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Considerations, clues and challenges: Gaining Ethical and Trust research approval when using the NHS as a research setting
Radiography 17 (2011) 260e264
Contents lists available at ScienceDirect
Radiography journal homepage: www.elsevier.com/locate/radi
Review Article
Considerations, clues and challenges: Gaining Ethical and Trust research approval when using the NHS as a research setting Leon Jonker a, b, *, Diane Cox a, Gill Marshall a a b
Faculty of Health & Wellbeing, University of Cumbria, Lancaster LA1 3JD, UK Research & Development Department, North Cumbria University Hospitals NHS Trust, Carlisle CA2 7HY, UK
a r t i c l e i n f o
a b s t r a c t
Article history: Received 16 August 2010 Received in revised form 19 October 2010 Accepted 9 December 2010 Available online 3 January 2011
Substantial changes have been made in recent years to the process of obtaining ethical and research governance approval for research projects in the NHS. The advent of the Integrated Research Application System (IRAS) has streamlined the process, providing a single point of entry. Ethical approval gained in one part of the country is now valid throughout the UK. The previous process of gaining research governance approval in NHS Trusts was maligned and it has been overhauled with the introduction of the National Institute of Health Research (NIHR) Coordinated System for gaining NHS Permission. In addition to updating the reader about the new processes around gaining ethical and Trust approval for research within an NHS setting, essential research project documentation needed for submission are discussed. The aspects of a proposal that Ethics Committees and Trust R&D Departments consider when reviewing applications are highlighted. The implemented changes to the research approval processes will mostly benefit large multi-centre studies; small scale unfunded studies and student projects are potentially at risk of being marginalised in the quest for a streamlined ethics and NHS Trust research governance approval process. However, researchers’ familiarity with the approval system should minimise rejection rates and delays. Ó 2011 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.
Keywords: NHS Ethics Governance Research Approval Consent
Background Whilst the current ethics and research governance process may seem arduous it exists for very sound reasons. Historically, highly unethical research has been undertaken, causing harm unnecessarily to people. Experiments carried out on Jews, gypsies and other population groups by the Nazi Doctor Joseph Mengele and others are well known.1 Several more unethical experiments took place in the 20th century, before and after the Second World War. It is fair to speculate that most people would now be horrified e.g. by The Tuskegee Syphilis Study that took place in the 1930s which prospectively investigated the effects of untreated syphilis in people in the southern United States.2 Even in the 1960s, well after the implementation of the Nuremburg code of 1947, there was the Willowbrook Study, which involved deliberately infecting mentally retarded children with the hepatitis virus. Some children were fed extracts of stools from infected individuals.3 In the context of trials such as those above, the declaration of Helsinki was drawn up by the World Medical Association, first in 1964 and updated most recently in 2008. This provides a framework of ethical principles on * Corresponding author. Faculty of Health and Well Being, University of Cumbria, Fusehill Street, Carlisle CA1 2HH, UK. Tel./fax: þ44 01228 814689. E-mail address: [email protected] (L. Jonker).
which the current research ethical approval process in the UK is based.4 Both the Nuremburg Code and the Declaration of Helsinki have had a significant impact on how research is conducted and how research proposals are assessed.
Introduction Research of a social nature or research with a more clinically orientated theme commonly occurs in the NHS. In order to ensure research participants are subjected to ethical procedures and that patient information and data are not misused, guidelines are in place in the NHS. Consequently, before a research project can commence it will have to be approved by a Research Ethics Committee (REC) and also by the Research and Development (R&D) Department(s) of NHS Trust(s) where the research is to occur. In England the Department of Health plays a central role in research ethics services. Different bodies are responsible in the devolved nations: the Department of Health, Social Services and Public Safety (Northern Ireland), Scottish Executive (Scotland) and National Assembly (Wales). Fortunately, all RECs in the UK have adopted the standard operating procedures issued by that National Research Ethics Service. Depending on the project and employment status of the researchers, approval may also have to be sought from NHS
1078-8174/$ e see front matter Ó 2011 The College of Radiographers. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.radi.2010.12.004
L. Jonker et al. / Radiography 17 (2011) 260e264
Trust(s) for clearance to work on their premises. There have been major changes made to all these processes in recent years. Most applicants who use the Integrated Research Application System (IRAS) will only apply to a REC and NHS Trust; other bodies to which one can apply such as the National Information Governance Board and Social Care Research Ethics Committee are not covered in this review. Similarly, the additional processes involved for clinical trials involving medicinal products (CTIMPs) are beyond the scope of this article, as a CTIMP also requires approval from the Medicines and Healthcare products Regulatory Agency. Preparations before ethics and NHS R&D submission Research projects vary greatly, thereby making a “one size fits all” REC and NHS R& D approval service hard to achieve. Nonetheless certain aspects of a submission to an Ethics Committee and NHS R&D Department need to be taken into account regardless of the nature of the project. For the latter this is referred to as Trust R&D approval in the remainder of the text. The first thing to ensure before entering the REC and Trust R&D approval process is that all supporting documentation is in place. REC and Trust R&D Committees are increasingly keen to see evidence of peer review for studies and projects, regardless of whether it concerns a student project, a single site unfunded pilot study or a multi-centre funded clinical trial. Such a review is good practice and should be seen as developmental and useful. Having e.g. patient questionnaires and other key information, such as patient information sheets and data collection tools, reviewed by a peer can also be beneficial. If the research directly involves patients then the appropriate language and terminology should be used e the participation organisation INVOLVE can assist in involving patients in study design (www. involve.org.uk). Table 1 shows a typical process of applying for REC and Trust R&D approval for a single site research project with no external funding, involving for example patients attending a radiology department, but not a trial testing the efficacy of medicinal products such as contrast agents. Although no timeline is given for this example project process, the time it takes to develop a proposal and
Table 1 Typical flow of approval process for research in the NHS. Step
Action
1
Write protocol/proposal and supporting documents, such as patient information leaflet, consent form, questionnaire, if applicable Submit or gain peer review Amend protocol and supporting documents if required. Prepare IRAS form (both REC and R&D forms) Contact Medical Director or Nursing Director for sponsorship signature on behalf of the NHS Trust. In case of University employees, ask R&D Director or Faculty Lead. Ensure that everything is in place and that documents have version number and date, both on file name and within documents themselves. Submit to REC committee for approval Usual process: await REC outcome so that the documents submitted to R&D department are documents approved by REC. For University employees: arrange Research Passport to allow working in the NHS. Submit to NHS Trust’s R&D department for approval Commence study once approvals have been obtained Notify REC and R&D department if amendments are made the protocol of the project, or any other alterations that require notification. Submit annual reports and final report at end of project.
