1. What types of research do NRECs review?
NRECs currently review three types of research: clinical trials of investigational medicinal products, clinical investigations of medical devices, and performance studies of in vitro diagnostic medical devices. Other forms of research are reviewed by local research ethics committees based at research institutions and hospitals. The scope of review of the NRECs is determined by EU Regulations in the areas of Clinical Trials of Investigational Medicinal Products (CTIMP) (EU No. 536/2014), Clinical Investigations of Medical Devices (EU No. 2017/745), and Performance Studies of In Vitro Diagnostic Medical Devices (EU No. 2017/746). Applicants should determine if their study meets the scope of NREC review; however, where an applicant is in any doubt as to whether their study falls under the EU Clinical Trials Regulation, EU Medical Devices Regulation or EU In Vitro Diagnostic Medical Devices Regulation, both the HPRA and the National Office for Research Ethics Committees can assist.
2. What if an applicant is unsure of the route to take for ethics approval of their study?
If a study meets the definition of a clinical trial of investigational medicinal products (CTIMP), from May 2021, applicants can submit an application for ethics review to the NREC-CT.
If a study meets the definition of a clinical investigation of a medical device under the EU Medical Devices Regulation, as of 26 May 2021 applicants must submit it for review by the NREC-MD.
If a study meets the definition of a performance study of an in vitro diagnostic medical device under the EU In Vitro Diagnostic Medical Devices Regulation, as of 26 May 2022, applicants must submit it for review by the NREC-MD.
3. How are NRECs established?
The Minister for Health appoints National Research Ethics Committees (NRECs) in select areas of health research. The Minister has established NRECs in the initial priority areas of clinical trials of investigational medicinal products, clinical investigations of medical devices, and performance studies of in vitro diagnostic medical devices in line with the EU Regulations in these areas: the EU Clinical Trials Regulation No. 536/2014, EU Medical Devices Regulation No. 207/745, and EU In Vitro Diagnostic Medical Devices Regulation No. 2017/746 respectively. The National Office launched a public call for Expressions of Interest for NREC membership in December 2020 with the view to attain the diverse membership base required to consider applications likely to be made to the NRECs. We welcomed Expressions of Interest from individuals with varied expertise, experiential knowledge, and with and without prior REC experience. The NRECs for Clinical Trials (NREC-CT) and Medical Devices (NREC-MD) were formally appointed in May 2021.
4. Who decides the membership of the NRECs?
The Minister for Health decides on the formal appointments to the NRECs. The National Office manages the assessment process following a public call for Expressions of Interest for NREC membership and forwards a recommendation for the NREC(s) for consideration by the Minister for Health for appointment. Recommendations are made on individuals’ merits and not necessarily in a representative capacity, mindful of the balance of expertise and perspectives required. Member recommendations are also informed by appropriate representation of both ‘expert’ and ‘lay’ members in line with best practice. Where in the view of the National Office there is likely to be a particular gap in expertise or representation, we may approach prospective Members to invite an Expression of Interest.
5. What is the mixed-model REC system?
The mixed-model system of research ethics review is provided for by the NREC Bill, which will strengthen the health research infrastructure in Ireland. This means that NRECs will work alongside local RECs, each with clearly defined remits, to ensure that Irish health research is underpinned by the highest ethics standards. The mixed-model system will be supported by parallel reforms in research governance led by the Research & Development Team at the HSE.
6. In what areas will future NRECs be established?
The Minister for Health will establish NRECs in select health research areas of national strategic importance. In this regard, the Head of the National Office for Research Ethics Committees will make recommendations. In the first instance, NREC remits will pertain to those areas for which Ireland has a legislative obligation, including clinical trials of investigational medicinal products, clinical investigations of medical devices, and performance studies of in vitro diagnostic medical devices. Future NRECs may be established in such areas as assisted human reproduction and genomics.
7. What about studies involving ionising radiation?
Studies involving ionising radiation represent a regulated remit for health research and, as such, will be encompassed in the national system of research ethics review. The National Office is working with the Department of Health and local REC stakeholders to find an appropriate mechanism for review of studies involving ionising radiation, recognising the niche expertise required. It is expected that a national route for ethics review of studies involving ionising radiation for medical purposes will be developed in 2022. In the meantime, such applications should continue to be directed to existing ‘recognised RECs’ under this remit.
8. Will decisions taken by the NRECs be made public?
The National Office is committed to transparency. We make the minutes of NREC meetings and details of decisions taken publicly available on our website.
9. Should single-site studies be directed to NRECs for ethics review?
Yes; if the study falls within the remits of health research defined for the NRECs, it should be submitted to the National Office for review.
10. Could you clarify what happens with non-trial clinical multicentre studies – local research ethics committee (LREC) or NREC?
