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EDITORIALS: Charles Warlow Clinical research under the cosh again BMJ 2004; 329: 241-242 [Full text]

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Rapid Responses published:

Ethics committees and Oncological Terrain: “Who controlls controllers?”.

Sergio Stagnaro   (30 July 2004)

Are Ethics Committees Ethical?

Peter A West   (30 July 2004)

Clinical audit does not escape the cosh

Jonathan R Bayly   (30 July 2004)

Research governance

Barbara A Sen   (31 July 2004)

Research Governance and multi-centre health services research.

Thomas E Locker, Suzanne Mason- Senior Clinical Lecturer, Professor Jon Nicholl - Director Medical Care Reserach Unit, Professor Susan Read- Chair in Nursing Research University of Sheffield School of Nursing and Midwifery   (2 August 2004)

ETHICS SHOULD BE UNIVERSAL AND IMPARTIAL

Kaushal R Pandey   (3 August 2004)

Ethics committees are not the bad guys!

Tim M Reynolds   (3 August 2004)

Time for institutional review boards?

Tom Meagher   (5 August 2004)

In research, one size will not fit all

Peter N Furness   (9 August 2004)

The view from a REC

Jammi N Rao   (11 August 2004)

Will it ever recover from the blow?

David L J Freed   (11 August 2004)

Frustrating Bureaucracy in Clinical Research

Peter A Goulden   (11 August 2004)

Ethics committees

John M Walshe   (12 August 2004)

Clinical Research: ethics committees are not the problem

Anthony S. Wierzbicki   (17 August 2004)

Palliative care research: catch 22

Lara J Alloway, Irene J Higginson   (18 August 2004)

Ethical Review - seeking a balance

Sir John Pattison, Professor Terry Stacey, Director, Central Office of Research Ethics Committees   (18 August 2004)

