First published online August 20, 2007
British Journal of Radiology (2007) 80, 774-777
© 2007 British Institute of Radiology
doi: 10.1259/bjr/98488679
COREC and IRMER — is co-existence achievable?
Andy Rogers, MIPEM
Medical Physics Department, Nottingham University Hospitals NHS Trust, Nottingham NG5 1PB, UK
Correspondence: Andy Rogers, Medical Physics Department, Nottingham University Hospitals NHS Trust, City Hospital Campus, Hucknall Road, Nottingham NG5 1PB, UK. E-mail: andy.rogers{at}nuh.nhs.uk
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Abstract
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The competitive pressures within clinical research are severe, and the need for a streamlined process to enable first-class research is self-evident. Conflict between ethical approval processes and legal requirements for the use of radiation within research has hindered such streamlining and has led to a call for action. This Commentary explores the background to this conflict and describes recent initiatives to generate a smoother process and unblock bottlenecks in relevant approval systems. It concludes by suggesting ways to improve the integration of these systems.
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Introduction
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For many years, and probably since the turn of the century, some of us in the radiological community who have a role in either research or its governance have been expressing concerns at the difficulty of reconciling the needs of investigators and the requirement to fulfil the legal obligations of the Ionising Radiation (Medical Exposure) Regulations 2000 (IRMER) [1] in the field of research radiation exposure. Furthermore, although IRMER has been the focal point of this unrest, there is a need to review the interaction of research and development (R&D) governance with other aspects of the radiation regulatory framework. This Commentary seeks to explain the history of these difficulties, describe the current initiatives in this area and, finally, from a personal viewpoint, make recommendations for improvement. In this Commentary, any reference to IRMER refers to the version current at the time of reference.
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Background
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For many years, research ethics committees (RECs) have provided the ethical oversight to the use of radiation in clinical research. They were formally established in 1991 and, throughout the 1990s, were further developed through Department of Health guidance, including the establishment of multicentre RECs in 1997 [2]. However, the new multicentre RECs often found themselves in a highly iterative process with local RECs when evaluating applications for ethical approval. To bring some order to this process and to help streamline it, the UK government established in 2000 the Central Office for NHS Research Ethics Committees (COREC; recently renamed the National Research Ethics Service (NRES)). COREC instigated the online application process and oversaw the development of the ethics application form. It also developed a central set of REC operating procedures to harmonize the REC approach to applications.
Along with these ethical developments, the government had reacted to various well-publicized incidents and their reports, e.g. the Griffiths report into the clinical and research practices in the Department of Paediatrics at the University Hospital of North Staffordshire NHS Trust, by publishing a comprehensive research and governance framework for the NHS [3].
In parallel with these developments, the European Union issued a new directive on medical exposures [4] that led, in 2000, to the enactment of the IRMER. These regulations superseded the Protection of Patients Undergoing Medical Exposure or Treatment Regulations 1988 and, most importantly for research, extended the scope of these regulations to include those exposures undertaken as part of research studies. The intent of these regulations was to protect patients as they progressed through the "care pathway" of medical exposures, whether for diagnosis, treatment, research, medico-legal, occupational health or health-screening purposes. For research, IRMER required all patients exposed within research studies to have given proper consent (participant information sheets (PISs) generally required a statement regarding the radiation risks); furthermore, some form of dose control was enabled via the setting of dose constraints or targets, depending upon the nature of the exposures within the study. IRMER did not explicitly define a research exposure but, in application, described the regulations as applying to "the exposure of patients or other persons voluntarily participating in medical or biomedical, diagnostic or therapeutic, research programmes". In the associated IRMER guidance notes [5], paragraph 6.6 stated that "such research should be subject to a dose constraint based on the total dose from all radiodiagnostic procedures in the protocol".
All of the above was in the political and commercial context of a growing unease at the bureaucracy involved with initiating and carrying out clinical trials in the UK. The pharmaceutical industry claimed that this led to costs and delays. The government's response was to set up a review in 2005 by Lord Warner [6] into the operation of RECs, the full recommendations of which have yet to be implemented.
