Informed Consent and Medical
Research
Fr. Kevin Doran
Originally published in Studies, September 2004
1. The expanding role of research in
healthcare
It is by watching what happens in the course of a treating patients, and by taking note of how various remedies work in various situations, that doctors, nurses, and midwives have always developed their professional skills. Medical research is as old as medicine itself, and is an integral element of good healthcare. In recent times, however, medical research has become more structured and more extensive in its scope.
Scientific knowledge has advanced very rapidly in modern times, and this has impacted greatly on healthcare. The knowledge gained about cellular biology, about genes and chromosomes, and about bacteria and viruses has stimulated the research which has led to new treatments. Research into the eating habits and life-styles of people makes its own contribution. Information is gathered, analysed, evaluated and applied. Alongside this, a whole raft of new technology has made it possible to diagnose and treat illnesses more successfully.
The essential ethos of healthcare is related to the prevention of illness and disease, the care and healing of those who are sick, and the relief of pain. Healthcare is not about research, but rather the reverse. The purpose of medical research is to serve healthcare, and the well-being of the patient must always take precedence. The person must not be lost sight of, either literally or figuratively, in a maze of wires, tubes and autoclaves.
The contemporary emphasis on individual
rights and freedoms found its earliest political expression towards the end of
the eighteenth century in the growth of movements for liberal democracy,
especially in the Unites States and in
2. The principal issues in research ethics
In healthcare facilities and academic institutions research ethics committees are entrusted with the responsibility of ensuring that all research is carried out in accordance with ethical principles. It may be helpful, at this stage, if we explore some of the fundamental ethical principles which apply to medical research involving human subjects.
a. Consent
Drawing on the scholastic distinction between deliberate action (actus humanus voluntarius), and what merely happens to or in a human being (actus hominis), Karol Wojtyla (Pope John Paul II), argues that the essential characteristic of personal action (including the act of participation) is freedom. He goes on to emphasise the importance of the relationship between freedom and truth. [3] Consent is only an expression of a person’s freedom if it is appropriately informed.
When I give my informed consent to take part in medical research, this participation is an expression of my personal freedom and has the capacity to be an act of generous self-giving. If, by contrast, I am involved in medical research without my knowledge or informed consent, then I become a means to an end, an object rather than a personal subject. The requirement of informed consent is a fundamental principle in ethical codes both with respect to healthcare generally and specifically with respect to medical research. Other ethical principles relate in one way or another to informed consent.
b. Confidentiality and the Integrity of
Research
By agreeing to participate in research, I accept that others will have access to information about me which would not be generally known. They are only given this access in order to facilitate the research. This means that, although the results of the research may become widely known, information about me personally will not be disclosed. This is why research ethics committees must satisfy themselves before research begins that adequate measures have been put in place to protect the confidentiality of personal information.
Informed consent to take part in research can only be freely given when the purpose of the participation is clear. Whether I give samples of blood or tissue, or provide information, I expect that what I have given will be used for the purpose for which I have given my consent. If somebody subsequently decides to use what I have given for another purpose, without seeking fresh consent for this new research, this conflicts with the principle of informed consent.
c. Safety and freedom from unreasonable
burdens
Informed consent must also take account of the likely consequences of participation in research. If I participate in a research project, I need to know what I will be expected to do, what others may do to me. I will need to know how often and for how long these things will happen, and what the likely consequences and side-effects will be. Particular care must be taken to ensure that people who are sick are not subjected without good reason or with ureasonable frequency to burdensome procedures, especially if this is unlikely to lead to any benefit to themselves. If there is some prospect of therapeutic benefit, whether for myself or for another person, or for humanity as a whole, then it is not unreasonable to accept some level of risk, provided the risk is not out of proportion to the likely benefit.
d. The Right to Opt out
Because the person takes precedence over the research, the consent to participate in research is never absolute or irreversible. Just as I am free to consent or not to consent in the first instance, I remain free to withdraw my consent at any stage without having to justify that decision to anyone. In order to ensure that consent remains free, ethical codes such as the Declaration of Helsinki insist that a decision to opt out of research should not have any implications for the provision of medical treatment.