2 3 4 5
6
7 8
9 10 11 12
13
261
to have it reviewed can be lengthy which needs to be factored in when planning a project. The next sections will concentrate on the ensuing steps of this example. Supporting documentation It is key to ensure that the project documents are written in a clear, understandable, concise format and that they contain all the required information, as this is likely to make the REC and Trust R&D approval process smoother. It essentially means REC and Trust R&D Committees do not have to ask for corrections or additional information, thereby minimising delays. The research protocol or research proposal is an essential part of a research project. A protocol should allow others to appraise the background to a study, the hypothesis, methodology and other information regarding the project.5 Ideally, as with a materials and methods section of a peer-reviewed paper, it should also be possible for someone else to replicate the research using the “recipe” set out in the protocol without necessarily having prior knowledge of the subject or the setting of the research. This protocol should form the basis of any publication that is produced from the work. A research protocol must essentially address points congruent with the requirements set out by REC. A typical table of contents for a research protocol will contain the following sections: Title page (including contact details), Abstract, Introduction, Aims (sometimes divides into primary and secondary aims), Study type, Subjects (inclusion/exclusion criteria), Interventions (if applicable), Outcome measures, Sample size (if quantitative), Study administration (sponsor, liability), Flowchart, References. Inevitably, the structure of a protocol can vary depending on the nature of the project. For projects involving interviews, for example, there may be an appendix contained within the protocol with an outline of interview questions. Whilst the structure of different research protocols will vary, all need to cover the essentials of how a project is undertaken, who is involved, how analysis takes place and who takes responsibility for what. In addition to the protocol, other supporting documents may have to be written, such as a consent form and a patient/participant information leaflet (PIL). These documents are required if patient or NHS employee input is needed; it allows them to be fully informed about the study and the implications, before deciding whether to participate or not. A PIL should introduce the project and its aims e in lay terms and explain clearly yet concisely what will happen to anyone taking part in the project. The risks and/or (indirect) benefits of taking part should also be covered and options for obtaining further information before committing should be given. A PIL and consent form should have the study title and local NHS Trust header on it. One aspect that is important throughout the research project process is for documents to be given a version number and date. Not only is it compulsory for submission to REC and NHS R&D Departments, it is also helps to keep track of all the updated versions of proposals, protocols and supporting documents such as patient information leaflets, interview schedules and questionnaires. Integrated research application process All studies and projects within the NHS are not always classed as ‘research’. A piece of work can also fall into the category ‘service evaluation’, ‘audit’ or possibly ‘surveillance’. So before deciding to apply for REC and NHS Trust research approval it is wise to check whether a project requires ethical and/or NHS R&D approval. If a project is deemed to be service evaluation, audit or surveillance then NHS R&D approval is not required, although ethical aspects of any project should always be considered.6 If, after consulting the National Research Ethics Service (NRES) guidelines, a project does
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fall under ‘research’ then the process of gaining REC and NHS Trust research governance approval is applicable. REC and Trust research approval processes have an identical starting point: the Integrated Research Application System (IRAS) with website address www. myresearchproject.org. REC application There are various elements to be taken into account to ensure a research project is ethical. Table 2 summarises what RECs focus on when reviewing an application. Broadly speaking these considerations apply for any type of project, from a relatively straightforward and short student project to a complex multi-centre randomised controlled clinical trial. In the UK, the National Research Ethics Service (NRES) co-ordinates all RECs and the processes that go with reviewing and administering research projects e see also www.nres. npsa.nhs.uk. Many first-time users of IRAS find the submission processes for REC approval confusing. When a form is completed and the researcher is ready to submit the project, a ‘submission’ button in IRAS allows them to do this. However, this is not actually a hard copy submission of the project. All that this achieves is for the ‘draft’ watermark to be removed from the application form and for a portable document format (PDF) file to be generated of the application form. Further actions as required for actual submission i.e. the PDF file to be printed off and signed by the chief investigator and sponsor’s representative before being sent in the post along with 6 copies of the study protocol to REC. NRES actually prefers researchers to phone up to book an appointment for the time the project will be reviewed by REC, depending on their meeting dates and only once this is agreed then to ‘submit’ the IRAS form.7 In the authors’ opinion this is a weakness in the process, because following these instructions will leave only 4 days to gather signatures from e.g. the sponsor’s representative which may be rather challenging. Submitting and printing off the IRAS form first, to gather the signatures, and then phoning up to book an REC appointment would be less of a rush. Once an appointment is made it is not compulsory, but nevertheless highly recommended, to attend the meeting at which the research project is reviewed. Attending in person gives the researcher the opportunity to clarify matters, to defend certain choices that have been made and to demonstrate commitment to the project. An outcome of the application is usually received within a few weeks of the meeting. NHS research governance RECs consider a research project from a patient’s perspective. In contrast the NHS R&D Departments tend to review what the local impact will be of a proposed research project (although patient
