. The author’s observations are compelling. For example, early on he writes, “reading about alcoholic and cirrhotic patients who have given consent for controlled trials of esophageal variceal sclerosis,. . .I often wonder how much they understood of what they have signed.” He later states, “cancer patients are worth money in most clinical trials.. . .” He further comments, “getting to a new drug early almost guarantees a publication, so that academic clinicians are anxious to be among the first to study them.. . .” Ultimately, the author advocates for more complete disclosure practices by clinicianinvestigators. Stanley B, Sieber JE, Melton GB: Em6

pirical studies of ethical issues in research. Am Psychol 1987; 42:735–741 This article identifies areas in which empirical studies of ethical issues in research are needed. This research agenda is organized into three categories: 1) communication between the researcher and participants, 2) competency of research subjects, and 3) regulatory processes and behavior of researchers. Previous studies are noted and persisting questions are raised in an effort to develop “more informed public policy and ethical standards” for psychiatric research. II. SPECIAL ETHICAL CONSIDERATIONS IN PSYCHIATRIC INVESTIGATION Alexander JR, Lerer B, Baron M: Ethical issues in genetic linkage studies of psychiatric disorders. Br J Psychiatry 1992; 160:98–102 The process of collecting family data in genetic linkage studies is riddled with ethical dilemmas such as protecting confidentiality and minimizing harm. Diagnostic interviews of family members can be intrusive and may reveal unsought diagnoses, creating an ethical bind for the interviewer, who must maintain some degree of therapeutic responsibility in this process. The authors present a research agenda that addresses the unique ethical issues raised by genetic linkage studies of psychiatric disorders. Appelbaum PS, Rosenbaum A: Tarasoff and the researcher. Am Psychol 1989; 44:885–894 The Tarasoff decision states that psychotherapists have a duty to protect identifiable others from the violent intentions of patients, overriding obligations of confidentiality. The authors speculate that this duty may be deemed by the courts as relevant to researchers whose study patients also may carry out violent acts. Issues that investigators should consider when developing VOLUME 22 • NUMBER 1 • SPRING 1998

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protocols that may involve potentially dangerous research patients are outlined. Cole JO: Research barriers in psychopharmacology. Am J Psychiatry 1977; 134: 896–898 This is an early commentary on the societal forces that interfere with progress in psychopharmacological investigation, such as human rights groups and regulations. The author expresses concern that the “patients least able to give informed consent are most in need of the benefits of research.” He suggests that such patients will suffer greatly because of the barriers “erected by pressure groups and regulatory agencies. . .[that] impede or threaten to destroy all research.” This brief essay is valuable for its stark depiction of the controversy surrounding research progress vs. exploitation of experimental subjects. Davidson HA: Legal and ethical aspects of psychiatric research. Am J Psychiatry 1969; 126:237–240 The author examines the role of the relationship between physician-investigator and patient in the conduct of psychiatric research. This brief summary touches on dilemmas within the arenas of informed consent and privileged communications and confidentiality. Concluding that these problems “cannot be programmed into a computer,” the author states that each psychiatrist must be responsible for his or her conduct and personal judgment. Delano SJ, Zucker JL: Protecting mental health research subjects without prohibiting progress. Hospital and Community Psychiatry 1994; 45:601–603 This brief article discusses regulations issued by New York State in 1990 regarding the conduct of human research. The authors consider special ethical issues in three areas: dilemmas posed by “incapable subjects,” challenges of surrogate consent, and the process of overriding “patient objections.” They conclude that the regulations attempt to balance “the protection of a potentially vulnerable population, respect for their inACADEMIC PSYCHIATRY

dividual autonomy, and the conduct of appropriate research.” This piece covers some of the controversial aspects of human experimentation and explains one state’s efforts to create regulations that extend beyond current federal guidelines. Eichelman B, Wikler D, Hartwig A: Ethics and psychiatric research: problems and justification. Am J Psychiatry 1984; 141:400–405 A cogent and concise argument for continued psychiatric research based on the ethical principle of nonmaleficence. Competent psychiatric research directly limits potential harm by identifying the risks and benefits of innovative treatments. The difficult process of informed consent in vulnerable psychiatric patients should not preclude research that may benefit this population. Current federal regulations for well-designed ethical research are reviewed. Fulford KWM, Howse K: Ethics of research with psychiatric patients: principles, problems, and the primary responsibilities of researchers. Journal of Medical Ethics 1993; 19:85–91 The authors present four ethical principles specific to research—knowledge, necessity, benefit, and consent—and describe the difficulties in their implementation. They suggest that these principles are essential because of the ethical bind that arises when the best interest of the individual patient is overridden by the need to advance medical science. They discuss several issues related to experimentation involving psychiatric patients and identify the special burdens shouldered by researchers in this area. Kantor JE: Ethical issues in psychiatric research and training, in Annual Review of Psychiatry, Vol 13, edited by Oldham JM, Riba MB. Washington, DC, American Psychiatric Press, Inc., 1994, pp. 323–342 The author argues for a fluid, adaptable, case-based approach to ethical practice and research. Ethical aspects of the physi7