Ethics committees and Oncological Terrain: “Who controlls controllers?”. 30 July 2004
Sergio Stagnaro, Specialist in Blood, Gastrointestinal, and Metabolic Diseases. Researcher in Biophysical Semeiotics Via Erasmo Piaggio 23/8 16037 Riva Trigoso (Genova) Italy Send response to journal: Re: Ethics committees and Oncological Terrain: “Who controlls controllers?”.	Sir, certainly there is a need of the regulation of clinical research by ethics committees, although they sometimes “may impede and delay research, sometimes even to distort the methods so much that the conclusions are flawed and patients damaged—an unintended unethical consequence” (1). As regards my latest clinical researches (2, 3), however, I have willingly ignored all italian ethics committees, not to speak of national and international differences, but not patient’s advantage and “my” conscience, as I did always. I’dd like to be told, in addition, what these honourable authorities all over the world, without exception, are thinking about Oncological Terrain and its Melatonin-Adenosine therapy associated to proper diet, ethymologically speaking? (2,3). In fact, there is a line of demarcation, that divides individuals in two clear-cut parts: on the one hand, who "may" be involved by cancer, and, on the other hand, who will surely not involved by malignancy (See website HONCode 233736, www.semeioticabiofisica.it), according to my theory of Single Patient Based Medicine, now-a-days recognized also by EU Competent Authorities for European Health Planning, for Cancer Primary Prevention, http://europa.eu.int/comm/health/ph_information/documents/ev_20030710_co01_en.pdf , wherein they quote a Rapid Response of mine from BMJ. Finally, another question: “Who controll controllers?”. 1) Warlow C. Clinical research under the cosh again. BMJ 2004;329:241-242 (31 July), doi:10.1136/bmj.329.7460.241 2) Stagnaro-Neri Marina, Stagnaro Sergio. Introduzione alla Semeiotica Biofisica. Il Terreno oncologico”. Travel Factory SRL., Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm 3) Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Ediz. Travel Factory, Roma, 2004. Competing interests: None declared
Are Ethics Committees Ethical? 30 July 2004
Peter A West, Director YHEC Ltd, University of York, York YO10 5NH Send response to journal: Re: Are Ethics Committees Ethical?	Sir, We too have had some difficulties in getting our research approved by ethics committees. While we accept the need for them and their important role, there is clearly a danger that the balance is shifted so far towards patient and staff protection that research becomes undoable. In a study involving interviewing doctors and their secretaries about waiting list management, we were asked to include in the information to staff details of how we would respond if we found that staff were doing something wrong, e.g. hiding waiting patient files away in a cupboard to keep the list down. It seemed to us that this, along with a wide range of potential abuses, were things that NHS staff should not be doing and that we would be justified in reporting them to local managers. But to include this or other such threats in information to recruit staff for an interview on administrative matters seemed to risk protecting staff who were misbehaving from scrutiny while also discouraging the rest of the staff from joining in. Should I, before interviewing a doctor, warn them that if I see them abusing patients I will report it or should I assume that they will expect this? I attended an ethics committee and at one stage all 12 members seemed to be taking turns at asking me questions. I pointed out that I had not been advised of the procedures of the meeting in detail, had not signed a consent form to this interrogation and had not received prior notice of their questions, all steps they expected me to take in my research. I also pointed out that I did not see how they could do their business if they applied their own standards and that I thought what they were doing and what I was proposing to do were equally reasonable, balancing the interests of the parties involved. We also had a study challenged on the grounds that asking junior doctors to fill in a short form, taking a maximum of 1-2 minutes after dealing with an urgent call to a patient, would threaten patients' health because of the short staffing of hospitals. We asked that the ethics committee report the hospitals where this was seen as likely to occur, on the grounds that even without our form (to be filled in for a period of one or two weeks) such hospitals were perilously close to being unfit for patients. We are not aware of any action taken by this ethics committee. We want to do things in a way that is ethical to staff and patients and which gives the DH, our usual client for research involving staff and patients, information on how managerial and service changes are going. We note that all manner of service changes can be brought it without ethical approval, since they are not research but service. But if the service has been changed, surely it is worth finding out whether anyone is benefiting, even at the risk of imposing a little on the time of staff and patients. Ethics committees are in danger of becoming (in the eyes of researchers) organisations where people seek as hard as they can for potentially adverse effects from research, rather than organisations which balance the need for an ethical approach to patients and staff, which I fully endorse, with the need to find our more about what the NHS does well or badly. It is the lack of an apparent willingness to strike a balance which researchers, committed to an ethical approach, find so frustrating. Competing interests: YHEC is a contract research company that carries out funded research for the DH, NHS and pharmaceutical and health care appliance sectors. The author is a non-executive director of an NHS hosital trust.
Clinical audit does not escape the cosh 30 July 2004
Jonathan R Bayly, Clinical Lead, Gloucestershire Primary and Community Care Clinical Audit Group Agriculture House, Sandhurst Lane, Gloucester GL2 9AS Send response to journal: Re: Clinical audit does not escape the cosh	In my experience Local Research Ethics Committees do take a close interest in audit projects and guidance on the margins where it bumps up against research often generates intense debate. Here too one often feels the process of ethical approval as more of a 'dead weight' than a supportive and positive procedure. Patient and carer surveys are becoming more valuable in primary care to identify the quality of service as performance managed protocol driven chronic disease management cuts across the patient's agenda. Patient/Public Involvement (PPI) is a key aim for clinical audit as in all areas of the NHS. It appears to me that there is a desperate need for a subset of the often lengthy documentation and a 'fast track' approach to low risk audit activity that would allow such surveys not to be held back by the intense bureaucracy that would appear more appropriate for an international multi-centred randomised controlled trial. Competing interests: None declared
Research governance 31 July 2004