safety and well-being is included in their appraisal too). The way these bodies function is based on a document called Research Governance Framework RGF, produced by the Department of Health.8 As this document does not set out strict guidelines on how R&D Departments in NHS Trusts should operate, there is variability in set-up of R&D Departments throughout the UK. Some Trusts host regular committees, whereas other Trusts rely on one or two people to review and approve research projects. In essence, however, those charged with Trust R&D governance consider a host of aspects when evaluating a research project. They assess if the chief investigator and/or principal investigator (CI/PI) adequately qualified to carry out the research. One aspect of research training that several R&D Departments insist upon e even if the research study does not involve a medicinal product e is for researchers to have attended a course in Good Clinical Practice.9 Within a GCP course, the history and importance of research, informed consent, good practice in record keeping and the role of REC is discussed. GCP needs to be renewed once every two to three years. No strict guidelines have yet been issued on renewal requirements, further diminishing its validity and credibility. Trust’s R&D Departments will check if a study is covered by NHS indemnity, and if not whether the sponsor has taken out separate insurance. It is checked if projects involve the use of radio-nuclides; if so, Administration of Radioactive Substances Advisory Committee (ARSAC) must be involved. Financial implications, conflicts of interest, potential public relations risks and data protection risks and measures are taken into account. A Trust’s R&D Department will assess if the research project can be physically carried out e is there space, staff and equipment capacity, and have all relevant departments been informed and do they support the research? The latter should be considered carefully by researchers when compiling a research proposal. How will patients be identified and approached; if input from radiographers or radiologists is required, will they have the (protected) time and inclination to do so? If these potential issues are not ironed out beforehand, the project may be delayed or even impossible to carry out. A comprehensive ethical and scientific review of a submitted research project is not indicated within NHS Trusts R&D Committees; however, in practice they can and do comment on such issues and sometimes can reject an application on ethical and/or scientific grounds. If the trial is multi-centre trust approval has to be gained at each site. The authors’ experience is that gaining the approval of several trusts R&D Committees can be a contradictory, lengthy and tedious process. If the project runs across several NHS Trusts then each NHS Trust will have its own IRAS site specific information (SSI) form. An SSI form basically summarises the project for each particular Trusts and identifies the local researchers involved and deviations from the protocol, if any. National Institute for Health Research (NIHR)
Table 2 Summary of ethical review questions. Item
Questions asked
Aims
Is there a valid scientific question that is likely to produce new information? Are aims feasible? Do the potential benefits outweigh the potential risks? Does it involve vulnerable groups (children, mentally incapacitated patients) How are subjects recruited and are they given sufficient information about what the research involves? Are there processes in place for gaining informed consent? Who will have access to data, is data anonymised and stored confidentially? For biological samples, what are usage, storage and/or destruction arrangements?
Risk Participants Recruitment Consent Data Samples
Recently, the Department of Health introduced the National Institute for Health Research (NIHR) which has had a major impact on Trust R&D governance. The NIHR is the organisation responsible for the implementation of the Coordinated System for gaining NHS Permission.10 Researchers can have their project processed through CSP, by selecting this option on the IRAS application form, but there are some conditions attached to this. Projects can only be reviewed and processed through CSP if they are funded by an external grant. If a project has been awarded funding then the body which awarded the funding will have to be on a list of recognised funders. This list includes NIHR funding, national research councils such as MRC, organisations such as the Wellcome Trust and now also research grants awarded by the College of Radiographers. A major advantage
L. Jonker et al. / Radiography 17 (2011) 260e264
of having a suitable project processed through CSP is that the project is listed on the NIHR National Portfolio.11 This then qualifies a project to receive support from the NIHR in NHS Trusts where the project is carried out. In order to boost clinical research in the UK, the NIHR funds 25 research networks, Comprehensive Local Research Networks (CLRNs) which in turn funds (clinical) researchers with the aim to improve research activity in the NHS. If a project is not on the National Portfolio then this beneficial support and infrastructure is not available. The Research Passport Formerly, if not already working for both an NHS Trust and a University, academics used to be issued with an honorary contract to work in a hospital or primary care trust. Often, academics would have to attend induction days in NHS Trusts and undergo occupational health screening. Conversely, clinical staff and allied healthcare professionals were issued with an honorary contract to work in Universities and other further education establishments. This changed with the introduction of the Research Passport which streamlined the process so that e.g. academics working with several NHS Trusts could make just one application for the necessary permissions.12 The new situation mainly benefits those researchers who are involved in larger multi-centre research studies. A Research Passport enables an academic to complete a single application form and to submit this with evidence of employment, immigration and health status to one NHS Trust. Once this NHS trust has scrutinised and approved the application, a researcher is issued with a letter of access. Subsequent NHS Trusts should accept the completed Research Passport and issue a letter of access, without asking for further information or application. For NHS staff there is no need for a Research Passport if they wish to do research in a different Trust form the one they are employed by e a letter of access should suffice. A major hurdle for researchers based at Universities that traditionally have not been very research active is that support