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cian-patient relationship are outlined and then applied to general and psychiatric research practices. A unique strength of this chapter is its brief review of the ethical issues inherent in the psychiatric traineepatient and trainee-supervisor relationships. Klerman GL: Scientific and ethical considerations in the use of placebo controls in clinical trials in psychopharmacology. Psychopharmacol Bull 1986; 22:25–29 The author outlines the historical background of clinical investigation in psychopharmacology, with attention to the consensus that arose in the scientific community around the need for control groups and placebo trials. The role of ethical constraints in study design are considered. O’Leary KD, Borkovec TD: Conceptual, methodological, and ethical problems of placebo groups in psychotherapy research. Am Psychol 1978; 33:821–830 Ethical aspects of placebo-design studies in the special and often neglected context of psychotherapy research are discussed. Though it represents an early conceptual piece in the literature of research ethics, the issues raised by the authors continue to be relevant and illuminating. Stanley BH, Stanley M: Psychiatric patients in research: protecting their autonomy. Compr Psychiatry 1981; 22:420–427 The authors argue for systematic, empirically based approaches to competency testing with individual research subjects who are mentally ill. They describe the negative consequences of less individualized, more global protections in psychiatric research, including undermining patient autonomy, further stigmatizing psychiatric illnesses, and “infantalizing” the mentally ill. Differences between five theoretical tests of competency are illustrated through case discussion. The need for additional research into the competency of psychiatric patients as a special group is then presented. Sturges JS, Sternberg DE: Family concerns about hospitalizing a patient in 8

a psychiatric research unit. Hospital and Community Psychiatry 1985; 36:1187– 1191 The authors present the special concerns, expectations, and misconceptions of the families of psychiatric patients involved in research protocols. Case illustrations are provided and discussed. Psychoeducational, alliance-building, and other interventions are described to help families of psychiatric patients. U.S. Congress, Office of Technology Assessment, Mental Disorders and Genetics: Bridging the Gap Between Research and Society (Publ. No. OTA–BP–H–133). Washington, DC, US Government Printing Office, September, 1994 This excellent background paper prepared by the Office of Technology Assessment focuses on recent findings and societal implications of genetic research in psychiatry. It concisely outlines key ethical issues in human genetics research, such as special confidentiality, research review, and informed consent issues and unique psychosocial risks, that arise in genetic studies. This work is informative and represents a nice primer in research ethics. Wing J: Ethics and psychiatric research, in Psychiatric Ethics, edited by Bloch S, Chodoff P. Oxford, UK, Oxford University Press, 1981, pp. 279–294 A thoughtful overview of the basic ethical principles related to psychiatric research, including the balance of good and harm, informed consent, confidentiality, and committees on the ethics of research. This chapter integrates British and American perspectives. Winston ME, Winston SE, Appelbaum PS, et al: Commentary: can a subject consent to a “Ulysses Contract”? Hastings Cent Rep 1982; 12:26–28 The “Ulysses Contract” refers to the story of Ulysses, who asked that his men refuse his requests while he was “under the irresistible influence of the Sirens’ lovely song.” Analogous to the psychiatric reVOLUME 22 • NUMBER 1 • SPRING 1998

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search circumstance in which protocol patients lose decisional ability while participating in, for example, “wash-out” periods prior to experimental psychotropic drug administration. This series of commentaries focuses on consent issues in the case of a severely ill young man diagnosed with schizophrenia and tardive dyskinesia. III. INFORMED CONSENT, CAPACITY, AND RESEARCH INVOLVING VULNERABLE POPULATIONS Abrams R: Dementia research in the nursing home. Hospital and Community Psychiatry 1988; 39:257–259 The author provides a balanced perspective on the ethical aspects of site and subject recruitment and of informed consent in dementia research involving nursing home residents. Appelbaum PS, Roth LH: Competency to consent to research: a psychiatric overview. Arch Gen Psychiatry 1982; 39:951– 958 Excellent, comprehensive discussion of competency and of four increasingly strict competency standards: 1) evidencing a choice in terms of research participation; 2) factual understanding of the issues; 3) rational manipulation of information; and 4) appreciation of the nature of the situation. The authors describe the standards in light of a number of policy goals such as autonomy, rationality, beneficence, respect for persons, justice, encouragement of research, subject satisfaction, ease of test administration, and optimal use of timing. The authors conclude that empirical research is needed to clarify the relative value of the competency standards offered. Drane JF: Competency to give an informed consent: a model for making clinical assessments. JAMA 1984; 252:925–927 A “sliding scale” standard of competency is offered as a framework for informed consent in clinical decision making. ACADEMIC PSYCHIATRY

This scale “requires an increasingly more stringent standard as the consequences of the patient’s decision embodies more risk.” Dresser R: Wanted: single, white male for medical research. Hastings Cent Rep 1992; 22:24–29 This paper focuses on the perceived ethical problem of the disproportionately high number of white males used as medical research subjects in the United States. The author expresses concern that conclusions based on such studies may not always be generalizable to women and racial minorities, and argues that exclusion of these groups is a “glaring moral mistake.” This paper is interesting in light of the larger discussion of exploitation of potentially vulnerable subjects in research endeavors, which historically discouraged the inclusion of women, racial miniorities, the young, the old, the institutionalized, and the cognitively compromised. Ironically, this protective stance may have led to the “overuse” or burdening of white males as research subjects. Gaylin W: The competence of children: no longer all or none. Hastings Cent Rep 1982; 12:33–38 The author first discusses the conditions that limit competence: limits of consciousness, limits of intelligence, limits of rationality, limits of knowledge and perception, limits of experience, and limits of age. He then describes “how much say” children should have in four different kinds of decisions (high risk/low gain, low risk/high gain, high risk/high gain, and low risk/low gain) and provides examples from medical care and scientific research. Though its emphasis is on children, this piece is valuable in considering ethical aspects of experimentation and clinical care involving people whose competence is in any way compromised. Helmchen H: Problems of informed consent for clinical trials in psychiatry. Control Clin Trials 1981; 1:435–440 The author briefly reviews some evi9

