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Ethical Principles Governing Research in Child and Adolescent Psychiatry
Ethical Principles Governing Research in Child and Adolescent Psychiatry KERIM MUNIR, M.B., M.P.H.,
AND
FELTON EARLS, M.D.
Abstract. This paper examines the ethical principles governing research in child and adolescent psychiatry. The guidelines for protection of children and adolescents as research subjects are discussed. These include the principle of nonmaleficence and beneficence (the risk-benefit ratio), the principle of autonomy (informed consent and confidentiality), and the principle of justice (fair distribution of benefits and burdens of research). In the light of recent national efforts to help promote responsible research practice, the ethical standards relating to the protection of scientific integrity as well as research advocacy, training, and stewardship are also discussed. J. Am. Acad. Child Adolesc. Psychiatry, 1992, 31, 3:408-414. Key Words: ethics, child and adolescent psychiatry, research. The 1990s will very likely be host to an intensification of child and adolescent mental health research. This new ferment in the field has been heralded by a recent report of the Institute of Medicine (10M) calling for an urgent provision of resources to develop a "critical mass" of well-trained research personnel to fund a wide range of basic and clinical research projects and to broaden the number of "centers of excellence" in child and adolescent psychiatry (10M, 1989a). The 10M report has become the foundation for a national research plan submitted to Congress (U.S. Department of Health and Human Services [USDHHSj, 1990) and recently approved for implementation (USDHHS, 1991). It is timely, then, to examine the ethical standards that govern the conduct of research in child and adolescent psychiatry. The first part of this paper describes the ethical principles relating to protection of subjects in pediatric and mental health research in general. These guidelines alone do not ensure responsible conduct of research. In the light of national efforts promoting improved practice, the paper highlights the recommendations of another 10M report on regulation of the research environment (10M, 1989b). Finally, the paper discusses the ethics of research stewardship and training critical for the implementation of the national research plan in the future (USDHHS, 1990). The ethical principles introduced in this article only guide research applications. The use of the principles in specific cases is the responsibility of individual investigators and their institutions. A seriously deficient knowledge base on the causes and effective treatment of child and adolescent
Accepted July 6, 1991. Dr. Munir is Assistant Professor of Psychiatry, Division of Child and Adolescent Psychiatry, the Cambridge Hospital, Harvard Medical School, and Dr. Earls is Professor of Human Behavior and Development, Department of Maternal and Child Health, Harvard School of Public Health and Professor of Child Psychiatry, Harvard Medical School. The authors thank Drs. Leon Eisenberg, Myron L. Belfer, and James C. Beck for their valuable comments. This work was supported by NIMH grant K07-MH00826-02 (to K.M.). Reprint requests to Dr. Munir, Division of Child and Adolescent Psychiatry, the Cambridge Hospital, 1493 Cambridge Street, Cambridge, MA 02139. 0890-8567/92/3103-O408$03.00/0©1992 by the American Academy of Child and Adolescent Psychiatry.
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mental disorders makes research a top priority in the field. Nonetheless, a clear understanding of ethical principles is necessary to sustain this effort toward the ultimate goal of improving the mental health of children and adolescents. Protections for Subjects The Declarations of Helsinki (World Medical Association, 1975) and the Nuremberg Code (Trials of War Criminals, 1946-49) are the international charters that guide human investigations and medical experiments (Beauchamp and Childress, 1983). They declare unequivocally that the "concern for the interests of the subject must always prevail over the interests of science and society." They state that "the voluntary consent of the human subject is absolutely essential.' They also state explicitly that an individual must understand the nature of the proposed research well enough to make an informed decision. They demand that the purpose and content of an investigation as well as its duration, potential effects on the subjects' health, and all the inconveniences associated with the research be disclosed well in advance to potential subjects (Beauchamp and Childress, 1983). The USDHHS federal regulations guide all human investigations in the United States (USDHHS, 1983a). These federal regulations define a subject as a "living individual about whom an investigator conducting research obtains (1) data through intervention or interaction or (2) identifiable private information." All organizations applying for funding from the Public Health Service are required to appoint Institutional Review Boards (IRBs) to ensure protection for research subjects. Regardless of the federal requirements, most institutions have their local IRBs comprised of clinicians, researchers, patient advocates, lay members, and others knowledgable in the fields of law and ethics. There are three basic principles that underlie the judgments made by the IRBs: (1) the duty of nonmaleficence and beneficence (assessment of the risk-benefit assumed by each subject); (2) the principle of autonomy (informed consent, protection of privacy, and confidentiality); and (3) the principle of justice (the fair distribution of benefits and burdens of research and the equitable selection of subjects). Each one of these principles presents special problems in both pediatric and mental health research. J. Am. Acad. Child Adolesc. Psychiatry, 31 :3, May 1992
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Tne Principle of Nonmaleficence and Benefi cence The assessment of the risk-benefit ratio requires that the risks be minimized in proportion to the anticipated benefits. The USDHHS regulations impose responsibilities on IRBs depending on the degree of risk and the extent of likely benefit for each child subject. Minimal risk is defined as that "ordinarily encounte red in daily life or during the perfo rm ance of routine physica l or psychol ogical te sts" (USDHHS, 1983a). Research is classified in four risk categories: (1) minimal risk; (2) greater than minimal risk but with prospect of direct benefit .to individual subjects; (3) greater than minimal risk and without direct benefit but likely to yield generalizable knowledge about the subject's disorder or cond ition; and (4) not other wise approvabl e but presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health and welfare of subjec ts. In all circumstances where researc h involves greater than minim al risk, it must be ju stified by the anticipated direct benefit to the child. In cases of no such direct benefit , the IRBs must find that the research represents a minor increase over minimal risk. The research must also be commensurate with each child's individual experience and must be likely to yie ld ge nera lizable know ledge abou t their co ndition (USDHHS, 1983b). Research in which a child patient stands to gain directly from a therapeutic (clinical) procedure raises less ethical problems than research where there is no such direct therapeutic benefit. Nontherapeutic research is generally not ethically justified when it involves more than minimal risk and when the primary aim is the acquisition of knowledge for other pediatric subjects. An example is the use of children as "normal" controls in procedures where they have no direct gains, but face discernible risks, pain, or discomfort. The regulations exempt from formal IRB review research involving children in established educational settings, research involving observation of public behavior, use of educatio nal tests, and collection of existing data, documents, records, or specimens. Surveys may be exempted except in cases in which subjects can be identified or responses may be prone to legal liability. In psycholo gical studies involving children and adolescents, a major difficult y is the advance anticipation of risk. For examp le, direct interviewing of children by means of structured interviews has been shown to be a useful method of obtaining data for both therapeutic and nontherapeutic res earch purp oses (Edel brock and Cos tello , 1988). The growing interest in such interviews as a research tool has engendered an increasing concern about their effects. Most such interviews do not involve any harm or serious discomfort to participants. Herjanic et al. (1976) reported a ratio of I:63 unfavorable to favorable/neutral responses to such direct interview s of children and their parents. Many children perceive these interviews as enjoyable, but it is difficult to predict which few children may be seriously upset by them (Graham, 1984). The concern is that some children, when asked to participate in studies involving tests or questionnaires, may begin a priori to assume (or believe) that there may be something wrong with them . IRBs are obliged to J. Am.Acad. Child Adolesc. Psychiatry, 31:3, May 1992
