Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Crisis in Ethical Committees
- Jeremy Wood (21 September 2005)
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Radical Ethics?
- Rachael S Carrick (23 September 2005)
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Ethics or bureaucrethics?
- Luis Justo (28 September 2005)
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Losing sight of ethics in research ethics review
- Mark H Wilson (11 October 2005)
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And who shall guide the guides?
- Desmond R Laurence (6 November 2007)
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Scientific Studies
- Hugh Mann (7 November 2007)
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Re: And who shall guide the guides?
- John Saunders (15 November 2007)
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Re: Re: And who shall guide the guides?
- Desmond R Laurence (25 November 2007)
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Re: Re: Re: And who shall guide the guides?
- Emily Jackson (3 December 2007)
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And who shall guide the guides?
- Desmond R Laurence (7 December 2007)
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Re: Re: Re: And who shall guide the guides?
- Ian T Gilmore, John Saunders (13 December 2007)
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And who shall guide the guides?
- Desmond R Laurence (19 December 2007)
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Who guides the guides? favouring the illegal
- Desmond Laurence (19 February 2008)
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Re: Who guides the guides? favouring the illegal
- Hugh T Davies (3 March 2008)
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Who guides the guides: ethics and the law
- John Saunders (5 March 2008)
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Re re : And who shall guide the guides? Favouring the illegal.
- Desmond R Laurence (7 March 2008)
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Re: And who shall guide the guides? And legal advice from whom?
- Desmond Laurence (27 April 2008)
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Re: And who shall guide the guides? Illegal clinical trials to get Research Ethics Committee assent.
- Desmond R Laurence (12 February 2009)
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And who shall guide the guides? Obeying the law, sometimes
- Desmond R. Laurence (28 July 2009)
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Jeremy Wood, Consultant Surgeon QEII Hospital, Welwyn Garden City, Herts. AL7 4HQ
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By coincidence I read the editorial by Ashcroft, Newson and Benn hours after having dictated my letter of resignation from our local LREC. This year a reorganisation of the LRECs in Hertfordshire has been imposed by the region, reducing the number from three to two. This occurred despite many members of the existing comittees having genuine and well argued reservations about the change. Such consultation as took place was little more than a token exercise that explored issues such as venues and dates rather than the wisdom of whole exercise. As a result, the workload of the two remaining LRECs has increased from a lunch time meeting to one that is unlikeley to take less than half a day with the preparation a similar committment. As a busy clinician it is very difficult to devote this amount of time to what is after all a voluntary and unpaid role. I was not surprised to learn that two other members have also resigned. I believe that clinicians such as myself, who have not only daily patient contact but also a research back ground and a resulting higher degree, provide a useful and worthwhile perspective within the spectrum of different viewpoints LREC members bring. If we are to provide the safeguards to the ethical practice of research society appears to demand, whilst still promoting a vibrant body of research within the NHS (something society also values when it benefits from the outcomes) LRECs need to be carefully cultivated. At the moment this does not appear to be happening and this editorial suggests things are unlikely to improve in the short term at least. Competing interests: None declared |
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Rachael S Carrick, Trainee Clinical Psychologist Exeter University, School of Psychology, Washington Singer Laboratories, Exeter EX4 4QG
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In presenting the limitations of Lord Warner's commissioned Review of research ethics committees, Ashcroft et al make little of the absence of a service user perspective in Lord Warner's report. The authors very rightly note that criticism from the public and patients is "less audible", but this underplays the gravity of this missing viewpoint. The authors of this piece correctly point out that ethics is not about following formal rules; it is about debate, deliberation and consensus. However, I would emphasise that this consensus should include the input of patients where they are willing and able to do so. Without this, ethics will remain something professionls do 'for' people, not with them. Patients' views of research ethics remains an area that is not given due consideration. There are some pieces of research currently being undertaken, including my own, that are seeking to address this. By giving people who are mental health service users or who have chronic health problems the opportunity to express their opinions on the priorities of research ethics committees I hope that a shared view between professionals and patients can be reached, contributing to a more ethical process of ethical review. Competing interests: I am currently researching into service users' ethical priorities for psychological research |
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Luis Justo, Bioethics Chair Universidad Nacional del Comahue - Argentina