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dence for the influence of duration and intensity of psychiatric illness and personality type on the process of informed consent. He discusses patients’ ambivalence around consent decisions in some detail. He suggests that consent is best seen as a continual process, based on the integrity and scrupulousness of the clinician or clinician-investigator. A call for further empirical research into the process and consequences of informed consent is made. Macklin A: Bound to freedom: the Ulysses contract and the psychiatric will. University of Toronto Faculty of Law Review 1987; 45:37–68 The author extensively reviews legal and philosophical issues related to voluntary commitment of psychiatric patients, relevant to discussions of psychotropic research entailing “wash-out” periods that often lead to re-emergence of psychotic symptoms and may transiently compromise patients’ decisional abilities. Markson L et al: Cognitively impaired subjects. Ann Intern Med 1989; 111:843– 848 This excellent position paper from the American College of Physicians concisely states the conditions under which research on incompetent patients is ethically defensible: 1) if subjects are protected adequately, including appropriate informed-consent measures; 2) if risks and benefits for each individual have been evaluated; 3) if risks have been minimized; 4) if the information sought is genuinely helpful and cannot be obtained through experimentation with less vulnerable subjects; and 5) if the scientific ideas and methods are sound. Four positions statements held by the American College of Physicians are then offered. They concern prospective consent by potential research subjects, factors to be considered in proxy and surrogate decision making, the need for special protections for the chronically ill and institutionalized, and the need for regulations and review processes 10

around research involving incompetent subjects. Meisel A, Roth LH: What we do and do not know about informed consent. JAMA 1981; 246:2473–2477 The authors review empirical studies with respect to the elements of informed consent: disclosure of information, subject/ patient competency and understanding, decision process, and voluntariness. They comment on the paucity of “meaningful empirical studies,” particularly in the investigation of the more intangible factors of understanding and voluntariness. An excellent analysis of problems with current studies is presented, including failure to document what physicians actually tell their patients, use of recall as the measure of understanding in informed consent, over-reliance on decision making in hypothetical—not in vivo —situations, neglect of temporal issues in consent, inappropriate generalization, and investigator bias. The authors conclude that in trying to separate data from “fiction” surrounding informed consent, they find “very little wheat and much chaff.” Melnick VL, Dubler NN, Weisbard JD, et al: Clinical research in senile dementia of the Alzheimer type: suggested guidelines addressing the ethical and legal issues. J Am Geriatr Soc 1984; 32:531–536 This document presents guidelines for Alzheimer’s disease research formulated by a special task force from the National Institute on Aging. The guidelines are applicable and helpful in the investigation of other psychiatric diagnoses. Miller LJ: Informed consent: I–IV. JAMA 1980; 244:2100–2103, 2347–2351, 2556–2558, 2661–2662 This series describes the historical emergence and ramifications of the legal doctrine of informed consent, which “transforms the essence” of the doctor-patient relationship “into contract.” With numerous case illustrations, the author discusses medicolegal aspects of standards of disclosure, VOLUME 22 • NUMBER 1 • SPRING 1998

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determination of proximate cause for bad outcomes, consent forms, defensive strategies to inadequate consent claims, and other issues. This series is valuable for its historical and legal perspective and raises issues directly applicable to the clinical investigator/physician-patient relationship. Munir K, Earls F: Ethical principles governing research in child and adolescent psychiatry. J Am Acad Child Adolesc Psychiatry 1992; 31:408–414 The principles of nonmaleficence, beneficence, autonomy, and justice as they pertain to child and adolescent psychiatric research are reviewed. The author hopes to promote “responsible research practice” by improving ethical standards related to scientific integrity and research advocacy, training, and stewardship. Romano J: Reflections on informed consent. Arch Gen Psychiatry 1974; 30:129– 135 In this early piece, the author explores the ethical problems of performing nontherapeutic research on children at high risk for schizophrenia. The process of informed consent is traced historically, and the author highlights issues of privacy and confidentiality with respect to these risk studies. He argues for teaching clinically based ethics during medical education and residency training. Roth LH, Meisel A, Lidz CW: Tests of competency to consent to treatment. Am J Psychiatry 1977; 134:279–284 Five tests of competency to consent to treatment are presented with case illustrations: 1) evidencing a choice, 2) “reasonable” outcome of choice, 3) choice based on “rational” reasons, 4) ability to understand, and 5) actual understanding. The authors describe an observable bias in clinical practice favoring the treatment of “treatable” patients in the absence of serious risks. They conclude that “judgments of competency go beyond semantics or straightforward applications of legal rules; such judgments reflect social considerations and societal biases as ACADEMIC PSYCHIATRY