examine the risks posed by these interviews based on their duration, style, and content, and the age and circumstances of the children. In addition, they need to authorize procedures for dealing with hazards (e.g., suicidal ideation, physicalor sexual abuse) uncovered in the interview process. A new area of research in child and adolescent mental disorders is the development of methods to probe the human genome and visualize the structure and function of the brain . To date, many IRBs will have had little experience in judging the efficacy of these techniques in the study of psychiatric disorders in children and ado les ce nts. Investigat ors pioneering these genetic and other technological methods (e.g., positron emission tomograph y studies) with children must accept the spe cial duty of educating their review boards. During randomized clinical trials, when the effec ts of receiving a new or untried treatment are compared with the effects of receivi ng an accepted treatment, a paradox exists (Angell, 1984; Wing, 1984). One line of ethical reasoning asserts that a parent volunteering a child for random assignment may be sacrificing the child's health for the good of the study and that of future patients. On the other hand, such a decision is ethically warranted if a reasonable likelihood exists that the new therapy may be better than the previous one or the "standard treatment" is of limited efficacy and the new method is theoretically superior. What is usual and customary may be not necessarily efficacious. In pediatrics, the use of an experimental treatment as though it is " standard therapy," however, has serious ethical and legal con sequences (Holder, 1985 a; Lan tos and Frader, 1990). In child and adolescent psych opharm acology , the rapid emergence of new antidepressa nts, anticonvulsants, and other psychotropic agents as innovative therapies requires that they be carefully assesse d by means of controlled prospective trials. Such trials, as are currently being undertaken, guide the establishmen t of risks and benefits of new treatments. Because uncertaint y in medical science is inevitable, results of clinical trials, however, cannot be the sole basis for making complex therapeutic decisions (Lantos and Frader, 1990). There are additional ethical dilemmas. Some clinician-investigators may support the introduction of innovative uncont rolled treatment s based on experience or anecdotal reports. In other cases, market incentives may create added pressures for the rapid approval and use of treatments. The situation is further complicated by the lack of adequate Food and Drug Administration guidelines for use of novel psychotropic agents in children and adolescents. Principle of Autonomy A fundamental ethical concern for the protection of vulnerable subjec ts is the application of the principle of autonomy in obtai ning informed consent. Children who are unable to give free or informed consent, like other susceptible individuals such as pregnant women, mentally handicapped , homeless, persons with HIV/AIDS, prisoners or citize ns of countries where personal choice is severely limited, require special protections (Angell, 1988; Barry, 1988) . The pediatric guidelines for informed consent are described in the National Research Act (PL. 93-348). The regulations adopt
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the recommendations of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (USDHHS, 1983a). Informed consent in pediatric research means permission of parents (biologica l or adoptive) or " guardians" (individuals authorized under state or local law to consent on behalf of the child). As a general rule in research involving minimal risk, it is sufficient to obtain the informed consent of one parent; in research with greater than minimal risk, the permission of both parents should be sought whenever possible. In addition to requiring informed consent by a parent or other legal guardian, the regulations make adequate provisions for soliciting assent from the child subjects themselves. Choice is important for older children and adolescents, particularly if the research involves no direct benefits to them. Individual IRBs define assent guidelines by taking into account the ages, maturity, and the psychological state of the children. The IRBs may waive the assent requirement in special circumstances, e.g., therapeutic research that is likely to be of direct benefit to the subjects. A signed parent consent form alone is not sufficient to establish the process of consent, nor does it provide protection from liability. The process is enhanced by the use of clear, simple, and age-appropriate language in all the materials given to parents or children. In addition, parents need to be allowed adequate time to discuss the project with family or friends to make thoughtful decisions about participation. Nonetheless, a written consent form is generally required to document that the process of consent (discussion between the investigator and the parent) has taken place. In particular, the use of medical jargon in nontherapeutic or epidemiological studies is not ethically permissible. These labels may cause undue parental misconception and anxiety (Appelbaum et al., 1987). Because the predictive power of screening tests in child mental health is also limited, when a study design ca ll s for the use of such tests to identify "risk groups," it is important that the results not mislead parents or schools. It is essential to guard the confidentiality and respect the privacy of subjects. Breach of confidentiality is usually attributable to careless leaks of information to unauthorized persons, e.g., documents left unattended, lack of security in the clinical records system or the name list. Other problems arise because of carelessness in computer linking , data storage, and supervision of the project staff (Wing, 1984). If the research data contain sensitive information that may create legal problems for the subjec ts should the records be subpoenaed (e.g., HIV serostatus), the researcher may obtain federal certificates of confidentiality from the USDHHS and the Department of Justice (Levine, 1986). These certificates allow identificati on of research subjects to be withheld and provide protections for investigators to seek legal counsel to have the subpoenas overruled (Holder, 1985b). Children who are wards of the state are protected from being involved in research unless it is intended to be of direct benefit to them. They may be involved in studies posing greater than minimal risk only if such research is related to their status as wards, or is conducted in schools or in settings in which the majority of child subjects are not 410
wards. In all cases, consent is required from a child advocate who has no conflict of interest with the research. In research involving abused or neglected children for whom parental consent may not be reasonable, the IRB may also substitute parental consent by consent obtained from a child advocate. Principle of Justice
The principle of justice is concerned with the fair and just distribution of the benefits and burdens of research. This means that the subjects should be chosen for reasons directly related to the scientific question under study, not because they are easily available and/or able to be easily manipulated (Department of Health, Education, and Welfare, 1979). No single group, especially the disadvantaged or the handicapped, should be asked to bear a disproportionate share of this burden. When children or their parents depend on a physician researcher for medical care, they may feel that refusing to participate in a study might jeopardize their future care, notwithstanding reassurances on the consent form that such refusal cannot affect their care in any way. Clinical research in child and adolescent psychiatry or pediatrics frequently involves this situation and assumes that the protection offered by the informed consent process comes by way of the responsible physician who does not unreasonably inform or persuade patients to be subjected to unnecessary tests, procedures, or treatments. Not uncommonly, however, parents may be susceptibile to volunteer their children to enter a study based on the power of their physician's suggestion and by other influences, such as whether the investigator is " nice" or the hospital is highly regarded (Lind, 1990). Recruitment can also be influenced by unreasonable amount of payment offered to the subjects in compensation. As for individual physicians referring patients, "finder's fees" should never be offered, nor should referral be made as a courtesy or to gain favor with colleagues. Patient referral is a professional necessity that is likely to help serve the best interests of the patient (Lind, 1990). This is a principle that has helped foster medical progress in the past and is likely to bring the worlds of practice and research closer together. The use of children or other vulnerable populations for research is ethically justified if those populations' advocates believe that the research will improve the understanding or treatment of the condition producing the subjects' illness and dependency. For example, it is likely that patients who participate in randomized clinical trials need to get what is the best available therapy for their condition. Finally, in the words of one investigator: "a project that will almost certainly do nobody any harm, but is equally likely to do nobody any good, is not worth undertaking" (Wing, 1984).
