Education And Debate For and against

No consent should be needed for using leftover body material for scientific purposesForAgainst

BMJ 2002; 325 doi: http://dx.doi.org/10.1136/bmj.325.7365.648 (Published 21 September 2002) Cite this as: BMJ 2002;325:648

Papers p 634

In Britain the Alder Hey scandal brought to public attention the fact that body material left over after diagnostic procedures may be used for teaching and research—usually without the patient's consent. Paul van Diest argues that, Alder Hey apart, this practice has not caused protest, mainly because the alternative would be to discard the material. He argues that self determination is not an overriding principle in the case of material that is otherwise thrown away. Julian Savulescu, however, cites cases where patients have felt “used” when their tissue has been kept without their consent. He argues that the best way to retain tissue for research is through educating and encouraging people to donate their redundant tissues, not by taking them without their knowledge

For

  1. Paul J van Diest (pj.vandiest{at}vumc.nl), professor of oncological pathology
  1. Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, Netherlands
  2. University of Oxford, Oxford OX1 3LZ

    During diagnostic procedures larger samples of body fluids and tissues are usually collected than strictly necessary for primary testing, “just in case.” The big advantage is, of course, that the patient does not need to be bothered if further testing is required. Furthermore, therapeutic surgical procedures usually yield large samples from which only a part is needed for diagnostic confirmation. All this leads to a vast volume of leftover samples, which are usually stored in laboratories for a period to serve the direct interest of the patient. Consent for this use is implicit in the consent obtained from patients for the diagnosis and treatment of their disease.

    However, when the current disease period has ended a dilemma emerges with regard to this leftover body material: to discard or to keep? To discard saves costs and space, but to keep the material has many advantages, not least for patients themselves. During the course of a disease the pathologist often has to return to such material for additional or new diagnostic procedures or prognostic tests. This applies especially to histopathological material but it also applies to a lesser extent to body fluids. In addition, within the framework of genetic counselling, it is crucial to re-evaluate relevant archival material of (potentially) affected family members as new DNA tests are developed. So, it is first for the patient's own benefit that leftover material needs to be kept for many years.

    In addition, this leftover material is a rich source for research and teaching and for control samples for diagnostic and prognostic tests. It is hardly necessary for a medical audience to give examples of the merit in this. Over recent years, however, it has been argued increasingly that patients should give their consent for this type of reuse.1 This may vary from “no objection” toa system where the patient is asked on each occasion that the material is reused. It is easy to imagine that the latter system will inevitably lead to the material no longer being available for further use, as patients will move and die, and in the end family members will be more and more difficult to trace.

    Any system requiring any kind of consent will take time and money that might be better spent on research itself. Furthermore, some patients will refuse. Together, these facts will hinder the reuse of leftover material for the worthy purposes I have described. These serve the advancement of medicine and thereby humankind in general.

    What is the problem?

    Which problem are we trying to solve by introducing a consent system? The old system, under which specific consent was not obtained, has not caused any major concerns. The worst documented affair I have come across is the (non-commercial) provision of meninges to a company preparing meninx allografts for medical use. Even in the Alder Hey affair, 2 3 in which a British hospital was criticised for retaining children's organs after autopsy without the knowledge of the parents, the problem was not so much the storage and reuse of the material as the fact that it had not been used for the intended diagnostic procedures. Why then do we need to take draconian measures to protect patients' rights that are apparently not endangered?

    I have heard only three proper arguments why patients might refuse consent to the use of their leftover material. Firstly, if all the leftover material is used for other purposes there might be none left if the patients themselves need more diagnostic procedures during the course of their disease. That is a practical issue that can be solved by ensuring that a defined quantity of material has to remain when reusing material. Secondly, privacy may be breached. Again, the material should be coded or used anonymously.

    Self determination v solidarity

    The third argument is the “right of self determination”: that the material belongs to the patient, who therefore has the right to decide what is done with it. In the case of leftover body material this should not be the overriding principle. If material is left over we have the choice of discarding it or using it for the advancement of medicine. Self determination over the use of one's tissue is in practice limited. Every day we lose millions of cells from our skin, we excrete stools and urine, and we cut out hair and nails—and rarely do we show any signs of wanting to keep these body elements under our control. Even after we have died we are allowed to undertake only a limited number of actions with our own bodies.

    Graphic Every day we excrete stools and urine—and rarely show any signs of wanting to keep these body elements under our control

    Instead I would appeal to the concept of solidarity. Current knowledge used to diagnose and treat today's patients has been obtained from research using data and material from patients from the past. Current diagnostic procedures can be performed reliably only by including appropriate positive and negative control samples from previous patients. Likewise, future patients can be optimally diagnosed and treated only by using material from today's patients. For me the principle of solidarity takes priority over the right of self determination.