much as they reflect matters of law and medicine.” Roth LH, Appelbaum PS, Lidz CW, et al: Informed consent in psychiatric research. Rutgers Law Review 1987; 39:425– 441 This excellent, substantial document outlines legal cases, federal regulations, and ethical issues related to informed consent in psychiatric research. The authors describe informed consent as “both an ideal and a necessity” in the efforts to acquire a better understanding of complex psychiatric illnesses. IV. EMPIRICAL STUDIES REGARDING THE ETHICAL ASPECTS OF RESEARCH Appelbaum PS, Roth LH, Lidz CW: The therapeutic misconception: informed consent in psychiatric research. Int J Law Psychiatry 1982; 5:319–329 This piece focuses on the specific issue of what researchers tell human subjects who enroll in scientific protocols. The authors look at two empirical studies (one involving patients with schizophrenia and one involving patients with borderline personality disorder), with particular attention to the information received by patients and patients’ decisions to participate in the experiments. The authors conclude that research patients “carry strong expectations” of personal therapeutic benefit (“the therapeutic misconception”) when involved with psychiatric studies, a factor that must be considered in the conduct of ethical research. Appelbaum PS, Grisso T: The MacArthur Treatment Competence Study I, II, III. Law and Human Behavior 1995; 19:105–174 An extensive, 3-site study involving 498 individuals in 3 groups (patients with schizophrenia or major depression, patients with ischemic heart disease, nonpatient community volunteers) was conducted to investigate treatment-related decision-mak11

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ing abilities. In this landmark study, patients with mental illness demonstrated more decisional vulnerabilities on several measures when acutely psychiatrically ill when compared with medically ill individuals and nonpatients. These deficits greatly improved, however, once treatment was instituted and acute symptoms had abated. The authors draw several important conclusions of relevance to psychiatric research ethics, most notably their statement that mental illness does not always compromise individual patients’ decisional abilities and that treatment interventions may serve to correct many decision-making deficits that do arise. Cassileth BR, Zupkis RV, SuttonSmith K, et al: Informed consent—why are its goals imperfectly realized? N Engl J Med 1980; 302:896–900 This report describes an in vivo study of 200 cancer patients who, within 1 day of signing consent forms for chemotherapy, radiation therapy, or surgery, completed a written questionnaire and a test of their recall about the consent process. Although 75% of the patients felt that consent explanations were important because they helped patients to decide about their personal health care, only 60% understood the nature and purpose of the procedure and 55% could correctly identify a single risk of the proposed treatment they had just consented to undergo. Three factors were related to recall of consent information: educational level, medical status, and the attention patients paid to reading the consent form. Relevant to the consent process in clinical research, this study is valuable in demonstrating concretely several problems of obtaining informed consent. Cassileth BR, Lusk EJ, Miller DS, et al: Attitudes toward clinical trials among patients and the public. JAMA 1982; 248:968– 970 This is a unique study looking at the views of 104 cancer patients, 84 cardiology patients, and 107 members of the general 12

public about participation in clinical research. Interestingly, 71% of those who responded to the anonymous, written survey approved of patients serving as research subjects, primarily because they felt that medical research benefits society and increases medical knowledge. Nearly all (97%) felt that helping future patients would be extremely or moderately important to them if they were research subjects. When asked what their reasons would be if they personally participated in research, however, advancing medical science was a far less common motivation (23%) than was the wish to get better health care (52%). As stated by the authors, this work depicts the clear difference between personal decisions and choices or beliefs involving “hypothetical others.” Daugherty C, Ratain MJ, Grochowski E, et al: Perceptions of cancer patients and their physicians involved in phase I trials. J Clin Oncol 1995; 13:1062–1072 This novel and important study considered the perceptions and motivations of cancer patients (n⳱27) who were actually participating in Phase I clinical trials (doseescalation/dose-determination studies) and their oncologists (n⳱18). Phase I trials are designed to study the predictability, tolerability, and reversibility of toxic effects from experimental agents, which, at the administered doses, are unlikely to offer direct medical benefit to patients. Nevertheless, the authors found that 85% of patients decided to participate in the hope of therapeutic benefit. Patients’ belief that they had no better option (89%) and their trust in the treating oncologist (70%), trust in the treating institution (67%), and/or trust in the referring physician (63%) greatly influenced the patients’ decisions to participate. While 93% of the patients thought that they understood most or all of the information provided about the trials, only 33% were able to state the purpose of the trial in which they were participating. Oncologists were highly variable in their perceptions of probVOLUME 22 • NUMBER 1 • SPRING 1998

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ability of benefit to patients enrolled in the clinical trials. The import of this study is its clear documentation of patients’ personal motivations and vulnerabilities. Edlund MJ, Craig TJ, Richardson MA: Informed consent as a form of volunteer bias. Am J Psychiatry 1985; 142:624–627 The authors reviewed two nontreatment studies of tardive dyskinesia and examined numerous published articles in three psychiatric journals for evidence that researchers understood and/or acknowledged selection bias related to informed consent. Simply put, they looked at whether published researchers explicitly considered how the exclusive use of consenting patients may alter research results. Requiring informed consent, the authors concluded, led to both false-positive and false-negative findings in the tardive dyskinesia studies. The journal review indicated that scientific reports neglect this problem in interpretations of study results. This study is of great importance for its discussion of the impact of ethics regulations upon scientific design and outcomes. Grossman L, Summers F: A study of the capacity of schizophrenic patients to give informed consent. Hospital and Community Psychiatry 1980; 31:205–206 This is a brief report of 20 patients diagnosed with schizophrenia who underwent a clinical evaluation, verbal intelligence testing, and a simulated informed-consent process for receiving an experimental medication. Sixty percent of the study patients agreed to receive the medication, although only 15% fully understood this decision. The authors conclude that “only a small portion of schizophrenics may be able to give fully informed consent as required by law.” High DM: Research with Alzheimer’s disease subjects: informed consent and proxy decision making. J Am Geriatr Soc 1992; 40:950–957 Alzheimer’s disease patients are “on a path of declining capacity to give consent.” ACADEMIC PSYCHIATRY