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The problems created by multiple IRBs and by the regulatory expansion should constitute a sobering lesson for underdeveloped countries. Each day more clinical trials are migrating to poor countries, stimulated by low costs, people virgin of treatment who may be easily induced to participate in trials in exchange for a modicum medical care, and more lenient or absent regulations.(1)(2) To build local protective legislation to avoid exploitation and abuse the lesson from the North should be useful. But there is a danger of lapsing into “bureaucrethic” thinking, assuming that a labyrinth of regulations will stop abuse attempts, either coming from international pharma or from its academic country representatives. The likely consequence of such alternative would be to make scientists and ethicists perform as antagonical groups, and that is a setting to be carefully avoided. The lesson to be drawn lies in the need to change the conception of “science” as a technical issue and “ethics” as an accesory requirement arising from righteous minds. The best system to change this is education, which needs a complete overhaul, in a humanistic approach to life from which research ethics cannot be absent. Regulations are another way to protect patients, but if this means more formularies to be filled by irritated scientists, the meaning of the issue will be lost in a muddle of paperwork and will not contribute to the task of creating a common ethical frame in research. There are two additional suggestions which could ease the transition from the existent world of “unsupervised science” to a new one of “ethically-conscious research”. One is participatory research and the other are interdisciplinary fora in which researchers and ethicists exchange views. Participatory research means that citizens engaged in any research process should get involved on its control, from the planning to the publishing moment.(3) Participation could reduce vulnerability to exploitative practices.(4) Fora are another way for researchers and ethicists to create understanding bridges. The work of SIDCER(5) and its regional fora is a good example. FLACEIS (Latin American Forum of Health Research Ethics Committees) is actively working to create a constructive debate between actors in the process of research and its ethical review, currently bringing together more than 100 members in fertile deliberations. References 1. Chien K, Chien L. The new Silk Road. Nature 428, 11 March 2004, 208-209. 2. Sinha G. Outsourcing Drug Work: Pharmaceuticals ship R&D and clinical trials to India. Scientific American, August 16, 2004. http://www.sciam.com/article.cfm?articleID=00033282-DBF5-10F9- 975883414B7F0000. Access 28/8/2004. 3. Justo L, Erazun F, Villarreal J. La investigación participativa como derecho: ¿posibilidad o utopía? Perspectivas Metodológicas 2004, Vol.4 No.4, 73-82. 4. Justo L. Participatory research: A way to reduce vulnerability. American Journal of Bioethics 2004; 4 (3): 18-19. 5. See http://www.who.int/sidcer for the detail of regional fora. For FLACEIS see http://www.flaceis.org. Competing interests: None declared |
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Mark H Wilson, Director of Medical Ethics Health Research Associates, Ottawa, k2b 6j4
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. Ashcroft’s et al’s concerns about ethics review becoming a culture of efficiency at the expense of serious ethical reflection are echoed in North American reports that call for the cultivation of a research ethics culture. (1) Shrinking time for ethical deliberation and consensus building in ethics review is not uncommon in North American where research ethics committees (RECs) are over worked and under resourced. More clinical trials are being conducted now than ever and the volume and pace of review is very demanding so that drugs and medical devices can enter a global market quickly. Trying to meet the demands of a highly competitive and commercial global market place has led RECs in North America to cut ethical corners that have resulted in scandal. (2) The North American regulatory climate offers some possible signs to heed in the direction of research governace in the UK. As a greater alliance between industry, government and academia has evolved, economic priorities and values have gained ascent in research institutions and governace bodies along with a bureaucratic approach to ethics that is losing sight of research subject’s rights and interests. A national report noted “that most Canadian research institutions and sponsors have a far better idea about what happens to research funding than what happens to research subjects; and institutions sees ethics as little more than an administrative step in the efficient processing of research proposals."(1) Economic interests also shape the regulatory terrain at higher political altitudes. The FDA and Health Canada serve to protect the health and safety of the public and to promote the economic benefits of research. A noted tension between the two aspects of their mandate – public health safety and economics - is heightened by these agencies having shortened the time for drug review under industry influence. This has led to the questionable approval of drugs that pose a public health threat. (3) Conflict of interest haunts a politicized North American regulatory terrain where economic interests take priority over ethics. One wonders about the future direction, character, and outcome of regulatory reform in the UK given the North American experience. The narrow remit guiding reform and short or token consultation noted by Ashcroft et al suggests that a government agenda drives the centralization of ethics review. Whose interests will this agenda best serve? And how will centralized review affect research subjects’ rights and welfare – the protection of which remains in principle the purpose behind the historical existence of research ethics review. The REC system lacks transparency, a key ingredient of public accountably. The recent UK Health Committee report noted that industry influence in the NHS and regulatory bodies is pervasive and it identified tensions in regulatory affairs between public health interests and industry, noting that the Health Minister can not serve two masters. (4) All of this resembles the tension laden and conflicted north American regulatory experience which has produced ill results. Given industry influence, power, and strategies to promote its interests, coupled with the UK governments’ attempt to promote research an important sector of the economy, the concern has been raised that centralized review might accommodate economic interests at the expense of research subject’s rights and welfare. (5) One can only hope that ethical tunnel vision will not prevail in the UK regulatory culture as it has in North America. Time will tell. 1.Institute of Medicine, Responsible Research: A Systems approach for Protecting Research subjects, Washington DC, 2002. McDonald M. The governance of human research involving human subjects. Ottawa, Law Commission of Canada, 2000. 2.Doug Payne, Report Slams UBC ethics. The Scientist, November 15, 2004. 3.Kamran Abbasi, Is drug regulation failing ? BMJ;329: November 2004. 4.House of Commons Health Committee. The Influence of the Pharmaceutical Industry. London: House of Commons 2005. 5.Thomas Faunce, Paul Gatenby. Flexner’s medical oversight reprised? Contemporary medical education and the health impacts of corporate globalisation. Medical Education; Volume 39; Issue 10 Page 1066 - 1074, October 2005. Competing interests: None declared |
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Desmond R Laurence, Professor emeritus, university of london 37 Denning Road London NW3 1ST
