NREC-CT reviews clinical trials of investigational medicinal products, as determined by EU Regulations in the area of clinical trials of investigational medicinal products (CTIMP) (EU No. 536/2014).

Yes; to enable a smooth transition, the majority of ‘recognised RECs’ have agreed to continue to provide research ethics review for CTIMPs during a defined period. Accordingly, both the NREC-CT and ‘recognised RECs’ will have authority to review CTIMPs, and therefore will collectively support this important research area, from May to December 2021.

The concurrent operation of NREC-CT and ‘recognised RECs’ over the transition period will maintain momentum in clinical trial research while maximising opportunity for preparedness at a national level for the EU Clinical Trials Regulation (CTR) (EU No 536/2014). In line with the anticipated application of the EU CTR in January 2022, it is essential that Ireland has a fully operational national system for CTIMP regulation and review, including returning nationally applicable ethics opinions, following processes in line with international best practice. Importantly, 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 CTR, in addition to the EU Medical Device Regulation (EU No 2017/745). This will be best achieved by a cohesive system of independent NRECs supported operationally by the National Office; correspondingly, existing ‘recognised RECs’ will not have authority to review CTIMPs after the transition period. This will not affect the local REC jurisdiction in relation to health research that falls beyond the scope of the defined remit of the NRECs.

We recognise that this transition represents a major change to the research environment and our goal is to make it as seamless as possible; this will require coordination, communication, and a degree of patience from the parties involved, in particular the National Office, local RECs and the research community.

The EU Clinical Trial Regulation (EU CTR) No 536/2014 was adopted and entered into force in 2014. The timing of its application depends on confirmation of the full functionality of the Clinical Trial Information System (CTIS), the centralised EU portal and database for clinical trials. The EU CTR becomes applicable six months after the European Commission publishes notice of this confirmation. The European Medicines Agency (EMA) and Member State representatives are developing a ‘go-live’ plan for the CTIS with a working assumption of a ‘go-live’ date of January 2022. The National Office and HPRA are represented on a number of the Member State working groups and are committed to staying abreast of developments with the EU CTR and CTIS.

The responsibility for review of substantial modifications to ongoing studies, previously approved by local RECs (including ‘recognised REC’), which now fall within the remit of the NREC-CT, lies with the NREC-CT. 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 more information on substantial modifications please visit our website.

Submission of a substantial modification should be accompanied by the NREC Substantial Modification form, any relevant documentation as designated by the form, and evidence of fee payment. All changes to documentation should be captured through tracked changes.

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 modification. This documentation should include the original REC submission, cover letters and approval letters for any substantial modifications, and the most recent version of the documents.

Further details on substantial modifications can be found here.

Only the modification; the reach of the NREC’s decision on a substantial modification relates only to the ‘question‘ before it (ie, the change proposed in the amendment application). Substantial modifications are reviewed in line with NREC processes and  may require  access to documentation that supported the original REC approval for context, which may inform the NREC decision on the modification; however the ongoing study itself is not subject to NREC approval..

When applying to the NREC-CT, Applicants are asked to use the NREC-CT 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-CT review on the Standard Application Form for Non-clinical Trials, currently used for medical device studies in the local REC system. 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.

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 clinicaltrials@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-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 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 ethics and regulatory approval.  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 pending EU Regulation for clinical trials (EU No 536/2014). 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.

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.

Following the submission deadline, the National Office validates all applications.  This means we check if the application falls within the scope of NREC-CT, 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-CT 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. The outcome for validation is not issued until the cut-off date has passed.

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 trials of investigational medicinal products ongoing prior to May 2021, the safety reporting relationship is established to the NREC-CT from the time it reviews a substantial amendment. The process for the assessment of safety reporting will necessarily change under the EU CTR. In this regard, the specific role of the NREC-CT in safety reports will be further be clarified.

Assessment of safety reports and notifications will be undertaken by the HPRA.

For clinical trials that have not transitioned to the NREC system, they should continue to report to the local REC where they received their initial ethics approval.

If your study involves the exposure to ionising radiation where the exposure or intervention is experimental or beyond the standard of care, an additional appendix must be submitted with the application - https://www.nrecoffice.ie/nrec-ct-combination-studies/.

This appendix much be signed by either a radiation oncologist or radiologist.

It  up to the applicant to determine whether the use of ionising radiation in conjunction with a CTIMP is beyond the standard of care or for experimental purposes.

If your study involves a medicinal device in combination with a medicinal product, an an additional appendix must be submitted with the application - https://www.nrecoffice.ie/nrec-ct-combination-studies/.

Please note, certain combination studies are a subject to both NREC-CT and NREC-MD review, for example studies carried out under both CTD/ CTR and MDR or IVDR, particularly if the study is subject to review by both CT and MD team of the HPRA. In such cases, a separate application to NREC-MD is necessary. For more information on the NREC-MD application process, please visit the NREC-MD website.