Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
The Ethics of Cost
- R V Hazlehurst (8 May 2000)
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Author's reply
- Joanna Tully (9 May 2000)
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A European issue
- Alain Braillon (19 May 2000)
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Should multi-centre research ethics committee approval alone be sufficient?
- David Dunn (23 May 2000)
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Multicentre Research Ethics Committees
- Dan Shears (23 May 2000)
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LRECs have a constructive role in multicentre research
- Christine Brown (26 May 2000)
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Role of LRECs in review of MREC decisions
- Peter A Andrews (4 June 2000)
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Ethical review of multicentre research
- Donal Manning (20 June 2000)
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R V Hazlehurst, GP Dounby Surgery and Balfour Hospital, Orkney.
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Contributors to various of the articles in the 29th April edition complain about the cost to them of seeking approval from local ethics committees. Have they considered the cost of these trials, to the local health services in remote areas? I practice in Orkney and a number of my patients have been enrolled in two multi-centre trials, which involve repeated treatments or follow up in the nearest centre of excellence 300 miles across the North Sea in Aberdeen. A standard return air fare from Orkney to Aberdeen is £250 (I note that most of the authors of these articles are from urban areas, whence they could expect to cross the Atlantic for considerably less than this). Let's suppose that 10 patients, out of a total population of 20,000, were enrolled on each of these trials and each trial involved 5 trips to Aberdeen. That would mean our Health Board having to fund £25,000 in travel costs alone. Is this one of the "local factors" which should be taken into consideration by our ethics committee? I can certainly think of more ethical uses for that amount of Health Service funding, which do not simply subsidise the dividends paid to British Airways shareholders. |
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Joanna Tully, Clinical Research Fellow Institute of Child Health
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Editor, Hazlehurst comments on the cost to local health authorities of participating in multi-centre research and the role of local ethics committees in sanctioning costly local research. There is no doubt that this is an issue that local ethics committees should be considering. The cost to an individual health authority or hospital trust is a "local factor" and as such falls under the remit of consideration by LREC's. From the point of view of our study, the only cost to local institutions was that of a small amount of staff time to take a sample of blood and two swabs. All other costs were budgeted and accounted for in our original grant application and were therefore borne by the funding charity. Had we been expecting individual trusts to contribute significant financial resources to the study (such as £25,000!) we would have had no problem with answering their queries on this aspect of our ethics application. It is not these real local issues that caused the frustration and unnecessary delays described in our paper. There is a distinct difference between this kind of financial consideration and requests for minor changes to documents or significant delays in responding. We do appreciate the important role that local ethics committees play, and the point made here by Hazlehurst illustrates this perfectly. It seems to me that there is no more appropriate a role for a local ethics committee than that described here. Joanna Tully (author)
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Alain Braillon
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To the editor - Tully and colleagues (1) evaluated the new system of review by multicentre research ethics committees in England. In France, since 1990 the system for review is organized by law. The committees named "commitees for the protection of the people who participate to research" a more exact definition of their role, are organized by the ministery of health. There are 46 commitees: one by region but 14 for Ile de France which concentrates 40% of research activities. They must communicate their decision within 5 weeks, and approval given by any commitee have national acceptance. The added value of local committees is not clear: Procedures or regulation are lacking and enforcement would be hardly possible, activity is low and conflicts of interesset may exist. Suitability of local researchers and of the site is an important issue, however, considering the stakes of multicentre research, this point is crucial for the sponsor and usualy he is the one who has this information. The main main issue is not national but European. National regulations or laws for research vary from country to country and differ from ICH procedures. Pharmaceutical compagnies are able to deal with this burden which is an obstruction for institutional research. A prospective study as this one (1) is lacking at the European level but the case report (2) by Cornu and colleagues is revealing. Alain Braillon MD
1 Tully J, Ninis N, Booy R, Viner R. The new system of review by multicentre research ethics commitees : prospective study. BMJ 2000;320:1179-82 2 Cornu C, Cano A, Melis GB, Boissel JP, UTERP Pilot Study Group. Could institutional clinical trials exist in Europe? Lancet 1999;353:63-4 |
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David Dunn
