Responsibility in Investigations on Human Subjects

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IN INVESTIGATIONS ON Reprinted from the Report of the Medical Research Council

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Responsibility in Investigations on Human Subjects STATFMENT BY THE MEDICALM EARCH CfXJNCIL During the last fifty years, medical knowledge has advanced more rapidly than at any other period in its history. New understandings, new treatments, new diagnostic procedures and new methods of prevention have been, and are being, introduced at an ever-increasing rate; and if the benefits that are now becoming possible are to be gained, these developments must continue. Undoubtedly the new era in medicine upon which we have now entered is largely due to the marriage of the methods of science with the traditional methods of medicine. Until the turn of the century, the advancement of clinical howledge was in general confined to that which could be gained by observation, and means for the analysis in depth of the phenomena of health and disease were seldom available. Now, however, procedures that can safely, and conscientiously, be applied to both sick and healthy human beings are being devised in profusion, with the result that certainty and understanding in medicine are increasing apace. Yet these innovations have brought their own problems to the clinical investigator. In the past, the introduction of new treatments or investigations was infrequent and only rarely did they go beyond a marginal variation on established practice. Today, far-ranging new procedures are commonplace and such are their potentialities that their employment is no negligible consideration. As a result, investigators are frequently faced with ethical and sometimes even legal problems of great difficulty. It is in the hope of giving some guidance in this difficult matter that the Medical Research Council issue this statement. A distinction may legitimately be drawn between procedures undertaken as part of patient-care which are intended to contribute to the benefit of the individual patient, by treatment, prevention or assessment, and those procedures which are undertaken either on patients or on healthy sdbjects solely for the purpose of contributing to medical knowledge and are not themselves designed to benefit the particular individual on whom they are performed. The former fall within the ambit of patient-care and are governed by the ordinary rules of professioqal conduct in medicine; the latter fall within the ambit of investigations Important considerations flow from this distinction. Procedures contributing to the benefit of the individual In the case of procedures directly connected with the management of the condition in the particular individual, the relationship is essentially that between doctor and patient. Implicit in this relationship is the willingness on the part of the subject to be guided by the judgment of his medical attendant. Provided, therefore, that the medical attendant is satisfied that there are reasonable grounds for believing that a particular new procedure will contribute to the benefit of that particular patient, either by treatment, prevention or increased understanding of his case, he may assume the patient's consent to the same :n as to whel I and it may t,: ine this. Beca ment he consti hich aims to pi. he latter are i: ion feature of a nteer in the f 5 Id be clearly I :nt of the subji ture and cons btained by UI estigator as in I persons is of j lians of minor of no partic

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extent as he would were the procedure entirely established practice. It is axiomatic that no two patients are alike and that the medical attendant must be at liberty to vary his procedures according to his judgment of what is in his patients’ best interests. The question of novelty is only relevant to the extent that in reaching a decision to use a novel procedure the doctor, being unable to fortify his judgment by previous experience, must exercise special care. That it is both considerate and prudent to obtain the patient’s agreement before using a novel procedure is no more than a requirement of good medical The second important consideration that follows from this distinction is that it is clearly within the competence of a parent or guardian of a child to give permission for procedures intended to benefit that child when he is not old or intelligent enough to be able himself to give a valid consent. A category of investigation that has occasionally raised questions in the minds of investigators is that in which a new preventive, such as a vaccine, is tried. Necessarily, preventives are given to people who are not, at the moment, suffering from the relevant illness. But the ethical and legal codsiderations are the same as those that govern the introduction of a new treatment. The intention is to benefit an individual by protecting him against a future hazard; and it is a matter of professional judgment whether the procedure in question offers a better chance of doing so than previously existing measures. In general, therefore, the propriety of procedures intended to benefit the individual-whether these are directed to treatment, to prevention or to assessment-are determined by the same considerations as govern the w e of patients. At the frontiers of knowledge, however, where not only are many procedures novel but their value in the particular instance may be debatable, it is wise, if any doubt exists, to obtain the opinion of experienced colleagues on the desirability of the projected procedure. Control subjects in investigations of treatment or prevention c.-..Jy.-..a* + advanced by the method of the controlled clinical trial. Over recent years, the development of treatment and prevention has been waiting, as in the past, on the slow accumulation of general experience to determine the relative advantages and disadvantages of any particular measure, it is now often possible to put the question to the test under conditions which will not only yield a speedy and more precise answer, but also limit the risk of untoward effects remaining undetected. Such trials are, however, only feasible when it is possible to compare suitable groups of patients and only permissible when there is a genuine doubt within the profession as to w h i c wYO treatments or preventive regimes is the bejteL In these circumstances it is justifiable to give to a proportion of the patients the novel procedure on the understanding that the remainder receive the procedure previously accepted as the best. In the case when no effective treatment has previously been devised then the situation should be fully explained to the participants and their true consent obtained. Such controlled trials may raise ethical points which may be of some difficulty. In general, the patients participating in them should be told frankly that two different procedures are being assessed and their co-operation invited. Occasionally, however, to do so is contra-indicated. For example, f o awaken patients with a possibly fatal illness to the existence of such doubts about have arisen as to v suggestion and it m: to determine this. E of the Council that without question ih trial is under an obli any treatment he o be in the better inter Procedures not of dir The preceding coi subjects which aims tl values can be recogn whether the latter a that has no relevance illness, such as met; persons to some char it may be necessary function and its react The common feature to the particular indi must volunteer in tht It should be cleai afford no defence in that the law protects In investigations of tl true consent of the s i By true consent i: of the nature and c, consent obtained by particular care is nec to the investigator as The need for obtai been generally recog constitutes such evide himself in the preser by other evidence tha is of little value. . The situation in I disordered persons is I and guardians of mir which are of no par of harm. Whilst En

