The retraction by the research subject of his or her free and informed consent: an historical-ethical explanation
Gonzalo Herranz, Departamento de Bioética, Universidad de Navarra
Intervención en Conferencia internacional de la UNESCO
París, 1998
Gonzalo Herranz (Spain/Espagne)
Professor of Medical Ethics/Professeur d’Éthique Médicale
School of Medicine, University of Navarre/Faculté de Médecine, Université de Navarre
Introduction
It is a well known fact that a non-negligible proportion of biomedical research projects fail to reach an adequate level of scientific quality and are lost as valid elements for the building of basic science or the definition of acceptable clinical practice. One significant source of research failure is the occurrence of protocol violations1 on the part of the research subjects. They more or less deliberately retract the promise they made when granted their consent.
It is not easy to offer accurate data on this phenomenon. Its intensity shows wide variations, from irretrievable spoiling of whole research projects when a substantial number of patients drop-out prematurely and without explanation, to the mere blemishes, such as occasional lapses from treatment or evaluation schedules, which disfigure an otherwise correct clinical trial. Although it is said that the subject’s non-compliance or withdrawal constitute everyday problems, its incidence depends apparently on a number of factors such as the project’s design and duration, its target population, the incidence of side-effects, the lack of improvement with the experimental treatment, dissatisfaction with researchers or difficulties in communication. From 15% to 40%, occasionally more, research subjects fail to adhere to the experimental procedure, with the resulting untoward outcomes of reduced between-group differences, increased sample size requirements, loss of statistical strength, and increased cost.
The question I would like to discuss is this: Is there an explanation for such a deviant conduct? In other words, how a subject, after seriously granting his or her free and informed consent to the protocol requirements, behaves so inconsistently with his or her own promises?
From Nuremberg to Helsinki
In my view, there is a close relationship between the lax behavior of many research subjects and the loose rules for consent retraction contained in the most influential ethical guidelines on human experimentation: the (1975) Declaration of Helsinki II2 and the legal and ethical directives derived from it. Parenthetically, the (1964) Declaration of Helsinki I3, when it deals with the subject’s consent in clauses II.1. and III.3. does not make any reference to consent retraction neither to the freedom to withdraw. Apparently, those guidelines have failed to shape the participation of human subjects in biomedical research as a moral enterprise, free and, at the same time, responsible and committed. Instead, they have favored an unconcerned attitude towards research, resulting at last in an over-autonomous and carefree type of subject.
But in the beginning it was not so. To understand the history of the subject’s retraction from informed consent, I think it is worth considering for a moment the changes the research subject’s ethos sustained when the Code of Nuremberg4 was absorbed in the Declaration of Helsinki.
Let us compare the clauses of both documents on the termination of the subject’s participation in research. They are as follows:
# 9 of Nuremberg: During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical and mental state where continuation of the experiment seems to him to be impossible.
# I.9 of Helsinki: In any research on human beings, each potential subject (...) should be informed that he or she (...) is free to withdraw his or her consent to participation at any time
The differences are so obvious that one can speak of a Nuremberg type and a Helsinki type of informed consent to research. Surprisingly, the Helsinki type of consent does not create any new ethical condition in the subject. No commitment has been acquired by him or her, since he or she remain equally free to continue in the experiment as they were free to enter into it before granting their consent. The dynamic of the Helsinki type of consent leads to an ever increasing “liberalization” of the subject’s role in research. In the United States, for example, the Belmont Report5 and all the subsequent federal regulations6 include among the general conditions for informed consent the following requirement: to provide each subject with a statement that “the subject may discontinue participation in any time without penalty or loss of benefits to which the subject is otherwise entitled”. In 1990, some British guidelines are still more indulgent: the subjects must be told that they “will be free to withdraw at any time without giving a reason and without in any way impairing their care”7.
By contrast, the consent of the Nuremberg type makes a difference. The research subjects, free as they are to consent or to refuse their participation in the research project, once their consent to the procedure has been given, are in a new ethical ground, because they seriously take their role as subjects. They remain free, but decide to be no more absolutely free, because they understand their free and informed consent as a commitment to remain in the experiment and not to bring it to an end until they have some sound reason, as that of reaching a mental or physical state where continuation of the experiment seems to them to be seriously inconvenient.
In essence, the Nuremberg type of consent merges freedom with responsibility and commitment. On the part of the subject, at least in theory, such consent is consistent with a high degree of ethical maturity and with a deeper understanding of the value and purpose of the scientific endeavour, with its inherent cost of reasonable risk, of effort, endurance and self-sacrifice. The Helsinki type of consent is strongly biased towards liberty and does not pretend to establish any bond beyond the fleeting willingness of the moment. In contrast to the Nurembergian subject who has a self-imposed duty to justify his or her withdrawal from the experiment on a serious reason (the impossibility, subjective at least, to continue with it), the Helsinkian subjects have no obligation to justify their dropping-out. They are entitled to withdraw nonchalantly, without a word, by simply disappearing from the stage.
