This Week in BMJ | Editor's Choice | Press releases | Advertisement details

Education & debate Saturday 12 April 1997

Informed consent in medical research

Is the demand for informed consent absolute? In the first of this pair of articles a professor of medical ethics argues that the principle of informed consent to participate in medical research is fundamental if patients are competent volunteers. Consent is not needed when patients are incompetent to give it (young children, unconscious patients, etc); when research uses only medical records; and when stored human tissue is used. Before publishing the results of such research, however, journals must ensure that certain minimal conditions are complied with. In the second article an oncologist argues that journals should be free sometimes to publish research in which patients have not given fully informed consent. He points to the practical difficulties of obtaining fully informed consent from all patients and, because of this, poor recruitment into trials. He suggests that a helpful approach would be to obtain "blanket" approval at the outset of treatment for inclusion in studies that might be in progress during the patient's illness - accepting that the doctor would always act in good faith and be prepared to explain treatments at any time.

Journals should not publish research to which patients have not given fully informed consent - with three exceptions

Len Doyal

See Papers p 1071, 1077, Education & debate 1111, Personal view 1134

Fifty years ago, the immorality of which clinicians are capable in the name of medical research was made clear at Nuremberg.(1) The code of research ethics which was articulated to judge them was uncompromising about the importance of informed consent in preventing such outrages against humanity from occurring again.(2) Volunteers competent to do so should choose whether or not to participate in medical research after being given correct information about the "nature, purpose, and duration of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment." Participants should not be subject to "force, fraud, deceit, duress ... or coercion." (3)

It took almost 30 years for many medical researchers to accept the full implications of this doctrine of informed consent. The prevailing attitude during this period was that the Nuremberg code primarily applied to Nazis and similar fanatics.(4) Such optimism became quickly tarnished in the late 1960s and '70s with the recognition that in the United States and the United Kingdom, for example, horrors continued to be inflicted on vulnerable groups in the name of medical progress. By the late '80s it was obvious that this problem knew no national boundaries.(5)

As a result, the professional and legal regulation of medical research has been made more rigorous, with the right of volunteers to informed consent remaining at its heart.(5) Yet some now argue that things have gone too far and that full disclosure of information to research subjects who are competent may not always be warranted.(6) Local research ethics committees have allowed research to proceed with variable standards of informed consent, and journals have published the results of studies where no consent was obtained.(7-10)

In this paper I oppose such moves through arguing that, with three exceptions, the principle of informed consent to participate in medical research should remain inviolate. The focus of discussion will be on competent patients who volunteer for either therapeutic or non-therapeutic research. No one questions the strict right of healthy volunteers to informed consent. I will outline a draft editorial policy for medical journals for the rejection of research where informed consent has not been appropriately obtained. Interestingly, had it been adopted at least three papers would not have appeared or be appearing in the BMJ.(8-10)

The moral and legal importance of informed consent

Patients who volunteer for medical research can face risks over and above those normally encountered in their everyday lives. The degree of such risks can often be known only after the research has been completed. Professional pressure can lead researchers to underestimate inconvenience and hazard, misleading volunteers in the process.(11) Volunteers must have accurate and detailed information about potential risks in order to protect themselves. Equally, for them to weigh up their personal willingness to face such hazards against whatever motivations they might have for participation, volunteers must also have adequate information about goals, methods, and possible benefits of the research.

To deny volunteers such information is a clear breach of their moral rights. Our abilities to deliberate, to choose, and to plan for the future are the focus of the dignity and respect which we associate with being an autonomous person capable of participation in civic life. Such respect is now widely regarded as essential for good medical care and should dominate the practice of medical research.(12) This is especially important in the case of volunteers who are patients and who, despite their vulnerability, often accept extra inconvenience and risk in the public interest, sometimes with no potential benefit to themselves.

This moral emphasis on informed consent is reflected by the law.(13) Legally, a battery is committed if volunteers who participate in medical research are touched without being provided with adequate information about what the researchers propose to do and why. The specific circumstances under which different interventions under investigation will be offered should also be communicated (for example, whether the participants will be randomised). Researchers will be negligent if they do not adhere to their professional duty to communicate adequate information about risks. Here the standard of disclosure is stronger than for ordinary treatment. Prudent researchers should warn volunteers of risks in the detail that any "reasonable person" would want, and researchers should recognise and attempt to satisfy specific informational needs of individual volunteers (such as those relating to language or employment).