Protection of Ethical Standards and Scientific Integrity Bertrand Russell (1961) envisaged the study of ethics in two parts: (1) what is good on its own account (based on individual, societal, or cultural values) and (2) moral values of co nduct. Skeptical of appealing to a belief in "conscience" in framing moral rules, he pointed to two difficulties: first, that ' 'conscience says different things to different people; and second, that there were "mundane causes of J.Am. Acad. Child Ado/esc. Psychiatry, 31:3, May 1992
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conscientious feelings" (Russell, 1961). David Hume' s A Treatis e ofHum an Nature, akin to the Copernican revolution in astronomy, was the first to portray man not as a divine being, but as a figure dominated by conflictin g desires. David Hume (1969, first published in 1739) characterized moral philosophy as " the understanding, the passions, morals, politics, and criticism: in short, the entire science of man discovered empirically and systematically." Such a picture of moral frailty foretells the need for scientists (as others in society) to be subjected to regulation. The law, not ethics, has already become the arbiter of medical practice (McLeish, 1990). In medical research, the universities, hospitals, or other institutions where scientists practice (not funding agencies or journals) have traditionally been responsible for ensuring scientific integrity. It has long been acknowledged, however, that the USDHHS regulations and the IRB system provide only minimum ethical standards and thus cannot be relied upon to ensure ethical conduct. The federal regulations define scientific misconduct as: "1) serious deviation, such as fabrication, falsification, or plagiarism, from accepted practices in carrying out research or in reporting the results of research; or 2) failure to comply with the federal requirements affecting specific aspects of the conduct of research, e.g., the protection of human subjects and the welfare of laboratory animals" (USDHHS, 1988). In a survey of academic institutions conducted by Greene et al. (1985) only 25% (116 of 500) had adopted rules for dealing with allegations of misconduct. Furthermore, most institutions believed that existing faculty disciplinary mechanisms could adequately handle misconduct. In 1988, in response to serious occurrences of misconduct as well as other violations of professional norms, Harvard Medical School was among the first in the nation to adopt policies relating to performance of scientific research by all faculty, trainees, and research personnel. The school codified supervision of research training, data recording and retention, responsible authorship, and compliance with written laboratory procedure s (Tosteson, 1988). This was soon followed by a university policy distinguishing between acceptable and unaccept able conflicts of interest and conflicts of commitment relating to research and other professional activities (Bok, 1988; Faculty of Arts and Sciences, 1989). In 1989, the 10M Division of Health Sciences Policy published a report to assist the National Institutes of Health (NIH), other government agencies, universities, professional societies, and journals to improve the quality and integrity of research practices (10M, I989b). Taking into account the need to maintain the academic freedom, creativity, and primary responsibility of institutions, the 10M made the following summary recommendations: ( 1) NIH should expand its efforts to evaluate investigations of scientific misconduct, implement data audits, and emphasize quality over quantity of publications, e.g., limit the number of publications that can be considered as part of a grant application ; (2) universities and research centers should adopt guidelines to clarify expectations about ethical standards, review authorship practices, reduce pressures for excessive publicati on, provide form al in stru ct ion in research, de si gn ate faculty members to promote its practice, and monitor the J. Am. Acad. Child Adolesc. Psychiatry, 31:3, May 1992
supervisory and training practices; and (3) journals and other professio nal organizations should develop educational and training activities to improve the integrity and quality of research. They should study the issue of rights and responsibilities of all parties to research data, promote responsible authorship policies, and establish procedures for responding to allegations of misconduct in published research (10M, 1989b). The 10M recommendations have since led to the establishment of the NIH Office of Scientific Integrity, charged with providing advisory support to institutions, including the review of investigations involving miscondu ct, conflicts of interest, and sanctions. As of July 1990, all institutions with training grants were required to have course s to promote responsible research practices (NIH Guide, 1989). By 1992, NIH will require all grantee and applicant institutions to provide assurances that they have adopted procedures to encourage responsible research practices (USDHHS, 1988). Journals and professional organizations have also sponsored programs to address the concerns on ethics and integrity in research, such as the First International Conference on Peer Review in Biomedical Publication held in 1989 in Chicago (Research on Editorial Peer Review, 1990). After this meeting, several leading journals revised their policies on repetitive publication, supernumerary authorship, institutional responsibilities for disclosure, notification of research misconduct in publication, and the use and misuse of peer review (International Committee of Medical Journal Editors, 1988). The Journal of the Am erican Medical Association now requires its prospective authors to include a signed pledge that they will produce the raw study data upon request, take public responsibility for the validity of their work, disclose potential financial conflicts of interest, certify that they have participated in the work, and have reviewed and approved the final manuscript , which is a requirement aimed at eliminating "honorary authorship" (Lundberg and Flanag in, I 989). The editorial policy of the New England Journ al of Medicine expects: (1) all authors "to have taken care to ensure the integrity of the work"; (2) authors of research articles ' 'to disclose any commercial associations that might cause a conflict of interest in connection with the submitted article"; and (3) authors of all review articles and editoria ls "to have no financial associatio n with a company whose product figures prominently in the article or with a company making a competitive product." According to its editor, this policy excludes many experts of unquestioned integrity from writing review articles, " but is felt important to support the reader' s unwavering trust in these types of articles" (Reiman, 1990). The Ame rican Journal of Psychiatry requires that " each author should have participated sufficiently in the work to take public responsibility for the content." The jo urnal defines three authorship credit criteria (which must all be met), including: "substantial contributions to (a) conception and design, or analysis and interpretation of data, and (b) drafting the article and revising it critically for important intellectual content, and on (c) final approval of the version to be published." The journ al also requires that all forms of support 411
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(including, in particular, drug company support) be acknowledged. Although authors are required to disclo se any commercial or financial involvements that might present an appearance of a conflict of interest in connection with the submitted article, the decision to share this information with the readership is left to the discretion of the journal editor (see Informat ion for Authors, American Journal of Psychiatry). The Journal of the American Academy of Child and Adolescent Psychiat ry currently requires that research be condu cted ethically with due re gard to informed co nsent, permi ssion to publi sh, and confidentiality, and expects that all authors take full responsibility for the content of a submitted manuscript (see Notes for Authors, Journal of the American Academy of Child and Adolescent Psychiatry). It is recommended by this article that the Notes for Authors request investigators to describe explicitly the informed consent (and assent) procedures involving parents, children, and adolescents. The Journal currently requires written approval of a manuscript by all authors who sign an expressed transfer of copyright ownership in the event of publication. In this certification process, this article additionally recommends that the authors be required to state that they: (1) all participated in the work and have review ed and approved the final version of the manu script and (2) take responsibility for its integr ity. It is also recommended that the Journal require the following information to be disclosed to the Editor at the time of submission: (1) description of the substantial contribution of each author to the submitted work in study conception, design, or data analysis and in drafting, revision, and preparation of the final version of the manuscript to discourage supernumerary or exclusionary authorship practices; (2) institutional, commercial affiliations of the authors that pose a conflict of interest or conflict of commitment, including corporate consultantships or any vested interests; and (3) fundin g sources (including, in particular, funding by pharmaceuti cal companies) that have, either in part or in whole, supported the work and the dates of the entire project period. The Notes for Authors currently requi re that all manuscripts submitted to the Journal ' ' represent original material and have not been submitted or accepted elsewhere, either as a whole or in substantial part,' The ethical obligations of the authors can be further expanded to require that all previous publications arising from the same or overlapping study samples not merely be referen ced, but the salient characteri stics of the subjects selected for study again described, includ ing a description and justification in the Method s section for any scientific overlap with previously publi shed work. This is not only a requirement aimed to discourage repetitive publication practice s (10 M, 1989b), but is convenient for the reader who has all the information ava ilable there and then to form an inform ed opinion about the work. This article also recommends that the Notes for Author s define editorial policy on conflict of interest regarding review articles invited by the Editor. One policy trend of peerreviewed medical journals is to exclude experts from writing special articles if there is even an impression of conflict of intere st or conflict of commitment (Relman, 1990). As in 412
all fields of science, such confl icts in child and adolescent mental health research are also expected to become an increasingly important ethical concern (10M, 1989b; Tosteson, 1988). In child and adolescent psychiatry, for example, such ethical conflicts may arise in circumstances where investigators invited to write on the efficacy of a medication treatment, on the utilization of services, or on the reliabilit y of diagnostic measurements have affiliations with a pharmaceutical company from which they received noncompeting funds for a clinical trial or received other financial benefits from a medical review comp any that they serve as a paid panelist or consultant or from a company marketing a diagnostic manual or software from which they receive commissions, respectively. An absoluti st interpretation of such ethical issues by journals, at best, promotes the principle of responsible authorship and cultivates the trust of their readership ; at worst, it excludes experts of unquestioned integrity from writing review articles. In this regard, the ethical responsibility of jou rnal editors in servi ng the goals of science and the public good need not be compromised.
Protection of National Research Goals Perhap s more important than policies regulat ing or encouraging integrity in science is the prevailing definition of what is good in scientific endeavor as an important force influencing public policy and fundin g of resear ch. In other words, "ethics is related to politics: it is an attempt to bring the collecti ve desires of a group to bear upon individuals; or conversely. it is an attempt by an individual to cause his desires to become those of his group" (Russe ll, 1961, p. 232). In medical research, the public health significa nce of a disorder is traditionally regarded as a litmus test guiding Public Health Service fundin g allocations. In the national scene, legislators may have differing commitments based on their own prioriti es as well as pressures from their constituencies and lobby ists. It is incumb ent on all scientists who choose to influence their field that they get to know their political leader s (Trivelpiece, 1988). The national plan for research in child and adolescent psychiatry (USDHHS, 1990) is comparable with that in adult psychiatry more than a decade ago, reflected at that time in Pr e sident Ca r te r 's Commi s s ion on M ent a l He alth (USDHHS, 1978). Recognizing the insufficient knowledge about risk factors, prevention, and treatment, some professionals in child and adolesce nt mental health argued that there is more ethical justification for pursuing research than prescribing uncertain forms of treatment (Grah am, 1984). A distinct advantage wielded by researchers in child and adolescent ment al health is that most people in society concur about the good of education and sound psycholo gical development for the youth. Politicians, by necessity, are inclined to show sympathy to these universal values. The utilitarian position of ethics espoused by Hume , Bentham, and J.S. Mill, as well as the modem principles of ju stice sustain such a distribution of resources to child ren in need so that they may become empowered (Rawls, 1971).