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The emergence of conflict
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During the early 2000s, the need to comply with both the Department of Health's R&D Governance Framework [3] and IRMER was causing problems at a local level. These problems were mainly based around two issues: firstly, what constituted a research exposure; and secondly, whether proper consent was obtained via a meaningful statement of radiation risk in the PIS.
The exact definition of a research exposure is difficult to determine, as it depends upon the context. However, in terms of the conflict emerging, the real issue was that the ethical consideration was mainly based upon the additional burden of risk to the participant. For example, in a multicentre study, the coordinating centre would often determine the amount of additional radiation exposure caused by increased levels of imaging. It was quite common for the "declared" additional radiation in the ethics submission to contain fewer additional scans than were deemed additional by other participating sites This left such participating sites having to decide whether or not the study should take place at that site, as it clearly had not had proper ethical consideration in terms of their local clinical practice. It also made the setting of local dose constraints for the research study, required for IRMER compliance, problematic. Confusion also existed in the radiological community over what a "dose constraint" meant in the context of a clinical trial.
The knock-on effect of this was that in many cases the PIS was deemed inadequate by participating sites, especially if the amount of additional radiation exposure was deemed higher than that at the coordinating centre. This also contravened the requirements of IRMER and made local IRMER compliance difficult.
The net effect of these conflicts was a delay whilst sites sought clarification and, in more extreme cases, a refusal of a site to participate in a multicentre study. This was to the detriment of research as a whole, as well as to local patients and researchers.
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Current initiatives
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Following an initial approach by the Institute of Physics & Engineering in Medicine to COREC to try to find a solution to these difficulties, COREC set up a working party with representatives from COREC, the Health Protection Agency (HPA), the NHS R&D Forum (a network for those involved in planning and managing research) and various professional bodies with an interest in the matter. The remit of this working party was to redesign the COREC application form such that suitable information regarding the radiation exposure of the participants in a study was gathered both to enable a proper ethical consideration of the study and to provide participating sites with information to ensure their compliance with IRMER requirements.
Initial attempts to achieve this led to versions 5.0 and 5.1 of the form. It was thought that, by defining a "lead Practitioner" for the trial, local sites could use this person as their IRMER Practitioner. This had the perceived advantage of allowing this individual, who essentially justified the exposures in terms of their clinical suitability to achieve the study's scientific objectives, to also act as the IRMER Practitioner. It also seemed to offer the advantage of simplicity. However, this approach had two major disadvantages: you could not have a single central IRMER Practitioner for the use of radioactive materials (their required Administration of Radioactive Substances Advisory Committee (ARSAC) certificates are site specific), and, more importantly, HPA lawyers deemed this illegal under IRMER, as IRMER stipulates a local "justification". Therefore, to carry on with this approach would require honorary contracts for the lead Practitioner at each and every site in a multicentre trial. A new approach was thus required.
A redesigned form (version 5.2) was the result of this rethink. The philosophy was to de-couple the COREC application form from local IRMER issues, while allowing the information within it to facilitate IRMER compliance. Furthermore, guidance notes for investigators and radiation professionals [7] were developed to increase their understanding of the intent of the new system.
This "new" system attempted to achieve the working party remit by:
- Gathering information on all radiation exposures as defined by the research protocol.
- Producing a radiation risk assessment (undertaken by a medical physics expert) that assessed the total risk to participants from their radiation exposure but, more importantly, also assessed the range of additional radiation risk to participants as it varied across participating sites. The assessment does this by taking into account the range of doses delivered for a given examination by the participating sites and the range of additional/normal examinations undertaken by participating sites, within the total defined by the protocol. As part of this risk assessment, some form of dose constraint was also required to be set for the study.
- Producing a statement regarding the appropriateness of the additional exposures in terms of the study objectives (by a lead Clinical Radiation Expert(s)).
It was hoped that this system would provide RECs with suitable information to carry out a robust ethical consideration whilst also providing local sites with the complete range of radiation exposures within the study to facilitate their compliance with IRMER.