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The recent articles by Tully et al. and Lux et al. highlight the problems in the two-tier research ethics committee system for multi-centre studies.1,2 A number of suggestions are proposed in the articles and accompanying editorial to lighten the administrative burden that the current system places on researchers. There is a more fundamental point, however, that was not raised: if a national ethic is accepted what is the rationale for requiring local research ethics committee (LREC) approval after multi-centre research ethics committee (MREC) approval has been obtained? The changes requested and comments received from local research ethics committees (LREC), tabulated by Tully et al., are not enlightening. First, the non-local changes requested (67% of total requests) were outside the remit of the LREC. Although the authors found that some of the general criticisms were constructive there is a strong disincentive to modify the study protocol since, by the rules, this would mean re- submission to MREC and then to each individual LREC. Second, the relatively small number of local changes and comments ranged from the trivial (e.g. LREC number to be written on local documents) to issues that the local investigator with the trial sponsor would almost certainly have considered anyway (e.g. ethnic mix to be considered). There were thus no tangible benefits from an exercise that both delayed the start of the study and involved considerable effort. Incidentally, the reported cost of the application (£6132) took no account of labour costs (both of the research team and of the 125 individual Trusts in processing the applications) nor of the cost to the environment of 100,000 pages of paper. Any re-assessment of the current system for reviewing multi-centre studies should be fundamental and consider whether MREC approval alone is sufficient. 1. Tully J, Ninis N, Booy R, Viner R. The new system of review by multicentre research ethics committees: prospective study. BMJ 2000; 320:1179-82. 2. Lux AL, Edwards SW, Osborne JP. Responses of local research ethics committees to a study with approval from a multicentre research ethics committee. BMJ 2000; 320:1182-83. David Dunn
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Dan Shears
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Dear Editor - I read with interest the papers describing the difficulties of applying to The Multi - Centre Ethics Committee (MREC) and subsequent Local Research Ethics Committees (LRECs) in order to gain approval for multi-centre studies (BMJ 29 April 2000). The dispassionate and scientific account given in the Tully et al1 paper, which appraises the workings of the MREC/LREC system and suggests some sensible modifications, is tempered by Lux et al`s2 less magnanimous critique which asserts that there is no evidence that the introduction of MREC has resulted in anything but the perpetuation of the old inefficiencies. Nicholl`s3 personal view is that Ethics Committee`s have in fact become barriers to ethical research, a state of affairs that is "immoral". Clearly feelings run high when faced with over-scrupulous ethics committees, when one is under pressure of time. It is not surprising, however, that in the light of recent media coverage of dead childrens` organs being taken without their parents consent, and the universal acceptance that we should be more accountable for mistakes and wrong doing, that Ethics committees are becoming more vigilant, if not pedantic, about the kinds of research that they are sanctioning in their Trusts. Doctors engaging in research are naturally, perhaps necessarily, impatient that they execute their research with the maximum of efficiency and feel horribly frustrated when impeded by the slow and lumbering process of careful and thoughtful consideration of matters ethical. I can identify with these feelings of frustration and impotence as I am in the final stages of wrestling with 21 ethics committees over my own multi-centre study, a process which has taken some 6 months, virtually full-time. Ethics committee`s exist to ensure that patients interest and rights are protected and best served by research and not infringed on by researchers impatience to collect their data and publish it. Researchers, by contrast, feel an acute sense of responsibility to their sponsor, particularly if it is a charitable organisation, and to the patients that their study might ultimately benefit. This sense of responsibility includes an urge to publish one`s findings in a timely fashion. Perhaps we might ease our frustration by allowing for a period of up to 6 months, to gain multiple LREC approval, in our grant applications. This would alert the sponsors of the problem who might themselves approach the MRECs if they were finding it unacceptable to employ clinicians for this period of time in order to undertake an essentially administrative task. Alberti4, in his editorial, calls for stronger guidance and support for the LRECs as well as a number of simplifications to the bureaucracy. I would strongly support simple measures such as a central register of LRECs made available through MRECs, standardised numbers of copies for applications to LRECs, and electronic (e-mail) applications that would rationalise the process and lower frustration as well as speed up timely commencement of research. On a broader scale, the LRECs should be made directly accountable to the MREC, having to justify any questions or suggested modifications through the chair of the MREC. To formalise the chain of accountability in this way, would appropriately relieve the LRECs of some of their responsibility, pertaining to non-local issues, which is likely to make the difference between them viewing MREC approved studies differently from local studies, or not. Dr. Dan Shears
References: 1. Tully J, Ninis N, Booy R, Viner R.The new system of review by multicentre research ethics committees: prospective study. BMJ 2000;320:1179-82. 2. Lux A L, Edwards S W, Osborne J P. Responses of local ethics committees to a study with approval from a multicentre research ethics committee. BMJ 2000;320:1182-3. 3. Nicholl J.The ethics of research ethics committees. BMJ 2000;320:1217. 4. Alberti K.Multicentre research ethics committees: Has the cure been worse than the disease? BMJ 2000;1157-8. |
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Christine Brown
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EDITOR - As medical researcher and local research ethics committee (LREC) chairman currently engaged in negotiating a multicentre research ethics committee approved application, we would like to sound a note of caution at Tulley et al's suggestion that approval should not be delayed because of non-local issues. As their own study demonstrates, LRECs often provide constructive criticism and are able to identify issues that multicentre research ethics committees have overlooked. In stating that "approval should not be delayed because of non-local issues" the assumption is that approval will be given. This is not necessarily the case. In a qualitative study involving in-depth interviews of patients detained under the category of psychopathic disorder of the Mental Health Act 1983, mutlicentre research ethics committee approval was sought because the tertiary nature of services led to recruitment of subjects within the boundaries of more than five local research ethics committees. The ethical issues surrounding interviewing mentally disordered offenders are complex and although considerable care and time were taken by the multicentre research ethics committee before granting approval, on application to the local research ethics committee further valid points were raised