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And who shall guide the guides? The new Royal College of Physicians (RCP) Guidelines for Research Ethics Committees [1] will lead Research Ethics Committee (REC) members to suppose that they may lawfully assent to clinical trials protocols which countenance that patient volunteers may be injured without a contractual right of compensation. Such a contractual right is indispensable: non- negligent harm occurs inherently and unpredictably in experimental research with human subjects. The RCP new Guidelines merely advise REC members to '. . . clarify whether (an applicant's) indemnity arrangements . . . extend to . . . (non -negligent injury)' (para 4.15). That enquiry is evidently to be an idle one; for the RCP Guidelines go on to endorse the Association of the British Pharmaceutical Industry (ABPI) Guidelines, which prescribe (for paid, healthy, trials subjects) a contractual right of compensation, but which withhold the same contractual right from unpaid patient trials subjects. The RCP's endorsement is astonishing; for it is manifestly unethical and (since 2004 [2]) has been unlawful, to purchase scientific advance through the ruination of injured patients. By law REC members must withhold assent from any protocol under which 'the rights, safety, and well-being of the trial subjects' do not 'prevail over the interests of science and society' [2]. The responsibilities of REC members for their decisions to give or withhold assent to a research protocol are their own inalienable legal responsibilities, from which no government official, and no professional body, has the power to absolve them. The RCP's new Guidelines fail to disclose its Committee for Ethical Issues in Medicine members' affiliations to the Department of Health; to the Medical Research Council; and to the pharmaceutical industry (all bodies which oppose the contractual right of compensation for non- negligent harm to patients). Nor does the RCP disclose financial interests, such as pharmaceutical industry funding of committee members' own research projects. It is a sad thing that a college of physicians can no longer even declare conflicts of interest, much less disentangle them; and that it can no longer prioritise the interests of patients. If REC members cannot do so either, then they may want to reflect that a REC member has personal legal liability for neglect of duty: patients seriously injured without right of compensation will simply sue the REC members. REC members may well then find themselves outside the protection of their (limited) appointing-authority indemnity. Desmond R. Laurence, Professor Emeritus of Pharmacology and Therapeutics, University of London. e-mail: d.laurence@virgin.net References: 1. Guidelines on the practice of ethics committees in medical research with human participants, Royal College of Physicians, Fourth edition, September 2007. 2. Sch.1 Pt2 (3) of the Medicines for Human Use (Clinical Trials) Regulations 2004. Competing interests: previously chairman and member of research ethics committees |
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Hugh Mann, Physician Eagle Rock, MO 65641 USA
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Let's recognize that scientific studies have many defects. First,
scientific studies
often reflect the bias of the scientist who conducts the study and
the financial
interests of the sponsor who pays for the study. For example,
studies that
recommend coffee are often conducted by scientists who drink
coffee and are
funded by coffee companies. Second, scientific studies ignore
competing
scientific theories. For example, pharmaceutical studies ignore
osteopathy,
homeopathy, naturopathy, acupuncture, and nutrition. Third, many
scientific
studies lack logic, predictability, and reliability, all of which are
essential to the
scientific method. For example, fifty percent of all scientific
studies are
contradicted by subsequent scientific studies, subjecting the
public to
misinformation, confusion, and apprehension. We must not
surrender our
common sense and independence to every scientific study or
theory. Life and
health are infinitely more complex than scientists realize or
admit. A lot of
science is just "lab oratory."
Competing interests: None declared |
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John Saunders, Chair of the Working Group; Chair, RCP Committee on Ethical Issues in Medicine Visitng professor, Bioethics Centre, University of Otago, PO Box 913, Dunedin 9054, New Zealand
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In an ethical clinical trial, there is genuine uncertainty about, or clinical equipoise (1) between, the benefits of one intervention rather than another. If nobody knows which intervention is best, the rational clinician would advise the rational patient to choose the intervention by chance (at random). An ethical clinical trial is no more than randomisation under conditions of uncertainty plus measurement (2). Non-negligent harm occurs every day inherently and unpredictably in clinical practice – and in daily life. (Most disease is a non-negligent harm). Ethical clinical trials are no different. The NHS has never offered indemnity for non-negligent injury and there is no “contractual right” for it to do so, as Laurence asserts. By contrast, the Association of the British Pharmaceutical Industry recommends indemnity for non-negligent injury even in patient trials (without legal commitment), recognising the controversies and distress that can so easily arise. The Royal College of Physicians (RCP) acknowledges that this inconsistency means that the situation for compensation in public sector bodies is less satisfactory (3). Healthy volunteers in phase one studies are, of course, in an entirely different position. There can be no genuine uncertainty/clinical equipoise about the intervention, for no intervention is indicated. It is false to suggest that trials are run to benefit future patients at the expense of present ones. Provided that the Research Ethics Committee (REC) has satisfied itself that genuine uncertainty/clinical equipoise exists, it will have discharged its “inalienable legal responsibility” to consider the prime importance of “the rights, safety, and well-being of the trial subjects” in the Clinical Trials Regulations that Laurence quotes. In an ethical trial these are no different from ordinary practice. The recently published Royal College of Physicians (RCP) Guidelines on the Practice of Ethics Committees in Medical Research do not permit scientific advance to be 'purchased' through the 'ruination of injured patients'. On the contrary, the RCP Guidelines clearly state that protection of 'the dignity, rights, safety and well-being of actual or potential participants' is the primary role of the REC (4). Indemnity issues are addressed in detail in sections 4.11 to 4.28 of the RCP Guidelines, as is the responsibility of