Q J Med 2003; 96: 305-307
© 2003 Association of Physicians
Variations in experience in obtaining local ethical approval for participation in a multi-centre study
From the Oxford Centre for Respiratory Medicine, Churchill Hospital, John Radcliffe NHS Trust, Oxford, UK
Received 6 December 2002 Accepted for publication 16 December 2002.
 |
Summary |
|---|
 Top Summary IntroductionMethodsResultsDiscussionReferences |
|---|
Background: The Department of Health recently issued guidance on how Local Research Ethics Committees (LRECs) should handle an Multi-centre Research Ethics Committee (MREC)-approved application. This process is intended as a rapid standardized approval process, facilitating the execution of clinical trials.
Aim: To evaluate if this guidance had led to an efficient process for obtaining local ethical approval.
Methods: Questionnaires were sent by post to Local Investigators of the 56 centres who had obtained LREC approval for the Multi-centre Intrapleural Streptokinase Trial.
Results: Replies were received from 51 centres (91%). A total of 25 296 pieces of paper and 62 h of photocopying time were required to meet the 51 LRECs' requirements. LREC meetings ranged from weekly to bimonthly, with only 24 (47%) having a ‘fast track’ system in place. Applications took a median of 27 (1–90) days from submission to first being considered, with local investigators spending 3.27 (0.5–15) h on each submission. Nineteen (37%) of the local investigators felt the LREC/MREC interface did not work well and 17 (33%) were at least partly deterred from participating in future trials.
Discussion: The guidelines do not seem to have been implemented by all LREC committees, leading to wide variation in local experience.
|
Introduction |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Since 1990, medical research has been assessed by Local Research Ethics Committees (LRECs). This was problematic for research studies involving participants over a wide geographical area, as each LREC assessed the research independently. The researchers, therefore, had to complete enormous numbers of forms, and different LRECs took conflicting views on key aspects of the research. This put multi-centre research in jeopardy, leading to the creation of Multi-centre Research Ethics Committees (MRECs) to try and combat this problem.
Studies approved by MRECs in the UK must then be submitted to the LRECs in each Health District for their approval. This process is intended as a rapid standardized approval process, facilitating the execution of clinical trials. The Department of Health issued interim guidance on how LRECs should handle an MREC-approved application in 1998. Shortly after this document was published, MREC approval for the Multi-centre Intrapleural Streptokinase Trial (MIST: ISRCTN-39138989) was obtained.
The Department of Health's document stated that LRECs should only ask the local investigator for one copy of the protocol, and the application should be considered by an executive sub-committee specifically set up to consider MREC-approved applications. This committee should meet within 2 weeks of receipt of the application and reject the application only for local reasons.1
We wanted to evaluate whether this guidance has led to an efficient process for obtaining local ethical approval.
|
Methods |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Questionnaires were sent to the Principal Local Investigator of 56 centres across the UK who had obtained LREC approval for the MIST trial. The MIST trial is a Medical Research Council/British Thoracic Society trial studying the role of intrapleural streptokinase vs. placebo in patients with pleural infection. The questions posed are listed in Table 1
. Where no response was received, a follow-up telephone contact was made to ensure a high response rate.
|
Statistical analysis
Median figures have been used, and ranges are shown in brackets unless otherwise stated. The statistical tests used were
2 and Mann-Whitney. All analyses were done with SPSS version 7.5.1.
|
Results |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Replies were received from 51 centres (91%). LRECs requested the local investigator to provide a median of four protocols (range 1–20). A total of 25 296 pieces of paper and 62 h of photocopying time were required to meet the 51 LRECs requirements. The frequency of the LREC meetings ranged from weekly to bimonthly, with only 24 (47%) having a ‘fast track’ system in place. Applications took a median of 27 (1–90) days, from submission to first being considered and a further 15 (0–425) days from the date of consideration to approval of LREC clearance.
The local investigators applying for LREC approval spent approximately 3.27 (0.5–15) h on each submission. This meant about 167 h of investigators time was spent in obtaining the 51 LREC approvals. Estimated costs of investigators and secretarial time, together with the costs of postage and photocopying, amounted to £6311.
In total, these committees raised 69 queries relating to the previously cleared protocol. Nineteen (37%) of the local investigators felt the LREC/MREC interface did not work well, and a third of them (17/51) were at least partly deterred from participating in future trials because of the ‘hassle experienced’ in obtaining local ethical approval for this study.
Of the 51 centres, 33 were District General Hospitals. They were less likely to have an executive sub-committee in place than were teaching hospitals (33% vs. 72%, p=0.008, 2). Hospitals with a LREC executive sub-committee required fewer copies of the protocol and application forms than those who did not: 4(1–13) vs. 8 (2–16), p<0.001, Mann-Whitney.