3. Therapeutic and non-therapeutic
research
Traditionally medical research falls into one of two categories, therapeutic (or clinical) and non-therapeutic (or non-clinical). The normal or traditional usage of the term therapeutic would mean that the research had the potential to benefit the health of the participant.[4] In recent times, however, some ambiguity has crept into the use of this terminology. There is a growing tendency to use the term therapeutic to describe research which has the potential to benefit the health of the group or category to which the participant belongs, or indeed of populations as a whole.
The term therapeutic is misused in this way with reference to embryonic research and human cloning. Destructive research on human embryos is routinely described as therapeutic because of the potential benefit to others, although clearly there is no benefit, therapeutic or otherwise, to the embryos themselves. Similarly, a spurious distinction is made between reproductive cloning and therapeutic cloning. In reality, of course, all cloning is reproductive, and cloning can only be therapeutic in the secondary sense that stem-cells or tissue from cloned human beings would be used in the treatment of other human beings.
What is of particular interest is the fact
that the blurring of the distinction between therapeutic and non-therapeutic
research seems to have made its way into recent revisions of the Declaration of Helsinki, and into other
international ethical codes and protocols. The
4. What about those who lack the capacity
to give informed consent?
The blurring of the distinction between therapeutic and non-therapeutic research would not appear to be quite so important in the case of adults who are competent to give informed consent. They remain free to decide, on the basis of the information available to them, whether or not they wish to participate in research which will not be of benefit to themselves, even if there is a reasonable element of risk involved.
The real problem arises in the case of a person who is not in a position to give informed consent, and whose participation in medical research is sought. Various categories of people might be included under this heading.
a)
Non-competent adults
Some adults are limited in their capacity to give informed consent because of psychiatric illness or mental handicap. The capacity to give consent will vary depending on the nature of the condition, and particularly whether the problem is physical or emotional. Some adults will never be able to give informed consent, while others may sometimes be able to give such consent.
b)
Minors
Minors are defined in recent Irish drug trials legislation as those under 16.[7] Depending on their age, and the nature of the research proposed, they may be more or less capable of understanding the implications of their participation in research, but they are regarded as legally incompetent to give informed consent. Adults who have a responsibility of care must ensure that the best interests of the minor are given priority in any decision about treatment, including treatment which involves an element of research.
a)
Vulnerable adults
Under certain circumstances, adults who might otherwise be regarded as competent, are particularly vulnerable. Included in this category might be adults who are subject to military discipline, prisoners, or people who are dependent as a result of poverty or homelessness. People in these categories may experience themselves as less free to refuse their consent, and may be more likely to comply whenever their availability to participate may be presumed.
5. Assent and proxy consent
a. best interests and presumed will
In the case of any person, adult or child, who is unable to give informed consent, normal medical treatment should always be provided on the basis that it is in the best interests of the person. The inclusion of such a person in research which holds out the prospect of therapeutic benefit for him or her may be appropriate, precisely because it may be reasonably seen to be in the best interests of the patient. An example of this would be the inclusion of a child or a mentally handicapped adult who is HIV positive in the trial of a new anti-retroviral drug, which may help to prevent the development of full-blown AIDS.
Recent European legislation regarding the control of drug trials requires, both in the case of minors and non-competent adults, that the consent of parents or guardians must represent the presumed will of the subject (i.e., the person who will be included in the trial). The legislation does not define what is meant by presumed will. It would seem reasonable, however, to presume that the will of any person would include the preservation of his own life and health, and the avoidance of unnecessary discomfort.
Strictly speaking, we should distinguish between consent and assent. When parents or legal guardians agree to the participation in therapeutic research of a person for whom they have a responsibility, they simply acknowledge that this course of action is consistent with the best interests of the patient. This is assent, rather than consent.
It is an entirely different matter when it is proposed to include a non-competent person in research which has no therapeutic potential for him or her. This would seem to assume a level of altruism which might indeed be present under other circumstances, but which those with the responsibility of care have no moral right to assume. According to Asim Sheikh, it would appear that – where a minor is concerned - the appropriate test in Irish law is whether this is a procedure to which a “reasonable parent” would consent.[8] We might well ask what is a reasonable parent, and would a reasonable parent consent to the inclusion of his or her child (a minor) in non-therapeutic research.