Barbara A Sen, Senior Lecturer Liverpool John Moores University, John Foster Building , Mount Pleasant Liverpool L3 5UZ Send response to journal: Re: Research governance	Barbara Anne Sen, Senior Lecturer School of Business Information Faculty of Business & Law Liverpool John Moores University John Foster Building 98, Mount Pleasant Liverpool L3 5UZ Email: b.a.sen@livjm.ac.uk EDITOR – I was extremely interested to see the issue of research governance being addressed across a range of areas in the BMJ of the 31st July. Having an interest in health related research from the perspective of an academic partner one area is commonly overlooked, that of professions allied to health who are research active, an example would be, my own information profession, though there are many more. Under the terms of the Research governance framework for health and social care1, such research active professionals are governed by the same ethical requirements as clinicians, having to follow the same lengthy procedures regardless of the often low risk nature of the research activity. The focus of the recent edition of the BMJ and most other literature concerning research governance is clinical. With much of the non-clinical research, the problems identified by the various authors writing in the 31 July edition of the BMJ, such as barriers to research, quality research, and cost effective research processes are further exasperated by the low or non-existent risk factors in much of the non- clinical research.2, What is needed is not a “one size fits all” approach. The changes to student projects approval will go some way to addressing just one aspect of the issue.3 However there are a great number of non clinical professionals allied to health carrying out research within the NHS, which means a diverse range of research activity exists. A recent survey of health information professionals working not just in the NHS but in academia, charities and the private sector, identified a range of both positive and negative aspects of the current research governance procedures.4 Positives being an improvement in the quality of research carried out; positive research outcomes adding to the knowledge base, changing workplace practices for the better and an improvement in research skills. Negative issues identified related to the slowing up of research projects and the bureaucratic issues surrounding the research process as a result of ethical processes, so much so that one respondent was driven to say that research governance “ is killing social science research”. Key issues identified were a need for more support with regard to training from the professional organisations, a view shared by Meredith5, and some form of fast tracking through the process for low risk projects. Meredith again supports this finding in the call for “appropriate research practices that are proportionate to the risks”5. The NHS is a multi-disciplinary organisation where many professions work together to provide excellent healthcare. The ethics procedures in place need to support and encourage effective research activity clinical and non-clinical across all those professions. 1. Department of Health. Research Governance framework for health and social care. DOH. http://www.dh.gov.uk/assetRoot/04/01/47/57/04014757 (accessed 30 July 2004) 2. Warlow, Charles. Clinical research under the cosh again. BMJ 2004; 329: 241 3. COREC (2004) Ethical governance and regulation of student projects. A draft proposal. http://www.corec.org.uk/applicants/docs/SPECs_proposal_DRAFT.doc Accessed 30 July 2004 4. B.A. Sen, C. Watts The impact of research governance for healthcare information professionals: results of a survey. Proceedings of ISHIMR The Ninth International Symposium on Health Information Management Research and using Research in Practice Workshop. 15-17 June 2004, Sheffield UK. 5. Meredith, Sarah. Commentary: Better support for investigators is essential. BMJ 2004; 329: 285 Competing interests: None declared
Research Governance and multi-centre health services research. 2 August 2004
Thomas E Locker, Research Fellow Medical Care Research Unit, University of Sheffield, S1 4DA, Suzanne Mason- Senior Clinical Lecturer, Professor Jon Nicholl - Director Medical Care Reserach Unit, Professor Susan Read- Chair in Nursing Research University of Sheffield School of Nursing and Midwifery Send response to journal: Re: Research Governance and multi-centre health services research.	Editor, Following the publication of a number of articles in the BMJ highlighting difficulties experienced with ethics and Research Governance [1,2], we wish to emphasise the serious problems that Research Governance is causing for multi-centre research into NHS services even when it is being commissioned by the National Health Service Research and Development programme and has Multi- Centre Research Ethics committee approval (MREC). In one study, staff in the University of Sheffield School of Nursing and Midwifery, are attempting to gain Research Governance (RG) approval for a multi-site survey of nurses. They have found that NHS organizations are interpreting the RG guidance in different ways and therefore researchers have to negotiate very different paths in even neighbouring trusts in order to undertake research. In an earlier study surveying nursing staff [3], an average of 12 hours of work per RG application was required to obtain research approval. If this figure were extrapolated to this current study, it would equate to 53 weeks of full time work for one member of the research team to cover the original 178 NHS organisations. Consequently the number of organisations from which the sample can be drawn for this study has had to be drastically reduced. A further example of the difficulties encountered is that many trusts require either the principal investigator or even a whole research team to have honorary contracts with them despite the fact that the researchers each have an honorary contract with at least one or more local trusts and have indemnity cover for the project from the University of Sheffield and through their individual memberships of the Royal College of Nursing. Obtaining these contracts frequently involves filling in long health questionnaires. In addition one principal researcher still had to provide names of 3 referees, despite being in a senior university position. It also took a lot of negotiation to have a clause about intellectual property rights removed from the contract, when the IPR belonged to DH. Another study involves interviewing members of staff in A&E departments in England and Wales for a total of three hours at each site [4]. The Research Governance applications for this study have involved varying degrees of scrutiny. In two Trusts approval has been granted following nothing more than a telephone call to the Research and Development department. However, in the vast majority a lengthy process of reviewing all the documentation relating to the study has been required. This often culminates in the need for an honorary contract to be issued and the accompanying Criminal Records Bureau and occupational health screening. Some Trusts have refused to accept Criminal Records Bureau checks performed by other Trusts and a number of the research staff on the project have had to divulge their health details to a large number of trusts. One researcher was asked to travel over three hundred miles for an eye test by one Occupational Health department. We are currently awaiting approval for a number of sites and in ten cases it is now over sixteen weeks since the original application was made. In these studies a considerable proportion of the funding has been expended on obtaining Research Governance approval. The many funding bodies in this country will need to take account of these increased costs when financing future studies. In these examples the need for the study has been determined by the Department of Health and scientific review of the proposals has been undertaken by them. The projects have been further scrutinised by an MREC. We find ourselves in the position of being contracted to undertake research in NHS organisations, the proposals having been shown to be scientifically and ethically sound, but having considerable barriers placed in our way by the very organisations we have been asked to study! We are calling on the Department of Health to urgently address this problem. We suggest that where the need for a study has been identified, the study design approved and funding awarded it should also be responsible for ensuring access to the NHS organisations it wishes to be studied. Governance issues should be addressed on a multi-centre basis through an organisation such as COREC, as with ethical considerations. We would be interested to know what local issues necessitate individual Research Governance applications at each site for multi-centre health services research studies such as these? 1. Warlow C. Clinical research under the cosh again. BMJ 2004;329:241-242 2. Jones AM, Bamford B The other face of research governance BMJ 2004;329:280-281. 3. Evaluation of the Modern Matron Role in a sample of NHS Trusts. http://www.shef.ac.uk/snm/research/modern_matron_evaluation.html 4. What are the organisational factors that influence waiting times in A&E? http://www.sdo.lshtm.ac.uk/pdf/access_mason_scientific.pdf Competing interests: None declared