the REC to satisfy itself that genuine uncertainty/clinical equipoise exists, in sections 5.4 to 5.20. As regards declaration of conflicts of interest, the Guidelines contain extensive biographical information on the members of the Working Group that produced them. The 21 members of the RCP Committee for Ethical Issues in Medicine exercised an overall supervision of the project only, as stated (5), as ultimately does Council of the College, and such declarations were not thought necessary. I note that Desmond Laurence fails to declare his own major interest as having been chiefly responsible for a previous edition of the Guidelines or indeed to make any declaration himself in the earlier edition. References 1 Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987;317:141-145 2 Ashcroft R. Giving medicine a fair trial. BMJ 2000;320:1686 3 Guidelines on the Practice of Ethics Committees in Medical Research with Human Participants, Royal College of Physicians, 4th edition, London, 2007. Para 4.22 4 Ibid Section 5.1 5 Ibid. Page xiii Competing interests: JS has been a local investigator in 5 commercial trials in the last 5 years without personal payment; attended sponsored meetings; done unremunerated work for RCP, MRC, the Department of Health, the National Research Ethics Service, the Department for Transport., the Health Protection Agency, Royal Society of Arts and Welsh Assembly Government. He is former chair of Gwent LREC and MREC for Wales. |
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Desmond R Laurence, Professor Emeritus, University of London 37 Denning Road, London NW3 1ST
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The Chairman of the Royal College of Physicians (RCP) Committee for Ethical Issues in Medicine seeks to counter my objection that its new guidelines for Research Ethics Committees (RECs) prescribe for RECs ethical standards which do not even meet the RECs’ legal obligations. The Chairman argues that, since (as is true) in routine clinical practice patients are not entitled to a right of compensation for non-negligent harm, patients participating in medical research are similarly not so entitled. It is hard to see how that argument could even begin to apply to, for example, the Chairman’s own ‘non-therapeutic invasive patient research’ (RCP guidelines, p.x). The RCP guidelines themselves rightly point out (para 3.4) that in research the ‘primary intention is to advance knowledge so that patients in general may benefit’. In routine medical practice, patients take risks for the benefit of themselves alone and not voluntarily on behalf of society as research subjects do. Society is greatly in debt to volunteers who are injured. Moreover, the Royal College is not free to lead RECs to disregard the law. The mandatory provision of a contractual right of compensation for serious non-negligent harm arises because ‘the rights, safety and well- being of the trial subjects shall (emphasis added) prevail over the interests of science and society’ [1]. Denial of compensation clearly breaches this statutory provision. The College’s Committee for Ethical Issues in Medicine is a major standing committee of the College. To state that it exercised an ‘overall supervision of the [Guidelines] only (emphasis added)’ simply will not do. And if it is indeed the case that the Council of the College delegates such an important document to a virtually unsupervised working party, the Council should have made a disclaimer that the words of the Working Party do not necessarily represent the views of the College. I am flattered to be told that my association with previous editions of the College Guidelines is a ‘competing’ interest that I should declare. It was modesty alone that prevented me from mentioning it. The Royal College having kindly published what it takes to be my competing interest, will it now publish the affiliations and competing interests of every member of its Committee for Ethical Issues in Medicine? Or must prospective research volunteers rather draw their own conclusions? Reference 1. Medicines for Human Use (Clinical Trials) Regulations 2004. Competing interests: Previously member of the Royal College of Physicians Committee for Ethical Issues in Medicine |
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Emily Jackson, Professor of Law London School of Economics, WC2A 2AE
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Schedule 3 Part 1 of the Medicines for Human Use (Clinical Trials) Regulations specifies a number of pieces of information that must be provided to the REC, or, in their absence, an explanation of why that information is not being provided. These include: (i) any provision for compensation in the event of injury or death attributable to the trial, (ii) details of any insurance or indemnity to cover the liability of the sponsor and investigator. For two reasons, it is evident that this part of the Regulations is not intended to make a contractual right of compensation for non-negligent harm mandatory. First, at the outset of Schedule 3 Part 1, it is clear that an explanation as to why this information is not being provided may, in certain circumstances, be an alternative to its provision. Secondly, the use of the word 'any' is important. RECs have a duty to consider 'any provision for compensation' and 'any insurance or indemnity', as opposed to 'the mandatory provision for compensation'. On the face of Schedule 3 Part 1 then, it would appear that RECs are entitled to consider applications which do not include such information. Of course it is true that the Regulations also specify that 'the rights, safety, and well-being of the trial subjects are the most important considerations and shall prevail over interests of science and society'. The RCP guidelines state this clearly at 5.1. Emily Jackson Competing interests: I have very recently become a member of the Royal College of Physicians Committee on Ethical Issues in Medicine. |
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Desmond R Laurence, Professor Emeritus of Pharmacology and Therapeutics, University of London 37 Denning Road,ondon NW3 1ST