Research Stewardship In the future, researchers in child and adole scent mental J. Am.Acad. Child Adolesc. Psychiatry, 31:3, May 1992
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health will be challenged by the quickening pace of research, the growing size of research teams, the explosion in computer and communication (information) technology, leading to greatly expanded analytic capabilities (lOM, 1989c), and the increasing cost, public visibility, and Congressional scrutiny of research. Other factors influencing the research environment include pressures to " publish or perish" (Maddox, 1988), emphasi s on publishing only " positive" research results (Angell, 1989), secrecy in research performance, and inadequate interaction between the young and more experienced researchers who are differentially affected by these forces (lOM, 1989b). Furthermore, in child and adolescent psychiatric research, uncertainty is rampant because disease concepts are not well developed, and ethical problems may also arise out of the application of disease theories to children who have no mental illness. As espoused by Wing (1984), not only a code of ethics but the quality of scientific investiga tio n is expe cted to suffer und er the se circum stances. Many academic programs of child and adolescent psychiatry are not well prepared to face an era of increased research intensity. The fellowship programs are often so small that the task of teaching trainees about ethical standards is likely to exceed their capabilities. One logical solution is to have the trainees participate in seminars conducted jo intly with departments of pediatrics, which must also deal with special ethical questions arising from research with children and adolescents (Leon Eisenberg, Pers. Commun .). Another suggestion is that trainees, in turn, sit in on the pediatric or psychiatric department IRB meetings. In these meetings, the trainee would experience the intensity of discussions relating to the scientific and ethical aspects of real life proposals. Because research is a team effort, it is also essential to allow explicit discussion about the role and responsibilities of trainees within departments. In larger departments or research centers, it may be possible to designate faculty members to promote the mentorship function of principal investigators and monitor their supervisory, training, and authorship pra cti ces. Th e transiti on al status of tra inees should not make them vulnerable to be embraced as aidesde-camp by principal investigators. Research is a formative process. The scientific curiosity and efforts need to be nurtured at each stage (inception, design, data collection, analysis, and writing) with full endorsement of contributions by participants. Current expectations of journals that all scientific contributions, funding sources, sponsorship of institutions, and affiliations (including conflicts of interest) be fully disclosed is consistent with this view (American Medical Association, 1990). Benetar (1990), writing on academic freedom in South Afri ca, recomm end s that the indi vidu als should be free, without coercion, to pursue academic work: teaching, researching, and publishin g. In the face of increasing interferen ce fro m political and ec onomic conflicts of inte re st, universities and research institutions should be allowed to maintain their autonomy in order to pursue their primary mission of advancement of knowledge. The need for such an explicit statement about stewardship is perhaps more obvious in a society like South Africa than in the United J.Am. Acad. Child Adolesc. Psychiatry, 31: 3, Ma y 1992
States. In the research arena, the future of innovation also depends first and foremost upon ideas and the freedom and opportunity to pursue them. The scientific community is still at an early stage of developing information and methods that pertain specifically to training in research ethics (National Institutes of Health Guide, 1990). Scientific and administrative leaders of universities, academic departments, and guest consultants or speakers can help promote future efforts. Ethics education, combined with individual mentorship, can help ensure that young scientists are prepared to accept responsibility for engaging in research. The institutions, in emphasizing the vigor of research efforts, also shoulder the primary obligation for promoting responsible research practice and training (Na tiona l In st itutes of Health Guide , 1990). The fundamental duty for ethical conduct in all domains, however, rests with the individual, whether he or she is a trainee, principal investigator, editor, or peer reviewer, and in the words of Karl Popper (1945), " can be shifted on to nobody else; neither to God, nor to nature, nor to society, nor to history" (Wing, 1984).
References Ameri can Med ical As sociation, Co uncil on Scient ific Affairs and Council on Eth ical and Judicial Affairs (1990), Conflicts of interest in m ed ical cen ter/i nd us t ry re sea rc h r elat ion ship s . JAMA , 263 :2790-2793. Angell, M. (19 84), Patient preferen ces in randomi zed clin ical trial. N. Eng!. J. Med., 3 10:1385-1387. - - ( 1988), Eth ical imperialism? Ethics in interna tional co llabo rative clini cal resea rch. N. Engl. J. Med., 319 :108 1- 1083 . - - (1989 ), Negative studies. N. Engl. J. Med., 321:464-466. Ap pelbau m, P. S., Roth, L. H., Lidz, C. W. et al. (198 7), False Hopes and Best Data: Consent to Research and the Therap eutic Misconception. Hastings Center Report . Barry , M. ( 1988), Ethical consi dera tions of hum an inves tigatio n in de vel op in g co untr ies : th e A IDS di le mm a. N. Engl . J . Me d., 319: 1083- 1085. Beauchamp, T. L. Childress, J. F. (1983), Principles of Biomedical Ethics, Second Edition, New York: Oxford University Press. Benatar, S. R. (1990), Viewpoint-academic freedom in South Afr ica . Lancet, 335: 1576- 1578. Bok , D. (1988 ), Ethics, the unive rsity and society. Harvard Magazine, (May -June) :39-50. Department of Health, Education and Welfare (1979), The Belmont Report: Ethical Principles and Guidelines f or the Protection of Human Subjects of Resea rch . (D HEW Publica tio n no. (05) 912065). Washington, D.C.: U.S. Go vern ment Print ing Office. Edelbrock, C. & Costello, A. J. ( 1988), Structured psychiatric interviews for childre n. In: Assessme nt and Diagnosis in Child Psychopa thology, eds. M. Rutter, A. H. Tu ma & 1. Lann. New York : Guil ford Pre ss, pp. 87-112. Faculty of Arts and Sciences ( 1989), Policies relating to research and other professiona l activ ities within and outside the Unive rsity. Harvard Gazette, December 1, p. 11. Graham, P. (1984) , Ethics and child psychiatry. In: Psychiatric Ethics, ed. S. Bloch & P. Chodoff. New York: Oxford University Press, pp. 235-254. Greene, P. J., Du rch, J. S., Horw itz, W. et al. (19 85), Pol icies for respo ndi ng to allegations of fraud in research. Minerva, 23:623625 . Herj anic, B., Hud son, R. & Kotloff, K. ( 1976), Does interviewing harm children. Res. Commun. Psychol. Psychiatry Behav., 1:52353 1. Holder, A. R. ( 1985a), Legal Issues in Pediatrics and Adolescent Medicine. New Haven : Yale Uni versity Press, pp. 123-142.
