NREC-MD reviews clinical investigations of medical devices, as determined by EU Regulations in the area of clinical investigations of medical devices – Medical Device Regulation (MDR; EU No. 2017/745). The MDR defines clinical investigations as “any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device.” 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 MDR, both the HPRA and the National Office can assist.

No; Applicants must now submit their applications for research ethics review of clinical investigations of medical devices to the NREC-MD. The MDR has been applicable in Ireland since 26th May 2021. Therefore, all clinical investigations must now be authorised under the MDR, and will be issued with a single nationally applicable ethics opinion.

A pivotal component of the NREC system will be the return of a single nationally applicable ethics opinion following robust processes in line with international best practice. The NREC review process will run in coordination where necessary with the HPRA to ensure Ireland meets its Member State obligations to return a ‘single national opinion’ in relation to the EU Regulation for clinical investigations of medical devices (EU No 2017/745). This will be best achieved by a cohesive system of independent NRECs supported operationally by the National Office.

The NREC-MD will review clinical investigations of medical devices as defined in the Medical Devices Regulation (MDR; EU No 2017/745). Pre-clinical studies do not come under the MDR and therefore should be reviewed by the relevant local RECs. Early-stage clinical investigations can be regulated studies per the MDR so they may fall within the NREC-MD remit. When in doubt, Applicants should discuss the appropriate route for ethics review of their study with the National Office in advance.

For those ongoing medical device studies approved by local RECs under the Medical Devices Directive 93/42/EEC (‘old legislation’) that require a substantial amendment after MDR implementation, Applicants must apply to NREC-MD for review. For more information on substantial amendments please visit our Guide for substantial amendments.

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 along with the 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:

https://www.nrecoffice.ie/substantial-amendments/

Only the amendment; the reach of the NREC’s decision on a substantial amendment relates only to the ‘question‘ before it (ie, the change proposed in the amendment application). The NREC will likely have access to documentation that supported the original REC approval for context, which may inform the NREC decision on the amendment; however the ongoing study itself is not subject to NREC approval. To ensure clarity on the NREC’s role, the scope of the decision on substantial amendments will be made clear in the meeting minutes.

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. In such cases, Applicants must include an Application Appendix, which includes supplementary 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.

Applications that do not include the relevant documentation or information will be deemed invalid and will require resubmission for further consideration by the NREC-MD.

All applications should be sent as a zipped folder to devices@nrec.ie.

When applying to the NREC-MD, Applicants are asked to use the NREC-MD Application Form and submit it alongside the documentation listed on our website. All application documents should be numbered, and we ask that file names include version number and date.

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. In such cases, 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.

Applications that do not include the relevant documentation or information will be deemed invalid and will require resubmission.

All applications should be sent as a zipped folder to devices@nrec.ie.

.

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.

For more detail, please visit the specific National Office website  and the website of the Data protection Commission.

NRECs are not expected to undertake detailed expert scrutiny of the insurance policies pertaining to the research described in the application they review. The responsibility for ensuring that cover is sufficient and adequate lies with Applicants .

The NREC should receive an assurance from the Applicants that there are adequate insurance or indemnity arrangements in place for the potential legal liability arising from the research, and consider provision in proportion to the risk for compensation or treatment in the event of injury, disability or death attributable to participation.

In particular, this information must evidence that:

1. the insurance arrangements cover the research study concerned;
2. the sponsor and, except for Phase 1 trials, all protocol authors, investigators / collaborators and, where applicable, Site Management Organisations will all be protected by insurance or indemnity arrangements;
3. the arrangements will provide adequate cover to meet the potential liability assessed by the sponsor.

Where a site, sponsor or Investigator come under the Clinical Indemnity Scheme, the sponsor and / or Investigator is responsible for notifying the State Claims Agency of the research study.

Yes, Applicants must pay the relevant fee in advance of submission to the National Office for Research Ethics Committees. For NREC-MD, the fees are set by Statutory Instrument 260/2021, which gives national effect to the EU Medical Devices Regulation.  You can find out more about our fees at https://www.nrecoffice.ie/apply-2/fees/

The timelines for NREC decisions will be consistent with those required by the regulation for medical devices (EU No 2017/745 and S.I. 260/2021). In the first instance, the NREC-MD will review clinical investigations of medical devices monthly. Applicants submitting to the NREC-MD may expect a decision on a valid new application within 55 days and on substantial amendment within 45 days.

Following the submission deadline, the National Office validates all applications.  This means we check if the application falls within the scope of NREC-MD, if all necessary documentation is included, can be accessed and marked with version numbers and dates.

Applicants should normally receive notification of whether their application is ‘Valid’ or ‘Invalid’ within seven calendar days of validation, in line with the operational requirements of the particular NREC review process. Invalid applications will require resubmission if ethics review is to proceed. Typically, the NREC-MD will review all valid applications at full meeting and the National Office will inform the Applicant of the outcome of an ethics review within five working days of a meeting being held. Applicants must acknowledge the decision of the NREC-MD within 10 days of receiving it.

In line with current practice, from the time of NREC launch, 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 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.

All aspects of reporting, including annual and safety, reporting for studies previously approved by local RECs under the Medical Devices Directive 93/42/EEC have, as of 26 May 2021, moved to NREC-MD. On the submission of 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. Applicants must submit an Annual Report to the NREC within 30 days following the anniversary of the date on which approval was given and for every year thereafter for the duration of the study.

The submission of all such reports will be acknowledged in writing by the National Office.

The NREC-MD will be notified of the receipt of the report in the NREC-MD report which will be shared with NREC-MD committee members at full NREC meetings.

Templates for the Annual Progress report and End-of-Study report on the National Office website.

The reporting relationship from an ethics perspective for clinical investigations of medical devices approved under the ‘old legislation’ and ongoing on the date of effect of the EU MDR (26^th May 2021), lies with the NREC-MD. To ensure compliance with the MDR, Sponsors / Principal Investigators should, as of the 26^th May, notify the NREC-MD on all aspects for reporting, including annual reports, safety reports, and device deficiencies, and any other matter that requires an ethical decision or notification.

The requirement for a decision by, or report or notification to, the NREC-MD will be the ‘trigger’ for transfer of the relevant historical documentation on studies approved by the local REC system, to the National Office for the records of the NREC-MD; this will require coordination by the research team with the National Office.

In line with Article 68 of the MDR, in emergency situations, where consenting process may not be possible before the intervention, the applicant needs to ensure the following are true:

• Urgency: The urgency of the situation is caused by a sudden life-threatening /sudden serious medical condition, preventing participant to provide consent prior to the CI;
• Evidence: Previous research shows that the intervention is likely to benefit the prospective participant;
• Time pressure: There is a limited time window for the intervention, due to which informing and consenting prospective participants’ legal representatives needs to be deferred;
• Prior objections: The investigator needs to be able to confirm that they are not aware that the prospective participant objects to participation in research;
• Relevance: The intervention is directly relevant to the medical condition that led to the emergency situation;
• Can be only done in emergency situations: The research cannot be done in “normal” circumstances and can only be conducted in emergency situations;
• Minimal risk: The clinical investigation poses a minimal risk / burden on the prospective participant in comparison with the standard treatment;
• Consent sought without delay: Following the intervention informed consent is sought by the investigator without undue delay first from legal representatives and then from the participant when capable of consent;
• Data removal facilitated: If the participants/ their legal representatives don’t give a consent, they need to be informed that they can ask for their data to be removed from the study, which should be facilitated.