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Professor Emily Jackson argues that it is not in every case that a Research Ethics Committee (REC) need insist that a clinical trial sponsor provide to research subjects an enforceable right of compensation for serious injury suffered in the trial. So it had better be conceded at once that, where in a clinical trial application a REC finds itself somehow able infallibly to predict that in the proposed trial there will be no unpredictable event, then an enforceable right to compensation for non-negligent injury may lawfully be dispensed with. Professor Jackson goes on to mention, but she does not discuss, the Medicines for Human Use (Clinical Trials) Regulations 2004’s important provision that ‘The rights, safety, and well-being of the trial subjects are the most important considerations and shall prevail over the interests of science and society’. But clinical trials typically involve novel drug use, or other invasive procedures. Such experiments are employed precisely because their outcomes cannot be fully predicted. So the chance of unpredictable injury to subjects is inherent in such trials. Professor Jackson does not show, nor do the Royal College of Physicians (RCP) Guidelines for RECs explain, how in such research there can possibly be compliance with the statutory provision when a REC permits the sponsor to withhold from subjects an enforceable right of compensation for serious non-negligent injury. The words ‘rights’, ‘safety’ and ‘well-being’ are not specially defined in the legislation: each is used in its ordinary English sense. But even so, REC members would have welcomed from the RCP an informed discussion of the effect of these words, and of how RECs might implement them. But far from that, the RCP Guidelines merely (and wrongly) claim that there is ‘little that RECs can do’ to ensure that there is enforceable compensation for non-negligent injury to patient volunteers (para 4.15). Such compensation is a matter which the RCP Committee for Ethical Issues in Medicine seems curiously unable to address. But the Committee is certainly able to publish its members affiliations and competing interests. I again call upon it to do so. Competing interests: Previously member of the Royal College of Physicians Committee for Ethical Issues in Medicine. |
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Ian T Gilmore, President, RCP Royal College of Physicians, 11 St Andrews Place, London NW1 4LE, John Saunders
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The Royal College of Physicians wishes to respond to Desmond Laurence’s letter of 25th November in order to refute its allegations. The intention in research is new knowledge but the moral case for special indemnity is based upon risk, not intent. Provided genuine uncertainty/equipoise exists, there is no additional risk to patients and hence no requirement for arrangements for indemnity for non-negligent injury. Patients do not take a risk on behalf of society in ethical therapeutic trials. They take the same risks as anyone else. As stated in the latest edition of the Royal College of Physicians (RCP) ‘Guidelines on the practice of ethics committees’ (5.10), equipoise cannot exist in patho-physiological studies of the effects of disease (- which may involve, for example, taking blood samples or administering isotopes-) or in much observational research. Ethical justification rests upon considerations of minimal risk, as defined in the Guidelines (5.13). In these situations, it is the responsibility of the research ethics committee (REC) to satisfy itself that risk is indeed minimal where there is no possibility of benefit. The situation regarding compensation for non -negligent harm should be detailed in participant information materials (4.28). Such compensation arrangements are not available in such research in the NHS without proof of negligence. The rights, safety and well being of the individual do prevail over those of science and society, provided risk is minimal. To express this differently, the voluntary acceptance of a minimal risk in the interests of a third party does not create a moral obligation to be provided with a contract of indemnity without proof of negligence. Laurence’s assertions about the law are not accepted by legal opinion available to us both before and after publication, nor indeed by others. The RCP does not lead RECs to disregard the law as alleged. All working groups at the RCP are established by its Council, after application and review. In common with other reports, these Guidelines were reviewed, debated and amended by Council on completion. As previously stated, the College's Ethical Issues Committee (CEIM) provided overall supervision of the project only, and declarations of conflicting interest are not therefore required in this particular context. However, Desmond Laurence will be informed personally by letter of the declarations of conflicting interest by committee members and these will be published on the College’s website to ensure access for all. Professor Ian Gilmore MD FRCP
Professor John Saunders MD FRCP
Competing interests: (Ian Gilmore) President of the Royal College of Physicians, and Chairman of its Board of Trustees. |
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Desmond R Laurence, Professor Emeritus of Pharmacology and Therapeutics,University of London 37 Denning Road, London NW3 1ST
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The President of the Royal College of Physicians, and the Chair of its Committee for Ethical Issues in Medicine, assert that a Research Ethics Committee (REC) must determine whether, in a proposed trial, ‘clinical equipoise’ exists, and if it does not, whether there will be ‘minimal risk’. The President, and the committee Chair argue that, if the REC is able to determine that either of these obtains, then patient volunteers in the trial would be in no worse a position than are ordinary clinical practice patients. So there could be compliance with the Medicines for Human Use (Clinical Trials) Regulations 2004, even if the trial sponsor does not provide for patient volunteers the enforceable right of compensation for non-negligent injury. The Medicines for Human Use (Clinical Trials) Regulations 2004 state that ‘The rights, safety, and well-being of the trial subjects are the most important considerations and shall prevail over the interests of science and society’. That is the law. In relying on a supposed loophole of ‘clinical equipoise’, the Royal College has descended into intellectual muddle. Clinical trials are typically statistical studies. And statistical studies are only needed when the beneficial and adverse consequences of the clinical use of, for example, a particular new molecular entity cannot be adequately predicted. So valid calculations of ‘equipoise’, and ‘minimal’ risk, cannot in general be made. In research ‘clinical equipoise’, and ‘minimal risk’, are particularly elusive circumstances, usually identifiable only with hindsight. In general RECs will be unable reliably to ascertain that either of them has been certainly identified by the sponsor. The President, and the committee Chair, go on to say that the enforceable right of compensation for subjects who suffer non-negligent injury is ‘not available in . . . research in the NHS’. But that only shows that RECs are failing to require the NHS to observe the 2004 law. As members of RECs will know, advice and opinion from the Royal College, or from the Department of Health, do not have the force of law. REC members are liable personally if they are negligent, and they have only a limited appointing-authority indemnity. So they must be ready to justify themselves in court if they decide to dispense with the enforceable right of compensation for research subjects who suffer non- negligent injury. As do we all in daily life, REC members need always to make prior legal judgements about their own proposed actions. So it is clearly necessary that the Royal College now publish, in full, the ‘legal opinion [it obtained] both before and after publication [of its new Guidelines for RECs]’. Publication will enable REC members to judge for themselves of the scope and applicability of that hidden advice, and to evaluate it for themselves using their own common judgement and experience. Competing interests: Previously member of Royal College of Physicians Committee for Ethical Issues in Medicine. |