ETHICS SHOULD BE UNIVERSAL AND IMPARTIAL 3 August 2004
Kaushal R Pandey, Fourth year MBBS student TUTH, Nepal Send response to journal: Re: ETHICS SHOULD BE UNIVERSAL AND IMPARTIAL	Sometimes back I was attending a small program on Medical ethics in making clinical judgement as a part of ongoing regional research on the topic. We were asked to answer certain problem-based questions on the matter. It was then I realised how difficult is Ethics when I had to leave them unanswered eventhough the answer was in "yes" or "no". And the teacher himself was saying there is no definite answer that we could say is cent percent right. So making a decision in terms of all "yes" or all "no" is very difficult in the matter of ethics. We should seek an intermediate way out with the assessment of risk- benifit associated with the procedure. It is totally inappropriate for the ethical review boards to make decision virtually saying no to researches even when the decision is not benifiting the either party. It is also heartbreaking that there is no uniformity in such matter globally. This acts as comparative advantage or disadvantage to people in a country relative to other. Ethics is in basics guided by the priciple of protecting the human rights of the patient used as participant in the research. When it comes to human rights , there is a universal declaration of human rights which ensures equality to all in the article 2 as "everyone is entitled to all rights and freedoms set forth in this declaration". Such should be the matter in case of Ethics too. Finnally, Ethics should be universal and impartial so as to ensure the uniformity and steady progress of health science ultimately in the benifit of the patients and general population. Competing interests: None declared
Ethics committees are not the bad guys! 3 August 2004
Tim M Reynolds, Consultant Chemical Pathologist / Chairman South Staffordshire LREC / Member W Midlands MREC Queen's Hospital, Burton-on-Trent, DE13 0RB Send response to journal: Re: Ethics committees are not the bad guys!	This Letter has been submitted in response to the leader article on ethics committees,but could be considered to apply to all of the ethics papers in the July 31 issue of the BMJ: Prof Warlow claims that scientifically inappropriate flaws are forced into studies by ethics committees. Enforcing measures that ensure compliance with the law cannot be considered to be inappropriate; if research methods are illegal then the methods must be changed and it would be wrong for an ethics committee to fail to bring this to the attention of the researcher. It is not the ethics committee’s fault that the researcher is ignorant of the law, nor their fault that Parliament wishes to protect the population from the actions they wish to pursue. As a member of an ethics committee, I cannot comment on individual projects for reasons of confidentiality but it is frightening that ethics submissions (including patient information leaflets) are frequently written in language that even medical members of committees find impossible to comprehend. Whilst ethics committees and researchers have to cope with the impenetrable legalese in which UK & EU legislation is couched, it is not unreasonable to expect patients to be able to understand the projects they are invited to take part in – and that includes provision of information for people whose first language is not English (if appropriate). Many patient information sheets require a degree -level standard of medicalese to be understood and this cannot be appropriate. To expect researchers to provide comprehensible information is not unreasonable. Secondly, we find that a startling number of exceedingly well-funded projects are presented that whilst ethical from a participant’s perspective would be utterly unethical from a societal standpoint because they cannot be considered to be a good use of tax-payers’ or charity- donors’ money as they are clearly designed to "prove that", rather than "evaluate whether", a new policy is worthwhile. Often the project costs seem particularly extreme because of very small sample sizes and the presence of the already formulated conclusions in the project description. We are frequently forced to approve these projects with a shrug and within -committee depressed comment that “there being nothing unethical identified we are unable to reject this project”. Finally, I suggest that it is often not the ethics committee that causes problems, but they receive the blame. Whilst I must agree that the new ethics committee forms is long and complex, it is far less time- consuming than filling a different form for 20+ different committees, which was the norm just 12 months ago. If it takes 44 hours to complete an ethics form then the project must have been incompetently conceived and drafted at the outset. The major culprit in the eyes of many researchers however is the new R&D Governance industry that has arisen in the wake of clinical governance: R&D committee procedures now far outweigh the hassle involved in ethical review. Furthermore, even after approval by an ethics committee, R&D committees often request changes to patient information details, protocols etc that then require re-evaluation by the ethics committee and occasionally R&D-imposed changes have been rejected as unethical. This may be acceptable for single institution studies but for studies in multiple institutions cannot be allowed. This was one of the major driving forces behind the very changes in ethics committee procedures that lead to the single ethics submission form. I would therefore respectfully suggest that perhaps Prof. Warlow should attend an ethics committee meeting as an observer to see the dross that is frequently presented and perhaps he will re-evaluate his position. Ethics committees usually take the approach of attempting to help investigators develop ethical and scientifically valid studies: the two are not contradictory because a scientifically invalid study would be unethical as patients would be involved to no useful purpose. Competing interests: I am a member of West Midlands MREC and Chairman of SE Staffordshire LREC
Time for institutional review boards? 5 August 2004
Tom Meagher, Consultant Radiologist Stoke Mandeville Hospital, Mandeville Road, Aylesbury, HP21 8AL Send response to journal: Re: Time for institutional review boards?	As the demands of Ethics committees continue to grow it is easy to forget that the researchers institution shoulders the responsibility for research. With the recent and appropriate focus on research governance in the NHS, the researcher has to assuage both their own organisation in addition to the demands of the Ethics committee with similar information. Ideally an institution would ensure that the necessary methodology, literature search, statistical review, peer review and other parameters are carried out in advance of ethics submission and allow the ethics committee to focus on patient protection rather than the current muddle where it overarches every aspect of research. It may be timely to consider a different approach. Institutional review boards in the US combine the requirements of the institution and ethical review. The prospect of a single body evaluating all aspects of a research proposal would be a major improvement on the current situation. Researchers would benefit and patients safety need not be compromised. Competing interests: Trust Clinical Lead for Research