Thus, the author cautions that research to advance understanding of this disease requires careful ethical consideration in the recruitment of study subjects. Unique dilemmas in the informed-consent process and continued voluntary participation of individuals with “mild and fluctuating” cognitive impairment are addressed. Issues of advanced consent and consent by proxy are examined, and an agenda for further research on cognitively impaired subjects is proposed. Kalman TP, Talon NS, Frances A, et al: A controlled study of satisfaction among psychobiology research patients. Am J Psychiatry 1982; 139:344–347 The article covers empirical investigation into satisfaction among depressed adult psychiatric inpatients in relation to treatment setting, comparing a psychobiology study unit and a general psychiatric unit. Satisfaction levels were similar. Comparisons were made by analyzing completed (77% of initial sample) self-report questionnaires. The possibility of bias from the incomplete sample is addressed. The authors suggest that additional studies of the satisfaction among psychiatric research patients are needed to help foster public and institutional support. Kleinman I, Schachter D, Koritar E: Informed consent and tardive dyskinesia. Am J Psychiatry 1989; 146:902–904 Forty-eight stable outpatients diagnosed with schizophrenia who had received antipsychotic medications were included in this comparison study to examine retention of formally presented information about risks and benefits of neuroleptics. The authors found that a single informational session had a positive and relatively persistent (6-month follow-up) impact in the study population. Lane LW, Cassel CK, Bennett W: Ethical aspects of research involving elderly subjects: are we doing more than we say? Journal of Clinical Ethics 1990; 1:278–285; 13

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Fletcher JC: Commentary. Journal of Clinical Ethics 1990; 1:285–286 In the interest of identifying how ethical issues are described in the published geriatric clinical research, the authors undertook a targeted literature review and analyzed how ethical considerations are documented by researchers (e.g., confidentiality measures, Institutional Review Board approval, subject recruitment, etc). The results of this study suggest that there is a pattern of underreporting ethically important facets of research conducted on the elderly, a potentially vulnerable population. Lane and co-authors and Fletcher suggest that adequate documentation of scientific research is essential to assure readers that ethical standards have been maintained in human experimentation. Lidz CW, Meisel A, Osterweis M, et al: Barriers to informed consent. Ann Intern Med 1983; 99:539–543 A study is described in which “participant observers” spent time on two inpatient wards (medical and surgical) and an outpatient clinic (surgical) systematically studying how treatment decisions are made. The researchers documented routine clinical practice in these settings and performed semistructured interviews with 101 patients. A number of elements affecting informed-consent discussions were carefully identified, including patient and physician attitudes, trust in the doctor-patient relationship, the nature and chronicity of the illness, the clinical and institutional setting, and the number and kinds of decisions to be made. More important, the authors describe what they observed to be the optimal informed-consent context: “situations where treatment involves chronically ill patients who have to make a small number of decisions about treatments that they have experienced previously, and in which the center of medical responsibility is clear, there is a substantial chance that a real dialogue will take place.” Marson D, Ingram KK, Cody HA, et al: 14

Assessing competency of patients with Alzheimer’s disease under different legal standards. Arch Neurol 1995; 52:949–954 The authors present empirical evidence for the validity of a clinical vignette-based instrument to measure the level of competency exhibited by mild-to-moderate Alzheimer’s disease patients and normal control subjects when making medical treatment decisions. Competency status was assessed, using the model of Roth, Meisel, and Lidz described earlier (1977), with 5 progressively stringent standards: evidencing a treatment choice, making the reasonable choice, appreciation of the consequences of a choice, rational reasons for a choice, and understanding the treatment sitaution and choices. The severity of dementia in the Alzheimer’s disease patients correlated with their competency status as determined by this instrument. This research represents an important first step in an effort to standardize assessment of competency of Alzheimer’s disease patients for differing legal thresholds. Marson D, Cody HA, Ingram KK, et al: Neuropsychological predictors of competency in Alzheimer’s disease using a rational reasons legal standard. Arch Neurol 1995; 52: 955–959 This empirical study evaluates the predictive validity of performance on various neuropsychological tests in the determination of competency in Alzheimers’ disease patients using a “rational reasons” standard. The results, analyzed through very sophisticated statistical methods, suggest that cognitive functions requiring high frontal-lobe activity (e.g., word finding) appear to relate to the capacity to formulate rational reasons for treatment choice. Interestingly, global scores of dementia severity (e.g., Mini-Mental State Exam) were not strongly predictive of this high standard of competency. Studies such as this can help identify the specific cognitive functions involved in competent decision making for varying levels of risk. VOLUME 22 • NUMBER 1 • SPRING 1998

