Ethical review of research into rare genetic disorders
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《英国医生杂志》
1 Ethox Centre, Department of Public Health, University of Oxford, Oxford OX3 7LF, 2 Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, 3 Medical Ethics Unit, Imperial College London, London W6 8RP, 4 Genetic Interest Group, London N1 3QP
Correspondence to: M Parker Michael.parker@ethox.ox.ac.uk
Although some work on rare diseases is clearly clinical investigation and some clearly research, much activity falls uneasily between the two. Where should we draw the line and how can we ensure research gets appropriate ethical review?
Introduction
Treating such cases as research creates important problems because of the process of ethical review. The first problem is that research ethics committees require consent to be closed—that is, samples must be used for a specific purpose and time which are clearly defined in advance. Small sample sizes in research into rare diseases mean that identifying disease-causing mutations is a type of informed fishing trip. The consent given is rarely capable of meeting the standards required.
Genetic research can be like an "informed fishing trip"
Credit: MICHIGAN TOURIST OFFICE
Secondly, ethics committees do not always view the methods used to research rare conditions as meeting required methodological standards.1 Lastly, research into rare conditions is criticised for its standards of confidentiality. Such research often involves studying unique or near unique cases, making it impossible for participants to be anonymous.
Defining this work as clinical investigation sidesteps these problems but creates a problematic regulatory loophole. We believe that researchers should accept the need for ethics review and encourage the development of a more sympathetic regulatory structure. Agreement is needed about when clinical investigation turns into research and what is appropriate ethical review of research into rare inherited disorders.
Research or clinical practice?
Developing tests and therapies for rare genetic disorders depends on a more sympathetic approach to the review of such research. What should be the appropriate process of research ethics review? The best way to consider this is in terms of the three problems identified earlier: consent, anonymity, and methodology.
Open ended versus closed consent
Except in exceptional circumstances, research participants should be included in studies only if they have given their valid consent. What ought to count as valid consent in research into rare conditions?
To be valid, consent must be voluntary, informed, and competently given. Research ethic committees have tended to interpret the requirement for informed consent to imply that such consent must be specific and closed. Consent is informed only if participants know in detail what is going to happen to them, what is going to happen to any sample taken from them, and when the research will be completed. In research into rare conditions it is not always possible to provide the participant with a detailed account of this kind. This need not imply, however, that informed consent is not possible. Given adequate support, research participants are able to understand the nature of rare disease research sufficiently well to enable them to give valid consent. The true test of validity, we suggest, is whether the participants have sufficient understanding of the research and of their part in it to enable them to make a reasoned and balanced assessment about whether to participate.
Anonymity
High standards of confidentiality and anonymity are important in research. When asked, patients and research participants consistently place high value on confidentiality. They also place high value on good quality research and the achievement of results.4 In rare disorders these goals need to be carefully balanced against the realities of such research. The appropriate balance between anonymity and research efficacy should be judged according to a combination of empirical evidence about what participants consider acceptable practice and recognition of the need to protect family members who do not want participate in research.
Rigorous methodology
It is unreasonable for ethics committees to apply inappropriate standards of research methodology to research on rare diseases. Research on small sample sizes requires different methods from those used in large trials. The review of research into rare inherited disorders should ensure that the research methods are appropriate to the task.
Summary points
Differentiating between clinical practice and research can be difficult in genetics
It is impossible for many genetic studies to meet current standards for ethical approval
Studies going beyond the immediate family should be defined as research
Ethics committees need to take into account the special problems of consent, anonymity, and method in research into rare diseases
Conclusions
Department of Health. Research governance framework for health and social care. London: DoH, 2003:para 1.9. www.dh.gov.uk/assetRoot/04/01/47/57/04014757.pdf (accessed 5 Apr 2004).
General Medical Council. Confidentiality: protecting and providing information. London: GMC, 2000.
Department of Health. Good practice in consent implementation guide: consent to examination or treatment. www.dh.gov.uk/assetRoot/04/01/90/61/04019061.pdf (accessed 13 Jul 2004).