may not be readily available to tackle all these new initiatives, like filling in a Research Passport application form, collating the necessary documentation, involving Occupational Health in health checks on the researcher, and obtaining CRB clearance if not held in certain instances. This, and other aspects of the process such as inconsistencies between Trust R&D departments, may delay research or dissuade potential researchers. Discussion Whilst it is of the utmost importance that all research in the NHS is conducted in an ethical manner the efforts made to improve the system, the process of reviewing and approving research proposals is lengthy, inconsistent and a topic of frustration for many researchers. The majority of complaints by researchers concerning REC and NHS Trust R&D approval are re the time necessary to get a project approved. Both clinical researchers and social researchers have made their frustrations public in the past.13e16 The NHS Trust R&D approval process possibly receives more criticism than the REC approval system, as illustrated by Galbraith et al. (2006) comment that ‘research governance approval is putting people off research’.17 Implementation of the Coordinated System for gaining NHS Permission should streamline this part of the research project approval process although teething problems are likely to be inevitable because the system is new. Recently, two researchers published their experience with CSP and were not overly complimentary about the system.18 However, their project was the first cross-border project involving Scotland and England which may have contributed to the delays they experienced with research approval in English Trusts. It is an indictment that the difficulty of negotiating NHS REC
263
and Trust R&D approval processes may have contributed to a reduction in applications to REC witnessed over the last few years. In 2004/5, a total of 9670 applications were made and in 2009/10 this figure had reduced to 6321.19 However, the number of applications for clinical trials, often involving multi-centres and present on the NIHR National Portfolio, shows an increasing trend in applications suggesting that potentially valuable smaller projects and student projects are the ones suffering. The authors know that expecting a student to negotiate this process and submit a dissertation within a year is not viable. Therefore, a two-tier system, one tier for small scale and low risk projects and another tier for interventional and high risk studies would potentially be beneficial. This would inevitably create the issue of who decides e and how the decision is made e what tier a project should fall into. The latest initiative, the Research Passport, can cause some initial frustrations amongst University research staff in particular because all NHS employees need to conduct research in a different trust is a letter of access. On the plus side, once in-situ the Research Passport should save time and effort in the long run. Conclusions The processes for REC and Trust R&D approval have changed considerably over the last few years. The latest amendments, including the introduction of the NIHR and related processes, are tailored towards large research studies and therefore more established researchers and research active organisations. For ‘small scale’ researchers who do not have the benefit of having large dedicated research support teams and who conduct non-funded research, the latest round of changes to the REC and NHS Trust approval system may not necessarily have brought about the improvements many such researchers hoped for. Nevertheless, the background provided here about how REC and Trust R&D Committees function may provide (new) researchers with insight to help optimise their applications and thereby to make the process more straightforward. Conflict of interest No funds were received in support of this study. LJ is partly funded by the Cumbria & Lancashire Comprehensive Local Research Network (C&L CLRN) for his position of R&D Manager at North Cumbria University Hospitals NHS Trust. The views and opinions in this article are the authors’ and do not represent those of the C&L Comprehensive Local Research Network or North Cumbria University Hospitals NHS Trust. References 1. Seildelman WE. Mengele medicus: medicine’s Nazi heritage. The Milbank Quarterly 1988;66:221e39. 2. Jones J. Bad blood: the Tuskegee syphilis experiment: a tragedy of race and medicine. New York: The Free Press; 1981. 3. Meaux JB, Bell PL. Balancing recruitment and protection: children as research subjects. Comprehensive Pediatric Nursing 2001;24:241e51. 4. Declaration of Helsinki [accessed 19.07.10], http://www.wma.net/en/30publi cations/10policies/b3/index.html; 2008. 5. O’Brien K, Wright J. How to write a protocol. Journal of Orthodontics 2002;29: 58e61. 6. http://www.nres.npsa.nhs.uk/applications/apply/is-your-project-research/ [accessed 28.06.10]. 7. http://www.nres.npsa.nhs.uk/applications/booking-your-application/ [accessed 19.07.10]. 8. http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/ PublicationsPolicyAndGuidance/DH_4108962 [accessed 19.07.10]. 9. Good clinical practice (GCP) Commission Directive 2005/28/EC. Official Journal of the European Union; 2005. 10. http://www.ukcrn.org.uk/index/clinical/csp.html [accessed 22.07.10]. 11. http://www.ukcrn.org.uk/index/clinical.html [accessed 22.07.10]. 12. http://www.nihr.ac.uk/systems/Pages/systems_research_passports.aspx [accessed 19.07.10].
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13. Elwyn G, Seagrove A, Thorne K, Cheung WY. REC and research governance in a multicentre study: add 150 days to your study protocol. British Medical Journal 2005;330:847. 14. Cook M, Cook G, Hodgon P, Reed J, Clarke C, Inglis O. The impact of research governance in the United Kingdom on research involving a national survey. Journal of Health Organ Management 2007;21:59e67. 15. Kielmann T, Tierney A, Porteous R, Huby G, Sheikh A, Pinnock H. The Department of Health’s research governance framework remains an impediment to multi-centre studies: findings form a national descriptive study. Journal of the Royal Society of Medicine 2007;100:234e8.
16. Mallick AA, O’Callaghan FJK. Research governance delays for a multicentre non-interventional study. Journal of the Royal Society of Medicine 2009;102: 195e8. 17. Galbraith N, Hawley C, De Souza V. Research governance. British Medical Journal 2006;332:238. 18. Thompson AGH, France EF. One stop or full stop? The continuing challenges for researchers despite the new streamlined NHS research governance process; 2010. 10:124. 19. http://www.nres.npsa.nhs.uk/news-and-publications/publications/generalpublications/ [accessed 22.07.10].