Multi-centre studies that do not involve a clinical trial of medicines for human use do not come under the imminent or existing EU Regulations, and therefore remain within the remit of the local RECs. Parallel reforms in research governance and the local REC system led by the R&D Team at the HSE will assist in streamlining REC approvals for multisite clinical studies in the future.
11. What about external organisations such as charities, services that do not have access to institutional RECs – where do they go the get ethical approval?
Both the NREC-CT and NREC-MD have defined health research remits in line with the respective relevant EU Regulations in clinical trials of investigational medicinal products, clinical investigation of medical devices and performance studies of in vitro diagnostic medical devices. Any research study that falls within the remits of the NREC-MD or NREC-CT must be reviewed through the NREC system. The NRECs will not review studies that do not come under these Regulations. For more information on research ethics committees in other areas of research, please consult https://hseresearch.ie/research-ethics/.
12. As an applicant, do I need to seek approval from my local REC in addition to the NREC?
No; NRECs are legislatively mandated to return decisions that are applicable nationally, and as such, the research community including local RECs, are expected to respect the outcomes from the NREC process. Conversely, an NREC will not revisit a decision made by a local REC within its local remit. In line with good research practice and research governance, applicants should secure the necessary local approvals required to conduct the research at each site and notify their local REC and Research Office or equivalent body in their institution of NREC decisions.
13.Can I use the currently used local forms for NREC review?
For practicality and to assist with a seamless transition of ethics review, until January 2022 the National Office will accept applications for NREC-CT or NREC-MD review on application documentation currently used in the local REC. It is a requirement of the NREC system that all applications forms are signed by the national Principal Investigator. Applications that have not been signed by the PI or are signed by the Sponsor will be considered invalid.
For clinical trials of investigational medicinal products, the format for application documentation will be revised in in January 2022 to meet EU CTR requirements; the research community will be informed of this in a timely manner.
The National Office will initially accept applications for NREC-MD review on the Standard Application Form for Non-clinical Trials, currently used for medical device studies in the local REC system. If the application is for NREC-MD, applicants must include an Application Appendix, which includes new questions found in the NREC-MD Application Form. In January 2022, the standard application form will be phased out and an updated NREC-MD Application Form will be required for all new study applications. These changes will be communicated to the research community closer to the transition.
14. Why is a Data Protection Impact Assessment required as part of the submission process?
Under the Health Research Regulations 2018, a data protection impact assessment (DPIA) is required when the assessment of the data protection implications of the health research indicates high risk to the rights and freedoms of individuals.
The NRECs will need to be assured that any research study is undertaken in accordance with national and European data protection legislation. For this reason, a DPIA will be required as part of an NREC application submission where relevant to the study. If a DPIA is not required for a study, a statement outlining why this is the case will be submitted as part of the application.
For the purposes of NREC review, the DPIA will need to be completed by the Data Controller of the research study. All DPIAs should be accompanied by evidence of DPO input – this could be in the form of comments from the DPO, a DPO signature, or an email from the DPO accompanying the DPIA to confirm they have assessed the DPIA and are satisfied with the DPIA.
Where the Data Controller is based in a non-EU country with an adequacy decision from the European Commission, the National Office will accept DPIAs reviewed by a person with the equivalent role and responsibilities as a DPO.
Where the Data Controller is situated outside of Ireland, the National Office strongly advises that the DPO of the lead Irish-based institution should be given the opportunity to review and provide comment on the DPIA.
The National Office will not be issuing an NREC-specific DPIA template. Instead, we will accept submissions using institutional DPIA templates.
15. Are NREC-approved studies recognised for insurance purposes under the Clinical Indemnity Scheme (CIS)?
The State Claims Agency has confirmed that for studies that fall under the Clinical Indemnity Scheme (CIS), an NREC approval is recognised for insurance purposes under the Clinical Indemnity Scheme (CIS). It is the responsibility of the applicant to notify the State Claims Agency of their study. This is an important requirement of research governance and for good research practice.
16. Are there fees associated with NREC reviews?
Yes, applicants must pay the relevant fee in advance of submission to the National Office for Research Ethics Committees.
For NREC-CT, in the first instance, the fees for ethics review are aligned with those currently in place for the local REC system. It is anticipated that in January 2022 a new fee structure will be required for the NREC-CT with application of the EU Clinical Trials Regulation (CTR). These fees will be determined in consultation with the relevant Government departments including the Department of Health and Department of Business, Enterprise & Innovation. Fees due under the EU CTR will represent a combined fee for both NREC and HPRA approval.
For NREC-MD, the fees in relation to the MDR applications are set by Statutory Instrument 260/2021, which gives national effect to the EU Medical Devices Regulation (MDR). The same fees apply for the performance studies of in vitro diagnostic medical devices applications. You can find out more about our fees here.