In research, one size will not fit all 9 August 2004
Peter N Furness, Consultant Histopathologist Leicester General Hospital LE5 4PW Send response to journal: Re: In research, one size will not fit all	Sir Congratulations for producing an issue highlighting the important but neglected issue of research ethics committees (RECs) inhibiting research. Those who argue that the solution is more support and better training for researchers are monumentally missing the point. To prove this, consider the discovery of Helicobacter pylori as the cause of peptic ulceration. This started as a curiosity-driven micro- research project with little apparent prospect of success; a pathologist merely reviewed 100 gastric biopsies, correlating the presence of bacterium-like structures with the presence of acute inflammation. 1 Today, even that project ought to be preceded by an REC application. A 68 page form plus protocols and all the associated paperwork and delay. What sort of support and education would persuade any sane person to jump through those hoops for such tiny project with such a slim hope of success? It is unequivocally the case that, if there is another Helicobacter-like discovery to be made, it can no longer be made by a researcher in the UK. At least, not by one who abides by the rules. COREC needs to consider the implications for society of that fact. For the problem is seriously exacerbated by COREC’s attitudes. In a mistaken attempt to produce reproducible processes they have imposed not only a huge ‘one size fits all’ application form on all types of research. They have also imposed a set of ‘one size fits all’ operating procedures on RECs. Surely simple uncontroversial studies using questionnaires or archival tissue samples might use a simpler process than that which is needed for dangerous interventions in sick children? Such suggestions have been dismissed. Were you joking when, in ‘Editor’s Choice’, you suggested that REC approval would be needed to ring up chief executives? The REC on which I sit recently considered an application to interview six members of the hospital consultant staff about their work practices. Complete with participant information sheet and consent form. With all the standard clauses such as 'If you are harmed by this research...'. To my amazement the committee not only took it seriously and followed its usual procedures, it demanded amendments! Reference 1. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1(8390):1311 -5. Competing interests: The author is involved in biomedical research and is a member of an LREC
The view from a REC 11 August 2004
Jammi N Rao, Director of Public Health, Chairman West Midlands MREC Birmingham B44 8BH Send response to journal: Re: The view from a REC	The BMJ issue of 31 July seems like its open season on research ethics committees (Refs 1-3). However as always there is another side to the story and I am both surprised and saddened that the BMJ’s editors, in their wisdom chose not to commission a paper from some one on an ethics committee to present a balancing view. I’ve been both an applicant to a REC and have been a member and a chairman of both an LREC and an MREC. Your anguished and hysterical contributors may find it worth their while to read this e- letter. The pace of change in recent times in the REC business has indeed been phenomenal. Most of the changes have been made expressly to deal with the stated interests of the research community. We now have a central allocation system, a website and a common application form. More REC members have had structured training now than ever before, There is now a uniform set of standard operating procedures and obfuscating delays are no longer possible; we have to respond within a set time. All REC members are voluntary and contrary to the popular perception of your 31 July contributors do wish to promote high quality and useful research. And yet we are seen as spoilers of the party. Let me give you my explanation of the apparent contradiction here. 1. There’s far too much useless research that comes before us. Present us with a well argued case for a clinical trial involving a disease where the treatment options are limited and the patient information sheet is well written and presents all the relevant facts in a clear and objective manner and the chances are that it will be approved straight away. Much of the research that comes before us sadly is not in this category. The PIS is written almost to confuse and confound if not actually mislead, the reason for the research appears unclear even to the researcher and the methodology is often suspect. So called health services research in particular – the kind that involves talking to chief executives – is loosely presented as evaluation but faced with the sort of questions that the ethics application form asks, it soon becomes obvious that the research is designed to find a predetermined answer. Sadly government departments are often guilty of funding such projects. Student research is the other large source of such harmless but also useless research projects – in my view they are useless not only as research but also educationally. 2. The COREC form comes in for a lot of criticism. But I believe it is lack of preparation and a lack of clear vision of what the project hopes to achieve that make the form appear daunting. Wald (Ref 2) for example lists all the documents needed for a complete application – research protocol, patient information sheet, patient questionnaire and consent form, among others. Is he suggesting that these would not have been necessary but for the need to apply for REC approval? Lay members of my committee in particular are amazed at the lack of ability of researchers to write clearly and simply – even the PIS. If researchers intend to seek truly informed consent then should they not spend a lot of time in writing and rewriting and field-testing their PIS? Maybe even seek help? Or do they simply dash off something for the ethics committee? And then howl when the REC returns it stamped 'not approved'? The COREC form is here to stay, and I do not see the relevance of Wald’s problems with large parts of it being irrelevant to his particular project. Enter ‘Not applicable’ Simple. What is the problem? The first rule of research that I was taught was to plan well, research the field, and spend a lot of time in the design phase. Those who follow this dictum will find the COREC form easy. Those who plunge into the COREC form as the first step on their research project will rightly and deservedly get a nasty shock. Believe me, when a researcher attends my committee, the lack of preparation shows. 3. Your correspondents are also guilty of visiting a multitude of others’ sins on the REC system. Research governance is a completely different set of arrangements and I have myself had to intervene on behalf of researchers with officious and petty R&D management offices in hospitals and trusts. I have also written to the NHS R&D unit to argue that R&D offices need much clearer and tighter guidance on what research projects they should be informed about. 4. ‘Involve patients and patient organisations’ is one of Warlow’s suggestions (Ref 1). I couldn’t agree more. In fact under the new system lay members have a bigger say on RECs than ever before; and they are often the most critical members of the quality of research studies that come before RECs. They are often the most critical of poorly designed so-called evaluative studies. 