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Desmond Laurence, Professor Emeritus of Pharmacology and Therapeutics University of London 37 Denning Road London NW3 1ST
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The Royal College of Physicians (RCP) is now advising Research Ethics Committee (REC) members that: a protocol [of a proposed clinical trial] should not be given [by a REC] an unfavourable opinion on the grounds of [the protocol’s] supposed illegality [1]. An illegal protocol will typically be one which denies to research subjects the protection prescribed by the Medicines for Human Use (Clinical Trials) Regulations 2004. Undoubtedly, a REC cannot give legal advice to trials sponsors. But as must we all, a REC must determine for itself that each of its own proposed actions is legal. And it is certainly not legal for a REC to procure the commencement of a clinical trial by expressing a favourable opinion of it, when it actually believes the trial to be illegal, and so has at that time no favourable opinion to give. The RCP’s advice is a serious error. But John Saunders, Chairman of the RCP’s Committee for Ethical Issues in Medicine, and an honorary professor in connection with Law in Healthcare, has recently said that ‘It is recognised that RECs cannnot reject a [proposed] protocol on legal grounds . . .’ [2]. Who recognises this, he does not say. Prospective trials subjects must, by law, be given every known fact that bears materially upon the decision to volunteer [3]. So if a REC were to follow the RCP’s advice, then prospective volunteers would have to be told that the REC’s ‘favourable opinion’ included an opinion that the trial was illegal, and that (for example) it appeared to deny to patient volunteers the protection the 2004 law demands for them. Prospective volunteers would then surely flee. So the RCP’s legal advice is hardly helpful to the Department of Health-sponsored UK Clinical Research Collaboration, which is calling for ‘large numbers of [new patient volunteers]’ for the purpose of ‘improving national health and increasing national wealth’. References: 1 Guidelines on the practice of ethics committees in medical research with human participants, 4th edition, Royal College of Physicians, September 2007, p.27, para 4.2. 2 Saunders J. Meeting the needs of the investigator and the REC member. Res Ethics Rev (2007) Vol 3, No.4, pp.111-112. 3 Medicines for Human Use (Clinical Trials) Regulations 2004, Sch.1, Pt. 2 (9). Competing interests: Previously member of the Royal College of Physicians Committee for Ethical Issues in Medicine: Contributor to previous editions of RCP Guidelines for Research Ethics Committees. |
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Hugh T Davies, Research Ethics Advisor, National Research Ethics Service National Research Ethics Service 4 to 8 Maple St London W1T 5HD
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Research Ethics committees and the law. In response to Professor Laurence (BMJ Letters Feb 19, 2008), it is clear RECs can not deliver a legal opinion and there are good reasons for this. Guidance is unambiguous. It is not part of their review and they are not accountable for a legal decision. The Research Governance for Health and Social Care (2nd edition, 2005) states in Section 3.12.7: "It is not the responsibility of research ethics committees described above to give legal advice" The Governance Arrangements for NHS Research Ethics Committees (GAfREC) (Section 9.11, July 2001) reiterates this advice: "It is not the role of the REC to offer legal opinion, but it may advise the applicant and the host NHS body whenever it is of the opinion that further expert legal advice might be helpful to them." This advice is, of course, almost identical to that expressed by the Royal College of Physicians in its Guidelines (section 4.2): "RECs should avoid expressing a legal opinion and a protocol should not be given an unfavourable opinion on the grounds of its supposed illegality. Should a committee believe that a proposal contravenes the law, it should ask the principal investigator to seek further independent legal advice." It is not necessary for the REC to review that advice as the REC's only function is to offer an ethical opinion and not a legal one. The responsibility for ensuring compliance with the law rests with the investigator, under the aegis of the research governance structures. Competing interests: I work as the Research Ethics Advisor at the National Research Ethics Service and have been involved in implementing guidance for RECs |
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John Saunders, Chair, Committee for ethical issues in medicine, Royal College of Physicians of London Nevill Hall Hospital, Abergavenny NP7 7AG
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Desmond Laurence’s latest assertions are fantasy. RECs do not “procure” the commencement of a trial by giving a favourable opinion of it if they have any concerns about its lawfulness. They are expected to advise the investigator to seek legal advice. This opinion is copied to those involved in Research Governance under the Standard Operating Procedures. Compliance with the law is the responsibility of the investigator. It is impossible to commence a trial that might be illegal without deliberately flouting the REC’s advice. Apart from that impossibility, a volunteer could not be told that a clinical trial included the REC’s opinion that a trial is illegal because the REC does not express a legal opinion (as Laurence incorrectly asserts). The restriction of the REC to expressing ethical opinion only is, of course, laid down by the Research Governance Framework, with which he appears unfamiliar. The logic of expressing an ethical opinion despite possible reservations about the law is no more unlawful than expressing a scientific or economic or literary or anything else opinion, despite reservations about the law. Ethics and law are not the same thing. It’s actually as simple as that. Competing interests: as previously declared |
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Desmond R Laurence, Professor Emeritus of Pharmacology and Therapeutics, University of London. 37 Denning Road London NW3 1ST