Genetic Interest Group. Minutes for research approval and rare genetic disorders workshop, 30 April 2003. www.gig.org.uk/docs/researchapproval2.pdf (accessed 13 Jul 2004).(M Parker, reader in medic)
Correspondence to: M Parker Michael.parker@ethox.ox.ac.uk
Although some work on rare diseases is clearly clinical investigation and some clearly research, much activity falls uneasily between the two. Where should we draw the line and how can we ensure research gets appropriate ethical review?
Introduction
Treating such cases as research creates important problems because of the process of ethical review. The first problem is that research ethics committees require consent to be closed—that is, samples must be used for a specific purpose and time which are clearly defined in advance. Small sample sizes in research into rare diseases mean that identifying disease-causing mutations is a type of informed fishing trip. The consent given is rarely capable of meeting the standards required.
Genetic research can be like an "informed fishing trip"
Credit: MICHIGAN TOURIST OFFICE
Secondly, ethics committees do not always view the methods used to research rare conditions as meeting required methodological standards.1 Lastly, research into rare conditions is criticised for its standards of confidentiality. Such research often involves studying unique or near unique cases, making it impossible for participants to be anonymous.
Defining this work as clinical investigation sidesteps these problems but creates a problematic regulatory loophole. We believe that researchers should accept the need for ethics review and encourage the development of a more sympathetic regulatory structure. Agreement is needed about when clinical investigation turns into research and what is appropriate ethical review of research into rare inherited disorders.
Research or clinical practice?
Developing tests and therapies for rare genetic disorders depends on a more sympathetic approach to the review of such research. What should be the appropriate process of research ethics review? The best way to consider this is in terms of the three problems identified earlier: consent, anonymity, and methodology.
Open ended versus closed consent
Except in exceptional circumstances, research participants should be included in studies only if they have given their valid consent. What ought to count as valid consent in research into rare conditions?
To be valid, consent must be voluntary, informed, and competently given. Research ethic committees have tended to interpret the requirement for informed consent to imply that such consent must be specific and closed. Consent is informed only if participants know in detail what is going to happen to them, what is going to happen to any sample taken from them, and when the research will be completed. In research into rare conditions it is not always possible to provide the participant with a detailed account of this kind. This need not imply, however, that informed consent is not possible. Given adequate support, research participants are able to understand the nature of rare disease research sufficiently well to enable them to give valid consent. The true test of validity, we suggest, is whether the participants have sufficient understanding of the research and of their part in it to enable them to make a reasoned and balanced assessment about whether to participate.
Anonymity
High standards of confidentiality and anonymity are important in research. When asked, patients and research participants consistently place high value on confidentiality. They also place high value on good quality research and the achievement of results.4 In rare disorders these goals need to be carefully balanced against the realities of such research. The appropriate balance between anonymity and research efficacy should be judged according to a combination of empirical evidence about what participants consider acceptable practice and recognition of the need to protect family members who do not want participate in research.
Rigorous methodology
It is unreasonable for ethics committees to apply inappropriate standards of research methodology to research on rare diseases. Research on small sample sizes requires different methods from those used in large trials. The review of research into rare inherited disorders should ensure that the research methods are appropriate to the task.
Summary points
Differentiating between clinical practice and research can be difficult in genetics
It is impossible for many genetic studies to meet current standards for ethical approval
Studies going beyond the immediate family should be defined as research
Ethics committees need to take into account the special problems of consent, anonymity, and method in research into rare diseases
Conclusions
Department of Health. Research governance framework for health and social care. London: DoH, 2003:para 1.9. www.dh.gov.uk/assetRoot/04/01/47/57/04014757.pdf (accessed 5 Apr 2004).
General Medical Council. Confidentiality: protecting and providing information. London: GMC, 2000.
Department of Health. Good practice in consent implementation guide: consent to examination or treatment. www.dh.gov.uk/assetRoot/04/01/90/61/04019061.pdf (accessed 13 Jul 2004).
Genetic Interest Group. Minutes for research approval and rare genetic disorders workshop, 30 April 2003. www.gig.org.uk/docs/researchapproval2.pdf (accessed 13 Jul 2004).(M Parker, reader in medic)