In short, unless they respect the right of volunteers to informed consent, researchers should be morally and, where possible, legally censured.

Arguments against informed consent

Despite the preceding arguments, some researchers maintain that there is now too much emphasis on informed consent for patient volunteers for medical research. Three reasons are usually given, although in practice they are often combined.

Firstly, patient volunteers might be distressed by detailed information about aims, methods, and risks.(14) To weigh up the balance of potential benefits over risks will entail a good understanding of both, and patients may discover for the first time how poor their prognosis really is. Further, patients may realise the full implications of randomisation - that neither they nor their doctor will know which intervention they will receive and that their doctor does not know what the best treatment is. Such patients may not want full disclosure of information but still wish to be included in trials thought by their clinicians to be in their best interests. To force unwanted information on them is needlessly cruel, may compromise recovery, and may keep patients from entering trials in sufficient numbers to make such trials possible.(15) Clinical researchers, therefore, should have more discretion about how much detail to communicate.

Secondly, while informed consent may be necessary for studies where there are considerable risks, it does not follow that it should be obtained for research where invasiveness and risks are negligible. This is especially so if the requirement for informed consent might jeopardise methodological rigour.(16) For example, knowledge of the aims of some research might bias responses to related therapies or questionnaires. Awareness of randomisation - including the possibility of inclusion in the placebo arm of an investigation - can equally confound results through biasing the attitudes and behaviour of volunteers.(17) If the research is worth doing and the risks are minimal then it is surely being obsessive to continue to insist on full disclosure of information.

And thirdly, the interests of the public in medical progress will be undermined by too much emphasis on the rights of individuals. Existing effective clinical interventions are based on the willingness of previous patient volunteers to participate in medical research. Thus it can be argued that patients receiving such care have a duty to promote further research for future generations. Yet we know that in the face of full disclosure of aims, methods, and risks of research, patients might not do their duty to serve the public interest - sometimes making the research impossible.(18) A more limited disclosure of information about the research might encourage more patients to volunteer.

It follows from these reasons that local research ethics committees should implement the clause in the Helsinki Declaration which states that there may be circumstances in which informed consent is not required.(19) Similarly, journals should publish the results of medical research approved by committees adopting this lower standard of disclosure.

Why these arguments should be rejected

Each of these arguments is flawed. Potential for distress is not a sufficient reason to deny patient volunteers full disclosure of information. Such arguments are extensions of a tired and discredited paternalism. If volunteers discover that information has been withheld, their distress and sense of betrayal may be far greater than that engendered by learning the truth.(20) This will particularly be so if participation has interfered with the achievement of other personal goals about which the researchers knew nothing. In any case, surveys have indicated that in ordinary therapeutic situations patients - even those who are terminally ill - want accurate information and are not necessarily upset by it. There is no reason to believe that this same desire does not apply all the more so to participants in medical research.(21-23)

Anticipated negligibility of risks does nothing to abate the right of patient volunteers to information about them. An acceptable hazard for one may be rejected by another.(24) Even minimally risky interventions (venepuncture and questionnaires, for example) can have unwanted side effects (bruising and depression). Equally, it is sometimes argued that minimal risks might justify the randomisation of patient volunteers without their consent (for example, in studies where one group is unknowingly used as a control). Yet some patients have been outraged to discover that they were used in a trial without their knowledge.(25) The fact that they faced small risks in the process was not the point. Aside from the potential distress to volunteers who discover that they were denied informed consent, such denial also jeopardises the reputation of the researcher, along with the enterprise of medical research. If patients feel that they might be inadequately informed, this fact in itself may dissuade them from participating in research.(26) The moral price of keeping volunteers in ignorance is too high and against the public interest.

It is unlikely that any of these arguments against informed consent would be taken seriously unless they were linked to the further belief that it is acceptable to compromise individual rights if the public interest demands it. Such arguments amount to justifying exploitation of individuals and ignore the objective harm which is inflicted upon them by disrespect for their autonomy. Harm of this kind should not be equated with physical damage or emotional distress and is therefore not affected by the level of risk of either. Rather it is an attack on human dignity: the harm is to the moral integrity of the uninformed volunteer.(27) Accepting the unconscionability of inflicting such harm in the public interest may well mean that some potentially fruitful medical research cannot be done because of the problem of under-recruitment. So be it; this is the price we pay for living in a society which is morally worth preserving, one where we treat each other with respect and where we take human rights seriously.