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Hugh Davies (BMJ Rapid Responses 3 March 2008) says that a Research Ethics Committee (REC) ought not to give legal advice to others. I had, of course, agreed with that myself, in the letter to which Hugh Davies responds: for a REC would be foolish to presume to dispense legal advice. The Royal College of Physicians (RCP) in its Guidelines for RECs (para 4.2) also agrees, but goes on to add something quite different, and quite extraordinary: ‘. . . and a protocol [of a proposed clinical trial] should not be given [by a REC] an unfavourable opinion on the grounds of [the protocol’s] supposed illegality’. [1] The Medicines for Human Use (Clinical Trials) Regulations 2004 is not an official’s opinion: it is the law. REC members are bound to obey it. And it provides that no-one may legally start a clinical trial unless a REC has expressed a favourable opinion upon its protocol. Hugh Davies is suggesting that REC members need not trouble to consider, in each clinical trial application before them, whether or not it is legal for them to express a favourable opinion of its protocol. Yet it is manifestly illegal for REC members to express a favourable opinion of a protocol which they believe to be illegal: because they have at that time no favourable opinion to express. There is nothing in what John Saunders has said (BMJ Rapid Responses 5 March 2008) which even attempts to counter this crucial point. For a REC may not abdicate to the sponsor its own legal responsibilities: the sponsor must persuade the REC that the protocol is legally compliant; or the sponsor must change the protocol so that it becomes compliant. Both John Saunders and Hugh Davies cite, as though they were law, guidelines issued by their respective organisations. But they are not law, they are opinion and advice. The decision-making of RECs is now governed by law. When official, professional, or any other guidelines are calculated to procure breaches of the law, those guidelines must, as a matter of law, be disregarded by RECs. Hugh Davies is a research ethics advisor, and he is the spokesman of the Department of Health’s National Research Ethics Service. If the Department wants to tell us that the RCP’s advice in its para 4.2 is legally correct, then it ought to detail a lawyer, and not just a composer of guidelines, to tell us exactly how, in law, that can be. And the RCP itself should now publish in full the legal opinion upon which it has said it relies [2], and it should identify the source of that opinion. For the RCP’s para 4.2 is not legally correct. It is a danger to the rights, safety, and well-being of volunteer clinical trials subjects when it leads them to participate in illegal trials. And it is a danger to the personal wealth of volunteer REC members when they unsuccessfully defend negligence claims. The consent given by trials subjects will not be legally valid unless they are told in advance that the REC has assented to the protocol irrespective of whether it believes the trial to be illegal; and that the REC may believe the protocol to be in breach of a law specifically intended to protect trials subjects. And it is the legal duty of the REC to see to it that prospective trials subjects will indeed be told of that situation. Even when endorsed, as we now see, by the Department of Health, the RCP’s para 4.2 is folly. The RCP must retract it. References 1 Guidelines on the practice of ethics committees in medical research with human participants, Fourth edition, Royal College of Physicians, September 2007, p.27, para 4.2 2 Correspondence between Laurence D R; Saunders J; Gilmore I T, http://www.bmj.com/cgi/eletters/331/7517 (Rapid Responses to Ashcroft et al.), (13 December 2007). Competing interests: Previously member of the Royal college of Physicians Committee for Ethical Issues in Medicine:Chairman of a Research Ethics Committee. |
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Desmond Laurence, Professor Emeritus University of London 37 Denning Road,London NW3 1ST
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No person may legally start a clinical trial unless a Research Ethics Committee (REC) has expressed a favourable opinion upon its protocol [1]. The Royal College of Physicians (RCP), in its new Guidelines on the Practice of Ethics Committees in Medical Research with Human Participants, advises REC members that they legally have, and should exercise, a power to express a favourable opinion of a clinical trial protocol when in truth they believe the protocol to be illegal [2]. I have argued that this (and other advice in the Guidelines) is incorrect legal advice which, if followed, would deprive ‘human participants’ of the protection the law prescribes [3]. In a published letter of 13th December 2007 the President of the RCP countered that my ‘assertions about the law are not accepted by legal opinion available [to the RCP] both before and after publication [of the Guidelines]’ [3]. Now a college of medical doctors is no natural repository of legal expertise. So when it is issuing legal advice for others to rely upon, ‘legal opinion available to us’ can only mean counsel’s opinion (from an eminent and independent QC). I subsequently pressed for the publication of the opinion [3]. On 4th March 2008 the President wrote to me refusing to publish it and refusing to name its source. It had ‘not been sought in the context of a formal legal opinion’. I am grateful to the President for his admission. But members of Research Ethics Committees have only a limited appointing-authority indemnity [4, 5]. So it will not do for the Royal College of Physicians to fob them off with views obtained informally from people whose qualifications, affiliations, conflicting interests and identities are all to be kept secret. If the College insists that the legal advice it presumes to issue is correct, let it now obtain and publish the ‘formal legal opinion’ of a QC who concurs. Email: d.laurence@virgin.net References: 1. Medicines for Human Use (Clinical Trials) Regulations 2004. No.1031. Part 3, 12. 2. Guidelines on the Practice of Ethics Committees in Medical Research with Human Participants, Fourth edition, Royal College of Physicians, September 2007, p.27 para 4.2. 3. Correspondence between Laurence D R; Saunders J; Gilmore I T, http://www.bmj.com/cgi/eletters/331/7517/587 (Rapid Responses to Ashcroft et al.), (2007-2008). 4. Department of Health: Governance Arrangements for NHS Research Ethics Committees (GAfREC) (Section A 4.14) www.dh.gov.uk publications GAfREC 5. Steiner T J. Indemnity for REC members. Research Ethics Review 2006; 2: 39. Competing interests: Previously member of Royal College of Physicians Committee for Ethical Issues in Medicine, and Chair of a Research Ethics Committee |