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effective treatment may not always be in their best interest; or suspicion may have arisen as to whether a particular treatment has any effect apart from suggestion, and it may be necessary to introduce a placebo into part of the trial to determine this. Because of these and similar difficulties, it is the firmopinion of the Council that controlled clinical trials should always bal an ned and supervjsed-by a group of inves*Jorsan&nzer b~ an individual a l o 3 . It goes without question €hWXinrdoctor taking part in such a collective controlled trial is under an obligation to withdraw a patient from the trial, and to institute any treatment he considers necessary, should this, in his personal opinion, be in the better interests of his patient. Procedures not of direct benefit to the individual The preceding considerations cover the majority of clinical investigations. There remains, however, a large and important field of investigations on human subjects which aims to provide normal values and their variation so that abnormal values can be recognized. This involves both ill persons and ' healthy ' persons, whether the latter are entirely healthy or patients suffering from a condition that has no relevance to the investigation. In regard to persons with a particular illness, such as metabolic defect, it may be necessary to know the range of abnormality compatible with the activities of normal life or the reaction of such persons to some change in circumstances such as an alteration in diet. Similarly it may be necessary to have a clear understanding of the range of a normal function and its reaction to changes in circumstances in entirely healthy persons. The common feature of this type of investigation is that it is of no direct benefit to the particular individual and that, in consequence, if he is to submit to it he must volunteer in the full sense of the word. It should be clearly understood that the possibility or probability that a particular investigation will be of benefit to humanity or to posterity would af€ord no defence in the event of legal proceedings. The individual has rights that the law protects and nobody can infringe those rights for the public good. In investigations of this type it is, therefore, always necessary to ensure that the true consent of the subject is explicitly obtained. By true consent is meant consent freely given with proper understanding of the nature and consequences of what is proposed. Assumed consent or consent obtained by undue influence is valueless and, in this latter respect, particular care is necessary when the volunteer stands in special relationship to the investigator as in the case of a patient to his doctor, or a student to his The need for obtaining evidence of consent in this type of investigation has been generally recognized, but there are some misunderstandings as to what constitutes such evidence. In general, the investigator should obtain the consent himself in the presence of another person. Written consent unaccompanied by other evidence that an explanation has been given, understood and accepted is of little value. The situation in respect of minors and mentally subnormal or mentally disordered persons is of particular difficulty. In the strict view of the law parents and guardians of minors cannot give consent on their behalf to any procedures which are of no particular benefit to them and which may carry some risk of harm. Whilst English law does not f i x any arbitrary age in this context,

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it may safely be assumed that the Courts will not regard a child of 12 years or under (or 14 years or under for boys in Scotland) as having the capacity to consent to any procedure which may involve him in an injury. Above this age the reality of any purported consent which may have been obtained is a question of fact and as with an adult the evidence would, if necessary, have to show that irrespective of age the person concerned fully understood the implications to himself of the procedures to which he was consenting. In the case of those who are mentally subnormal or mentally disordered the reality of the consent given will fall to be judged by similar criteria to those which apply to the making of a will, contracting a marriage or otherwise taking decisions which have legal force as well as moral and social implications. When true consent in this sense cannot be obtained, procedures which are of no direct benefit and which might carry a risk of harm to the subject should not Even when true consent has been given by a minor or a mentally subnormal or mentally disordered person, considerations of ethics and prudence still require that, if possible, the assent of parents or guardians or relatives, as the case may be, should be obtained. Investigations that are of no direct benefit to the individual require, therefore, that his true consent to them shall be explicitly obtained. After adequate explanation, the consent of an adult of sound mind and understanding can be relied upon to be true consent. In the case of children and young persons the question whether purported consent was true consent would in each case depend upon facts such as the age, intelligence, situation and character of the subject and the nature of the investigation. When the subject is below the age of 12 years, information requiring the performance of any procedure involving his body would need to be obtained incidentally to and without altering the nature of a procedure intended for his individual benefit. All who have been concerned with medical research are aware of the impossibility of formulating any detailed code of rules which will ensure .that irreproachability of practice which alone will suffice where investigations on human beings are concerned. The law lays down a minimum code in matters of professional negligence and the doctrine of assault. But this is not enough. Owing to the special relationship of trust that exists between a patient and his doctor, most patients will consent to any proposal that is made. Further, the considerations involved in a novel procedure are nearly always so technical as to prevent their being adequately understood by one who is not himself an expert. It must, therefore, be frankly recognized that, for practical purposes, an inescapable moral responsibility rests with the doctor concerned for determining what investigations are, or are not, proposed to a particular patient or volunteer. Nevertheless, moral codes are formulated by man and if, in the ever-changing circumstances of medical advance, their relevance is to be maintained, it is to the profession itself that we must look, and in particular to the heads of departments, the specialized Societies and the editors of medical and scientific journals. In the opinion of the Council, the head of a department where investigations on human subjects take place has an inescapable responsibility for ensuring that _- practice by those under his direction is irreproachable. , In the same way 1 themselves that supp to ensure that the : So specialized has general can rarely de; L particular type of invc specialized in this bri opinion on the justifi I every branch of medi that the profession in …