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Park LC, Slaughter R, Covi L, et al: The subjective experience of the research patient: an investigation of psychiatric outpatients’ reactions to the research treatment situation. J Nerv Ment Dis 1966; 143:199–206 This early and controversial study, undertaken prior to informed consent regulations, examined the subjective experience of 72 “neurotic” outpatients who unknowingly were involved in a placebo-controlled study conducted by clinician-trainees. The authors conclude that the a priori notion that patients would be “bothered by research procedures and by the idea and experience of being research subjects” was incorrect according to their results. They advocate for a close, continuous researcher-subject relationship and for full disclosure of research activities. The authors endorse an informed-consent process that “does not remove from the investigator primary moral responsibility for the welfare of the patient.” Sachs GA, Stocking CB, Stern R, et al: Ethical aspects of dementia research: informed consent and proxy consent. Clin Res 1995; 42:403–412 Separate, structured interviews were conducted with early dementia patients (n⳱42), their family proxy decision makers (n⳱64), and a reference group of elderly (n⳱60) about 4 hypothetical vignettes depicting increasingly invasive experiments (blood draw, brain autopsy, use of new medication, brain surgery, and new medication) to learn about elements influencing research enrollment decisions. The authors of this valuable study found that the dementia patients were more willing to take on the risks of experimental protocols, and for different reasons, than were their family proxies, suggesting that choices surrounding experimentation are distinctly personal and difficult to predict. Soskis DA: Schizophrenic and medical inpatients as informed drug consumers. Arch Gen Psychiatry 1978; 35:645–647 ACADEMIC PSYCHIATRY

Twenty-five patients with schizophrenia and 15 patients with medical diagnoses, matched with respect to demographic variables, were interviewed about knowledge of their own medications. Medical patients in this study better understood the need for their medicines and certain facts about their medicines (e.g., dose) than did the patients with schizophrenia. However, the schizophrenic patients appreciated the risks and side effects of psychotropic medications more fully. Far fewer schizophrenic patients (56%) than medical patients (93%) stated that they would accept their medicines if they “had a choice.” This finding is important with respect to psychiatric patients’ experience of self-determination in health care and the noncompliance issues that arise around neuroleptic prescriptions. Stanley B, Guido J, Stanley M, et al: The elderly patient and informed consent: empirical findings. JAMA 1984; 252:1302– 1306 Competency in an elderly and medically ill population (without psychiatric comorbidity) is empirically tested by examining the informed-consent process in hypothetical research scenarios. The results of this study suggest that elderly patients’ comprehension of consent material may be significantly poorer when compared with a younger population. Global intelligence ratings, educational level, and attention span could not explain this difference in comprehension. Despite this difference, the quality of reasoning and the “reasonable” choice regarding participation were statistically equivalent among the young and geriatric populations. The author argues that “although the quality of treatment decisions does not appear to be adversely affected by the poorer comprehension scores, a high level of comprehension of consent material may be a desirable goal in itself.” Stanley B, Stanley M, Lautin A, et al: Preliminary findings on psychiatric patients as research subjects: a population at risk? Am J Psychiatry 1981; 38:669–671 15

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In this interesting study, 27 psychiatric inpatients and 38 medical inpatients underwent a standard interview and were assessed according to the Brief Psychiatric Rating Scale. The researchers looked at three questions: whether mentally ill patients expose themselves to greater research risks than other patients; whether mentally ill patients refuse to participate in research with favorable risk-benefit ratios more often than nonpsychiatric patients; and whether degree of psychopathology correlates negatively with ability to give consent. A series of six hypothetical research studies with differing risks were presented in random order to assess patients’ willingness to participate in experimentation. No differences were found between the severely disturbed psychiatric patients and medical inpatients with respect to willingness to participate. Severity of psychopathology was a poor indicator of ability to assess research risks. On this basis, the authors suggest that “there may be a value to education, rather than special protection, of both psychiatric and medical patients concerning evaluation of research risks and benefits.” Warren JW, Sobal J, Tenney JH, et al: Informed consent by proxy: an issue in research with elderly patients. N Engl J Med 1986; 315:1124–1128 An empirical investigation to identify factors influencing consent by proxy for nursing home patients to participate in a study involving minimal risk is described. The proxies’ (99% family members) refusal (46%) was significantly correlated with the perceptions that “research should not be done in nursing homes, and that the study would disturb the patient, that the patient, if able, would refuse to participate. . .and that the proxy would refuse to participate in such a study if asked.” Disturbingly, 31% of those proxies who felt the patients would refuse such a study nevertheless gave their consent for the patients’ participation. This study dramatically depicts problems inherent in the informed-consent-by-proxy pro16

cess. The authors conclude that potential subjects, regardless of their competence, should always be allowed to refuse to participate in research. More work is needed to clarify the ethical and legal obligations involved in the process of consent by proxy. Weiss BD: Confidentiality expectations of patients, physicians, and medical students. JAMA 1982; 247:2695–2697 A novel survey study of 177 patients, 53 medical students, and 109 residents was performed regarding confidentiality of patient information. Patient and medical trainee perceptions differed greatly, for example, in their expectations that patient material would be mentioned to spouses (17% patients vs. 70% students, 51% residents); talked about at parties (18% patients vs. 57% students, 60% residents); described to colleagues at meetings for informal “second opinions” (69% patients vs. 81% students, 94% residents); and discussed in a way that the patient’s identity is known (23% patients vs. 55% students, 60% residents). Of relevance to research, however, were the differing expectations surrounding scientific presentations of “interesting” patient information at large meetings (51% patients vs. 77% students, 90% residents) or in medical journals (25% patients vs. 83% students, 28% residents). Such findings underscore the importance of protecting patient privacy and, whenever possible and appropriate, the need to clarify realities of confidentiality in medical and research settings. V. ADDITIONAL MATERIAL Additional resources (i.e., ethical codes, other bibliographies, and related texts) are shown in the Appendix. RECOMMENDATIONS AND CONCLUSIONS The educational, empirical, and policy issues surrounding the ethics of psychiatric VOLUME 22 • NUMBER 1 • SPRING 1998