Contents lists available at ScienceDirect
Radiography journal homepage: www.elsevier.com/locate/radi
Review Article
Considerations, clues and challenges: Gaining Ethical and Trust research approval when using the NHS as a research setting Leon Jonker a, b, *, Diane Cox a, Gill Marshall a a b
Faculty of Health & Wellbeing, University of Cumbria, Lancaster LA1 3JD, UK Research & Development Department, North Cumbria University Hospitals NHS Trust, Carlisle CA2 7HY, UK
a r t i c l e i n f o
a b s t r a c t
Article history: Received 16 August 2010 Received in revised form 19 October 2010 Accepted 9 December 2010 Available online 3 January 2011
Substantial changes have been made in recent years to the process of obtaining ethical and research governance approval for research projects in the NHS. The advent of the Integrated Research Application System (IRAS) has streamlined the process, providing a single point of entry. Ethical approval gained in one part of the country is now valid throughout the UK. The previous process of gaining research governance approval in NHS Trusts was maligned and it has been overhauled with the introduction of the National Institute of Health Research (NIHR) Coordinated System for gaining NHS Permission. In addition to updating the reader about the new processes around gaining ethical and Trust approval for research within an NHS setting, essential research project documentation needed for submission are discussed. The aspects of a proposal that Ethics Committees and Trust R&D Departments consider when reviewing applications are highlighted. The implemented changes to the research approval processes will mostly benefit large multi-centre studies; small scale unfunded studies and student projects are potentially at risk of being marginalised in the quest for a streamlined ethics and NHS Trust research governance approval process. However, researchers’ familiarity with the approval system should minimise rejection rates and delays. Ó 2011 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.
Keywords: NHS Ethics Governance Research Approval Consent
Background Whilst the current ethics and research governance process may seem arduous it exists for very sound reasons. Historically, highly unethical research has been undertaken, causing harm unnecessarily to people. Experiments carried out on Jews, gypsies and other population groups by the Nazi Doctor Joseph Mengele and others are well known.1 Several more unethical experiments took place in the 20th century, before and after the Second World War. It is fair to speculate that most people would now be horrified e.g. by The Tuskegee Syphilis Study that took place in the 1930s which prospectively investigated the effects of untreated syphilis in people in the southern United States.2 Even in the 1960s, well after the implementation of the Nuremburg code of 1947, there was the Willowbrook Study, which involved deliberately infecting mentally retarded children with the hepatitis virus. Some children were fed extracts of stools from infected individuals.3 In the context of trials such as those above, the declaration of Helsinki was drawn up by the World Medical Association, first in 1964 and updated most recently in 2008. This provides a framework of ethical principles on * Corresponding author. Faculty of Health and Well Being, University of Cumbria, Fusehill Street, Carlisle CA1 2HH, UK. Tel./fax: þ44 01228 814689. E-mail address: [email protected] (L. Jonker).
which the current research ethical approval process in the UK is based.4 Both the Nuremburg Code and the Declaration of Helsinki have had a significant impact on how research is conducted and how research proposals are assessed.
Introduction Research of a social nature or research with a more clinically orientated theme commonly occurs in the NHS. In order to ensure research participants are subjected to ethical procedures and that patient information and data are not misused, guidelines are in place in the NHS. Consequently, before a research project can commence it will have to be approved by a Research Ethics Committee (REC) and also by the Research and Development (R&D) Department(s) of NHS Trust(s) where the research is to occur. In England the Department of Health plays a central role in research ethics services. Different bodies are responsible in the devolved nations: the Department of Health, Social Services and Public Safety (Northern Ireland), Scottish Executive (Scotland) and National Assembly (Wales). Fortunately, all RECs in the UK have adopted the standard operating procedures issued by that National Research Ethics Service. Depending on the project and employment status of the researchers, approval may also have to be sought from NHS
1078-8174/$ e see front matter Ó 2011 The College of Radiographers. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.radi.2010.12.004
L. Jonker et al. / Radiography 17 (2011) 260e264
Trust(s) for clearance to work on their premises. There have been major changes made to all these processes in recent years. Most applicants who use the Integrated Research Application System (IRAS) will only apply to a REC and NHS Trust; other bodies to which one can apply such as the National Information Governance Board and Social Care Research Ethics Committee are not covered in this review. Similarly, the additional processes involved for clinical trials involving medicinal products (CTIMPs) are beyond the scope of this article, as a CTIMP also requires approval from the Medicines and Healthcare products Regulatory Agency. Preparations before ethics and NHS R&D submission Research projects vary greatly, thereby making a “one size fits all” REC and NHS R& D approval service hard to achieve. Nonetheless certain aspects of a submission to an Ethics Committee and NHS R&D Department need to be taken into account regardless of the nature of the project. For the latter this is referred to as Trust R&D approval in the remainder of the text. The first thing to ensure before entering the REC and Trust R&D approval process is that all supporting documentation is in place. REC and Trust R&D Committees are increasingly keen to see evidence of peer review for studies and projects, regardless of whether it concerns a student project, a single site unfunded pilot study or a multi-centre funded clinical trial. Such a review is good practice and should be seen as developmental and useful. Having e.g. patient questionnaires and other key information, such as patient information sheets and data collection tools, reviewed by a peer can also be beneficial. If the research directly involves patients then the appropriate language and terminology should be used e the participation organisation INVOLVE can assist in involving patients in study design (www. involve.org.uk). Table 1 shows a typical process of applying for REC and Trust R&D approval for a single site research project with no external funding, involving for example patients attending a radiology department, but not a trial testing the efficacy of medicinal products such as contrast agents. Although no timeline is given for this example project process, the time it takes to develop a proposal and
Table 1 Typical flow of approval process for research in the NHS. Step
Action
1
Write protocol/proposal and supporting documents, such as patient information leaflet, consent form, questionnaire, if applicable Submit or gain peer review Amend protocol and supporting documents if required. Prepare IRAS form (both REC and R&D forms) Contact Medical Director or Nursing Director for sponsorship signature on behalf of the NHS Trust. In case of University employees, ask R&D Director or Faculty Lead. Ensure that everything is in place and that documents have version number and date, both on file name and within documents themselves. Submit to REC committee for approval Usual process: await REC outcome so that the documents submitted to R&D department are documents approved by REC. For University employees: arrange Research Passport to allow working in the NHS. Submit to NHS Trust’s R&D department for approval Commence study once approvals have been obtained Notify REC and R&D department if amendments are made the protocol of the project, or any other alterations that require notification. Submit annual reports and final report at end of project.