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Desmond R Laurence, Professor Emeritus of Pharmacology and Therapeutics, University of London 37 Denning Road London NW3 1ST
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The Medicines for Human Use (Clinical Trials) Regulations 2004 make it illegal for anyone to start a clinical trial unless a Research Ethics Committee (REC) has expressed a ‘favourable opinion’ of the protocol [1]. The same law also sets out the basis upon which REC members shall arrive at their opinion, by imposing conditions and principles that apply to all clinical trials, including: “The rights, safety, and well-being of the trial subjects are the most important considerations and shall prevail over the interests of science and society” [Sch.1 Pt2(3)]. But in a move calculated to subvert the 2004 law, the Royal College of Physicians (RCP) has advised REC members that: “A protocol [of a proposed clinical trial] should not be given [by a REC] an unfavourable opinion on the grounds of [the protocol’s] supposed illegality” [2]. In a recent paper, the barrister Christopher Roy-Toole has shown that the RCP’s advice is ‘wrong in law’ [3]. The Department of Health and the RCP are now sending to all RECs a joint letter to ‘reassure’ the RECs that Roy-Toole is ‘erroneous’ [4]. But the DH/RCP derive their view from their own startling misrepresentation of Pt.2, S.7(3) of the 2004 law. For the passage they cite does not contain a statutory definition of the role of a recognised REC (as DH/RCP claim it does), nor does the passage absolve RECs from their duty under the law to provide reliable public assurance of patient protection. Happily, and as Roy-Toole has pointed out, RECs need only obey the law and should not act on mistaken views offered by official or professional bodies baffled by competing interests. As I have said elsewhere, if it were right that a REC could lawfully express a favourable opinion upon the protocol of what it believed to be an illegal clinical trial, then that fact would, as a matter of law, have to be declared to prospective patient or other volunteers [5]. The President of the RCP has declined to cite any legal authority supporting its bizarre legal advice to RECs. But a distinguished barrister, Sally Smith QC, sits on the RCP’s Committee for Ethical Issues in Medicine. In private correspondence with me Sally Smith has refused say whether or not she believes her committee’s advice (in para 4.2 of the RCP Guidelines) to be correct law. I now call upon Sally Smith QC publicly to answer that simple point, and publicly to cite legal authority for her answer. References: 1 Medicines for Human Use (Clinical Trials) Regulations 2004. No.1031. Parts 2,3, Schedule 1. www.opsi.gov.uk/si/si2004.20041031.html#sch1 (accessed August 2006) (minor revisions 2006) 2 Guidelines on the practice of ethics committees in medical research with human participants, Royal College of Physicians, Fourth Edition, September 2007, para 4.2 3 Roy-Toole, C., Illegality in the research protocol: duty of research ethics committees under the 2001 Clinical Trials Directive. Res Ethics Rev 2008; 4(3): 111-116 4 Taylor, C. Marc; Saunders, J.; & Davies, H., Letter: Research Ethics Committees and legal opinion (shortened version). Res Ethics Rev 2008; 4(4): 165-166 5 Laurence, D. R., Guide, Guide Thyself: Law & Order in Clinical Research. Res Ethics Rev 2008; 4(2): 69-72 Competing interests: Previously member of the Royal College of Physicians Committee for Ethical Issues in Medicine |
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Desmond R. Laurence, Professor Emeritus 37 Denning Road, London NW3 1ST
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Royal College of Physicians (RCP) Guidelines advise Research Ethics Committees (RECs) that ‘a [clinical trial] protocol should not be given [by RECs] an unfavourable opinion on the grounds of [the protocol’s] supposed illegality’ [1]. That is momentous legal advice; for without REC favourable opinion it is illegal for a clinical trial to proceed [2]. The Department of Health (DH) endorsed the RCP’s legal advice, in a published joint letter to the RECs [3]. But now the DH, through its National Research Ethics Service (NRES), has issued a new draft of its GAfREC (Governance Arrangements for Research Ethics Committees) [4]. The new draft accepts, at last, what I have been pointing out [5]. For DH/NRES now admits: ‘RECs must operate according to the law’. So RECs cannot, after all, express favourable opinion of clinical trials they in reality think illegal. For the law requires RECs to ensure that the ‘rights, safety, and well-being of the trial subjects . . . prevail over the interests of science and society’ [6]. But curiously, DH/NRES adds that RECs (when deciding whether or not to assent to research proposals before them) need only apply the criteria set out in law ‘where required’. So are we to understand that the Secretary of State is seeking to procure breaches of the law? For REC members will now ponder whether they have been ‘required’, by the trial sponsor or somebody, to apply the law’s criteria. Yet the requirement to obey the law arises only from the law itself. The Department’s notorious endorsement of the RCP’s indefensible subversion of the law puts REC members on enquiry. For REC members in breach of the law have unlimited personal liability to injured subjects. Legal advice offered to REC members by professional and public bodies decidedly does not have the force of law. REC members should demand the origin and provenance of such gratuitous advice. The RCP has admitted that it issued its advice to RECs (that they ought to assent to trials protocols they think illegal) without itself taking ‘formal legal opinion’ [7]. So will the DH now disclose what legal opinion it may have obtained supporting its own idea that the law need be obeyed sometimes, but sometimes need not? And may we know who is expected to profit from the breaches of the law the Department, and the Royal College, envisage? References 1. Guidelines on the practice of ethics committees in medical research with human participants: fourth edition. Royal College of Physicians, September 2007 (para 4.2) 2. Medicines for Human Use (Clinical Trials) Regulations 2004 (Statutory Instrument 2004, No.1031): Part 3(12): and Schedule 1: Part 2(3) 3. nres.npsa.nhs.uk/joint-letter-from-rcp-dh-and-nres 4. nres.npsa.nhs.uk/. . . /harmonized-gafrec-consultation :[para 3.2.10] 5. Correspondence between Laurence DR; Saunders J; Jackson E; Gilmore IT, http.bmj.com/cgi/eletters/331/7517 (Rapid Response to Ashcroft et al. 6 November 2007 to 12 February 2009) 6. See Ref 2 above: Schedule 1 : Part 2(3) 7. Personal communication from the President of the RCP, 4 March 2008. Competing interests: Professor Emeritus University of London: past member RCP Committee for Etical Issues in Medicine |
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