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Holder , A. R. (l 985b), When researchers are served subpoenaes . IRB 7:5-7. Hume, D. (1969), A Treatise of Human Nature. London, England: Pengu in Class ics (first published in 1739). !OM (l989a), National Academy of Scien ces. Report of a Stud y of the Committee of the Division of Men tal Health and Behavioral Medi cine. Research on Children and Adolescents with Mental. Beha vioral and Developm ental Disorders. Washington, D.C.: National Academy Pres s. - - (l 989b), National Academy of Scien ces. Report of a Study by a Committee of the Division of Health Scien ces Pol icy. The Responsibl e Conduct ofResearch in the Health Scie nces . Washington, D.C.: National Acade my Press. - - (I 989c), National Academy of Sciences. Committee on Science, Engineering and Publi c Policy. Report of the Panel on Inform ation Technology and the Conduct of Research. Inf ormation Technolog y and the Condu ct of Science: the User's View. Washington, D.C.: Nati onal Academy Press. International Committee of Medic al Journal Editors (1988) . Uniform requ irements for manu scripts submitt ed to biom ed ical jo urnals. An n. Intern. Med.• 108:258- 265. Lantos, J. D. & Frader, J. (1990), Extraco rporeal membrane oxygenation and the ethics of clinical research in pediatrics. N. Eng/. J. Med. , 323:409-413. Levine , R. J. (1986), Ethics and Regulation of Clin ical Research . Balt imore: Urban and Schwartzenberg, pp. 170-172. Lind, S. E. (1990), Sound ing board : finders' s fees for research subjects. N. Eng/. J, Med.• 323 :192- 195. Lundb erg, G. D. & Flanagin, A. ( 1989), New requir ements for authors: signed statements of authorship responsib ility and financial disclosure . lAMA, 14:2003-2004. Maddox , J. (1988), Why the pressure to publish? Natu re 333:493. M cL e ish , R. (1990), Easte r Tho ug h ts. Apri l 15, 1990 (W ES U 9004 15). Washington , D.c.: Natio nal Publi c Radio. Nation al Institut es of Health Guid e for Grants and Contract s (1989), Vol. 18, No. 45, December 22, p. I. - - (1990), Vol. 19, No. 30, August 17, p. I. Popper, K. R. (1945) , The Open Society and It's En emies, Vol. I., p. 62 and note 18. Lond on: Routledge Press. Rawls, J. (197 1), A Theory of Justice. Cambridge, MA: Harvard University Press. Reiman , A. (1990), New " informatio n to authors " - and readers (editorial). N. Eng/. J. Med., 323:56.
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Research on Editorial Peer Review (1990), Guard ing the Guardians. Selected Proceedin gs from the First International Congress on Peer Review in Biomedi cal Publi cation. lAMA, 263:1317-1438. Russell , B. (1961) , Science and Ethics, Religion and Science. New York: Oxford University Press, pp. 223-243. Trials of War Crimina ls before the Nuremberg Military Tribunals (1949), Control Council Law 2( 10), 181-1 82. Washington, D.C.: U.S. Governm ent Print ing Office. Trivelp iece, A. W. (1988), Influencing congress: ten comm andments (editorial). Science 241: 141. Tos teson, D. (1988), Harvard Medical School Memorandum. U.S. Congress ( 1988), House Committee on Government Operation s. Federal Response to Scientific Fraud and Misconduct. Hearings. September 29. USDHHS ( 1978) , Report of the President 's Commiss ion of Mental Health. Washington, D.C.: U.S. Government Printing Office. - - (l983a), Rules and Regul ations. Title 45 CFR Part 46, 116, January 26, 1981, revised as of March 8, 1983. - - (I 983b), Office of the Secret ary, Children Involved as Subj ects in Research: Additional Protections. Federal Register Vol. 48, No . 46, p. 9814-9820. - - (1986), National Institute s of Health . Guide for Grants and Contracts: Policie s and procedures for dealin g with possible misconduct in science. Vol. 15, No. 11. July 18. - - (1988), Public Health Serv ice. Responsibilitie s of PHS Awardee and Applicant Institut ions for dealin g with and reportin g possible miscondu ct in science. Title 42 CFR Part 50. Federal Register. Vol. 53, No. 181. September 19. - - (1990 ), A report requeste d by U.S. Congress submitted by the National Advisory Mental Health Council. National Plan f or Research on Child and Adolescent Ment al Disorders. National Insti tute of Mental Health. - - (199 1), Implem entation of the National Plan for Research on Child and Adole scent Ment al Disorders. Program Announcem ent (PA-9 1-46) . Public Health Service, Alcohol, Drug Abuse, and Mental Health Admin istration, and National Institute s of Ment al Health . Catalog of Federal Domesti c Assistance 93.242, 93.28 1 and 93.2 82. April, 1991. Wing, J. (1984), Ethics and psychiatri c research. In: Psych iatri c Ethics. eds. S. Bloch & P. Chodoff, New York: Oxford University Press, pp. 277-294. World Medical Assoc iation (1964), Declaration ofHelsinki. Helsinki, Finland. Geneva: World Health Organization.
J. Am. A cad. Child Adoles c. Psychi atry, 3 I :3, Ma y 1992
AND
FELTON EARLS, M.D.
Abstract. This paper examines the ethical principles governing research in child and adolescent psychiatry. The guidelines for protection of children and adolescents as research subjects are discussed. These include the principle of nonmaleficence and beneficence (the risk-benefit ratio), the principle of autonomy (informed consent and confidentiality), and the principle of justice (fair distribution of benefits and burdens of research). In the light of recent national efforts to help promote responsible research practice, the ethical standards relating to the protection of scientific integrity as well as research advocacy, training, and stewardship are also discussed. J. Am. Acad. Child Adolesc. Psychiatry, 1992, 31, 3:408-414. Key Words: ethics, child and adolescent psychiatry, research. The 1990s will very likely be host to an intensification of child and adolescent mental health research. This new ferment in the field has been heralded by a recent report of the Institute of Medicine (10M) calling for an urgent provision of resources to develop a "critical mass" of well-trained research personnel to fund a wide range of basic and clinical research projects and to broaden the number of "centers of excellence" in child and adolescent psychiatry (10M, 1989a). The 10M report has become the foundation for a national research plan submitted to Congress (U.S. Department of Health and Human Services [USDHHSj, 1990) and recently approved for implementation (USDHHS, 1991). It is timely, then, to examine the ethical standards that govern the conduct of research in child and adolescent psychiatry. The first part of this paper describes the ethical principles relating to protection of subjects in pediatric and mental health research in general. These guidelines alone do not ensure responsible conduct of research. In the light of national efforts promoting improved practice, the paper highlights the recommendations of another 10M report on regulation of the research environment (10M, 1989b). Finally, the paper discusses the ethics of research stewardship and training critical for the implementation of the national research plan in the future (USDHHS, 1990). The ethical principles introduced in this article only guide research applications. The use of the principles in specific cases is the responsibility of individual investigators and their institutions. A seriously deficient knowledge base on the causes and effective treatment of child and adolescent
Accepted July 6, 1991. Dr. Munir is Assistant Professor of Psychiatry, Division of Child and Adolescent Psychiatry, the Cambridge Hospital, Harvard Medical School, and Dr. Earls is Professor of Human Behavior and Development, Department of Maternal and Child Health, Harvard School of Public Health and Professor of Child Psychiatry, Harvard Medical School. The authors thank Drs. Leon Eisenberg, Myron L. Belfer, and James C. Beck for their valuable comments. This work was supported by NIMH grant K07-MH00826-02 (to K.M.). Reprint requests to Dr. Munir, Division of Child and Adolescent Psychiatry, the Cambridge Hospital, 1493 Cambridge Street, Cambridge, MA 02139. 0890-8567/92/3103-O408$03.00/0©1992 by the American Academy of Child and Adolescent Psychiatry.