Despite the discretion offered by the Helsinki Declaration to do otherwise, research ethics committees should be rigid in their application of the principle of informed consent to competent patients asked to participate actively in research.(19) They should not approve research proposals which breach it, and journals should not publish the results of such research, even if it has been so approved.

When informed consent is not necessary

The demand thus far has been that competent patients should be protected from exploitation by being allowed to evaluate for themselves whether or not participation is consistent with their best interests. Sometimes, however, research that is of potential importance should be permitted without the requirement of informed consent. Generally speaking, this will either be when patients are unable to provide consent because of their incompetence or when, for practical reasons, consent is difficult or impossible to obtain. Research without informed consent should be allowed to proceed and be published only in three circumstances.

Incompetence to give informed consent
Firstly, some categories of patient volunteers will be incompetent to give informed consent - for example, young and immature children, patients with learning disabilities, and unconscious or semiconscious patients in intensive care or accident and emergency.(28-31) To exclude them from participation in research specific to their conditions and treatments might deprive both them and others of potential benefit. To allow such research is not an affront to their human dignity if they really are incompetent to provide informed consent. We have no moral obligation to respect others in ways that are practically impossible. However, the levels of autonomy that patients who are thus incompetent do possess should still be respected (for example, if they resist participation then it should not be forced), and their vulnerability demands that they should be protected from harm (for example, if the research can be done on a less vulnerable group then it should be). Local research ethics committees should have the discretion to approve both therapeutic and non-therapeutic research involving incompetent patients, and journals should have the discretion to publish the results under certain conditions.(32) Minimally, it should be clear that:

There are important potential benefits from the research;

The research cannot be completed with patients or healthy volunteers who are able to provide informed consent;

Participation in therapeutic research will entail risks which are minimal in relation to the standard available treatment. For non-therapeutic research, this level should not exceed that associated with everyday life or minimally invasive therapeutic interventions;

Informed consent in research with incompetent children will always be obtained from someone with parental authority;

Informed "assent" for incompetent adults will ordinarily be sought from appropriate advocates (such as relatives) provided with the same information which would have been given to the patient if competent;

Such "assent" may not be required for therapeutic research with adults when it is impossible to obtain and when there is minimal risk, again, by comparison with standard available treatment (for example, research in intensive care and in accident and emergency medicine);

The purpose and methods of the research are explained after its completion to participants who were unable to consent to it but then regained their competence to do so. This does not amount to retrospective consent.

Conditions on use of medical records
Secondly, we have seen that informed consent should always be obtained from competent patients who are actively involved in medical research - where they either receive or are denied some form of intervention under investigation. However, some research occurs without such involvement and entails only the use of medical records. Normally, patients should give their explicit consent for their records to be accessed for this purpose; they should have received appropriate information about who will use them and why and about how confidentiality will be maintained. Yet suppose that the research is epidemiological, that patients might benefit from it in the long term but that for practical reasons informed consent cannot be obtained. Also assume that no further consequences should follow for such patients - for example, that there is no intent to ask the patient to receive or be denied any intervention as a result of the research. In spite of the arguments already outlined in favour of informed consent, should we allow this kind of research to proceed without it?(33)

The moral balance here is a fine one. If such research proceeds, there is little doubt that through not obtaining consent a moral wrong is being done. The issue is the degree of this wrong in light of the potential benefit which can follow for the patient - provided that confidentiality is maintained and no further active involvement is expected. Clearly, the public interest will also be served. This moral tension will be minimised through better informing patients about the importance of medical research and the desirability at times for their records to be accessed by researchers.(34) They should also be reassured about confidentiality and given the opportunity to decline. Yet these steps have not widely been taken. The most that can be said for now is that the moral balance favours local research ethics committees having the discretion to approve such research and journals to publish the findings. Minimal conditions are:(35- 36)

Access to the clinical record is essential for the completion of the research and consent is not practicable;

The research is of sufficient merit;

The research pertains to some future planning, preventive, or therapeutic initiative which may benefit the patients whose records are studied;

Where possible, identifiers have been removed from the parts of the record to which researchers have access; where not, patients will not be identifiable when the results are made public;

It is not anticipated that contact will be made with the patients as a result of research findings;

Access is restricted to specific categories of information which have been approved by the local research ethics committee;

Permission is obtained from the clinician responsible for the patient's care and, depending on the type of record and access concerned, the person responsible for its administration;

Researchers who are non-clinicians are formally instructed about their duty of confidentiality. They must also have a clinical supervisor who formally accepts professional responsibility for any breach of confidentiality that may occur.

