Clinical Trials

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Ethics

A clinical trial may only commence if the Ethics Committee concludes that the anticipated benefit justifies any risks. Trial subjects should be monitored to ensure that the anticipated benefits are justified. The Ethics Committee should safe guard the rights, safety and wellbeing of all trial subjects. Special attention should be paid to trials involving vulnerable subjects.

With the introduction of the EU Directive there were changes to the Research Ethic Committee (REC) procedures. The new UK ethics review system  involved further streamlining of the Ethical Committees into those that were ‘recognised’ and those that were ‘not recognised’ to review clinical trials that involved medicinal products. The Governance Arrangements for Research Ethics Committees (GAfREC) led to  the introduction of Multi Research Ethics Committees (MRECs)  and the continuation of Local Research Ethics Committees (LRECs).

Changes to procedures following the introduction of the EU Directive ' Medicines for Human Use (Clinical Trials) which came into force on 1st May 2004, involved:                                        

• decisions required to be delivered on a valid application within 60 days

• one decision being valid for the whole of the UK, (however before a study can start locally a smaller, much less involved site specific assessment must be undertaken n.b. information submitted  to the original ethics committee e.g. study protocol, patient information leafet may not be amended at this stage

•  a restriction of one written request for clarification or further information to applicants, with  the clock stopped whilst a response is awaited

The regulations enabled the UK Ethics Committee Authority (UKECA) to be established.

This UKECA grant ‘recognition’ to ethics committees (type II for single site status , type III for multi site status) and allow them to review protocols for trials that involve Investigational Medicinal  Products .

Those ethics committees that are not recognised may only review research protocols for trials that do not involve a medicinal product and are called  ‘Authorised Research Ethics Committees’.

Application for Ethics Approval

The Ethics Committee should obtain  from the researcher the following documents for approval:

• the detailed trial protocol

• subject recruitment procedures (e.g. advertisments)
• the proposed Patient Information Leaflet (PIL) and consent form
• safety Information pertaining to the IMP
• arrangements for compensation of subjects (payment)
• the researcher’s current CV
• a valid national application form (obtained from NRES website)

If the study involves a medicinal product and if the study is to take place in more than one Health Board (domain) then, when applying for ethics approval the application should be sent via the central allocation system. If the study is taking place in one Health Board area only, but will take place on more than one research site within this Health Board (domain) then an application to the local REC is more appropriate.   If the research is only to be undertaken on one single site and does not involve a medicinal product then application should be made to the local REC. A phone call to CAS is required to book in the application. The documentation should be submitted within 4 days of booking the application.

All RECs meet on a monthly basis to ensure that decisions can be made within 60 days.  Applicants submitting to a LREC may be asked to resubmit to a different LREC if there are no agenda slots available. The 60 day rule starts when the relevant REC receives a valid application. Confirmation that the application is valid should be sent within 5 days at which stage if the research is to be conducted across several domains (e.g. several NHS Trusts) then the Chief Investigator may instruct the Principal Investigator to apply locally for a Site Specific Assessment at each research site.

Applicants who have submitted a clinical trial protocol for review may now (post EU Directive) attend the meeting to clarify any points and hence facilitate the 60 day rule, however attendance is not compulsory.

Should clarification be required on a specific issue or further information be required prior to the REC being able to grant a ‘favourable’ or ‘ non - favourable’ opinion, then

a written request will need to be sent to the researcher from the chair or administrator of the ethics committee .

N.B. Each committee now only gets one chance to raise amendments with the researcher. The committee is not allowed to raise further issues not identified at the first review. Once a response is received from the investigator then the 60 day rule is reinforced.

Should the response that is received not be satisfactory then the same issues may be asked once again by the committee and the 60 day rule ('clock') is once again stopped whilst waiting on a response.  No new issues may be raised at this time.

The clinical trial may be accepted by the REC and a  favourable opinion granted or it may be rejected by the REC and a non - favourable opinion granted.

R and D Management Approval

In all cases researchers also need to obtain R and D Management approval prior to commencing a clinical trial. Ethics approval is conditional upon the Chief Investigator/Principal Investigator obtaining R and D Management approval. Even though ethics approval may be granted, the researcher may not start the trial until R & D management approval has been given.The 60 day rule ('clock') does not apply to R and D departments.

Multi Research Ethics Committees

Some research will be conducted as a multi-centre study, i.e a clinical trial conducted

according to a single protocol but at more than one site, and therefore by more than one investigator.

The 60 day rule starts when the relevant REC receives a valid application. Confirmation that the application is valid will be sent within 5 days at which stage if the research is to be conducted across several domains (e.g. several NHS Trusts) then the Chief Investigator may instruct the Principal Investigator to apply locally for a Site Specific Assessment at each research site.

Where the research is being undertaken on more than one study site (e.g.NHS Trust) then the local site assessor will report their findings to the multi research ethics committee (MREC) and it is then the responsibility of the MREC to issue the opinion to the Chief Investigator (Researcher with responsibility for research). Each time a site is approved for the study (from the original sites proposed), then the main MREC will re- issue the approval letter with the new site included. New sites will be added following the same process.

Amendments

An amendment is something that happens after the clinical trial has started, where as a revision is something that happens prior to the clinical trial starting.

Amendments and revisions are categorised into substantial and non substantial amendment/revision. Where a substantial amendment/review is required then this must be reported to the Ethics Committee that granted a favourable ethical opinion. Substantial amendments are all amendments that are not administrative in nature. The REC will give a decision about an amendment within 35 days. Should the amendment be rejected then the researcher may resubmit a modified  version of the amendment which the REC needs to review within 14 days.

 

 

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