As part of the wider effort to engage with radiation professionals over these issues, the Radiation Protection Committee of the British Institute of Radiology (BIR) organized a one-day meeting to discuss the newly available COREC form and to encourage debate about its implementation in the field. The meeting was subdivided into three distinct sections: a general introduction to the ethical and R&D governance systems and their evolution (which still continues as Lord Warner's commissioned report is implemented); a series of presentations describing the scope of radiation use in research, along with the doses and risks associated with those uses; and specific advice on how to fill out the COREC form, produce a PIS and develop local procedures for compliance with both R&D governance requirements and IRMER.
The key aspects of the meeting were:
- An important presentation by Mr Steve Evans (Royal Marsden NHS Foundation Trust, London), who urged fellow radiological professionals to estimate more realistic radiation risks by taking into account not only exposure but also age at exposure and expected longevity. In the majority of clinical studies, this approach leads to a much reduced estimate of risk. He also presented a simple colour-coded approach to radiation risk that used a green/amber/red system to band risks. Coupled with appropriate statements from a Clinical Radiation Expert about the necessity for the exposures, this system could lead to a more uniform consideration of radiation risk by an ethics committee.
- The similarity of concerns raised by the audience. In the main, these were (a) the difficulty of setting a dose constraint for a clinical study and (b) the confusion surrounding what is, and what is not, a research exposure.
Interestingly, in the case of nuclear medicine exposures, there was very little concern. The audience had a good grasp of what was required, even though the system was very different to the IRMER approach to research. It is quite possible, in a multicentre study, to have a nuclear medicine bone scan declared in the research protocol, which may be normal practice at some centres but additional to normal imaging strategies in others. All centres will need to include the dose in the calculation of study dose for IRMER, but only those centres where the scan is additional to normal practice will require an ARSAC certificate, because of the requirement to have a research ARSAC certificate only if the exposure is "additional to normal practice"!
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Possible solutions
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Given the situation outlined in the previous section, how should we move forward to create a simple effective support system for the use of radiation in research? There are probably two main issues that require attention: the radiation risk assessment for ethical consideration, and the interface between the ethical consideration and radiation regulation. For both, there is a need to ensure consistency and avoid duplication of effort.
Taking the radiation risk assessment first, how should we as radiation professionals approach this? In my view, the following initiatives should be adopted:
- The radiation risk that is estimated to be associated with radiation exposure should be as realistic as possible. Therefore, the estimation should take into account age at exposure and expected longevity. Models such as those proposed by Mr Evans or those more formally based upon, for example, the report from the US National Research Council [8] could be used. This approach would be in accordance with that proposed for specific medical risk assessments by the International Commission for Radiological Protection (ICRP) in its recent draft for consultation ("Radiation Protection in Medicine" [9]).
- The presentation of risk to the REC should be as simple as possible. A colour-coded system could be adopted with generalized statements about the level of risk. Coupled with statements regarding the suitability of the proposed clinical exposures from a clinical radiation expert, this would simplify REC deliberations. It is my view that such a system should be developed by COREC in conjunction with professional bodies.
- Regarding the issue of what exposures to include, I think that the current system of presenting the total (as defined by the research protocol) and an estimate of the range of additional exposures presents a REC with the most complete picture required for its consideration. This approach also allows for suitable risk statements to be prepared for the PIS (and modified at participating centres if their additional doses and risks are significantly different from the trial "norm"), thus aiding the obtaining of consent.
- Regarding the issue of what level of dose to ascribe to a given examination or treatment, I feel that a simplified approach is required. The benefit of surveying participating sites for their specific dose level for, say, a CT scan of the abdomen, is unclear given the large errors involved in estimating the risk from such exposures. An approach based upon national Diagnostic Reference Levels or mean national dose levels would be a far more effective approach. Again, such a system should be developed between COREC and the professional bodies.
Turning now to the need to eliminate potential conflict from the requirements of ethical consideration and legislative compliance, I make the following proposals:
- The use of the term "dose constraint" in the COREC application form should be dropped. The consensus seems to be that IRMER is best complied with through local procedures and the COREC form should not use IRMER terminology. Doses presented in the COREC form are for ethical consideration, not IRMER compliance. Therefore, terms such as "total study dose" and "range of additional doses" would suffice. It would also stop unnecessary debate as to how to present a dose constraint in the COREC form!