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mental disorders makes research a top priority in the field. Nonetheless, a clear understanding of ethical principles is necessary to sustain this effort toward the ultimate goal of improving the mental health of children and adolescents. Protections for Subjects The Declarations of Helsinki (World Medical Association, 1975) and the Nuremberg Code (Trials of War Criminals, 1946-49) are the international charters that guide human investigations and medical experiments (Beauchamp and Childress, 1983). They declare unequivocally that the "concern for the interests of the subject must always prevail over the interests of science and society." They state that "the voluntary consent of the human subject is absolutely essential.' They also state explicitly that an individual must understand the nature of the proposed research well enough to make an informed decision. They demand that the purpose and content of an investigation as well as its duration, potential effects on the subjects' health, and all the inconveniences associated with the research be disclosed well in advance to potential subjects (Beauchamp and Childress, 1983). The USDHHS federal regulations guide all human investigations in the United States (USDHHS, 1983a). These federal regulations define a subject as a "living individual about whom an investigator conducting research obtains (1) data through intervention or interaction or (2) identifiable private information." All organizations applying for funding from the Public Health Service are required to appoint Institutional Review Boards (IRBs) to ensure protection for research subjects. Regardless of the federal requirements, most institutions have their local IRBs comprised of clinicians, researchers, patient advocates, lay members, and others knowledgable in the fields of law and ethics. There are three basic principles that underlie the judgments made by the IRBs: (1) the duty of nonmaleficence and beneficence (assessment of the risk-benefit assumed by each subject); (2) the principle of autonomy (informed consent, protection of privacy, and confidentiality); and (3) the principle of justice (the fair distribution of benefits and burdens of research and the equitable selection of subjects). Each one of these principles presents special problems in both pediatric and mental health research. J. Am. Acad. Child Adolesc. Psychiatry, 31 :3, May 1992
ETH ICAL PRINCIPL ES GOVERNING RESEARCH
Tne Principle of Nonmaleficence and Benefi cence The assessment of the risk-benefit ratio requires that the risks be minimized in proportion to the anticipated benefits. The USDHHS regulations impose responsibilities on IRBs depending on the degree of risk and the extent of likely benefit for each child subject. Minimal risk is defined as that "ordinarily encounte red in daily life or during the perfo rm ance of routine physica l or psychol ogical te sts" (USDHHS, 1983a). Research is classified in four risk categories: (1) minimal risk; (2) greater than minimal risk but with prospect of direct benefit .to individual subjects; (3) greater than minimal risk and without direct benefit but likely to yield generalizable knowledge about the subject's disorder or cond ition; and (4) not other wise approvabl e but presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health and welfare of subjec ts. In all circumstances where researc h involves greater than minim al risk, it must be ju stified by the anticipated direct benefit to the child. In cases of no such direct benefit , the IRBs must find that the research represents a minor increase over minimal risk. The research must also be commensurate with each child's individual experience and must be likely to yie ld ge nera lizable know ledge abou t their co ndition (USDHHS, 1983b). Research in which a child patient stands to gain directly from a therapeutic (clinical) procedure raises less ethical problems than research where there is no such direct therapeutic benefit. Nontherapeutic research is generally not ethically justified when it involves more than minimal risk and when the primary aim is the acquisition of knowledge for other pediatric subjects. An example is the use of children as "normal" controls in procedures where they have no direct gains, but face discernible risks, pain, or discomfort. The regulations exempt from formal IRB review research involving children in established educational settings, research involving observation of public behavior, use of educatio nal tests, and collection of existing data, documents, records, or specimens. Surveys may be exempted except in cases in which subjects can be identified or responses may be prone to legal liability. In psycholo gical studies involving children and adolescents, a major difficult y is the advance anticipation of risk. For examp le, direct interviewing of children by means of structured interviews has been shown to be a useful method of obtaining data for both therapeutic and nontherapeutic res earch purp oses (Edel brock and Cos tello , 1988). The growing interest in such interviews as a research tool has engendered an increasing concern about their effects. Most such interviews do not involve any harm or serious discomfort to participants. Herjanic et al. (1976) reported a ratio of I:63 unfavorable to favorable/neutral responses to such direct interview s of children and their parents. Many children perceive these interviews as enjoyable, but it is difficult to predict which few children may be seriously upset by them (Graham, 1984). The concern is that some children, when asked to participate in studies involving tests or questionnaires, may begin a priori to assume (or believe) that there may be something wrong with them . IRBs are obliged to J. Am.Acad. Child Adolesc. Psychiatry, 31:3, May 1992
examine the risks posed by these interviews based on their duration, style, and content, and the age and circumstances of the children. In addition, they need to authorize procedures for dealing with hazards (e.g., suicidal ideation, physicalor sexual abuse) uncovered in the interview process. A new area of research in child and adolescent mental disorders is the development of methods to probe the human genome and visualize the structure and function of the brain . To date, many IRBs will have had little experience in judging the efficacy of these techniques in the study of psychiatric disorders in children and ado les ce nts. Investigat ors pioneering these genetic and other technological methods (e.g., positron emission tomograph y studies) with children must accept the spe cial duty of educating their review boards. During randomized clinical trials, when the effec ts of receiving a new or untried treatment are compared with the effects of receivi ng an accepted treatment, a paradox exists (Angell, 1984; Wing, 1984). One line of ethical reasoning asserts that a parent volunteering a child for random assignment may be sacrificing the child's health for the good of the study and that of future patients. On the other hand, such a decision is ethically warranted if a reasonable likelihood exists that the new therapy may be better than the previous one or the "standard treatment" is of limited efficacy and the new method is theoretically superior. What is usual and customary may be not necessarily efficacious. In pediatrics, the use of an experimental treatment as though it is " standard therapy," however, has serious ethical and legal con sequences (Holder, 1985 a; Lan tos and Frader, 1990). In child and adolescent psych opharm acology , the rapid emergence of new antidepressa nts, anticonvulsants, and other psychotropic agents as innovative therapies requires that they be carefully assesse d by means of controlled prospective trials. Such trials, as are currently being undertaken, guide the establishmen t of risks and benefits of new treatments. Because uncertaint y in medical science is inevitable, results of clinical trials, however, cannot be the sole basis for making complex therapeutic decisions (Lantos and Frader, 1990). There are additional ethical dilemmas. Some clinician-investigators may support the introduction of innovative uncont rolled treatment s based on experience or anecdotal reports. In other cases, market incentives may create added pressures for the rapid approval and use of treatments. The situation is further complicated by the lack of adequate Food and Drug Administration guidelines for use of novel psychotropic agents in children and adolescents. Principle of Autonomy A fundamental ethical concern for the protection of vulnerable subjec ts is the application of the principle of autonomy in obtai ning informed consent. Children who are unable to give free or informed consent, like other susceptible individuals such as pregnant women, mentally handicapped , homeless, persons with HIV/AIDS, prisoners or citize ns of countries where personal choice is severely limited, require special protections (Angell, 1988; Barry, 1988) . The pediatric guidelines for informed consent are described in the National Research Act (PL. 93-348). The regulations adopt
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the recommendations of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (USDHHS, 1983a). Informed consent in pediatric research means permission of parents (biologica l or adoptive) or " guardians" (individuals authorized under state or local law to consent on behalf of the child). As a general rule in research involving minimal risk, it is sufficient to obtain the informed consent of one parent; in research with greater than minimal risk, the permission of both parents should be sought whenever possible. In addition to requiring informed consent by a parent or other legal guardian, the regulations make adequate provisions for soliciting assent from the child subjects themselves. Choice is important for older children and adolescents, particularly if the research involves no direct benefits to them. Individual IRBs define assent guidelines by taking into account the ages, maturity, and the psychological state of the children. The IRBs may waive the assent requirement in special circumstances, e.g., therapeutic research that is likely to be of direct benefit to the subjects. A signed parent consent form alone is not sufficient to establish the process of consent, nor does it provide protection from liability. The process is enhanced by the use of clear, simple, and age-appropriate language in all the materials given to parents or children. In addition, parents need to be allowed adequate time to discuss the project with family or friends to make thoughtful decisions about participation. Nonetheless, a written consent form is generally required to document that the process of consent (discussion between the investigator and the parent) has taken place. In particular, the use of medical jargon in nontherapeutic or epidemiological studies is not ethically permissible. These labels may cause undue parental misconception and anxiety (Appelbaum et al., 1987). Because the predictive power of screening tests in child mental health is also limited, when a study design ca ll s for the use of such tests to identify "risk groups," it is important that the results not mislead parents or schools. It is essential to guard the confidentiality and respect the privacy of subjects. Breach of confidentiality is usually attributable to careless leaks of information to unauthorized persons, e.g., documents left unattended, lack of security in the clinical records system or the name list. Other problems arise because of carelessness in computer linking , data storage, and supervision of the project staff (Wing, 1984). If the research data contain sensitive information that may create legal problems for the subjec ts should the records be subpoenaed (e.g., HIV serostatus), the researcher may obtain federal certificates of confidentiality from the USDHHS and the Department of Justice (Levine, 1986). These certificates allow identificati on of research subjects to be withheld and provide protections for investigators to seek legal counsel to have the subpoenas overruled (Holder, 1985b). Children who are wards of the state are protected from being involved in research unless it is intended to be of direct benefit to them. They may be involved in studies posing greater than minimal risk only if such research is related to their status as wards, or is conducted in schools or in settings in which the majority of child subjects are not 410
wards. In all cases, consent is required from a child advocate who has no conflict of interest with the research. In research involving abused or neglected children for whom parental consent may not be reasonable, the IRB may also substitute parental consent by consent obtained from a child advocate. Principle of Justice
The principle of justice is concerned with the fair and just distribution of the benefits and burdens of research. This means that the subjects should be chosen for reasons directly related to the scientific question under study, not because they are easily available and/or able to be easily manipulated (Department of Health, Education, and Welfare, 1979). No single group, especially the disadvantaged or the handicapped, should be asked to bear a disproportionate share of this burden. When children or their parents depend on a physician researcher for medical care, they may feel that refusing to participate in a study might jeopardize their future care, notwithstanding reassurances on the consent form that such refusal cannot affect their care in any way. Clinical research in child and adolescent psychiatry or pediatrics frequently involves this situation and assumes that the protection offered by the informed consent process comes by way of the responsible physician who does not unreasonably inform or persuade patients to be subjected to unnecessary tests, procedures, or treatments. Not uncommonly, however, parents may be susceptibile to volunteer their children to enter a study based on the power of their physician's suggestion and by other influences, such as whether the investigator is " nice" or the hospital is highly regarded (Lind, 1990). Recruitment can also be influenced by unreasonable amount of payment offered to the subjects in compensation. As for individual physicians referring patients, "finder's fees" should never be offered, nor should referral be made as a courtesy or to gain favor with colleagues. Patient referral is a professional necessity that is likely to help serve the best interests of the patient (Lind, 1990). This is a principle that has helped foster medical progress in the past and is likely to bring the worlds of practice and research closer together. The use of children or other vulnerable populations for research is ethically justified if those populations' advocates believe that the research will improve the understanding or treatment of the condition producing the subjects' illness and dependency. For example, it is likely that patients who participate in randomized clinical trials need to get what is the best available therapy for their condition. Finally, in the words of one investigator: "a project that will almost certainly do nobody any harm, but is equally likely to do nobody any good, is not worth undertaking" (Wing, 1984).