5. Surprisingly none of your contributors offered a root cause analysis of the problem, let alone suggest a solution. Let me be so bold as to step into the breach. The fundamental problem has been to treat all research the same. The DH document known as GAfREC (Governance Arrangements for Research Ethics Committees) created a fundamental problem for all of us by defining far too loosely research that needs to be reviewed by a REC. If someone has labelled it research and if it has any connection with patients or with the NHS (premises, staff, anything) then, according to GAfREC, it needs ethical review. The solution therefore is to revisit this definition. And agree a measured approach to ethical review of selected types of clinical research. Maybe we could even put the onus on researchers involved in certain types of studies to decide if their prohject needs full and formal ethical review. Given more responsibility they might take greater care with their design and assume more responsibility for their decisions. REC approval is far too often seen as a rubber-stamping process. References 1. Warlow C. Clinical research under the cosh again. BMJ 2004; 329:241-242 2. Wald DS. Bureaucracy of ethics applications. BMJ 2004; 329:282-284. 3. Jones AM and Bamford B. The other face of research governance. BMJ 2004; 329:280-281. Competing interests: I am Chairman of rthe West Midlands MUlti-Centre Research Ethics Committee
Will it ever recover from the blow? 11 August 2004
David L J Freed, allergist (private) 14 Marston Rd, Salford M7 4ER Send response to journal: Re: Will it ever recover from the blow?	Editor It is the nature of bureaucracy (a) to breed bureaucrats and yet more bureaucracy, and (b) to stifle the activity it is set up to regulate, as any observer of human acticities can testify. The logical objective of every bureaucrat is a production-free world in which all of us spend our time regulating each other – and believe me we’ll have plenty to do. Just as mortice locks on doors and windows will deter the casual burglar but not the motivated professional, so too the ill-prepared or ill -funded researcher (like me) is put off from doing research altogether by the hazardous assault course of the Ethics Committee, and it's getting worse. Clinical research is being steadily suffocated as the red-tape becomes all-pervasive; our generation will probably witness the last death -throes of this once-useful activity. Moreover, given that few of us are prophets or psychics, most of us are somewhat uncertain (to greater or lesser degree) of what the outcome will be when we treat a patient, and thus every treatment is to some extent an experiment. One loophole which the bureaucrats have not yet stopped up is our clinical freedom to treat the patient in front of us as we think best. We can even do clinical research (of sorts) that way and call it audit. But mark my words friends, it is only a matter of time before every prescription will have to be scrutinized by a committee before being issued. And the patients? Tough – serve ‘em right for taking up our precious time by being ill. Can’t they see we’re busy? Competing interests: None declared
Frustrating Bureaucracy in Clinical Research 11 August 2004
Peter A Goulden, Clinical Research Fellow Medical Research Council, University of Southampton, Southampton General Hospital. SO16 6YD Send response to journal: Re: Frustrating Bureaucracy in Clinical Research	EDITOR - The recent editorial (1) and accompanying articles on difficulties various research groups had faced struck a chord with my own personal experience of bureaucracy in clinical research – this coupled with the potential for inefficiency of Ethics Committee clerical staff can be particularly infuriating and I would like to quote a recent example. Last week I wanted displayed a hospital poster advertising for volunteers for a clinical study which had received ethical approval and was told I could not display this without permission from the Local Ethics Committee. I dutifully sent copies of the poster with a covering letter by email and post to the Ethics Committee and following up with a telephone call a week later was told they were on the administrator’s desk waiting to be returned to me as a further paperwork would be required. To add insult to injury the email I had sent to eliminate postal delays had not been looked at as an administrator was on holiday and no-one could check her emails! Peter Goulden Clinical Research Fellow 1. Warlow C. Clinical Research under the cosh again. BMJ 2004;329:241 Competing interests: None declared
Ethics committees 12 August 2004
John M Walshe, Retired Hon consultant physician The Middlesex Hospital, London Send response to journal: Re: Ethics committees	I was pleased to read Professor Warlow’s leading article in the BMJ of 31st July (1) and the articles in this number of the Journal by three separate groups of research workers lamenting the difficulties with which the requirements of ethics committees now confront them. I have long been a critic of such bodies even though to take this attitude may not be politically correct; but then I doubt if I ever have been. In an address to The European Meeting on Health Orphans (2) I expanded on this subject in some detail l and discussed it again later in the Lancet (3)I believe I may have been one of the first to cast doubt on the benefits of such committees. May I quote myself, at some length from my 1988 article (2). ‘Next comes the ethical committee: what is its track record, how liberal is it and is amenable to reason ? Seeking permission from such a body is itself a risk. If the committee says’ yes’ the doctor is really no better off, if they say ‘no’ both he and the patient are irretrievably baulked; but to bypass the committee, the doctor must be convinced of his own intellectual integrity and also that his patient is convinced with his course of action ……. There is no escape from responsibility. But should things go wrong in the first testing of a new orphan drug, I tremble to think what a learned judge would say. He would, I suspect, be happily oblivious of the real issues involved and his strictures, however redolent with wisdom they may sound when uttered in a hushed and expectant courtroom, would bear scant relationship to the realities of the situation. I find it impossible to believe that any ethics committee, as at present constituted, would have permitted the first testing of penicillamine (4), trientine (5) or tetrathiomolybdate (6) for the treatment of patients with Wilson disease. Ethics committees were not in existence when I introduced penicillamine in 1955, I am not sure of the position when I first tested trientine in 1969 but they certainly were when I introduced tetrathiomolybdate in 1984. Had I sought permission in either 1969 or 1984 and been blocked how many patients would have died ? The ethics committees, as constituted today, need to be restructured and given a clearly defined and limited remit in which to work if they are not to bring medical research to a grinding halt. J.M.Walshe. References. (1) Warlow C. Clinical research under the cosh again. This time it is ethics committees. BMJ 2004: 329: 241-2 (2) Walshe JM. Health orphans: the academic viewpoint. J R C P 1988; 22: 177-9. (3) Walshe JM. Ethics committees. Lancet 1990; 336: 1194-5 (4) Walshe JM. Penicillamine. A new oral therapy for Wilson’s disease. Am J Med 1956; 21: 487-95 (5) Walshe JM. The management of penicillamine nephropathy in Wilson’s disease; a new chelating agent. Lancet 1969; II 1401-2 (6) Walshe JM. Copper; its role in the pathogenesis of liver disease. Seminars in Liver Disease. Vol 4. Thieme-Stratton Inc. New York 1984. 252- 63. Competing interests: None declared
Clinical Research: ethics committees are not the problem 17 August 2004