- Participating sites should be free to choose whatever "dose constraint" they require for their IRMER compliance. However, this should be done with the radiation risk assessment presented to the REC in mind. Assuming that a simplified system of presenting doses to RECs is developed, then this should not prove problematic.
- The use of the term "Medical Physics Expert" in the COREC form should remain. This does not exclude Radiation Protection Advisers with suitable expertise from filling out the radiation risk assessment. However, as the Medical and Dental Guidance Notes [10] explicitly list radiation risk assessments for research proposals as a duty of the Medical Physics Expert, I feel there is no reason to change the form.
Finally, referring back to the situation in the previous section regarding the need for a research ARSAC certificate in a trial involving nuclear bone scans, I would like to make the following two points regarding this issue:
- In terms of streamlining effort, I see no benefit in the requirement to have a research ARSAC certificate for a nuclear medicine scan that is carried out as if it were a normal diagnostic scan (assuming that a diagnostic ARSAC certificate exists for that site/practitioner). A clinical radiation expert has attested to the scan being required and the site/practitioner has already been "certified". The need for further scrutiny does not seem justified. Obviously this does not hold if the nuclear medicine scan is different from normal diagnostic practice, and this fact would need to be captured by the COREC application form. However, given that almost all ARSAC research certificates are granted and sent back only when information is missing, I do not feel that this is a major impediment.
- At present, the requirement to include all other imaging doses in the ARSAC research certificate application is a duplication of effort. The initiative by ARSAC and COREC to work together to minimize this effort is to be encouraged.
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Summary
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As described in this paper, there has been tension between the need for proper ethical consideration of research involving radiation and local compliance with legal requirements. This paper suggests a way forward to ensure that suitable and simple, but effective, radiation information is presented to RECs, whilst enabling local compliance with radiation regulations. There are still some specific systems relating to risk presentation and the most suitable examination-specific dose level to be developed. However, I feel that the clear separation of ethical consideration and local IRMER compliance is advantageous in this respect.
Finally, it is worth noting that, as clinical radiation professionals, we all have a responsibility to facilitate research that involves radiation by constructively engaging in this debate. This will enable the most effective systems to be developed to support research.
Received for publication January 23, 2007.
Revision received July 9, 2007.
Accepted for publication July 16, 2007.
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References
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- Department of Health. The ionising radiation (medical exposure) regulations 2000 SI 1059. London, UK: HMSO, 2000 (amended 2006)
- HSG(97)23, Ethics committees review of multi-centre research: establishment of multi-centre research ethics committees. London, UK: Department of Health, 1997
- Department of Health. Research governance framework for health and social care. London, UK: Department of Health, 2001
- Council of the European Union. Council Directive 97/43/Euratom of 30 June 1997 on health protection of individuals against the dangers of ionising radiation in relation to medical exposure. Official J Eur Com 1997; No L 180/22
- Department of Health. The ionising radiation (medical exposure) regulations 2000 (together with notes on good practice). Available from: http://www.dh.gov.uk/assetRoot/04/05/78/38/04057838.pdf [accessed on 23 January 2007]
- Department of Health. Report of the ad hoc advisory group on the operation of NHS research ethics committees. London, UK: Department of Health, 2005
- Approval for research involving ionising radiation (version 1, December 2006). Available from: http://www.nres.npsa.nhs.uk/docs/guidance/radiationguidance.pdf [accessed on 9 July 2007]
- Committee to assess health risks from exposure to low levels of ionizing radiation. BEIR VII Phase 2. Washington, DC: National Academies Press, 2006
- International Commission on Radiological Protection. Consultation document "Radiological protection in medicine". Available from: http://www.icrp.org/docs/Radiol_prot_in_medicine_ICRP_draft_12_Jan_2007.pdf [accessed on 23 January 2007]
- Institute of Physics and Engineering in Medicine. Medical and dental guidance notes – a good practice guide on all aspects of ionising radiation protection in the clinical environment. York, UK: IPEM, 2002
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BJR review of the year -- 2007
Br. J. Radiol.,
April 1, 2008;
81(964):
265 - 269.
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Abstract
Introduction