The time the local investigator had to spend on the LREC application was inversely correlated with their willingness to participate in the next multi-centre trial (2 (0.5–15) vs. 4 (2–15) h, p=0.001, Z=-3.18) and positively correlated with expressing the view that the MREC/LREC interface did not work well (2 (0.5–7) vs. 4 (1–15) h, p=0.005, Z=-2.84). Finally, the longer the time the application took to be approved, the more likely the researcher was dissatisfied with the current system (39 (1–120) vs. 90 (6–445) days, p=0.003, Z=-2.93).
|
Discussion |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Despite the recent Department of Health guidelines, local committees seem to differ widely in their response to applications.3–8 The two-tier system of ethical approval of multi-centre research was intended to ensure rapid ethical clearance of multi-centre studies, while also allowing review of local specific ethical issues and ensuring patient safety.2 The LREC role is particularly important, as they have unique understanding and knowledge of their populations and local factors that inform their decisions.3,4 Unfortunately, the results of this questionnaire suggest that this is not happening. In fact, the responses of the physicians involved in this study to this questionnaire suggest that some of them have found the process deeply frustrating. Some 39% (20/51) had to wait >2 months after submission, for clearance that should have been straightforward.
In contrast, there are many centres where the process worked well, indicating that the system can function effectively. In 37% (19/51) of respondents, clearance was achieved in <4 weeks, with little complexity. The 47% of centres that have an established ‘fast track’ system were significantly more effective than those that did not. These centres required fewer copies of the protocol and accompanying documents.
District General Hospitals should be encouraged to take part in trials, to ensure that entered patients are typical of ‘real patients' and to help facilitate dissemination of evidence-based practice. This questionnaire showed that District General Hospitals were less likely to have an executive sub-committee to deal with MREC approved applications. As a result, applications in these centres took longer to process, and were a greater deterrent to physicians taking part in future studies. This might be addressed by such centres (who are probably processing fewer protocols) being able to gain LREC approval from a larger, but still local, executive sub-committee.
The longer the application took to be processed (and greater the amount of time spent by the local consultant in dealing with the LREC application), the more dissatisfied the investigator tended to be with the current system, and the less likely to want to participate in the next multi-centre study.
At present there are over 100 LRECs in England and Wales, and the workload of these committees varies widely. Some are faced with <40 and some with >500 applications in any one year.2 This variation in workload may play a part in the national variation in application handling. Moves towards a common application form with electronic submission to reduce the amount of paper used and associated costs, will help address some of these problems.
At present the Department of Health interim guidance does not seem to have been implemented by all LREC committees. This has led to a wide variation in local researcher's experience in obtaining local ethical approval. Unnecessary delays and demands by the LRECs are costly, both in terms of consultant time and money, and may dissuade physicians from taking part in future Multi-centre trials. Improvement of this process would facilitate the execution of important clinical trials.
|
Notes |
|---|
Address correspondence to Dr N.A. Maskell, Oxford Centre for Respiratory Medicine, Churchill Hospital, John Radcliffe NHS Trust, Headington, Oxford OX3 7LJ. e-mail: nickmaskell{at}doctors.org.uk
|
References |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
1. NHS Executive. Interim Guidance: How Should an LREC Handle an MREC Approved Application? Ref Type: Report. London, Department of Health, 1998.
2. Alberti KG. Local research ethics committees. Br Med J 1995; 311:639–40.
3. Gilbert C, Fulford KW, Parker C. Diversity in the practice of district ethics committees. Br Med J 1989; 299:1437–9.
4. Middle C, Johnson A, Petty T, Sims L, MacFarlane A. Ethics approval for a national postal survey: recent experience. Br Med J 1995; 311:659–60.
5. Hotopf M, Wessely S, Noah N. Are ethical committees reliable? J R Soc Med 1995; 88:31–3.[Abstract]
6. Lux AL, Edwards SW, Osborne JP. Responses of local research ethics committees to a study with approval from a multicentre research ethics committee. Br Med J 2000; 320:1182–3.
7. Harries UJ, Fentem PH, Tuxworth W, Hoinville GW. Local research ethics committees. Widely differing responses to a national survey protocol. J R Coll Physicians Lond 1994; 28:150–4.[Web of Science][Medline]
8. Larcombe I, Mott M. Multicentre research ethics committees: have they helped? J R Soc Med 1999; 92:500–1.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A Smajdor, M R Sydes, L Gelling, and M Wilkinson Applying for ethical approval for research in the United Kingdom BMJ, October 16, 2009; 339(oct16_1): b4013 - b4013. [Full Text]
|
|
|
|
|
|
A. A Schnitzbauer, P. E Lamby, I. Mutzbauer, C. Zuelke, H. J Schlitt, E. K Geissler, and for the SiLVER05 Study Group Procedures for ethical review for clinical trials within the EU BMJ, May 22, 2009; 338(may22_1): b1893 - b1893. [Full Text]
|
|
|
|
 |
|
 E Angell and M Dixon-Woods Do research ethics committees identify process errors in applications for ethical approval? J. Med. Ethics, February 1, 2009; 35(2): 130 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D L H Hunter The ESRC research ethics framework and research ethics review at UK universities: rebuilding the Tower of Babel REC by REC J. Med. Ethics, November 1, 2008; 34(11): 815 - 820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L Elliott and D Hunter The experiences of ethics committee members: contradictions between individuals and committees J. Med. Ethics, June 1, 2008; 34(6): 489 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Glasziou and I. Chalmers Ethics review roulette: what can we learn? BMJ, January 17, 2004; 328(7432): 121 - 122. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Martyn The ethical bureaucracy QJM, May 1, 2003; 96(5): 323 - 324. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||