2 3 4 5
6
7 8
9 10 11 12
13
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to have it reviewed can be lengthy which needs to be factored in when planning a project. The next sections will concentrate on the ensuing steps of this example. Supporting documentation It is key to ensure that the project documents are written in a clear, understandable, concise format and that they contain all the required information, as this is likely to make the REC and Trust R&D approval process smoother. It essentially means REC and Trust R&D Committees do not have to ask for corrections or additional information, thereby minimising delays. The research protocol or research proposal is an essential part of a research project. A protocol should allow others to appraise the background to a study, the hypothesis, methodology and other information regarding the project.5 Ideally, as with a materials and methods section of a peer-reviewed paper, it should also be possible for someone else to replicate the research using the “recipe” set out in the protocol without necessarily having prior knowledge of the subject or the setting of the research. This protocol should form the basis of any publication that is produced from the work. A research protocol must essentially address points congruent with the requirements set out by REC. A typical table of contents for a research protocol will contain the following sections: Title page (including contact details), Abstract, Introduction, Aims (sometimes divides into primary and secondary aims), Study type, Subjects (inclusion/exclusion criteria), Interventions (if applicable), Outcome measures, Sample size (if quantitative), Study administration (sponsor, liability), Flowchart, References. Inevitably, the structure of a protocol can vary depending on the nature of the project. For projects involving interviews, for example, there may be an appendix contained within the protocol with an outline of interview questions. Whilst the structure of different research protocols will vary, all need to cover the essentials of how a project is undertaken, who is involved, how analysis takes place and who takes responsibility for what. In addition to the protocol, other supporting documents may have to be written, such as a consent form and a patient/participant information leaflet (PIL). These documents are required if patient or NHS employee input is needed; it allows them to be fully informed about the study and the implications, before deciding whether to participate or not. A PIL should introduce the project and its aims e in lay terms and explain clearly yet concisely what will happen to anyone taking part in the project. The risks and/or (indirect) benefits of taking part should also be covered and options for obtaining further information before committing should be given. A PIL and consent form should have the study title and local NHS Trust header on it. One aspect that is important throughout the research project process is for documents to be given a version number and date. Not only is it compulsory for submission to REC and NHS R&D Departments, it is also helps to keep track of all the updated versions of proposals, protocols and supporting documents such as patient information leaflets, interview schedules and questionnaires. Integrated research application process All studies and projects within the NHS are not always classed as ‘research’. A piece of work can also fall into the category ‘service evaluation’, ‘audit’ or possibly ‘surveillance’. So before deciding to apply for REC and NHS Trust research approval it is wise to check whether a project requires ethical and/or NHS R&D approval. If a project is deemed to be service evaluation, audit or surveillance then NHS R&D approval is not required, although ethical aspects of any project should always be considered.6 If, after consulting the National Research Ethics Service (NRES) guidelines, a project does
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fall under ‘research’ then the process of gaining REC and NHS Trust research governance approval is applicable. REC and Trust research approval processes have an identical starting point: the Integrated Research Application System (IRAS) with website address www. myresearchproject.org. REC application There are various elements to be taken into account to ensure a research project is ethical. Table 2 summarises what RECs focus on when reviewing an application. Broadly speaking these considerations apply for any type of project, from a relatively straightforward and short student project to a complex multi-centre randomised controlled clinical trial. In the UK, the National Research Ethics Service (NRES) co-ordinates all RECs and the processes that go with reviewing and administering research projects e see also www.nres. npsa.nhs.uk. Many first-time users of IRAS find the submission processes for REC approval confusing. When a form is completed and the researcher is ready to submit the project, a ‘submission’ button in IRAS allows them to do this. However, this is not actually a hard copy submission of the project. All that this achieves is for the ‘draft’ watermark to be removed from the application form and for a portable document format (PDF) file to be generated of the application form. Further actions as required for actual submission i.e. the PDF file to be printed off and signed by the chief investigator and sponsor’s representative before being sent in the post along with 6 copies of the study protocol to REC. NRES actually prefers researchers to phone up to book an appointment for the time the project will be reviewed by REC, depending on their meeting dates and only once this is agreed then to ‘submit’ the IRAS form.7 In the authors’ opinion this is a weakness in the process, because following these instructions will leave only 4 days to gather signatures from e.g. the sponsor’s representative which may be rather challenging. Submitting and printing off the IRAS form first, to gather the signatures, and then phoning up to book an REC appointment would be less of a rush. Once an appointment is made it is not compulsory, but nevertheless highly recommended, to attend the meeting at which the research project is reviewed. Attending in person gives the researcher the opportunity to clarify matters, to defend certain choices that have been made and to demonstrate commitment to the project. An outcome of the application is usually received within a few weeks of the meeting. NHS research governance RECs consider a research project from a patient’s perspective. In contrast the NHS R&D Departments tend to review what the local impact will be of a proposed research project (although patient