Albert DiIanni argues that, “it is a fact open to observation that most people act altruistically when an action seems important for the benefit of others, and it involves minimal risk or discomfort to oneself.” He goes on to argue that since children are human beings, they can be presumed to “have the same desires as other humans in terms of self-preservation and altruism.” [9] He argues, paradoxically, that a more subjective approach, which limits experimentation on children to situations in which the common run of people would be willing to volunteer themselves, is far safer than trying to derive conclusions about the volunteering of children from so-called objective moral premises.
Ashley and O’Rourke take a more protective position, and argue that “proxy consent is not licit in non-therapeutic experimentation, even when the risk is minimal.”[10] Their argument is based on the consideration that the presumed consent of the ward (the child or the non-competent adult) is merely hypothetical, and the only basis on which the guardian is entitled to act is the duty of care. The responsibility of the guardian, therefore, is limited exclusively to being an advocate and a jealous protector of the rights of the child.
Some degree of compromise is probably possible, on the basis that children do have the capacity to give some level of informed consent, even if they are not acknowledged to be legally competent. It would seem that a minor might ethically be allowed to participate in non-therapeutic research
In practice, then, a child of four might be allowed to give blood or tissue for research purposes, because he or she is capable of appreciating in advance that there will be some discomfort involved, and of understanding that this may “help other little boys and girls who are sick to get better.”
It is worth noting that that law in relation to non-competent adults is quite different to the law applying to minors. “Generally the rule of law is that no one can consent to any treatment on behalf of an adult patient. When the adult is unable to express consent by virtue of mental incapacity, then, in normal cases, a doctor can only act out of necessity when the treatment is in the patient’s best interest, for example, in a life-threatening emergency.”[11] Clearly this would not apply in the case of non-therapeutic research which, by definition, is not related to treatment.
Where medical research is concerned, there is a tendency, therefore, to offer a lower standard of protection to children than to non-competent adults. It is difficult to see how this can be justified. The Irish Medical Council published its revised Guide to Ethical Conduct and Behaviour in 2004. The guide insists on informed written consent and then, by way of exception indicates that those who are not competent to give consent may be included in research provided consent is obtained from a guardian, and that special care is exercised “in ensuring that the likely benefits to participants significantly outweigh the risks.”[12] The Medical Council, thus upholds the important distinction between therapeutic and non-therapeutic research and, unlike recent Irish and European law, does not discriminate against minors in this regard.
b. Individual rights and the benefit
of the group or class
Recent European legislation on the conduct of drug trials illustrates how the lower level of protection for minors may be seen to reflect a growing tendency to emphasise the good of the group at the expense of individual rights, and especially the rights of the more vulnerable. Directive 2001/20/EC was intended to streamline the process of approving new research proposals, and to ensure that research taking place outside of healthcare facilities or educational institutions would be subject to appropriate control. [13]
The directive outlines the procedures to be followed in relation to informed consent in respect of minors and of adults who are not competent. In the case of adults, both the Directive and the corresponding Irish statutory instrument require that “the interests of the patient will always prevail over the interests of science and of society” and that “there are grounds for expecting that administering the medicinal product to be tested will produce a benefit to the patient outweighing the risks, or produce no risk at all.”[14]
A different standard of protection is applied in both the directive and the regulation when referring to minors. As a condition for participation of a minor in a drug trial, the directive requires that “some direct benefit for the group of patients involved in the clinical trial is to be obtained from that trial,”[15] The requirement which we have already seen in respect of non-competent adults, namely that “the interests of the patient always prevail over that of science and of society,” also applies to minors in both the directive and the regulation.[16] In this case, however, it would appear to be in direct conflict with the possibility that, in practice, the right of a minor not to be included in a trial, can be set aside if the good of the group requires it. Clearly the interests of the patient do not always prevail over that of science and society. This has implications which extend far beyond the particular case dealt with in the Directive, because it implies that the individual can be used as a means to an end, and that the common good is, in some sense at least, to be equated with the good of society.
