Ethics, audit, and research: all shades of grey
http://www.100md.com
《英国医生杂志》
1 Oxford Centre for Enablement, Oxford OX3 7LD derick.wade@dsl.pipex.com
Decisions about the need for ethical review should be based on the morality of all actions rather than arbitrary distinctions between audit and research
Introduction
The Greek word ethika (and ethos, its root) referred to character, and both referred to the morality of actions. Morality is derived from mores, the Latin for character. Thus ethics applies to a person's character, referring to the morality of decisions and actions in all circumstances. Morality relates to any situation in which there are conflicts between different values.
Every clinical encounter has three components11: an epistemic part, when the situation is analysed and potential actions are identified; a pragmatic part, which identifies which of the potential actions are possible; and an ethical part, which identifies which of the potential actions is morally acceptable or preferred (that is, most compatible with the values of society, the patient, and the clinical team). If it is accepted that all clinical practice, including research, should be undertaken ethically, then the main issue is to decide when formal ethical scrutiny might be necessary. To help decide, the following questions could be asked of any study or change in practice:
How much does this deviate from current normal (accepted, local) clinical practice?
What is the (additional) burden imposed on the patients (or others)?
What (additional) risks are posed to the patients (or others)?
What benefit might accrue to the patients (or others)?
What are the potential benefits to society (future patients)?
The answers might determine when additional, usually external, ethical scrutiny should occur. The questions also apply to research on healthy people (because the change is from no clinical practice whatsoever) and to all other interested parties as well as participants. Similar questions could apply to normal clinical care, where some clinical decisions might benefit from additional ethical consideration by an external group.9
What factors influence need for ethical review?
If a study requires some form of ethical scrutiny, the next step is to consider what might constitute adequate scrutiny. One obvious mechanism is for a properly constituted, independent ethics committee to scrutinise the study. However, the conclusions of an ethics committee should not be accepted without question because the variation in decisions is well documented.16 17 This variation may be permissible,18 but any third party should always make its own judgment.
Case scenarios
Below are four examples of ethical dilemmas. We invite readers to respond to the questions raised through bmj.com
Scenario A
A cardiac surgery department with three surgeons receives a complaint from a patient that his surgeon had used an inferior technique such that he was left with continuing angina. The patient's friend, who was operated on by another surgeon in the same hospital using a more expensive technique, did well. The chief executive was worried about the death rate of the second surgeon and was also concerned that the technique used by the second surgeon costs 20% more. The third surgeon used both techniques, according to ill defined criteria. The chief executive proposed an audit, suggesting that every patient should be recalled at six months for angiography and stress testing for angina to determine whether the expensive technique led to a higher rate of arterial patency in the long term, and whether this was associated with less angina. Before this audit, the routine follow up was for patients to see a specialist nurse at three months: 80% were seen and 46% completed the SF-36 questionnaire. One hundred of 109 surviving patients returned for follow up, and all had angiography and exercise testing. Patients of the surgeon who always used the cheaper technique had more patent arteries and less angina than patients of the surgeon who always used the expensive method (P < 0.01); the third surgeon treated only 20 patients, and no statistical differences emerged. The results were written up because the chief executive felt that the findings would influence practice. There was no scrutiny by an ethics committee "because it was audit" and ethical considerations were not discussed in the paper.
Questions:
Should the study have taken place?
Should an ethical review have taken place before starting?
Should the journal publish the paper (a covering letter was received confirming that the local ethics committee had explicitly decided it was audit and did not need review)?
Scenario B
A letter from a clinic in Sweden suggests that melanoma is caused by viral infection with a specific parvovirus, previously not known but easily identified with monoclonal antibodies. A dermatology unit with slides from 100 melanomas excised over the past five years applies the antibody to the slides and finds evidence of virus in 40% of cases, whereas no slides of similar skin biopsies in other diseases showed infection. This is submitted as research, but without ethics committee approval and without consent from all patients (not least because 15 had died). The authors provide evidence that they had considered the matter, and indeed include a paragraph on the arguments. They specifically find that all 15 who died had evidence of infection, and conclude that there is a causal link.
Questions:
Should the researchers have sought external ethical review?
Should the journal publish the paper (peer review suggesting that the finding is novel and important, and that the methodology is sound)?
Scenario C
A registrar in a psychiatric hospital thinks that when a fire alarm goes off schizophrenic patients taking risperidone leave fast and congregate in the correct place, depressed patients leave slowly and congregate in the right place, and schizophrenic patients taking chlorpromazine do not bother to move unless asked, and then go to the wrong place. He has a theory that this relates to dopamine and serotonin concentrations affecting drive and ability to locate self in space. Fire alarms are quite frequent. He therefore structures observations over six months (eight fire alarms), and also notes the diagnoses and drugs taken. He finds that patients taking respiridone leave in half the time, and that patients taking drugs that affect serotonin usually get lost. This is submitted as research, but without any ethics committee approval "because there was no experimentation" (the fire alarms were all real).
