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are now receiving careful scrutiny by human experimentation committees, composed of both scientists and lay people. As social and behavioral and scientists in dental research, we have traditionally used human subjects in our investigations and, therefore, we are vitally coticerned with these issues. Many of us have served on Human Experimentation Committees and others have experienced great frustration dealing with committees or funding agency administratois relative to human experimentation.

I have asked the three people presenting papers and the two paper discussants to address the problems of human experimentation based on their own experiences in research and from several different levels: specifically, 1) the protection of the rights of individuals or groups who participate in social and behavioral investigations, 2) the development of human experimentation policy and 3) the effect of human experimentation regulations on the scope and direction of dental research.

Overview of ethical aspects of clinical studies HERSCHEL S. HOROWITZ

Community Programs Section, Caries Prevention and Research Branch, National Institute of Dental Research, Bethesda, Maryland, U.S.A. ABSTRACT - Research iti hutium sitbjeets should be conducted only if the rights atid welfare of the participants are protected. Prospective .study subjects ntust be given adequate information about all aspects of a study so that they can make a ratiotially exercised decision about participation; coercive techniques lo solicit participants should not be used. Research in hutiians may be classified in one of three categories: (1) research on treatment of existitig conditiotis; (2) researeh on prevetitive titeasttres; and (3) research other than for treatttient or prevetUioti, Different concerns and aspects of infortned consent assume particular itnportanee in each category. In research on the treattnent of existing conditions, untreated oi placebo-lreated eontrol groups are rarely justified if lhe condition is irreversible. In research on prevetitive tnethods prospective subjects should be infortned of the likelihood of receiving an ineffective treattnetit, if one or tnore placebo groups are included, A randomized clitucal trial is usually the best desigti for studies of prevetitive methods, Noti-randotnfzed desigtts, which are feasible and statistically valid, tnay be etnployed in order to avoid depriving sotne subjects frotn receiving effective prevetitive methods, Iti social or behavioral research, confidentiality of collected information and privacy of the subject are essential considerations.

Research that involves human subjects must be based upon scientific principles that provide a sound rationale for conducting the research. The justification for the research should be based upon findings obtained from adequately performed laboratory or animal experiments, findings from other clinical studies or a thorough knowledge of the scientific literature. Moreover, the design of a proposed elinieai study should permit an unequivocal interpretation of anticipated findings. Research involving human subjects should be conducted by or be under the supervision of clinical investigators who are scientifically qualified and experienced. All study personnel should be skilled

and exercise great care in carrying out the study's procedures. Research involving human subjects should be carried out only if the rights and welfare of the participants are adequately protected. Any predictable risks to the participants must be outweighed by the benefits they are likely to receive or by the importance of the knowledge that will be gained. Concern for the interests of participants must prevail over the interests of science or society, INFORMED CONSENT The informed consent of subjects who participate in a study must be obtained by methods that are

Syrnjjosiiun on etliical issues

adequate and appropriate. Consent should be obtained in writing from a subject or from his parent, guardian or authorized representative, and only after the study has been fully explained and, as iar as cati be ascertained, fully understood. In essence, prospective study participants or those responsible for them should be provided with sufficient information, in ea,sily comprehensible language, and have sufficient understanding of the elements of a research project and the attendant procedures to make a rationally exercised decision about participation. Participation inu,st be truly voluntary, and not coercive in any way. CLASSIFICATION OF CLINICAL RESEARCH IN HUMAN SUBJECTS Clinical research in human subjects may be classified in one of three categories: 1. Research concerned with the diagnosis, care or treatment of an existing disease or condition. 2. Research concerned with the prevention of a disease or condition to which a subject is likely to be susceptible. 3. Research not concerned directly with treating an existing disease or condition of the subject or preventing one to which lie is likely to be susceptible. Although concern for participants and the elements of informed consent mvist be maintained for research in all these categories, different concerns and aspects of informed consent assume particular importance in each type. RESEARCH ON TREATMENT OF EXISTING CONDITIONS A clinical investigator who conducts research concerned with the care or treatment of an existing oral condition or disease has an obligation to ensure that subjects who have the disease or condition under investigation receive or are referred for treatment. Untreated or placebo-treated control groups are rarely justified for research in this category, if the disease or condition is irreversible. In the treatment of a disease or condition, the potential benefits, hazards and discomforts of a new agent or method should be weighed against the same characteristics of the best currently available diagnostic and therapeutic measure. The new regimen should be investigated only if these comparative appraisals are favorable.