Protection of Ethical Standards and Scientific Integrity Bertrand Russell (1961) envisaged the study of ethics in two parts: (1) what is good on its own account (based on individual, societal, or cultural values) and (2) moral values of co nduct. Skeptical of appealing to a belief in "conscience" in framing moral rules, he pointed to two difficulties: first, that ' 'conscience says different things to different people; and second, that there were "mundane causes of J.Am. Acad. Child Ado/esc. Psychiatry, 31:3, May 1992
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conscientious feelings" (Russell, 1961). David Hume' s A Treatis e ofHum an Nature, akin to the Copernican revolution in astronomy, was the first to portray man not as a divine being, but as a figure dominated by conflictin g desires. David Hume (1969, first published in 1739) characterized moral philosophy as " the understanding, the passions, morals, politics, and criticism: in short, the entire science of man discovered empirically and systematically." Such a picture of moral frailty foretells the need for scientists (as others in society) to be subjected to regulation. The law, not ethics, has already become the arbiter of medical practice (McLeish, 1990). In medical research, the universities, hospitals, or other institutions where scientists practice (not funding agencies or journals) have traditionally been responsible for ensuring scientific integrity. It has long been acknowledged, however, that the USDHHS regulations and the IRB system provide only minimum ethical standards and thus cannot be relied upon to ensure ethical conduct. The federal regulations define scientific misconduct as: "1) serious deviation, such as fabrication, falsification, or plagiarism, from accepted practices in carrying out research or in reporting the results of research; or 2) failure to comply with the federal requirements affecting specific aspects of the conduct of research, e.g., the protection of human subjects and the welfare of laboratory animals" (USDHHS, 1988). In a survey of academic institutions conducted by Greene et al. (1985) only 25% (116 of 500) had adopted rules for dealing with allegations of misconduct. Furthermore, most institutions believed that existing faculty disciplinary mechanisms could adequately handle misconduct. In 1988, in response to serious occurrences of misconduct as well as other violations of professional norms, Harvard Medical School was among the first in the nation to adopt policies relating to performance of scientific research by all faculty, trainees, and research personnel. The school codified supervision of research training, data recording and retention, responsible authorship, and compliance with written laboratory procedure s (Tosteson, 1988). This was soon followed by a university policy distinguishing between acceptable and unaccept able conflicts of interest and conflicts of commitment relating to research and other professional activities (Bok, 1988; Faculty of Arts and Sciences, 1989). In 1989, the 10M Division of Health Sciences Policy published a report to assist the National Institutes of Health (NIH), other government agencies, universities, professional societies, and journals to improve the quality and integrity of research practices (10M, I989b). Taking into account the need to maintain the academic freedom, creativity, and primary responsibility of institutions, the 10M made the following summary recommendations: ( 1) NIH should expand its efforts to evaluate investigations of scientific misconduct, implement data audits, and emphasize quality over quantity of publications, e.g., limit the number of publications that can be considered as part of a grant application ; (2) universities and research centers should adopt guidelines to clarify expectations about ethical standards, review authorship practices, reduce pressures for excessive publicati on, provide form al in stru ct ion in research, de si gn ate faculty members to promote its practice, and monitor the J. Am. Acad. Child Adolesc. Psychiatry, 31:3, May 1992
supervisory and training practices; and (3) journals and other professio nal organizations should develop educational and training activities to improve the integrity and quality of research. They should study the issue of rights and responsibilities of all parties to research data, promote responsible authorship policies, and establish procedures for responding to allegations of misconduct in published research (10M, 1989b). The 10M recommendations have since led to the establishment of the NIH Office of Scientific Integrity, charged with providing advisory support to institutions, including the review of investigations involving miscondu ct, conflicts of interest, and sanctions. As of July 1990, all institutions with training grants were required to have course s to promote responsible research practices (NIH Guide, 1989). By 1992, NIH will require all grantee and applicant institutions to provide assurances that they have adopted procedures to encourage responsible research practices (USDHHS, 1988). Journals and professional organizations have also sponsored programs to address the concerns on ethics and integrity in research, such as the First International Conference on Peer Review in Biomedical Publication held in 1989 in Chicago (Research on Editorial Peer Review, 1990). After this meeting, several leading journals revised their policies on repetitive publication, supernumerary authorship, institutional responsibilities for disclosure, notification of research misconduct in publication, and the use and misuse of peer review (International Committee of Medical Journal Editors, 1988). The Journal of the Am erican Medical Association now requires its prospective authors to include a signed pledge that they will produce the raw study data upon request, take public responsibility for the validity of their work, disclose potential financial conflicts of interest, certify that they have participated in the work, and have reviewed and approved the final manuscript , which is a requirement aimed at eliminating "honorary authorship" (Lundberg and Flanag in, I 989). The editorial policy of the New England Journ al of Medicine expects: (1) all authors "to have taken care to ensure the integrity of the work"; (2) authors of research articles ' 'to disclose any commercial associations that might cause a conflict of interest in connection with the submitted article"; and (3) authors of all review articles and editoria ls "to have no financial associatio n with a company whose product figures prominently in the article or with a company making a competitive product." According to its editor, this policy excludes many experts of unquestioned integrity from writing review articles, " but is felt important to support the reader' s unwavering trust in these types of articles" (Reiman, 1990). The Ame rican Journal of Psychiatry requires that " each author should have participated sufficiently in the work to take public responsibility for the content." The jo urnal defines three authorship credit criteria (which must all be met), including: "substantial contributions to (a) conception and design, or analysis and interpretation of data, and (b) drafting the article and revising it critically for important intellectual content, and on (c) final approval of the version to be published." The journ al also requires that all forms of support 411
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(including, in particular, drug company support) be acknowledged. Although authors are required to disclo se any commercial or financial involvements that might present an appearance of a conflict of interest in connection with the submitted article, the decision to share this information with the readership is left to the discretion of the journal editor (see Informat ion for Authors, American Journal of Psychiatry). The Journal of the American Academy of Child and Adolescent Psychiat ry currently requires that research be condu cted ethically with due re gard to informed co nsent, permi ssion to publi sh, and confidentiality, and expects that all authors take full responsibility for the content of a submitted manuscript (see Notes for Authors, Journal of the American Academy of Child and Adolescent Psychiatry). It is recommended by this article that the Notes for Authors request investigators to describe explicitly the informed consent (and assent) procedures involving parents, children, and adolescents. The Journal currently requires written approval of a manuscript by all authors who sign an expressed transfer of copyright ownership in the event of publication. In this certification process, this article additionally recommends that the authors be required to state that they: (1) all participated in the work and have review ed and approved the final version of the manu script and (2) take responsibility for its integr ity. It is also recommended that the Journal require the following information to be disclosed to the Editor at the time of submission: (1) description of the substantial contribution of each author to the submitted work in study conception, design, or data analysis and in drafting, revision, and preparation of the final version of the manuscript to discourage supernumerary or exclusionary authorship practices; (2) institutional, commercial affiliations of the authors that pose a conflict of interest or conflict of commitment, including corporate