regarding patient confidentiality. As the local committee, following NHS guidelines felt they could not request non-local changes, the application was rejected in the first instance. Had the local research ethics committee been able to request changes that all parties subsequently agreed were necessary, then the considerable dismay resulting from rejection could have been avoided. We believe the suggested improvements of standardised forms submitted electronically and a national advisory body to aid communication, training and guidance would be welcomed by both researchers and committee members alike. The consequence of assuming that local research ethics committee approval will automatically follow multicentre research ethics committee approval may be an increase in research protocol rejections. A flat "no" is a greater obstacle to research than a tardy "yes, as long as…". Dr Christine Brown, Robert Baxter Research Fellow, Department of Mental Health, University of Exeter, Wonford House, Dryden Road, Exeter, EX2 5AF; The Reverend Dr Peter Goold, Chairman, Broadmoor Hospital Research Ethics Committee, Crowthorne, Berkshire RG45 7EG Dr Keith Lloyd, Head of Department, Department of Mental Health, University of Exeter, EX2 5AF |
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Peter A Andrews, Consultant Nephrologist, LREC member SW Thames Renal & Transplant Unit
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EDITOR- We read with interest the articles and commentary relating to the relative roles of Local and Multicentre Research Ethics Committees (LRECs and MRECs).1-4 However, we are concerned that they place undue emphasis upon the cost and delay engendered by the current two-tier system, and fail to recognise that LRECs have an important role in quality assurance. At our hospital, an MREC sub-committee was established in June 1999 with the aim of reducing the time and cost of considering MREC approved research protocols. The MREC sub-committee has never regarded itself as a rubber stamping exercise, and has always insisted on the right to comment on any issues arising from studies submitted where it feels that they have been missed or have not been properly addressed by previous reviewers. We have audited the 38 MREC submissions considered by the MREC sub- committee since its inception. Whilst 22 were reviewed and approved, 16 (42%) gave cause for significant concern. These issues were raised with the relevant MREC chairpersons, who provided explanation and reassurance in six cases. In a further six cases, our comments resulted in significant improvements to the previously approved protocol: grossly abnormal results to be reported to the patient's general practitioner; protocol tightened to ensure that a control group was disease-free; substantial changes to a poorly-worded questionnaire; corrected exclusion criteria with amended conflicting advice regarding contraception; addition of an information sheet for young children; corrected wording on a patient information sheet and consent form. We are awaiting a response from the MREC chairperson in the remaining four cases. Whilst we agree that multicentre research should not be unnecessarily delayed, local review helps to ensure that clinical research is of the highest clinical and ethical standard. In times of increased media and public concern, it is appropriate to record that a two-tier system offers an additional failsafe and may uncover important points that MRECs may have overlooked. Peter A Andrews consultant nephrologist, LREC member Steven L Hyer consultant endocrinologist, LREC member A Hervey Wilcox consultant chemical pathologist, LREC chairperson St Helier Hospital, Carshalton, Surrey SM5 1AA pa.andrews@btinternet.com We confirm that we have no competing interests. 1. Alberti KGMM. Multicentre research ethics committees: has the cure been worse than the disease? BMJ 2000; 320:1157-8 (29 April.) 2. Tulley J, Ninis N, Booey R, Viner R. The new system of review by multicentre research ethics committees: prospective study. BMJ 2000;320:1179-82 (29 April.) 3. Lux AL, Edwards SW, Osborne JP. Response of local research ethics committees to a study with approval from a multicentre research ethics committee. BMJ 2000;320:1182-3 (29 April.) 4. Nichol J. The ethics of research ethics committees. BMJ 2000;320:1217 (29 April.) |
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Donal Manning, Chairman, Wirral Health Authority Local Research Ethics Committee & Consultant Paediatrician Arrowe Park Hospital, Upton, Birkenhead
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The recent papers on multicentre research ethics committees1,2 did not seek the views of local research ethics committees. Wirral Health Authority Research Ethics Committee monitored the first two years of the system by reviewing aspects of multicentre committee approved studies. We agreed with multicentre committee ethical analysis in 60 (64%) of 93 studies. We identified substantial problems with patient information leaflets in 25, with other documentation in 5, and with study design in 3 studies. Fewer problems were identified in the second year (25% of studies) than in the first year (48% of studies) Problems identified in information sheets included the failure to explain the nature and purpose of the study, unclear indemnity arrangements, inadequate account of trial drug side effects, assumption of benefit from trial entry, inaccurate description of placebo, and failure to mention treatment alternatives. These problems are worrying given the importance of informed consent in research. We were particularly concerned to identify problems with study design. The most important was in a study comparing two bronchodilators to be delivered by different inhalers. The study drug was to be given by a device that the application stated was preferred by most patients. We felt that the results would be interpretable, and thus the study was unethical. The main concern expressed by local committees at the introduction of the new system was that problems in study design might be missed by single committee review. The old system provided a safety net in that design faults could have been picked up by at least one local committee. Indeed, Tully et al acknowledged that constructive criticism by local committees led to improvements in their study protocol1. Local committees would have more confidence in single committee review if multicentre study applications were accompanied by independent scientific critiques or referees’ comments. Requests to investigators for these, however, are often ignored. Another solution would be for multicentre committees to specialise, since each committee cannot represent all specialties. |
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