The latest version of the Declaration of Helsinki, published in 2002, argues that “medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research.”[17] It then goes on to devote three articles to the procedures to be followed when the person who is to be the subject of research is either legally incompetent or physically or mentally incapable of giving consent. The Declaration provides that consent may be obtained “from the legally authorised representative in accordance with applicable law.” [18] It also recognises that research should not be carried out on such persons unless “the physical / mental condition that prevents obtaining informed consent is a necessary characteristic of the research population.”[19] Surprisingly enough, it also seems to accept that the research may proceed initially without consent and that “consent to remain in the research should be obtained as soon as possible from the individual or a legally authorised surrogate.”[20] The right of a person not to be included in research which will not benefit him or her simply doesn’t appear.
In 2003, the Council of Europe published, a Draft Additional Protocol to the Convention on Human Rights and Biomedicine on Biomedical Research. The first of five conditions laid down in the document, for the involvement in research of a person without the capacity to consent is that “the results of the research have the potential to produce real and direct benefit to his or her health.”[21] Paradoxically the protocol goes on to say that “exceptionally and under the protective conditions prescribed by law” this condition may be set aside, provided the research is directed to “the attainment of results capable of conferring benefit to the person concerned or to other persons in the same age category, or afflicted with the same disease or disorder or having the same condition” and that “the research entails only minimal risk and minimal burden to the individual concerned.”[22]
On the question of the appropriate balance between the individual and society, DiIanni argues:
Where we
are dealing with defenceless and voiceless children, and in a climate which is
utilitarian and anti-child as is our own, we would do best to lean toward favoring the individual. We are living in a technological
society which has a bias toward the powerful, toward adults in full-fledged
maturity, toward control, and toward the pre-eminence of conscious, experienced
life.[23]
The truth of DiIanni’s
comment is to be seen in the fact that recent debate at the European Council of
Ministers on the use of so-called “supernumary” human
embryos as raw materials for stem-cell research took place, not under the
heading of healthcare, or even family or social affairs, but under the heading
of trade and competitiveness.
6. Research Protocols and Institutional
Consent
One of the clearest objectives of Directive 2001/20/EC was that a supervisory body would recognise research ethics committees for the purposes of approving drug trial protocols. It was intended that a single opinion would apply for each member state, (i.e., the decision of one recognised ethics committee would be sufficient for a trial to proceed anywhere in the state.
The single opinion does not mean that every healthcare facility will be obliged to participate in a drug trial just because it has been approved by a recognised committee. It may mean, however, that healthcare facilities with a particular ethos are no longer in a position to exercise any influence over the manner in which drug trials are structured, or the terms and conditions for participation which applied to the trial. These would come as part of the package, so to speak.
If, for example, drug trials were to routinely include minors on the basis of the potential benefit for the group rather than for the individual participant, this would automatically exclude hospitals with a Catholic ethos. It is quite common that research protocols relating to drug trials include the requirement that women of child-bearing age would be obliged to use contraceptives, or would be asked to consider an abortion in the event that a pregnancy did occur. If such protocols were to be routinely approved by REC’s, under the new regulations, hospitals with a Catholic ethos would be automatically excluded. Clearly if hospitals with a Catholic ethos were unable to participate in research, it would not be good either for the hospitals or for the research.
The regulation which gives effect to the
directive in
The challenge for the future is to find a way in which vital medical research can be facilitated, without compromising on the fundamental protections which are intrinsic to the ethos of medicine. The requirements of research must not dictate our ethics, but rather our ethos must regulate research.
Notes:
[1] Cf. Trials of War Criminals before the
2 Cf. Declaration of
3 Cf. Karol Wojtyla The Acting
Person.
4 Cf. Asim Sheikh. Genetic
Research and Human Biological Samples,
5 Declaration of Helsinki, adopted by the 41st World Medical Assembly, Hong Kong 1989.
6 Declaration of Helsinki, adopted by the 52nd World Medical Assembly, Edinburgh 2000, and amended by the World Medical Assembly, Washington 2002.
7 Cf. European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations, 2004, Part I, 4.1. (hereafter referred to as Clinical Trials Regulations 2004).