Anthony S. Wierzbicki, Senior Lecturer in Chemical Pathology St Thomas Hospital Lambeth Palace Road London SE1 7EH Send response to journal: Re: Clinical Research: ethics committees are not the problem	A colleague of mine is currently a member of an LREC in a district general hospital [1]. Until last year this helped researchers in preparing paperwork and improving local study designs prior to submission for ethical review. Nationally organised MREC-approved studies were briefly reviewed. Then the rules changed; details of MREC studies were not supplied and LREC workload fell, leading to disenchantment and inquorate meetings (after prescribed changes in the quorum). Consequently LREC merger and devolution re-arrangements were tried and failed. Despite this and the new long tedious REC form, local researchers still like the LREC. Sadly, as with many policies in the UK, the policy-makers have developed procedures that work well in committee rooms and not at all in real life. The problem is not the RECs; it is the parasitic R&D committee/governance structure. These committees require longer to approve simple questionnaires than LRECs ever did. They demand a proportion (20% to 120%) of any research income generated. Finally their legalistic pedantry delays final approvals for months by which time many trials with competitive recruitment structures have closed. The investigators’ justification for doing these studies is that the money raised can be used to fund departmental education, research and service demands without resort to time-consuming applications for non-existent funds or writing of grant proposals whose chances of approval rival those of winning the lottery. It is therefore little surprise that, despite the new strict time limits on ethical review, faced with no personal benefit except to pay for a despised new central bureaucratic structure that delivers little except delay, research is being abandoned. Finally, given the unwillingness of many Trusts to pay for anything except core work in the new consultants’ contract, we can expect clinical research in the NHS to be almost non-existent in the future. References 1. Warlow C. Clinical research under the cosh again. BMJ 2004; 329 : 241- 242 Competing interests: None declared
Palliative care research: catch 22 18 August 2004
Lara J Alloway, SpR in Palliative Medicine Dept of Palliative Care & Policy, Kings College London, Irene J Higginson Send response to journal: Re: Palliative care research: catch 22	This editorial1 gives an excellent overview of the recent increased regulation of clinical research by Research Ethics Committees (RECS). We would like to highlight the additional problems faced by researchers in palliative care. Palliative care research has long presented particular problems to RECs2 and we find ourselves in a catch 22 situation: RECs have limited experience in reviewing protocols, so have little knowledge of the problems associated with research in this patient group or standard clinical practice. A study we recently submitted to MREC: a randomized controlled trial comparing two drugs used in the symptomatic treatment of breathlessness was initially deferred by MREC with comments such as: “members were concerned about the level of action required by study participants……. be expected to take medication at set times on six occasions……” This is standard clinical practice; the aim of the study was to determine if a sustained release preparation was as effective. “Is it appropriate or ethical for such terminally ill patients to be asked to undertake such tasks in their final stages of life?” We aim to recruit an ambitious 120 patients, but they still commented “a larger randomized controlled trial may provide greater flexibility” This suggests a lack of understanding about the context of a palliative care study population. Although it has been argued that special ethical guidelines for palliative care research are not required as the ethical challenges are not unique3. The fact that only one request for further information by the RECs is now allowed and there is inadequate space on the corec form to give an overview of all the issues in this area of research. We risk having studies rejected unnecessarily. RECs therefore need generalized guidance about how to assess protocols and we call upon the international palliative care community to issue such guidance, allowing a more informed ethical review. We support MREC in promoting the needs of patients; but we have concerns about their lack of understanding of the issues in palliative care research. It is indeed unethical to operate in a context where there is a lack of evidence for interventions. References 1. Warlow C. Clinical research under the cosh again. BMJ 2004;329:241-2. 2. Stevens T, Wilde D, Amedzai SH, Rawson A, Wragg D. Palliative care research protocols: a special case for ethical review? Palliat Med 2003;17:482-490. 3. Casarett DJ, Karlawish JHT. Are special guidelines needed for palliative care research? J Pain Symptom Manage 2000;20:130-139. Competing interests: None declared
Ethical Review - seeking a balance 18 August 2004
Sir John Pattison, Director of Research and Development Department of Health, 79 Whitehall, London SW1A 2NS, Professor Terry Stacey, Director, Central Office of Research Ethics Committees Send response to journal: Re: Ethical Review - seeking a balance	In recent weeks there have been a number of articles and comments about Research Ethics Committees (RECS). Some have been very constructive in advising us on the need for change. Others have been less helpful, especially when based on error or misconception. Dr Nicholson’s editorial claimed that Research Ethics Committees (RECs) may be unable to function because of political control. There is not, and never has been, a proposal for “direct political control” of REC membership. He misses the point that the European Directive on Clinical Trials legally obliges the UK, as a Member State, to “take the measures necessary for establishment and operation of Ethics Committees”. Governments of all 25 Member States have to do this. We have done this by creating the United Kingdom Ethics Committee Authority. This consists simply of the Ministers of the four countries of the UK who have up to now been separately responsible for the existing NHS REC systems in their respective countries. The reference in the Directive to “independent” ethics committees refers to their independence from the researcher and the research organisation, not from Governments. Paradoxically, he criticises the decision to prohibit committees from reviewing applications from their own members, but if they continued to do so, they could hardly be acting independently. His claim that results of UK research could not now be used for regulatory purposes is simply unfounded. The independence of RECs relates to their decisions. There is nothing to suggest that they should be independent in their processes. When they were, it was a nightmare for researchers. Some 200 RECs had different processes, different forms, and no way of comparing notes on the issues. Nowadays, any research taking place broadly within the NHS requires only a single ethical review, irrespective of how many sites in the UK are involved. It only requires submission of the national electronic form, one paper copy of the form, and the supporting documents. All NHS RECs in the UK increasingly will operate in a standard fashion. Our UK benchmark is now that an applicant receives an answer within a maximum of 60 days. Repeated questions to researchers, which in the past took up a lot of time, are not allowed (only one written request for further information or clarification is permitted). The series of 5 linked articles in the edition of 29th July nicely exposes the dilemmas involved in ethical review of human research. It is all too easy to confuse three separate questions. What is considered ethically acceptable by society? How should research proposals be assessed against this? And how far can we go “at risk” in terms of simplifying the assessment process, bearing in mind the clear lack of understanding of the ethical issues in research displayed by some researchers? Parker et al. make a significant contribution on the first question, using