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research merit greater consideration, as evidenced by what is absent from this resource listing. We did not find extant curricular descriptions or bibliographies related to research ethics for psychiatry. With a few outstanding exceptions, we found tremendous need for second-generation empirical studies on the ethics of research including, and extending beyond, traditional formulations of informed consent and decisional abilities. In addition, we did not discover well-developed policies and position statements on the ethical dimensions of scientific design in psychiatric research despite recent and well-publicized controversies in our field. Taken together, as described next, these three areas constitute a compelling task for academic psychiatry.

motivational issues of the chronically mentally ill, the impact of overlapping relationships in psychiatric research and related determinants of research subject vulnerability, the value of psychiatric research participation in the context of new economic pressures in medicine, the ethical problems that arise from scientific discoveries (e.g., genetic findings, costly innovative diagnostic techniques, equivocal treatment outcomes), and the biases and benefits introduced by ethics “protections” upon research conduct and results. Further empirical work is essential in these and other areas, so that practices and philosophies around research ethics are grounded in experience, not speculation.

Education Development

How ethics of research properly translate into scientific policies also requires immediate attention. The controversies surrounding “washout” periods in psychotropic drug studies, pursuit of placebocontrolled trials as the “gold standard“ of human research, scientific use of confidential patient material, and the development of new guidelines for Institutional Review Boards are but four examples. Rather than later responding to broad governmental regulations or narrow court rulings that arise when problems are noticed and are based on considerations that do not heel closely to the values and circumstances of psychiatric inquiry, academic and organizational psychiatry should seek to articulate the profession’s ethical principles related to psychiatric research in advance. Considerable effort in these areas is imperative so that clinician-investigators are well trained and patients’ well-being and interests are scrupulously protected by our profession. Greater awareness of these issues related to psychiatric research ethics will yield significant benefits for the field of psychiatry. First, it will encourage academic psychiatrists to attend closely to the ethical

Educational issues that bear further inquiry include such questions as how to establish formal coursework addressing the ethical aspects of psychiatric clinical investigation; how best to teach residents about scientific methodology emphasizing the relationship between ethics and design issues; how to prepare psychiatric faculty to create valuable and rigorous ethics curricula, experimental protocols, and scientific policies at their institutions; and how to create meaningful and relevant continuing education on these topics for psychiatric practitioners. Empirical Investigation The need to conduct empirical investigation into the circumstance of the research patient is immense. We have just begun to appreciate crucial aspects of informed consent, decisional capacity, proxy consent, wishes of study participants, and other concerns central to scientific inquiry with human subjects. Issues requiring additional study include the special autonomy and ACADEMIC PSYCHIATRY

Policy Initiatives

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issues inherent in their clinical psychiatric research activities. Better appreciation of the fact that good ethics and good science coincide will help psychiatric research subjects and also foster scientific advancement. Second, increased awareness will prompt continued monitoring of research conduct and the refinement of guidelines for protocols involving psychiatric patients. Such efforts will ensure that the highest ethical standards are maintained throughout the field of psychiatry. Third, the need to explore the empirical basis of research ethics will become a clearer imperative in psychiatry, stimulating fruitful investigation. Finally, more attention to these issues will improve the efforts of psychiatric residency programs to integrate valuable medical ethics matters into their curricula effectively. These four benefits will enhance the experiences of trainees, patients, and research subjects for generations to come.

We have attempted to provide a review of published works of value to the field of psychiatric research ethics. This review is offered as a guide for psychiatric training programs and a tool for psychiatric educators. As new issues unfold in the area of research ethics, the resource listing will not provide all of the answers, but at a minimum it will make our trainees aware of what questions must be addressed in the discussion of research ethics and scientific conduct. The authors thank Drs. Teresita McCarty, Mark Siegler, and Joseph Fins for their help and encouragement in the development of this manuscript. This project was supported in part through a Young Investigator Grant (LWR) from the National Alliance for Research on Schizophrenia and Depression.

References

1. Wettstein RM: Research ethics and human subjects. Psychiatric Research Report 1995; Summer 10:1–14 2. “Panel examines ways to evaluate competency of research subjects.” Psychiatric News, April 7, 1995, pp. 6,30 3. Rothman KJ, Michels KB: The continuing unethical use of placebo controls. N Engl J Med 1994; 331:394–398 4. Eickelman B, Wikler D, Hartwig A. Ethics and psychiatric research: problems and justification. Am J Psychiatry 1984; 141:400–405 5. Fulford KWM, Howse K: Ethics of research with psychiatric patients: principles, problems, and the primary responsibilities of researchers. Journal of Medical Ethics 1993; 19:85–91 6. Viorst J: Listening at the keyhole: the Anne Sexton tapes. J Am Acad Psychoanal 1992; 20:655–658 7. Chodoff P: The Anne Sexton biography: the limits of confidentiality. J Am Acad Psychoanal 1992; 20:639–644 8. Weissberg JH: Therapeutic responsibility in the case of Anne Sexton. J Am Acad Psychoanal 1992; 20:633–638 9. Kantor JE: Ethical issues in psychiatric research and training, in Annual Review of Psychiatry, Vol