consultantships or any vested interests; and (3) fundin g sources (including, in particular, funding by pharmaceuti cal companies) that have, either in part or in whole, supported the work and the dates of the entire project period. The Notes for Authors currently requi re that all manuscripts submitted to the Journal ' ' represent original material and have not been submitted or accepted elsewhere, either as a whole or in substantial part,' The ethical obligations of the authors can be further expanded to require that all previous publications arising from the same or overlapping study samples not merely be referen ced, but the salient characteri stics of the subjects selected for study again described, includ ing a description and justification in the Method s section for any scientific overlap with previously publi shed work. This is not only a requirement aimed to discourage repetitive publication practice s (10 M, 1989b), but is convenient for the reader who has all the information ava ilable there and then to form an inform ed opinion about the work. This article also recommends that the Notes for Author s define editorial policy on conflict of interest regarding review articles invited by the Editor. One policy trend of peerreviewed medical journals is to exclude experts from writing special articles if there is even an impression of conflict of intere st or conflict of commitment (Relman, 1990). As in 412
all fields of science, such confl icts in child and adolescent mental health research are also expected to become an increasingly important ethical concern (10M, 1989b; Tosteson, 1988). In child and adolescent psychiatry, for example, such ethical conflicts may arise in circumstances where investigators invited to write on the efficacy of a medication treatment, on the utilization of services, or on the reliabilit y of diagnostic measurements have affiliations with a pharmaceutical company from which they received noncompeting funds for a clinical trial or received other financial benefits from a medical review comp any that they serve as a paid panelist or consultant or from a company marketing a diagnostic manual or software from which they receive commissions, respectively. An absoluti st interpretation of such ethical issues by journals, at best, promotes the principle of responsible authorship and cultivates the trust of their readership ; at worst, it excludes experts of unquestioned integrity from writing review articles. In this regard, the ethical responsibility of jou rnal editors in servi ng the goals of science and the public good need not be compromised.
Protection of National Research Goals Perhap s more important than policies regulat ing or encouraging integrity in science is the prevailing definition of what is good in scientific endeavor as an important force influencing public policy and fundin g of resear ch. In other words, "ethics is related to politics: it is an attempt to bring the collecti ve desires of a group to bear upon individuals; or conversely. it is an attempt by an individual to cause his desires to become those of his group" (Russe ll, 1961, p. 232). In medical research, the public health significa nce of a disorder is traditionally regarded as a litmus test guiding Public Health Service fundin g allocations. In the national scene, legislators may have differing commitments based on their own prioriti es as well as pressures from their constituencies and lobby ists. It is incumb ent on all scientists who choose to influence their field that they get to know their political leader s (Trivelpiece, 1988). The national plan for research in child and adolescent psychiatry (USDHHS, 1990) is comparable with that in adult psychiatry more than a decade ago, reflected at that time in Pr e sident Ca r te r 's Commi s s ion on M ent a l He alth (USDHHS, 1978). Recognizing the insufficient knowledge about risk factors, prevention, and treatment, some professionals in child and adolesce nt mental health argued that there is more ethical justification for pursuing research than prescribing uncertain forms of treatment (Grah am, 1984). A distinct advantage wielded by researchers in child and adolescent ment al health is that most people in society concur about the good of education and sound psycholo gical development for the youth. Politicians, by necessity, are inclined to show sympathy to these universal values. The utilitarian position of ethics espoused by Hume , Bentham, and J.S. Mill, as well as the modem principles of ju stice sustain such a distribution of resources to child ren in need so that they may become empowered (Rawls, 1971).
Research Stewardship In the future, researchers in child and adole scent mental J. Am.Acad. Child Adolesc. Psychiatry, 31:3, May 1992
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health will be challenged by the quickening pace of research, the growing size of research teams, the explosion in computer and communication (information) technology, leading to greatly expanded analytic capabilities (lOM, 1989c), and the increasing cost, public visibility, and Congressional scrutiny of research. Other factors influencing the research environment include pressures to " publish or perish" (Maddox, 1988), emphasi s on publishing only " positive" research results (Angell, 1989), secrecy in research performance, and inadequate interaction between the young and more experienced researchers who are differentially affected by these forces (lOM, 1989b). Furthermore, in child and adolescent psychiatric research, uncertainty is rampant because disease concepts are not well developed, and ethical problems may also arise out of the application of disease theories to children who have no mental illness. As espoused by Wing (1984), not only a code of ethics but the quality of scientific investiga tio n is expe cted to suffer und er the se circum stances. Many academic programs of child and adolescent psychiatry are not well prepared to face an era of increased research intensity. The fellowship programs are often so small that the task of teaching trainees about ethical standards is likely to exceed their capabilities. One logical solution is to have the trainees participate in seminars conducted jo intly with departments of pediatrics, which must also deal with special ethical questions arising from research with children and adolescents (Leon Eisenberg, Pers. Commun .). Another suggestion is that trainees, in turn, sit in on the pediatric or psychiatric department IRB meetings. In these meetings, the trainee would experience the intensity of discussions relating to the scientific and ethical aspects of real life proposals. Because research is a team effort, it is also essential to allow explicit discussion about the role and responsibilities of trainees within departments. In larger departments or research centers, it may be possible to designate faculty members to promote the mentorship function of principal investigators and monitor their supervisory, training, and authorship pra cti ces. Th e transiti on al status of tra inees should not make them vulnerable to be embraced as aidesde-camp by principal investigators. Research is a formative process. The scientific curiosity and efforts need to be nurtured at each stage (inception, design, data collection, analysis, and writing) with full endorsement of contributions by participants. Current expectations of journals that all scientific contributions, funding sources, sponsorship of institutions, and affiliations (including conflicts of interest) be fully disclosed is consistent with this view (American Medical Association, 1990). Benetar (1990), writing on academic freedom in South Afri ca, recomm end s that the indi vidu als should be free, without coercion, to pursue academic work: teaching, researching, and publishin g. In the face of increasing interferen ce fro m political and ec onomic conflicts of inte re st, universities and research institutions should be allowed to maintain their autonomy in order to pursue their primary mission of advancement of knowledge. The need for such an explicit statement about stewardship is perhaps more obvious in a society like South Africa than in the United J.Am. Acad. Child Adolesc. Psychiatry, 31: 3, Ma y 1992
States. In the research arena, the future of innovation also depends first and foremost upon ideas and the freedom and opportunity to pursue them. The scientific community is still at an early stage of developing information and methods that pertain specifically to training in research ethics (National Institutes of Health Guide, 1990). Scientific and administrative leaders of universities, academic departments, and guest consultants or speakers can help promote future efforts. Ethics education, combined with individual mentorship, can help ensure that young scientists are prepared to accept responsibility for engaging in research. The institutions, in emphasizing the vigor of research efforts, also shoulder the primary obligation for promoting responsible research practice and training (Na tiona l In st itutes of Health Guide , 1990). The fundamental duty for ethical conduct in all domains, however, rests with the individual, whether he or she is a trainee, principal investigator, editor, or peer reviewer, and in the words of Karl Popper (1945), " can be shifted on to nobody else; neither to God, nor to nature, nor to society, nor to history" (Wing, 1984).
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