Stored tissue from anonymous donors
The third exception where research is permissible without informed consent concerns the use of human tissue which is the byproduct of surgical intervention or other stored clinical material (for example, frozen serum). Such tissue or materials may have been recently removed and stored, or archived for considerable time. Where the link between the identity of patients and their stored material is broken, research may be conducted without further explicit consent, always assuming that it conforms to other moral principles governing good research.(37) Where the identity of the patient might become known to the researcher, the local research ethics committee must review and agree the research. Here again, the moral balance is a delicate one.(38) Consent need not necessarily be obtained, provided that the committee is satisfied that patients (if alive) might at some time derive benefit from the research under consideration, that there is no intent to further involve them in the research, and that adequate standards of confidentiality will be maintained. In general, similar rules apply as have been outlined above on the use of clinical records without consent, and journals should only publish accordingly.

This third exception does not apply to research into the genetic causes of or predispositions to disease where research materials have not been strictly anonymised and where there is any possibility of further patient contact. Here informed consent should always be obtained and counselling offered to people who are potential sources of such materials. If not, the results of such studies should not be published.(39)

Conclusion

The suffering and indignity which some medical research has visited upon unsuspecting and vulnerable patients must never be allowed to happen again. To ignore the lessons of the past through not taking the right of informed consent seriously is to insult the memory of those who paid such an unacceptably high price in the name of medical progress. This paper has argued that local research ethics committees and professional and academic journals like the BMJ should not approve or publish research which violates this right. Three exceptions have been outlined. Further work is required, however, to clarify the moral foundations of these exceptions, including the nature and scope of the duty of individuals to act in the public interest. For now, the reasonably strict interpretation of the principle of informed consent developed here should be seen to be consistent with such interest even if this means that some potentially worthwhile research is not allowed to proceed or be published. In the words of Hans Jonas: "Society would indeed be threatened by the erosion of those moral values whose loss, possibly caused by too ruthless a pursuit of scientific progress, would make its most dazzling triumphs not worth having." (30-40)

I thank Lesley Doyal, Claire Foster, Richard Nicholson, Daniel Wilsher, and Jennian Geddes.

References

1 Leaning J. War crimes and medical science. BMJ 1996;313:1413-5.

2 Appelbaum P S, Lidz C W, Meisel A. Informed consent: legal theory and clinical practice. New York: Oxford University Press, 1987:212.

3 Nuremberg Code. BMJ 1996;313:1448.

4 Rothman D J. Ethics and human experimentation: Henry Beecher revisited. N Engl J Med 1987;317:1195-9.

5 McNeill P M. The ethics and politics of human experimentation. Cambridge: Cambridge University Press, 1993:17-36, 53-115.

6 Tobias J S, Houghton J. Is informed consent essential for all chemotherapy studies? Eur J Cancer 1994;30A:907-10.

7 Harries H J, Fentem P G H, Tuxworth W, Hoinville G W. Local research ethics committees. J R Coll Physicians 1994;28:150-4.

8 McArdle J M C, George W D, McArdle C S, Smith D C, Moodie A R, Hughson A V M, et al. Psychological support for patients undergoing breast cancer surgery: a randomised study. BMJ 1996;312:813-7.

9 Dennis M, O'Rourke S, Slattery J, Staniforth T, Warlow C. Evaluation of a stroke family care worker: results of a randomised controlled trial. BMJ 1997;314:1071-6.

10 Bhagwanjee S, Muckart D, Jenna P M, Moodley P. Does HIV status influence the outcome of patients admitted to a surgical intensive care unit? BMJ 1997;314:1077-81.

11 Evans D, Evans M. A decent proposal - ethical review of clincial research. Chichester: Wiley, 1996:62-7.

12 Doyal L. Needs, rights and the moral duties of clinicians. In: Gillon R, ed. Principles of health care ethics. Chichester: Wiley, 1994:217-30.