8 Asim
Sheikh. Genetic Research and Human
Biological Samples,
9 Albert DiIanni. “Volunteering Children for Medical Experiments,” in Linacre Quarterly, Vol. 56, No. 1, Feb. 1989, 36
10 Benedict Ashley & Kevin
O’Rourke. Health Care Ethics: A Theological Analysis.
11 ibid., 29
12 Irish Medical
Council. Guide to Ethical Conduct and
Behaviour, 6th ed.,
13 Directive
2001/20/EC of the European Parliament and
of the Council, of
14 Clinical Trials Directive 2001, article 5 (h) & (i); also Clinical Trials Regulation 2004, Schedule 1, Part 5, # 11 & 17
15 Clinical Trials Directive 2001, Art. 5 (e); also Clinical Trials Regulation 2004, Schedule 1, Part 5, # 12.
16 Clinical Trials Directive 2001, Art. 5 (i); also Clinical Trials Regulation 2004, Schedule 1, Part 5, # 18
17 Declaration
of
18 ibid., # 24.
19 ibid., # 26.
20 ibid.
21 Council of
22 ibid, Ch. V, Art. 15.2
23 Albert DiIanni, ibid., 37.
24 Clinical Trials Regulation 2004, Part 2, # 6 (3) & (4)
Bibliography:
Ashley Benedict & Kevin O’Rourke. Health Care Ethics: A Theological Analysis.
Council of
Dept of Health and Children.
European Communities (Clinical Trials on Medicinal Products for Human Use)
Regulations,
DiIanni, Albert. “Volunteering Children for Medical Experiments,” in Linacre Quarterly, Vol. 56, No. 1, Feb. 1989, 36
European Parliament. Directive 2001/20/EC of the European Parliament and of the Council, of 4 April 2001: on the approximaton of the laws regulations and administrative provisions of the Member Statea relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use.
Irish Medical Council. Guide to Ethical Conduct and Behaviour, 6th ed.,
Sheikh, Asim. Genetic Research and Human Biological Samples,
Trials of War Criminals before the
Wojtyla, Karol. The Acting Person.
World Medical Association. Declaration
of
________. Declaration of Helsinki, adopted by the 41st World Medical Assembly, Hong Kong 1989.
________. Declaration of Helsinki, adopted by the 52nd World
Medical Assembly, Edinburgh 2000, and amended by the World Medical Assembly,
Washington 2002.
[1] Cf. Trials of War Criminals before the
[2] Cf. Declaration of
[3] Cf. Karol Wojtyla The Acting
Person.
[4] Cf. Asim Sheikh. Genetic
Research and Human Biological Samples,
[5] Declaration of Helsinki, adopted by the 41st World Medical Assembly, Hong Kong 1989.
[6] Declaration of Helsinki, adopted by the 52nd World Medical Assembly, Edinburgh 2000, and amended by the World Medical Assembly, Washington 2002.
[7] Cf. European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations, 2004, Part I, 4.1. (hereafter referred to as Clinical Trials Regulations 2004).
[8] Asim Sheikh. Genetic Research
and Human Biological Samples,
[9] Albert DiIanni. “Volunteering Children for Medical Experiments,” in Linacre Quarterly, Vol. 56, No. 1, Feb. 1989, 36
[10] Benedict Ashley
& Kevin O’Rourke. Health Care Ethics: A Theological Analysis.
[11] ibid., 29
[12] Irish Medical
Council. Guide to Ethical Conduct and
Behaviour, 6th ed.,
[13] Directive 2001/20/EC of the European Parliament and of the Council, of
[14] Clinical Trials Directive 2001, article 5 (h) & (i); also Clinical Trials Regulation 2004, Schedule 1, Part 5, # 11 & 17
[15] Clinical Trials Directive 2001, Art. 5 (e); also Clinical Trials Regulation 2004, Schedule 1, Part 5, # 12.
[16] Clinical Trials Directive 2001, Art. 5 (i); also Clinical Trials Regulation 2004, Schedule 1, Part 5, # 18
[17] Declaration of
[18] ibid., # 24.
[19] ibid., # 26.
[20] ibid.
[21] Council of
[22] ibid, Ch. V, Art. 15.2
[23] Albert DiIanni, ibid., 37.
[24] Clinical Trials Regulation 2004, Part 2, # 6 (3) & (4)