safety and well-being is included in their appraisal too). The way these bodies function is based on a document called Research Governance Framework RGF, produced by the Department of Health.8 As this document does not set out strict guidelines on how R&D Departments in NHS Trusts should operate, there is variability in set-up of R&D Departments throughout the UK. Some Trusts host regular committees, whereas other Trusts rely on one or two people to review and approve research projects. In essence, however, those charged with Trust R&D governance consider a host of aspects when evaluating a research project. They assess if the chief investigator and/or principal investigator (CI/PI) adequately qualified to carry out the research. One aspect of research training that several R&D Departments insist upon e even if the research study does not involve a medicinal product e is for researchers to have attended a course in Good Clinical Practice.9 Within a GCP course, the history and importance of research, informed consent, good practice in record keeping and the role of REC is discussed. GCP needs to be renewed once every two to three years. No strict guidelines have yet been issued on renewal requirements, further diminishing its validity and credibility. Trust’s R&D Departments will check if a study is covered by NHS indemnity, and if not whether the sponsor has taken out separate insurance. It is checked if projects involve the use of radio-nuclides; if so, Administration of Radioactive Substances Advisory Committee (ARSAC) must be involved. Financial implications, conflicts of interest, potential public relations risks and data protection risks and measures are taken into account. A Trust’s R&D Department will assess if the research project can be physically carried out e is there space, staff and equipment capacity, and have all relevant departments been informed and do they support the research? The latter should be considered carefully by researchers when compiling a research proposal. How will patients be identified and approached; if input from radiographers or radiologists is required, will they have the (protected) time and inclination to do so? If these potential issues are not ironed out beforehand, the project may be delayed or even impossible to carry out. A comprehensive ethical and scientific review of a submitted research project is not indicated within NHS Trusts R&D Committees; however, in practice they can and do comment on such issues and sometimes can reject an application on ethical and/or scientific grounds. If the trial is multi-centre trust approval has to be gained at each site. The authors’ experience is that gaining the approval of several trusts R&D Committees can be a contradictory, lengthy and tedious process. If the project runs across several NHS Trusts then each NHS Trust will have its own IRAS site specific information (SSI) form. An SSI form basically summarises the project for each particular Trusts and identifies the local researchers involved and deviations from the protocol, if any. National Institute for Health Research (NIHR)
Table 2 Summary of ethical review questions. Item
Questions asked
Aims
Is there a valid scientific question that is likely to produce new information? Are aims feasible? Do the potential benefits outweigh the potential risks? Does it involve vulnerable groups (children, mentally incapacitated patients) How are subjects recruited and are they given sufficient information about what the research involves? Are there processes in place for gaining informed consent? Who will have access to data, is data anonymised and stored confidentially? For biological samples, what are usage, storage and/or destruction arrangements?
Risk Participants Recruitment Consent Data Samples
Recently, the Department of Health introduced the National Institute for Health Research (NIHR) which has had a major impact on Trust R&D governance. The NIHR is the organisation responsible for the implementation of the Coordinated System for gaining NHS Permission.10 Researchers can have their project processed through CSP, by selecting this option on the IRAS application form, but there are some conditions attached to this. Projects can only be reviewed and processed through CSP if they are funded by an external grant. If a project has been awarded funding then the body which awarded the funding will have to be on a list of recognised funders. This list includes NIHR funding, national research councils such as MRC, organisations such as the Wellcome Trust and now also research grants awarded by the College of Radiographers. A major advantage
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of having a suitable project processed through CSP is that the project is listed on the NIHR National Portfolio.11 This then qualifies a project to receive support from the NIHR in NHS Trusts where the project is carried out. In order to boost clinical research in the UK, the NIHR funds 25 research networks, Comprehensive Local Research Networks (CLRNs) which in turn funds (clinical) researchers with the aim to improve research activity in the NHS. If a project is not on the National Portfolio then this beneficial support and infrastructure is not available. The Research Passport Formerly, if not already working for both an NHS Trust and a University, academics used to be issued with an honorary contract to work in a hospital or primary care trust. Often, academics would have to attend induction days in NHS Trusts and undergo occupational health screening. Conversely, clinical staff and allied healthcare professionals were issued with an honorary contract to work in Universities and other further education establishments. This changed with the introduction of the Research Passport which streamlined the process so that e.g. academics working with several NHS Trusts could make just one application for the necessary permissions.12 The new situation mainly benefits those researchers who are involved in larger multi-centre research studies. A Research Passport enables an academic to complete a single application form and to submit this with evidence of employment, immigration and health status to one NHS Trust. Once this NHS trust has scrutinised and approved the application, a researcher is issued with a letter of access. Subsequent NHS Trusts should accept the completed Research Passport and issue a letter of access, without asking for further information or application. For NHS staff there is no need for a Research Passport if they wish to do research in a different Trust form the one they are employed by e a letter of access should suffice. A major hurdle for researchers based at Universities that traditionally have not been very research active is that support may not be readily