Questions:
Should the registrar have sought external ethical review (he discussed it with the senior ward nurse)?
Should the journal publish it (assuming that they decide that it is of interest)?
Scenario D
A UK study in 2002 randomised patients with stroke to general medical wards or to a stroke unit. The study had approval from an ethics committee and was submitted for publication. The editor knows that patients were randomised to known inferior care (in general medical wards), which is generally considered unethical. However, in the UK many patients are still unable to receive stroke unit care. Should the study be published?
Questions:
Was it ethical to randomise patients to a known inferior treatment in the circumstances?
Should the journal publish it, and if so should they insist on an ethical commentary?
However, the external review does not need to be the same for all studies or situations. Current UK and European practice needs urgent review to encourage proportionate review focused on the ethical issues.19 Proportionality should also apply to obtaining consent from the participant, just as it already applies to all other clinical encounters that, in principle, require consent. If the burdens or risks are small, then implicit consent is adequate, but if the burdens or risks are larger then a more formal procedure is used with its rigour varying according to circumstances.
Ethical scrutiny should continue after the study is complete, especially when it is submitted for publication. Journals generally consider that all research must be approved by an ethics committee and that audit does not need such approval. They devolve responsibility for ethical scrutiny to ethics committees. This approach is inadequate because research and audit cannot be distinguished and because ethical judgments vary. Journals should consider the moral aspects of any study submitted. They can discharge their duty in several ways: accepting the opinion of an ethics committee, obtaining their own external ethical review, considering the ethical position themselves, or asking the author to discuss the ethical dilemmas within the paper and allowing readers to decide morality for themselves.
Lead investigators: one way forward?
Warlow C. Clinical research under the cosh again. This time it is ethics committees. BMJ 2004;329: 241-2.
Smith R. Audit and research. BMJ 1992;305: 905-6.
New Zealand Research Development Office. Distinguishing research and audit. www.adhb.govt.nz/rdo/Distinguishing_research_and_audit_090604.pdf (accessed 10 Sep 2004).
United Bristol Healthcare NHS Trust Clinical Audit. How to tell the difference between audit and research. Bristol: UBHT, 2000. www.ubht.nhs.uk/ClinicalAudit/docs/HowTo/CA%20&%20Research.pdf (accessed 10 Sep 2004).
Wilson A, Grimshaw G, Baker R, Thompson J. Differentiating between audit and research: postal survey of health authorities' views. BMJ 1999;319: 1235.
Choo V. Thin line between research and audit. Lancet 1998;352: 337-8.
Carr ECJ. Talking on the telephone with people who have experienced pain in hospital: clinical audit or research? J Adv Nurs 1999;29: 194-200.
Yentis SM. Ethics again—hoops, loops and principles. Anaesthesia 2004;59: 313-7.
Rix G, Cutting K. Clinical audit, the case for ethical scrutiny? Int J Health Care Qual Assurance 1996;9: 18-20.
Christchurch School of Medicine and Health Sciences. Is ethical approval required from the Canterbury ethics committee for the project? www.chmeds.ac.nz/research/approval.pdf (accessed 10 Sep 2004).
Sadler JZ, Hulgus YF. Clinical problem solving and the biopsychosocial model. Am J Psychiatry 1992;149: 1315-23.
Thames Valley Research and Development Support Unit. Research ethics. www.hsru.ox.ac.uk/rdsc/ethics.htm (accessed 11 Sep 2004).
Sulch D, Melbourn A, Perez I, Kalra L. Integrated care pathways and quality of life on a stroke rehabilitation unit. Stroke 2002;33: 1600-4.
Kinn S. The relationship between clinical audit and ethics. J Med Ethics 1997;23: 250-3.
Edwards SRL, Lilford RJ, Braunholtz D, Jackson J. Why "underpowered" trials are not necessarily unethical. Lancet 1997;350: 804-7.
While AE. Ethics committees: impediments to research or guardians of ethical standards? BMJ 1995;311: 661.
McWilliams R, Hoover FJ, Hamosh A, Beck S, Beaty T, Cutting G. Problematic variation in local institutional review of a multicenter genetic epidemiology study. JAMA 2003;290: 360-6.
Edwards SJL, Ashcroft R, Kirchin S. Research ethics committees: differences and moral judgement. Bioethics 2004;18: 408-27.
Jamrozik K. Research ethics paperwork: what is the plot we seem to have lost? BMJ 2004;329: 286-7.
O'Neill O. Accountability, trust and informed consent in medical practice and research. Clin Med 2004;4: 269-76.