    Why we shouldn't ask for consent

    • Less material will be available for scientific purposes

    • Bureaucracy

    • The right of self determination is relative, especially for leftover material

    • The principle of solidarity—helping others—is more important

    • Lack of consent has not caused problems in the past

    • Patients' privacy and interests can be safeguarded without a consent system

    • The practical alternative for leftover body material is to discard it: that helps no one

    Safeguards

    Of course, patients need guarantees if their consent is not required for this reuse. The material must be encoded or used anonymously; enough material should remain to serve the patient's (and family's) own needs; and the reuse should be for useful non-commercial purposes, necessitating review of all proposals by a scientific review board. Furthermore, it is only fair to inform patients that when they are treated in hospital their material may be reused according to these criteria. We have largely forgotten that courtesy and should do a better job from now on. The events in Alder Hey became an issue largely because parents were not told about the possible prolonged storage of body material.

    When reuse does not meet the above criteria, then patients should be asked for consent. Experience with tissue banks where consent has been obtained from patients for further wider use have been favourable.46 Furthermore, more watertight procedures may be required when transferring material between institutions for similar reasons.—Paul J van Diest

    Footnotes

    • Competing interests None declared.

    References

    1. 1.
    2. 2.
    3. 3.
    4. 4.
    5. 5.
    6. 6.

    Against

    1. Julian Savulescu (julian.savulescu{at}philosophy.ox.ac.uk), Uehiro chair in applied ethics
    1. Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, Netherlands
    2. University of Oxford, Oxford OX1 3LZ

      Why should doctors obtain consent for the things they do to patients? Legally consent is necessary to avoid a charge of battery. This is necessary for any touching of the patient. Consent must be valid—that is, freely given by a competent person, informed of the risks and benefits of the procedure and its alternatives.

      But consent is central to medicine for deeper ethical reasons. Firstly, consent is important because information derived from tissue specimens can harm people. It can reveal health information which the individual may find distressing and which may have implications for that person's family, reproduction, insurance, and employment. Because of the possibility of deriving large amounts of information from genetic specimens and the linking of databases of information, it may be difficult to protect the confidentiality of such information. By giving consent, an individual voluntarily takes on the risk and, if he or she is rational, will ensure risk is minimised to a reasonable level.

      Secondly, consent is important to respect the autonomy of mature people. Each mature person should be the author of his or her own life. Each person has values, plans, aspirations, and feelings about how that life should go. People have values which may collide with research goals (see box 1). To ask a person's permission to do something to that person is to involve her actively and to give her the opportunity to make the project a part of her plans. When we involve people in our projects without their consent we use them as a means to our own ends.



      Embedded Image

      Lots of uses for the surplus—but shouldn't we ask first?

      Box 1: Who cares about tissue?

      “In a ‘unique case’ tissue donors [in the United States] are taking legal action over the way their contributions to research have been used. A group of parents of children suffering from Canavan, a deadly genetic disease, are suing the scientist who was approached to begin developing molecular probes to trace the disease to its source.

      The parents had helped the scientist get started by setting up a registry of families, contributing tissue, and helping to recruit tissue donors. A gene was identified and a genetic test developed. Then the scientist's employer obtained a patent on the gene and began licensing a test.

      The terms of the licence meant that access to the test was restricted and the Canavan Foundation was forced to stop offering free genetic screening. The scientist acknowledges that the contribution of tissue and ‘seed money’ from the Canavan parents helped him to get started, but the hospital that employed him provided $1m [£0.6m; Embedded Image1m] a year and ‘in return asked him to turn over any marketable intellectual property.’

      According to one of the parents who lost a child to Canavan disease, the legal battle ‘is not about the Canavan families wanting a piece of the pie’; it is about ‘having a say in how their contributions are used.’”1

      One of the most notorious examples of using a research participant is the case of John Moore. Moore had a rare form of hairy cell leukaemia. His physician removed his spleen and, unbeknownst to Moore, developed a potentially lucrative cell line from it. Moore subsequently travelled from Seattle to California several times, believing it was for treatment while in reality it was to provide tissue to continue the promising research. Though the United States supreme court rejected Moore's claim that he had a proprietary interest in the cell lines, it found that his doctors had breached their fiduciary duty to obtain informed consent for the procedures they performed on him.2

      There are many reasons why consent should be sought for research on redundant tissue (box 2). If participants consent they can be identified. They can then be given a report of the results of the research. All participants should receive a report of the research to which they contribute. This can have varying degrees of specificity. The results may have health implications for them directly—for example, they may be at raised risk of bowel cancer and benefit from surveillance. Or it may alert them more generally to the need for clinical follow up and how that can be obtained—for example, that mutations for their condition are being identified and they should consult a clinical geneticist.