17. What is the expected turnaround time for an NREC decision?
The timelines for NREC decisions will be consistent with those required by the pending EU Regulation for clinical trials (EU No 536/2014) and the existing Regulation for medical devices (EU No 2017/745). In the first instance, the National Office has established an NREC meeting schedule that facilitates clinical trials of investigational medicinal product applications to be considered twice per month and clinical investigations of medical devices and performance studies of in vitro diagnostic medical devices to be considered monthly.
The National Office is currently collaborating with the HPRA to run a CTR National Collaboration Project with select volunteer applicants to prepare for a ‘single national opinion’ by testing the processes and timelines required for the EU CTR; in this regard, the timing of an NREC decision will be coordinated with the regulatory decision of the HPRA. When the EU CTR is applicable (anticipated January 2022), the NREC-CT will work to the timelines set out in the EU CTR. Currently, applicants submitting to the NREC-CT may expect a decision on a valid application within 60 days.
For clinical investigations of medical devices, applicants submitting to the NREC-MD may expect a decision on a valid application within 55 days.
18. What if an ongoing study originally approved by a local REC requires a substantial amendment?
The responsibility for review of substantial amendments to ongoing studies, previously approved by local RECs (including ‘recognised RECs’), which now fall within the remit of the NREC-CT or NREC-MD, lies with the respective NREC. In this case, the applicant will be requested to provide all original documentation that supported the original local REC approval, to the National Office. The National Office and the local REC may share information in relation to the study in question to support informed ethics review and oversight of the study. Such amended studies will report to the NREC thereafter including annual, final, and safety reporting.
For NREC-CT, the transition to the NREC system is triggered by a substantial amendment. Once a study transitions to the NREC system through the submission of a substantial amendment, the National Office will take on the role of monitoring and reporting for that study.
For NREC-MD, the transition of all ongoing clinical investigations of medical devices to the NREC system is triggered by submission of a substantial amendment, or notification of non-substantial amendment, safety report, device deficiency report or annual report.
For more information on substantial amendments please consult our guide to substantial amendments.
19. What documents are required for submission of a Substantial Amendment?
Submission of a Substantial Amendment should be accompanied by the NREC Substantial Amendment form, any relevant documentation as designated by the form, and evidence of fee payment.
In the case of studies previously approved by local RECs, historical documents from the study should also be submitted within one month of submission of the Substantial Amendment. This documentation should include the original REC submission, cover letters and approval letters for any substantial amendments, and the most recent version of the documents.
Further details on Substantial Amendments can be found here.
20. What role will the NRECs take on in relation to safety reporting?
In line with the Medical Device Regulation, the Clinical Trials Directive, and the In Vitro Diagnostic Medical Devices Regulation, applicants must notify the relevant NREC about urgent safety measures, suspected serious unexpected adverse reactions, and submit annual safety reports for notification, related to studies approved by the NREC.
For clinical trials of investigational medicinal products ongoing prior to May 2021, the safety reporting relationship is established to the NREC-CT from the time it considers a substantial amendment. All correspondence around safety reporting should include the assigned NREC code (21-NREC-CT-xxx) to ensure orderly tracking of clinical trials. Safety reports for studies that have not yet transitioned should continue to report to the local RECs.
All safety reports will be acknowledged in writing (i.e., via an email response) by the National Office. The National Office is not in a position to return a signed copy of the Safety Cover Form. The National Office does not accept password protected safety notifications and will not issue acknowledgement of receipt in instances where encrypted or password protected documents have been sent.
The process for the assessment of safety reporting has changed under the EU CTR and all safety notifications will be submitted through the CTIS and/or EudraVigilance platform. Please review the following document for further information - https://www.nrecoffice.ie/wp-content/uploads/Appendix-1-NREC-CT-Operational-Framework-CTR-DRAFT-V1.0.pdf
For clinical investigations of medical devices ongoing prior to May 2021, the safety reporting relationship is established to the NREC-MD from the implementation of Medical Device Regulations – 26 May 2021.
Assessment of safety reports and notifications will be undertaken by the HPRA.
21. What about annual reporting for ongoing studies previously approved by a local REC?
All aspects of reporting, including annual and safety reporting for studies previously approved by local RECs under the Medical Devices Directive should as of 26 May 2021 move to the NREC-MD. On the submission of the first report (annual or safety), we ask the applicant to also submit all relevant study documentation, such as original application documents and previous annual reports.
For clinical trials that have not yet transitioned to the NREC system, they should continue to report to the local REC where they received their initial ethics approval.
22. What if a research institution or local REC has a query on an NREC-approved study?
The National Office seeks to work in partnership with research institutions and local RECs and is pleased to answer any queries on the NREC process including sharing summary information on applications receiving approval. Queries should be directed to email@example.com.