Jamrozik K. The case for a new system for oversight of research on human subjects. J Med Ethics 2000;26: 334-9.(Derick T Wade, professor of neurological)
Decisions about the need for ethical review should be based on the morality of all actions rather than arbitrary distinctions between audit and research
Introduction
The Greek word ethika (and ethos, its root) referred to character, and both referred to the morality of actions. Morality is derived from mores, the Latin for character. Thus ethics applies to a person's character, referring to the morality of decisions and actions in all circumstances. Morality relates to any situation in which there are conflicts between different values.
Every clinical encounter has three components11: an epistemic part, when the situation is analysed and potential actions are identified; a pragmatic part, which identifies which of the potential actions are possible; and an ethical part, which identifies which of the potential actions is morally acceptable or preferred (that is, most compatible with the values of society, the patient, and the clinical team). If it is accepted that all clinical practice, including research, should be undertaken ethically, then the main issue is to decide when formal ethical scrutiny might be necessary. To help decide, the following questions could be asked of any study or change in practice:
How much does this deviate from current normal (accepted, local) clinical practice?
What is the (additional) burden imposed on the patients (or others)?
What (additional) risks are posed to the patients (or others)?
What benefit might accrue to the patients (or others)?
What are the potential benefits to society (future patients)?
The answers might determine when additional, usually external, ethical scrutiny should occur. The questions also apply to research on healthy people (because the change is from no clinical practice whatsoever) and to all other interested parties as well as participants. Similar questions could apply to normal clinical care, where some clinical decisions might benefit from additional ethical consideration by an external group.9
What factors influence need for ethical review?
If a study requires some form of ethical scrutiny, the next step is to consider what might constitute adequate scrutiny. One obvious mechanism is for a properly constituted, independent ethics committee to scrutinise the study. However, the conclusions of an ethics committee should not be accepted without question because the variation in decisions is well documented.16 17 This variation may be permissible,18 but any third party should always make its own judgment.
Case scenarios
Below are four examples of ethical dilemmas. We invite readers to respond to the questions raised through bmj.com
Scenario A
A cardiac surgery department with three surgeons receives a complaint from a patient that his surgeon had used an inferior technique such that he was left with continuing angina. The patient's friend, who was operated on by another surgeon in the same hospital using a more expensive technique, did well. The chief executive was worried about the death rate of the second surgeon and was also concerned that the technique used by the second surgeon costs 20% more. The third surgeon used both techniques, according to ill defined criteria. The chief executive proposed an audit, suggesting that every patient should be recalled at six months for angiography and stress testing for angina to determine whether the expensive technique led to a higher rate of arterial patency in the long term, and whether this was associated with less angina. Before this audit, the routine follow up was for patients to see a specialist nurse at three months: 80% were seen and 46% completed the SF-36 questionnaire. One hundred of 109 surviving patients returned for follow up, and all had angiography and exercise testing. Patients of the surgeon who always used the cheaper technique had more patent arteries and less angina than patients of the surgeon who always used the expensive method (P < 0.01); the third surgeon treated only 20 patients, and no statistical differences emerged. The results were written up because the chief executive felt that the findings would influence practice. There was no scrutiny by an ethics committee "because it was audit" and ethical considerations were not discussed in the paper.
Questions:
Should the study have taken place?
Should an ethical review have taken place before starting?
Should the journal publish the paper (a covering letter was received confirming that the local ethics committee had explicitly decided it was audit and did not need review)?
Scenario B
A letter from a clinic in Sweden suggests that melanoma is caused by viral infection with a specific parvovirus, previously not known but easily identified with monoclonal antibodies. A dermatology unit with slides from 100 melanomas excised over the past five years applies the antibody to the slides and finds evidence of virus in 40% of cases, whereas no slides of similar skin biopsies in other diseases showed infection. This is submitted as research, but without ethics committee approval and without consent from all patients (not least because 15 had died). The authors provide evidence that they had considered the matter, and indeed include a paragraph on the arguments. They specifically find that all 15 who died had evidence of infection, and conclude that there is a causal link.
Questions:
Should the researchers have sought external ethical review?
Should the journal publish the paper (peer review suggesting that the finding is novel and important, and that the methodology is sound)?
Scenario C
A registrar in a psychiatric hospital thinks that when a fire alarm goes off schizophrenic patients taking risperidone leave fast and congregate in the correct place, depressed patients leave slowly and congregate in the right place, and schizophrenic patients taking chlorpromazine do not bother to move unless asked, and then go to the wrong place. He has a theory that this relates to dopamine and serotonin concentrations affecting drive and ability to locate self in space. Fire alarms are quite frequent. He therefore structures observations over six months (eight fire alarms), and also notes the diagnoses and drugs taken. He finds that patients taking respiridone leave in half the time, and that patients taking drugs that affect serotonin usually get lost. This is submitted as research, but without any ethics committee approval "because there was no experimentation" (the fire alarms were all real).