An ethical explanation
Curiously, only a small number of authors have studied the ethics of the research subject’s retraction. More surprisingly, no reference is made by them to the Nuremberg doctrine. Its #9 has been systematically ignored or at least has received very scant comment.
The bioethicists of the early times thought that, after a reasonably free and adequately informed consent for research was asked for and granted, a new relationship was tied between researcher and subject. In Paul Ramsey’s opinion, for example, such relationship tends to stay in time, establishes a voluntary association of free men in a common cause, follows a cardinal canon of loyalty, and unites them in the great human adventure of searching for cure of all man’s diseases8.
Levine9 asks himself that once the research subjects have begun to serve in such a role, can they be construed to have made a commitment? He suggests that agreement to participate in research is a form of promise. In his view, promises may be broken ethically only by justifying reasons, not simply at the whim of the promisor. He rejects the possibility of punishing withdrawal, not only on account of respecting the subject’s freedom, but also to prevent the serious hazards for the subject’s health derived from an abrupt or unfriendly withdrawal.
Lisa Newton has also dealt with the question on whether agreement to participate in research can be held or not as a promise that must be kept10. She criticizes the current research guidelines, where autonomy –the voluntariness to participate– is the only factor that has any weight. This constitutes a very strange situation, in view of the fact that research is not carried out for fun, for free, or (only) for the enhancement of the reputation of the investigator, but for the real increase in knowledge in areas of vital importance. When a subject withdraws, the research is necessarily rendered less significant and reliable, and the benefits expected from the human, technical and financial resources committed to it, are spoiled or lost.
A possible solution
It could be concluded that if the freedom to withdraw at any time without giving a reason is not counterbalanced with a sensible and respectful warning to the subject on the scientific, social and economic consequences of premature or unjustified withdrawal, then the whole ethical process of securing consent becomes awfully weakened. The autonomy of the research subject must mix freedom with commitment. Every human being of adult years and sound mind would become at least perplexed if he were told that his serious and free informed acceptance to participate in a sound research project is a blank and uncompromising decision. It is not easy for him to accept that willful withdrawal and faulty compliance are deeds as good as the adherence to the protocol. It could seem to him that biomedical research is more on the side of a child’s game than in an adult business.
It is necessary, in my opinion, to reintroduce in the contents of the information given to elicit the research subject’s consent a reasoned and realistic account of the consequences of unjustified withdrawal and poor compliance. Only then is the research subject in the correct condition to decide, because he can conjugate knowledge, freedom and responsibility. That is the message that Nuremberg has been sending us for the past 50 years. In my view, a change must be introduced in the Basic Principle 9 of the current version of the World Medical Association’s Declaration of Helsinki, to include among the elements about which the research subject must be informed the consequences derived from poor compliance or unjustified withdrawal. In this way, the subject’s consent becomes more rich in freedom and conscientiousness.
Bibliography
(1) Pocock SJ. Clinical Trials. Chichester: John Wiley & Sons, 1993: 172-186.
(2) World Medical Association. Declaration of Helsinki: Recomendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects (September 1989). Handbook of Declarations. Ferney-Voltaire: World Medical Association, 1995: 17 C.
(3) World Medical Association. Declaration of Helsinki: Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects (June 1964). N Engl J Med 1964;261:473.
(4) United States Adjutant General’s Department. Trials of War Criminals Before Nuremberg Military Tribunals Under Control Council Law No. 10. The Medical Case. Washington: U.S. Government Printing Office, 1947. Vol.2, pp 181-183. Reproduced in Ladimer I, Newman RW, eds. Clinical Investigation in Medicine. Legal, Ethical and Moral Aspects. An Anthology and Bibliography. Boston: Boston University Law-Medicine Research Institute, 1963: 116-119.
(5) National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report. Ethical principles and Guidelines for the Protection of Human Subjects of Research. DHEW Publication No. (OS) 78-0012. Washington, 1978.
(6) Department of Health, Education, and Welfare. Protection of Human Subjects: Policies and Procedures. Fed Register 1973;38:31738-31749.
(7) Royal College of Physicians. Research Involving Patients. A Report. London: Royal College of Physicians, 1990: 17.
(8) Ramsey P. The patient as Person. New Haven: Yale University Press, 1970: 1-11.
(9) Levine RJ. What Should Subjects Be Told About Withdrawing from a Protocol? IRB: A Review of Human Subjects Research 1981;3(9): 9-10.
(10) Newton L.H. Agreement to Participate in Research: Is That a Promise? IRB: A Review of Human Subjects Research 1984;6(2):7-9.