Non-CTIMP Standard Conditions

RESEARCH IN HUMAN SUBJECTS OTHER THAN CLINICAL TRIALS OF INVESTIGATIONAL MEDICINAL PRODUCTS

After ethical review – guidance for sponsors and investigators

This document sets out important guidance for sponsors and investigators on the conduct and management of research with a favourable opinion from a Research Ethics Committee. Please read the guidance carefully. A failure to follow the guidance could lead to the committee reviewing its opinion on the research.

This document should be read in conjunction with the UK Policy Framework for Health and Social Care Research which sets out principles of good practice in the management and conduct of health and social care research in the UK including responsibilities for the four elements of research transparency:

1. Registration

1.1 All research should be registered in a publicly accessible database. We expect all researchers, research sponsors and others to meet this fundamental best practice standard.

1.2 For clinical trials it is a condition of the REC favourable opinion that these are registered on a public registry before the first participant is recruited and no later than six weeks after.

For this purpose:

clinical trials are defined as the first four project categories in IRAS project filter question 2; and
a 'public registry' means any registry on the WHO list of primary registries or the ICMJE list of registries provided the registry facilitates public access to information about the UK trial.

2. Commencement of the research

2.1 It is assumed that the research will commence within 12 months of the date of the favourable ethical opinion. The REC must be notified of the start date of the study.

2.2 The research should not commence at any site until the local Principal Investigator (PI) or research collaborator has obtained management permission from the organisation with responsibility for the research participants at the site.

2.3 If the research does not commence within 12 months of the favourable opinion being issued, the Chief Investigator should send a written explanation for the delay. A further written explanation should be sent after 24 months if the research has still not commenced.

2.4 If the research does not commence within 24 months, the REC may review its opinion.

3. Duration of ethical approval

3.1 The favourable ethical opinion of the REC for a specific research study applies for the duration of the study, except where action is taken to suspend or terminate the opinion, subject to approved substantial amendments. Where the duration of the study is to be extended beyond the period specified in the application form, there is no need to notify or seek approval from the REC.

3.2 The favourable ethical opinion provides legal authority to hold “relevant material” for research on premises which are not licensed by the Human Tissue Authority (in England, Northern Ireland and Wales only – this requirement does not apply in Scotland). Where a favourable ethical opinion provides this legal authority, “relevant material” can be held under the terms of the ethical opinion until the end of the period declared in the application; and approved by the REC.

3.3 Samples may be held after the end of study date has been reached, for verification or quality checking of the research data. This should be detailed in the protocol which is approved by the REC and should be for a defined period of time (and no longer than 12 months). After this period legal authority to hold any “relevant material” for this project on premises which are not licensed by the Human Tissue Authority will expire (in England, Northern Ireland and Wales only - this requirement does not apply in Scotland). To ensure that any continued storage of “relevant material” for this project is lawful (in England, Northern Ireland or Wales), either the tissue must be held on premises with a storage licence from the Human Tissue Authority, or an application made for ethical review of another project before the favourable ethical opinion (including the additional time after the declaration of the end of study, if applicable) of the existing project expires. Otherwise the tissue would need to be destroyed in accordance with the HTA Codes of Practice and Standards on Research (code E).

4. Amendments

4.1 If it is proposed to make a substantial amendment to the research, the Chief Investigator should submit a substantial amendment to the REC via the Integrated Research Application System (IRAS)

4.2 A substantial amendment is any amendment to the terms of the application for ethical review, or to the protocol or other supporting documentation approved by the REC that is likely to affect to a significant degree:

(a) the safety or physical or mental integrity of the research participants

(b) the scientific value of the research

4.3 A substantial amendment should not be implemented until a favourable ethical opinion has been given by the Committee, unless the changes to the research are urgent safety measures (see section 8). The Committee is required to give an opinion within 35 days of the date of receiving a valid amendment.

4.4 Amendments that are not substantial amendments may be made at any time and do not need to be notified to the Committee. However, notifying the REC of changes to the contact details for the research team and study sponsor is strongly encouraged.