Questions:
Should the registrar have sought external ethical review (he discussed it with the senior ward nurse)?
Should the journal publish it (assuming that they decide that it is of interest)?
Scenario D
A UK study in 2002 randomised patients with stroke to general medical wards or to a stroke unit. The study had approval from an ethics committee and was submitted for publication. The editor knows that patients were randomised to known inferior care (in general medical wards), which is generally considered unethical. However, in the UK many patients are still unable to receive stroke unit care. Should the study be published?
Questions:
Was it ethical to randomise patients to a known inferior treatment in the circumstances?
Should the journal publish it, and if so should they insist on an ethical commentary?
However, the external review does not need to be the same for all studies or situations. Current UK and European practice needs urgent review to encourage proportionate review focused on the ethical issues.19 Proportionality should also apply to obtaining consent from the participant, just as it already applies to all other clinical encounters that, in principle, require consent. If the burdens or risks are small, then implicit consent is adequate, but if the burdens or risks are larger then a more formal procedure is used with its rigour varying according to circumstances.
Ethical scrutiny should continue after the study is complete, especially when it is submitted for publication. Journals generally consider that all research must be approved by an ethics committee and that audit does not need such approval. They devolve responsibility for ethical scrutiny to ethics committees. This approach is inadequate because research and audit cannot be distinguished and because ethical judgments vary. Journals should consider the moral aspects of any study submitted. They can discharge their duty in several ways: accepting the opinion of an ethics committee, obtaining their own external ethical review, considering the ethical position themselves, or asking the author to discuss the ethical dilemmas within the paper and allowing readers to decide morality for themselves.
Lead investigators: one way forward?
Warlow C. Clinical research under the cosh again. This time it is ethics committees. BMJ 2004;329: 241-2.
Smith R. Audit and research. BMJ 1992;305: 905-6.
New Zealand Research Development Office. Distinguishing research and audit. www.adhb.govt.nz/rdo/Distinguishing_research_and_audit_090604.pdf (accessed 10 Sep 2004).
United Bristol Healthcare NHS Trust Clinical Audit. How to tell the difference between audit and research. Bristol: UBHT, 2000. www.ubht.nhs.uk/ClinicalAudit/docs/HowTo/CA%20&%20Research.pdf (accessed 10 Sep 2004).
Wilson A, Grimshaw G, Baker R, Thompson J. Differentiating between audit and research: postal survey of health authorities' views. BMJ 1999;319: 1235.
Choo V. Thin line between research and audit. Lancet 1998;352: 337-8.
Carr ECJ. Talking on the telephone with people who have experienced pain in hospital: clinical audit or research? J Adv Nurs 1999;29: 194-200.
Yentis SM. Ethics again—hoops, loops and principles. Anaesthesia 2004;59: 313-7.
Rix G, Cutting K. Clinical audit, the case for ethical scrutiny? Int J Health Care Qual Assurance 1996;9: 18-20.
Christchurch School of Medicine and Health Sciences. Is ethical approval required from the Canterbury ethics committee for the project? www.chmeds.ac.nz/research/approval.pdf (accessed 10 Sep 2004).
Sadler JZ, Hulgus YF. Clinical problem solving and the biopsychosocial model. Am J Psychiatry 1992;149: 1315-23.
Thames Valley Research and Development Support Unit. Research ethics. www.hsru.ox.ac.uk/rdsc/ethics.htm (accessed 11 Sep 2004).
Sulch D, Melbourn A, Perez I, Kalra L. Integrated care pathways and quality of life on a stroke rehabilitation unit. Stroke 2002;33: 1600-4.
Kinn S. The relationship between clinical audit and ethics. J Med Ethics 1997;23: 250-3.
Edwards SRL, Lilford RJ, Braunholtz D, Jackson J. Why "underpowered" trials are not necessarily unethical. Lancet 1997;350: 804-7.
While AE. Ethics committees: impediments to research or guardians of ethical standards? BMJ 1995;311: 661.
McWilliams R, Hoover FJ, Hamosh A, Beck S, Beaty T, Cutting G. Problematic variation in local institutional review of a multicenter genetic epidemiology study. JAMA 2003;290: 360-6.
Edwards SJL, Ashcroft R, Kirchin S. Research ethics committees: differences and moral judgement. Bioethics 2004;18: 408-27.
Jamrozik K. Research ethics paperwork: what is the plot we seem to have lost? BMJ 2004;329: 286-7.
O'Neill O. Accountability, trust and informed consent in medical practice and research. Clin Med 2004;4: 269-76.
Jamrozik K. The case for a new system for oversight of research on human subjects. J Med Ethics 2000;26: 334-9.(Derick T Wade, professor of neurological)