13 Kennedy I, Grubb A. Medical law - texts and materials. London: Butterworths, 1994: 1042-67.

14 Tobias J, Souhami R. Fully informed consent can be needlessly cruel. BMJ 1993;307:1199-201.

15 Collins R, Doll R, Peto R. Ethics of clinical trials. In: Williams CJ, ed. Introducing new treatments for cancer: practical, ethical and legal problems. New York: Wiley, 1992:49-65.

16 Kanis J, Bergmann J. Full consent may bias outcome of trials. BMJ 1993;307:1497.

17 Barer D. Patients' preferences and randomised trials. Lancet 1994;344:688.

18 Baum M. The ethics of randomised controlled trials. Eur J Surg Oncol 1995;21:136-7.

19 Helsinki Declaration. BMJ 1996;313:1448.

20 Bok S. Lying. Brighton, Sussex: Harvester, 1978.

21 Fallowfield L, Ford S. Lewis S. Information preferences of patients with cancer. Lancet 1994;344:1576.

22 Kerrigan D D, Thevasagayam R S, Woods T O, McWelch I, et al. Who's afraid of informed consent. BMJ 1993;306:298-300.

23 Deber R. Physicians in health care management. 7. The patient-physician partnership: changing roles and the desire for information. Can Med Assoc J 1994;151:171-6.

24 Martin D, Meslin E, Kohut N, Singer P. The incommensurability of research risks and benefits: practical help for research ethics committees. IRB 1995 March-April:8-10.

25 Research without consent continue in the UK. Bull Inst Med Ethics 1988; 40:1315.

26 Thornton H M. Breast cancer trials: a patient's viewpoint. Lancet 1992;339:44-5.

27 Crisp R. Medical negligence, assault, informed consent and autonomy. Journal of Law and Society 1990;17:77-89.

28 Mason J K, McCall Smith R A. Law and medical ethics. London: Butterworths, 1994:369-74.

29 Fulford K, Howse K. Ethics of research with psychiatric patients: principles, problems and the primary responsibilities of researchers. J Med Ethics 1993;19:85-91.

30 Dresser R. Mentally disabled research subjects: the enduring policy issues. JAMA 1996;276:67-72.

31 Biros M, Lewis R, Olson C M, Runge J W, Cummins R O, Fost N. Informed consent in emergency research: consensus statement from the coalition conference of acute resuscitation and critical care researchers. JAMA 1995;273:1283-7.

32 Royal College of Physicians. Guidelines on the practice of ethics committees in medical research involving ethics committees. London: RCP, 1996.

33 Wald N, Law M, Meade T, Miller G, Alberman E, Dickenson J. Use of personal medical records for research purposes. BMJ 1994;309: 1422-4.

34 Baum M. New approach for recruitment into randomised controlled trials. Lancet 1993;341:812-4.

35 East London and City Health Authority. Guidelines for the completion of application forms - research ethics committee. London: ELCHA, 1996.

36 Working Group to the Royal College of Physicians Committee on Ethical Issues in Medicine. Independent ethical review of studies involving medical records. J R Coll Physicians 1994;28:439-43.

37 Nuffield Council on Bioethics. Human tissue - ethical and legal issues. London: Nuffield Foundation, 1995:23-9, 39-54.

38 Clayton E W, Steinberg K W, Khoury M J, Thomson E, Andrews L, Ellis Khan M J, et al. Informed consent for genetic research on stored tissue sample. JAMA 1995;242:1786-92.

39 Nuffield Council on Bioethics. Genetic screening - ethical issues. London: Nuffield Foundation, 1993:29-40.

40 Jonas H. Philosophical reflections on experimenting with human subjects. In: Freund P A, ed. Experimentation with human subjects. New York: George Braziller, 1970:1-31.

St Bartholomew's and The Royal London School of Medicine and Dentistry,
Queen Mary and Westfield College,
University of London,
London E1 2AD
Len Doyal, professor of medical ethics

Feedback

To view responses to our request for feedback on various articles regarding informed consent within this issue, please click here.

---

Current contents | Classified ads | Find | BMA | Local editions | Extras
Advice to authors | Reprints | Subscriptions | Feedback | Home

---