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Because subjects with existing diseases or conditions are freqiicntly tinder duress and in a dependent relationship to the clinical investigator or other personnel of a research project, every effort must be made to respect the rights and to safeguard the personal dignity of these subjects. For research in this category, the basic element of informed consent that requires disclosure of appropriate alternative procedures assumes prime importance. The refusal of a subject with an existing disease to participate in a study should not influence a wellfunctioning doctoi'-patient relationship. RESEARCH ON PREVENTIVE MEASURES In many studies of preventi\'e methods, subjects in a control grotip are given or are asked to use a placebo. Subjects in a control group must not be informed of their grotip-assignment because this knowledge may affect their behavior relevant to the disease or condition under investigation, but it is not ethical to give a placebo to volunteers who believe they are receiving an effective regimen. Subjects who are being recruited for studies should be informed of the likelihood or chances of their receiving a placebo. It is empliasized that lhe control group should not be asked to engage in any practice that may have a harmful effect on the dcntilion or its surrounding tissues. Neither should subjects in a control group be asked to refrain from usual practices that may have a beneficial effect on oral tissues. In studies in which there is uncertainty about the value of a new therapy or preventive agent or in which there is disagreement about the relative merits of regimens to be included, a randomized clinical trial is usually the best design. From an ethical standpoint, an intellectually honest admission is tacitly made in a randomized clinical trial that the best treatment regimen is not known and, therefore, that an ethical course of action dictates that subjects be assigned strictly randomly to groups. In order to avoid depriving subjects in control groups from receiving benefits in studies of agents or methods that are known to be effective, nonrandomized designs, that are feasible and stati.sticallv valid, may often ha\'e to be employed. One such design is the evaluation of the effects of a preventive regimen by dcterrnining the prevalence of a disease or condition in a population that has participated in a prcN'entive program and com-

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paring the findings with the prevalence observed in the same population before the measure or procedure was instituted. Another of these alternative designs consists of comparing a population that is participating in a preventive regimen, concurrently with a suitable reference population that is not exposed to the regimen. Because the design of a research project in human subjects must be scientifically rational, as well as ethically acceptable, there must be concern that, after meeting the ethical requirements of a review committee, the design of a study has not been compromised to the point where it is no longer scientifically valid. It is not ethically proper to conduct a study with a design that has been altered in order to protect certain subjects but which can no longer validly answer the questions originally posed by the investigation. RESEARCH OTHER THAN FOR TREATMENT OR PREVENTION Research in this category usually results in no therapeutic or preventive benefit to the participants, and thus, it may have no direct value to them. Because no therapeutic benefit is anticipated, the ethical consideration that requires advisement about alternative procedures is usually inapplicable in this type of research. It is essential, however, that such research have a solid scientific foundation, expand existing knowledge and yield useful results for the good of society. It is especially important that maximal confidentiality of information be maintained when behavioral or social research concentrates on the beliefs, practices or habits of participants. Moreover, confidentiality should be assured in studies in which demographic information of a personal n attire is elicited, e.g. information on education or income. In social research, privacy of the subject or respondent is an important, if not the principal, ethical concern. Privacy of a subject is invaded if any of his affairs are made public that he wishes to remain private. Intrusion upon one's privacy is not justified solely in the interests of developing new scientific knowledge on matters of ptiblic importance. A guarantee of confidentiality may be necessary to secure consent from members of a population who perceive that their very participation may involve some risk, e.g. users of drugs, shoplifters or homosexuals. A principal risk of harm in some

social science inquiries stems from the disclosure of private matters to which potential socially harmful responses are made. Interviewers in open-ended social research projects often are trained to induce cooperation, develop rapport with respondents and lead into sensitive areas of privacy, which may be considered coercive techniques, OTHER CONSIDERATIONS The question of whether payments to participants in scientilic investigations constitute an improper inducement is difficult to answer. It is likely that the poor, the very young, the very old, the unemployed and the incarcerated may be highly susceptible to offers of even small monetary rewards for participation in research. If this suggestion is correct, such research may be biased and, moreover, the monetary inducement may be considered coercion. Other forms of inducement, e.g. appeals to prestige or offers of feedback concernhig skills or personality may also be subtly or indirectly constrained. A research project should be terminated immediately if evidence develops that deleterious effects are associated with the treatment regimens. Moreover, consideration should be given to terminating long-term field studies ahead of schedule if it becomes apparent for whatever reasons, e.g. negative interim findings or excessive loss of participants, that the answer or conclusion will be equivocal. An investigator's conscience should demand ethical behavior. It is not satisfactory, however, merely to behave ethically; one must also do what is in accordance with sound scientific knowledge. In essence, ethical research consists of studies in which the questions being asked can be answered validly and in which the rights and welfare of participants arc fully protected. ADDITIONAL READING 1, BYAK, D , P , , SIMON, R , M , , FRiEtjt.wALD, 'W, T,, Scuit.KSSEI.MAN, J, J,, D E M I . T S , D , L , , Et.t.ENBEtiG, J, H,, GAIL,