rare diseases as a case study. Projects in such areas often perplex ethics committees, and some informed and intelligent debate (especially based on research involving the families concerned, as they propose) can only help committees develop consistency in future ethical review. Ward et al. offer a useful summary of the issues related to access to individuals and their data in epidemiological research. We are glad they acknowledge the advantages of the change in process since their own application. They would now require only one application for the sort of study they undertook (as opposed to the 213 they had to make in 1998). The initial thrust of the paper by Jamrozik is to be critical of the new national application form. However, his ensuing well-crafted arguments make a good case for a comprehensive assessment of the researcher’s understanding of the ethical issues in research. How wonderful it would be if all applications came from researchers who fitted his description of the “ideal applicant”. If we could only be confident that this were the case, the application form could be very simple indeed. But as he says, to submit an ideal application, researchers require thorough training in both the methods and the ethical issues relating to research in human subjects or their tissues or data. All ethics committees would applaud his plea for better training of researchers in research ethics, and his concept of the “accredited researcher” has considerable merit. His own experience as a member of RECs, with almost half the applications being rejected at first submission, reveals that we are far from this ideal state. He in fact makes a strong case for a comprehensive application form that prompts the “less than ideal” applicant to think about all the potential ethical problems. We take seriously any criticism about the application process. We all want the system to be as helpful as possible to researchers. Equally, any member of any REC in the UK could produce a wealth of “horror stories” related to the proposals that they are asked to review. The papers by Wald and by Jones et al. rather starkly demonstrate how far we are from every applicant being the epitome of Jamrozik’s “ideal researcher”. Wald was making an application during the time of transition from the old to the new system, . But even so he could have saved himself a lot of time, effort and phone calls if he had read the “question-specific guidance” which is published with the application form on the COREC web-site and to which he was referred by COREC staff. It explains nearly all the questions, and often states what the ethics committee is looking for in the answers. He would, for example, have found descriptions and URLs for the two reference numbers (ISRCTN and EudraCT) for which he claims no guidance was given. Part A of the form contains many questions which he claims are not related to ethical review. Many will disagree with him. Conflict of interest of the researcher, indemnity (for the protection of participants), and the confidentiality of information and data have for many years been considered internationally as core ethical issues, and we can all think of failures that damage public trust in research. Part B is divided into sections which are specific to particular activities (e.g description of the medicinal product, the use of stored tissue, use of additional radiation etc). These sections do not appear unless a box is ticked in the “sieving” question A5. For nearly all research, very substantial portions of the form are simply not activated, so it is normally far shorter than the maximum 57 pages. Indeed, for many epidemiology projects only one page of Part B appears – the page where the applicant signs. Then, the total form length is 21 pages. Many pages have questions that, for most research, involve ticking a box (although space has to be left in case a narrative answer is also required). Part C looks at the suitability of the local investigator (such as qualifications and research experience) and the adequacy of site facilities. Most people would regard it as unethical to go ahead without checking these. For clinical trials of medicines at least, the ethics committee is now legally obliged to consider them. Part D was an attempt to be helpful to researchers by unifying the information required by R&D Departments, not by ethics committees. It has now been withdrawn, but may yet reappear if the UK R&D community can agree on a nationally acceptable dataset. We have no doubt that quite a number of the silent majority of several hundred other applicants who have successfully, but quietly, completed applications to ethics committees since the new form was introduced. They too will have had some problems. However, sensible email enquiries , calls to the help-line and reference to the question- specific guidance have worked for them. Our strong advice to applicants is to print out and look at the form very early on when planning their research, so that they can reflect on the ethical requirements and build them into their plans. Leaving it to the last minute and treating it as a separate exercise will inevitably cause frustration. Failure to read the comprehensive advice is clearly self-defeating,. Complaints about the length of time to fill in the form relate more to the failure to consider in advance the ethical issues involved, than the need to sit in front of a screen and keyboard. If the ethical issues are properly covered in the design of the study , the actual completion of the form at the keyboard does not take long . Seeking and up-dating informed consent is fundamental to good practice in research involving human participants. Jones and Bamford’s claim that they were “unaware of the requirement,” to describe their research accurately to participants suggests a need for the sort of training Jamrozic recommends. Employers of researchers are responsible for developing the research culture in their organisation. This duty applies to NHS employers as much as to universities. As well as supporting their staff, employers do have to hold them to account for their professionalism in research involving patients,. When the NHS employer is also funding the study, it should come as no surprise to anyone if its R&D managers intervene over undocumented changes in design or inaccurate consent forms. It can only be good for research if NHS bodies work closely with ethics committees to maintain the high standards that patients have right to expect. No-one pretends the current application form or the process is perfect and it will be reviewed again this autumn. We welcome constructive criticism at this and any other time. if there is a sustainable case for omitting certain questions from the form or having a different, shorter, process for certain groups of applicants or low risk proposals (as has been suggested by some) then we would like to hear it. 1. Nicholson R. Another threat to research in the United Kingdom. BMJ 2004; 328: 1212-3. 2. Directive 2001/20/EC of the European Parliament and of the Council on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. 3. Parker M, Ashcroft R, Wilkie AOM, Kent A. Ethical review of research into rare genetic disorders. BMJ 2004; 329: 288-9. 4. Ward HJT, Cousens SN, Smith-Bathgate B, Leitch M, Everington D, Will RG, Smith PG. Obstacles to conducting epidemiological research in the UK general population. BMJ 2004; 329: 277-9. 5. Jamrozik K. Research ethics paperwork: what is the plot we seem to have lost? BMJ 2004; 329: 286-7. 6. Wald SD. Bureaucracy of ethics applications. BMJ 2002; 329: 282- 4. 7. Jones AM, Bamford B. The other face of research governance. BMJ 2004; 329: 280-281. 8. COREC website: http://corec.org.uk Sir John Pattison Director of Research & Development, Department of Health Professor Terry Stacey Director, Central Office Department of Health of Research Ethics Committees Competing interests: None declared