4.5 Further guidance on amendments is available in IRAS help.

5. Changes to sites

5.1 Confirmation of capacity and capability (for NHS/HSC sites in England, Wales and Northern Ireland or management permission (for NHS sites in Scotland and all non-NHS sites) should be obtained from the participating organisation where it is proposed to:

include a new site in the research, not included in the list of proposed research sites in the original REC application
appoint a new PI or Local Collaborator at a research site
make any other significant change to the conduct or management of a research site.

NHS Sites

5.2 In the case of NHS/HSC sites, the REC’s favourable opinion for the study will apply to any new sites and other changes at sites provided that confirmation of capacity and capability (for NHS/HSC sites in England, Wales or Northern Ireland) or NHS management permission (for NHS sites in Scotland. New NHS/HSC sites do not require a favourable ethical opinion.

Non-NHS Sites

5.3 For clinical investigations of medical devices, changes at non-NHS/HSC sites require review by the REC which reviewed the application for the research. The non-NHS/HSC Site Assessment Form along with a substantial amendment and the relevant supporting documentation should be submitted to the Research Ethics Committee.

5.4 For other study types (except for CTIMPs), there is no requirement to notify the Committee of the inclusion of new non-NHS/HSC sites or other changes at non-NHS/HSC sites.

Guidance on how to work with sites is provided in the IRAS help section.

6. Urgent safety measures

6.1 The sponsor or the Chief Investigator, or the local Principal Investigator at a research site, may take appropriate urgent safety measures in order to protect research participants against any immediate hazard to their health or safety.

6.2 The REC should be notified within three days that such measures have been taken, the reasons why and the plan for further action.

7. Serious adverse events

7.1 A Serious Adverse Event (SAE) is an untoward occurrence that:

(a) results in death

(b) is life-threatening

(d) results in persistent or significant disability or incapacity (e) consists of a congenital anomaly or birth defect (f) is otherwise considered medically significant by the investigator.

7.2 A SAE occurring to a research participant should be reported to the Committee where in the opinion of the Chief Investigator the event was related to administration of any of the research procedures, and was an unexpected occurrence.

7.3 Reports of SAEs should be provided to the REC within 15 days of the Chief Investigator becoming aware of the event, in the format prescribed by the HRA and published on the website.

8. Conclusion or early termination of the research

8.1 The Chief Investigator should notify the REC in writing that the research has ended within 90 days of its conclusion. The conclusion of the research is defined as the final date or event specified in the protocol, not the completion of data analysis or publication of the results.

8.2 If the research is terminated early, the Chief Investigator should notify the REC within 15 days of the date of termination. An explanation of the reasons for the early termination should be given.

8.3 Reports of conclusion or early termination should be submitted in the form prescribed by the HRA and published on the website.

9. Final report

9.1 A final report on the research should be provided to the REC within 12 months of the conclusion of the study.

10. Reporting results

10.1 Other than research for educational purposes and early phase trials, the findings, whether positive or negative, should be made accessible, with adequate consent and privacy safeguards, in a timely manner after they have finished.

10.2 Where appropriate, information about the findings of the research should be made available, in a suitable format and timely manner, to those who took part in it, unless otherwise justified.

11. Review of ethical opinion

11.1 The REC may review its opinion at any time in the light of any relevant information it receives.

11.2 The Chief Investigator may at any time request that the REC reviews its opinion, or seek advice from the REC on any ethical issue relating to the research.

12. Serious breaches of Good Clinical Practice or the protocol

12.1 To ensure that the REC is able to keep the favourable ethical opinion under review, the sponsor should report to the REC any serious breaches of the protocol or of the principles of Good Clinical Practice. A “serious breach” is defined as a breach of the protocol or, of the principles of Good Clinical Practice which is likely to affect to a significant degree the safety or physical or mental integrity of the research participants, or the scientific value of the research. There is no requirement to notify minor breaches of GCP or the protocol.

12.2 Reports of serious breaches should give details of when the breach occurred, the location, who was involved, the outcome and any information given to participants. An explanation should be given and the REC informed what further action the sponsor plans to take.

13. Long Term Studies

Long Term Studies Investigator are responsible for ensuring that the study procedures and documentation are updated in light of legislative or policy changes and also for reasons of good practice (e.g. standards for supporting documentation). This should be documented in the progress report to the REC (see above) and, where necessary, an amendment (see above) should be submitted to the REC. The REC may review its opinion in light of legislative changes or other relevant developments.