M, Ii, & WARE, J. H,: Randomized elitiieal trials. New Engl. /, Med. W76: 295: 74-80, 2, CouNctt, ON DENTAL Rt,si:AR(;iT, AMERIIIAN Dt;NT,\L As-

soct.viioN: Ethical guidelines for clinical investigation: ethical policy of the Atiieriean Dental Association regarding the use of human subjects in clinical research, /, Am. Dent. Assoe. 1973: 86; 687-689, 3, HOROWITZ, H , S,: Ethical considerations of study partieipants in denial caries elinieai trials. Community Dent. Oral Epidemiot. 1976: 4: 43-50, 4, Mtt.t.s, D. H,: Whither infortned consent? /, Am. Med. Assoc. 1974: 229: 305-310,

Syntfjosiinn on ethical issues 261 5, RL'T,STEIN, D , D , : The ethical design of ltutnan experitnents, ]ti: FREUND, P , A, (ed,): Experimentation with human subjects. George Braziller, New York 1970, pp, 38,3^01, 6, VEAfctt, R, M,: Ethical ptiticiples iti medical experimentation. In: Rivt.tN, A, M, & TIMI'.\NE, P , M , (eds,): Ettiical and legal issues of sociat experimentation. The

Btookittgs Iti.sliltition, Washington, D,C, 1975, pp, 2 1 59, 7. Ationytitous: Biotnedical research: A revised code of ethics. l\'HO Chronical 1976: 30: 360-362, 8, Detital ethics and elitiieal ttials. Editorial, Ilr. Dent. J. 1975: 138: 41-42,

Social sciences research: ethical and policy implications LOIS K . COHEN National Institute of Dental Research, Bethesda, Maryland, U.S.A. ABSTRACT - Ethical issues are raised about the conduct of social research in ttie detital field particularly with respect lo the use of survey methodology atid aggregated dala. Problems a.ssociated with respotident idetilifiers, open-ended atid probitig c|uesliotiitig, privacy of sitbject-tnatter, eottmiitnity contattiination atid burden, grou]o stereotyping, knowledge of law violatioiLs, tnis-use of data banks, re-use of data, effects of disclostirc, and refertal for treattnetit are discussed. The natural atid the cotitrived social experitnents are reviewed as well as the issue of tieeded research on the effects of regulalion on seienee and on the protection of privacy.

This paper is an attempt to examine the practices and policies which protect human subjects in the course of social science inquiries related to dentistry. The social sciences, as distinct from the behavioral sciences, are disciplines which aim to discover the structure of society, to identify forces that hold groups together or weaken their ties, and to learn the conditions which transform social life. The primary disciplines are sociology, cultural anthropology, political science, and economics, but aspects of geography, history, and law fit into the social science category as well. SOCIAL SURVEYS The method of inquiry most frequently employed by social scientists is probably the survey, a method used to gather information about a large population by sampling a few of its people. Even the most rigorously designed survey entails some risks. One risk is the identification of individual respondents

and their views or behaviors at any stage of data collection, coding, processing, or reporting. It may appear to be easy to state at the beginning of a survey encounter that the responses will be reported in aggregate, and that no pcnsonal reference or separate identifying codes will be retained. But the ability of the investigator to assure that private information will not become public depends on how much siu'veillancc and control the principal investigator has over the staff of support personnel who handle, code, process and analyze the data. Unique identifiers or information which will permit someone else to identify a respondent, such as code numbers, photographs, names and addresses, present problems for record-keeping and retention. It is clear that there is a need to protect against unauthorized access to records during phases of data acquisition, processing, and storage, but perhaps the danger is not so obvious when less than fully-trained professionals are given access to such

Overview of ethical aspects of clinical studies.

258 HOROWITZ are now receiving careful scrutiny by human experimentation committees, composed of both scientists and lay people. As social and behav...
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