      Different types of redundancy

      Must consent always be obtained for research on redundant tissue? It is important to distinguish four different kinds of redundant tissue.

      (1) Tissue already obtained as a part of clinical procedures

      Examples: pathology archives, tissue specimens held for laboratory quality assurance purposes, etc.

      Consent should generally be sought. But in cases of research on tissue obtained many years ago or for large population studies this may be difficult. If consent is impossible or impracticable, it may be permissible to conduct the research in the absence of consent in certain situations. The Australian National Health and Medical Research Council's National Statement on Ethical Conduct in Research Involving Humans,3 issued in 1999, offers some guidance. The statement explicitly outlines factors that may be taken into account by an ethics committee in deciding not to require consent (15.8):

      • the nature of the clinical condition for which the tissue was originally given

      • the difficulty or intrusiveness in obtaining consent

      • the possibility of deidentifying or anonymising the tissue to protect confidentiality

      • the extent of risk to privacy or well being of donors

      • the possibility of commercial exploitation.

      (2) Tissue obtained for research

      Examples: blood taken for study of genes in cardiovascular disease, etc.

      If researchers want to use tissue specimens for new research they should obtain consent unless the scope of the consent given for the previous research covers the new research. For example, consent for research into the genetic contribution to cardiovascular disease would probably cover sequencing a new mutation of a lipoprotein gene.

      (3) Tissue about to be obtained clinically where research is also envisaged

      Example: patients are having regular blood tests in hospital and researchers wish to take an extra 5 ml of blood for research

      If doctors know that spare tissue will be used for research in advance of performing a procedure then they should disclose that to the patient. It may be material to the patient's decision to have the procedure. It is also necessary to prevent the appearance that the procedure is being performed for research purposes disguised as clinical care and to declare any conflict of interest.

      Whether there is a sound basis for having an attachment to one's tissues is a complex issue. However, as the Alder Hey scandal illustrates, people have strong emotions in relation to their body. There can be strong cultural grounds for rejecting certain research projects. For example, Moari people place special significance on brain and placental tissues. And people do care how research proceeds (box 1).

      (4) Tissue obtained where future research is not envisaged

      Example: tumour specimens from surgery to be stored in pathology laboratories.

      Box 2: Reasons for obtaining consent

      • Research on tissue can harm patients by disclosing health or other information resulting in discrimination in employment or insurance (breach of confidentiality)

      • Patients may have values regarding research, especially commercial research or genetic research (see box 1). Research may be a “consequence material to the patient's consent”

      • Seeking consent promotes public confidence in medicine and research, prevents exploitation, and regulates the behaviour of researchers

      • It may benefit participants by allowing the identity of participants to be known and results with implications for the health of participants to be reported to them (and their families)

      • It may benefit researchers by allowing further information and samples to be gathered from participants and to link databases

      • It allows sensitivity to be shown towards cultural values

      • It empowers research participants and may enable them to share in profits of research

      RETURN TO TEXT

      If it is not envisaged that specific research will be conducted on a specimen obtained as a part of a clinical procedure then consent for research cannot be obtained. Yet such specimens may be a valuable research resource in the future. We respect people as persons by educating them, by being open, and by giving them the chance to express themselves and their values. Every consent form for medical procedures should include reference to the possibility of research being conducted on redundant tissue and the patient should be given an opportunity to express any objections to this.

      This should not be seen as a substitute for consent but rather as a way of alerting researchers to people who have some kind of objection to research. This should not be a carte blanche for ethics committees to approve future research, but it will be one factor among others for the committee to decide whether specific consent will be required.

      The duty of easy rescue

      One of the most basic moral duties is the “duty of easy rescue”: when the benefits to others of a person performing some act are significant and the cost to that person is minimal, then he or should perform the act. People should have a beneficent attitude to the use of tissues excised or removed as a part of their clinical care. But morality should not be enforced. The best way to enhance the bank of tissues available for research is through education and encouraging people to donate their redundant tissues to research, not by requiring it or taking them without their knowledge.—Julian Savulescu

      Footnotes

      • Competing interests None declared.

      References

      1. 1.
      2. 2.
      3. 3.