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13, edited by Oldham JM, Riba MB. Washington, DC, American Psychiatric Press, Inc, 1994, pp. 343–364 10. Stone AA: Psychiatry’s undiscovered country. Am J Psychiatry 1994; 151:953–955 11. Munir K, Earls F: Ethical principles governing research in child and adolscent psychiatry. J Am Acad Child Adolesc Psychiatry 1992; 31:408–414 12. Roberts LW, McCarty T, Lyketsos C, et al: What and how psychiatry residents wish to learn about ethics. Academic Psychiatry 1996; 20:131—143 13. Anzia DJ, La Puma J: An annotated bibliography of psychiatric medical ethics. Academic Psychiatry 1991; 15:1–17 14. Sider RC: Ethics, in Core Readings in Psychiatry: An Annotated Guide to the Literature, 2nd Edition, edited by Sacks MH, Sledge WH, Warren C. Washington, DC, American Psychiatric Press, Inc, 1995 15. Siegler M, Singer PA, Schiedermayer DL: Medical ethics: an annotated bibliography. Philadelphia, PA, American College of Physicians 1988. 16. Zambler TS, Viederman M, Fins JJ: Ethical, legal, and psychiatric issues in capacity, competency, and informed consent: an annotated bibliography. Gen Hosp Psychiatry 1996; 3:155–172

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APPENDIX.

Additional Resources

Ethical Codes 1. American Medical Association: Code of Medical Ethics: Current Opinions With Annotations, 1994 Edition. Chicago, IL, American Medical Association, 1994 2. American Psychological Association. Ethical principles of psychologists and code of conduct. Am Psychol 1992; 47:1597–1611 3. American Psychiatric Association: The Principles of Medical Ethics: With Annotations Especially Applicable to Psychiatry, 1992 Edition. Washington DC, American Psychiatric Press, Inc., 1992 Bibliographies 1. Anzia DJ, La Puma J: An annotated bibliography of psychiatric medical ethics. Academic Psychiatry 1991; 15:1–17 2. Sider RC: Ethics, in Core Readings in Psychiatry: An Annotated Guide to the Literature, Second Edition, edited by Sacks MH, Sledge WH, Warren C. Washington DC: American Psychiatric Press, Inc., 1995, pp. 456–460 3. Siegler M, Singer PA, Schiedermayer DL: Medical ethics: an annotated bibliography. Philadelphia, PA, American College of Physicians, 1988 4. Zambler TS, Viederman M, Fins JJ: Ethical, legal, and psychiatric issues in capacity, competency, and informed consent: an annotated bibliography. Gen Hosp Psychiatry 1996; 18:155–172 Related Texts 1. Appelbaum PS, Gutheil TG: Clinical Handbook of Psychiatry and the Law, Second Edition. Baltimore, MD, Williams & Wilkins, 1991 2. Berg JM, Karlinsky H, Loewy FH (eds): Alzheimer’s Disease Research: Ethical and Legal Issues. Toronto, Canada, Carswell, 1991 3. Bloch S, Chodoff P: Psychiatric Ethics. Oxford, UK, Oxford University Press, 1981 4. Dokecki PR, Zaner RM (eds): Ethics of Dealing With Persons With Severe Handicaps: Toward a Research Agenda. Baltimore, MD, Paul H. Brookes, 1986 5. Dyer AR: Ethics and Psychiatry: Toward a Professional Definition. Washington, DC, American Psychiatric Press, Inc., 1988 6. Freund PA (ed): Experimentation With Human Subjects. New York, George Braziller Press, 1970 7. Katz J: Experimentation With Human Beings. New York, Russell Sage Foundation Press, 1972 8. Lazarus JA (section ed): Ethics, in Review of Psychiatry, Vol 13, edited by Oldham JM, Riba MB. Washington, DC, American Psychiatric Press, Inc., 1994, pp. 319–459 9. Levine RJ: Ethics and Regulation of Clinical Research. Baltimore, MD, Urban & Schwartzenberg, 1981 10. Lidz CW, Meisel A, Zerubavel E, et al: Informed Consent: A Study of Decisionmaking in Psychiatry. New York, Guilford, 1984 11. Masters WH, Johnson VE, Kolodny RC, et al (eds): Ethical Issues in Sex Therapy and Research. Boston, MA, Little, Brown, 1980 (continued)

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APPENDIX.

Additional Resources (continued)

12. Melnick VL, Dubler NN (eds): Alzheimer’s Dementia: Dilemmas in Clinical Research. Clifton, NJ, Humana Press, 1985 13. President’s Commission for the Protection of Human Subjects of Biomedical and Behavioral Research: Protecting Human Subjects. Washington, DC, Government Printing Office, 1981 14. Seiber JE (ed): NIH Readings on the Protection of Human Subjects in Behavioral and Social Science Research: Conference Proceedings and Background Papers. Bethesda, MD, University Publications of America, 1984 15. Simon RI: Clinical Psychiatry and the Law, Second Edition. Washington, DC, American Psychiatric Press, Inc., 1992 16. Sr’am RJ, Bulyzhenkov V, Prilipko L, et al: Ethical Issues of Molecular Genetics in Psychiatry. New York, Springer-Verlag, 1991 17. Tancredi LR (ed): Ethical Issues in Epidemiologic Research. New Brunswick, NJ, Rutgers University Press, 1986 18. President’s Commission for the Protection of Human Subjects of Biomedical and Behavioral Research: Whistleblowing in Biomedical Research: Policies and Procedures for Reports of Misconduct. Washington DC, Government Printing Office, 1981 19. White L, Tursky B, Schwartz GE (eds): Placebo: Theory, Research, and Mechanisms. New York, Guilford, 1985

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