available to tackle all these new initiatives, like filling in a Research Passport application form, collating the necessary documentation, involving Occupational Health in health checks on the researcher, and obtaining CRB clearance if not held in certain instances. This, and other aspects of the process such as inconsistencies between Trust R&D departments, may delay research or dissuade potential researchers. Discussion Whilst it is of the utmost importance that all research in the NHS is conducted in an ethical manner the efforts made to improve the system, the process of reviewing and approving research proposals is lengthy, inconsistent and a topic of frustration for many researchers. The majority of complaints by researchers concerning REC and NHS Trust R&D approval are re the time necessary to get a project approved. Both clinical researchers and social researchers have made their frustrations public in the past.13e16 The NHS Trust R&D approval process possibly receives more criticism than the REC approval system, as illustrated by Galbraith et al. (2006) comment that ‘research governance approval is putting people off research’.17 Implementation of the Coordinated System for gaining NHS Permission should streamline this part of the research project approval process although teething problems are likely to be inevitable because the system is new. Recently, two researchers published their experience with CSP and were not overly complimentary about the system.18 However, their project was the first cross-border project involving Scotland and England which may have contributed to the delays they experienced with research approval in English Trusts. It is an indictment that the difficulty of negotiating NHS REC
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and Trust R&D approval processes may have contributed to a reduction in applications to REC witnessed over the last few years. In 2004/5, a total of 9670 applications were made and in 2009/10 this figure had reduced to 6321.19 However, the number of applications for clinical trials, often involving multi-centres and present on the NIHR National Portfolio, shows an increasing trend in applications suggesting that potentially valuable smaller projects and student projects are the ones suffering. The authors know that expecting a student to negotiate this process and submit a dissertation within a year is not viable. Therefore, a two-tier system, one tier for small scale and low risk projects and another tier for interventional and high risk studies would potentially be beneficial. This would inevitably create the issue of who decides e and how the decision is made e what tier a project should fall into. The latest initiative, the Research Passport, can cause some initial frustrations amongst University research staff in particular because all NHS employees need to conduct research in a different trust is a letter of access. On the plus side, once in-situ the Research Passport should save time and effort in the long run. Conclusions The processes for REC and Trust R&D approval have changed considerably over the last few years. The latest amendments, including the introduction of the NIHR and related processes, are tailored towards large research studies and therefore more established researchers and research active organisations. For ‘small scale’ researchers who do not have the benefit of having large dedicated research support teams and who conduct non-funded research, the latest round of changes to the REC and NHS Trust approval system may not necessarily have brought about the improvements many such researchers hoped for. Nevertheless, the background provided here about how REC and Trust R&D Committees function may provide (new) researchers with insight to help optimise their applications and thereby to make the process more straightforward. Conflict of interest No funds were received in support of this study. LJ is partly funded by the Cumbria & Lancashire Comprehensive Local Research Network (C&L CLRN) for his position of R&D Manager at North Cumbria University Hospitals NHS Trust. The views and opinions in this article are the authors’ and do not represent those of the C&L Comprehensive Local Research Network or North Cumbria University Hospitals NHS Trust. References 1. Seildelman WE. Mengele medicus: medicine’s Nazi heritage. The Milbank Quarterly 1988;66:221e39. 2. Jones J. Bad blood: the Tuskegee syphilis experiment: a tragedy of race and medicine. New York: The Free Press; 1981. 3. Meaux JB, Bell PL. Balancing recruitment and protection: children as research subjects. Comprehensive Pediatric Nursing 2001;24:241e51. 4. Declaration of Helsinki [accessed 19.07.10], http://www.wma.net/en/30publi cations/10policies/b3/index.html; 2008. 5. O’Brien K, Wright J. How to write a protocol. Journal of Orthodontics 2002;29: 58e61. 6. http://www.nres.npsa.nhs.uk/applications/apply/is-your-project-research/ [accessed 28.06.10]. 7. http://www.nres.npsa.nhs.uk/applications/booking-your-application/ [accessed 19.07.10]. 8. http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/ PublicationsPolicyAndGuidance/DH_4108962 [accessed 19.07.10]. 9. Good clinical practice (GCP) Commission Directive 2005/28/EC. Official Journal of the European Union; 2005. 10. http://www.ukcrn.org.uk/index/clinical/csp.html [accessed 22.07.10]. 11. http://www.ukcrn.org.uk/index/clinical.html [accessed 22.07.10]. 12. http://www.nihr.ac.uk/systems/Pages/systems_research_passports.aspx [accessed 19.07.10].
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13. Elwyn G, Seagrove A, Thorne K, Cheung WY. REC and research governance in a multicentre study: add 150 days to your study protocol. British Medical Journal 2005;330:847. 14. Cook M, Cook G, Hodgon P, Reed J, Clarke C, Inglis O. The impact of research governance in the United Kingdom on research involving a national survey. Journal of Health Organ Management 2007;21:59e67. 15. Kielmann T, Tierney A, Porteous R, Huby G, Sheikh A, Pinnock H. The Department of Health’s research governance framework remains an impediment to multi-centre studies: findings form a national descriptive study. Journal of the Royal Society of Medicine 2007;100:234e8.
16. Mallick AA, O’Callaghan FJK. Research governance delays for a multicentre non-interventional study. Journal of the Royal Society of Medicine 2009;102: 195e8. 17. Galbraith N, Hawley C, De Souza V. Research governance. British Medical Journal 2006;332:238. 18. Thompson AGH, France EF. One stop or full stop? The continuing challenges for researchers despite the new streamlined NHS research governance process; 2010. 10:124. 19. http://www.nres.npsa.nhs.uk/news-and-publications/publications/generalpublications/ [accessed 22.07.10].