The process of ethical approval

1. The process of ethical approval Helena Prady Senior Research Nurse

2. Objectives • Definitions • Sponsor • Chief Investigator • Principal Investigator • The process of approvals • Regulatory body • Ethics • R&D • Other • Other considerations for set up of trials

3. Sponsor "sponsor" means, in relation to a clinical trial, the person who takes responsibility for the initiation, management and financing (or arranging the financing) of that trial. The Medicines for Human Use (Clinical Trials) Regulations 2004 • Often a commercial company eg Actelion • Can be the Chief Investigator’s employer Medicines for Children Research Network

4. Chief Investigator (CI) The authorised health care professional….who takes primary responsibility for the conduct of the trial. • Undertakes many duties delegated by the sponsor • Usually one CI for each trial but if international, there will be a CI in each country Medicines for Children Research Network

5. Principal Investigator (PI) The investigator responsible for the research at a site • There should be one PI for each research site. • In the case of a single-site study, the CI and the PI will normally be the same person. Medicines for Children Research Network

6. ‘Approvals’ needed • Medicines for Human Use Regulatory Authority • Only is drug or device trial • Research Ethics Committee • Main • Local • Local R&D approval • May be Trust, University, PCT • Others • Depend on type of research

7. The Integrated Research Application System Is a single system for applying for the permissions and approvals for health and social care / community care research in the UK • Administration of Radioactive Substances Advisory Committee (ARSAC) • Gene Therapy Advisory Committee (GTAC) • Medicines and Healthcare products Regulatory Agency (MHRA) • Ministry of Justice • NHS / HSC R&D offices • NRES/ NHS / HSC Research Ethics Committees • National Information Governance Board (NIGB) • Social Care Research Ethics Committee

8. Medicines for Human use Regulatory Authority • UK regulatory body • Their approval is a Clinical Trials Authorisation (CTA) • The Sponsor applies for this • Only needed for clinical trials of Investigational Medicinal Product or devices • 30 calendar day timeline from receipt of valid application

9. Medicines for Human use Regulatory Authority • Before giving authorisation, the MHRA consider the science of the research: • What is the question • Has it been researched before • Animal + human • What adverse events were reported • Is the protocol relevant • Are the patients appropriate • Peer reviewed • How drug to be manufactured • Statistics • + + +

10. Main Research Ethics Committee • The Sponsor or Chief Investigator applies to MREC • Documents considered include • Protocol • Patient information sheets and consent forms • Other information for patients • GP letter • CV and training of Principal Investigator • Their approval is ‘favourable opinion’ • 60 calendar day timeline from receipt of valid application

11. Main Research Ethics Committee MREC consider the ethicalness of the trial • What type of patient is it? • Paediatrics/ vulnerable adult • What are they required to do? • Amount of blood testing • Number of visits • Invasive/ non routine assessments • Consent process – including recruitment • Patient information leaflets etc • Age related understandable • ? To be translated • Travel expenses to be paid?

12. Local Research Ethics Committee • Consider local issues • Suitability of site • Suitability of researchers • Some studies eg qualitative, may be exempt from LREC approval (but always require R&D)

13. Trust R&D • National Institute for Health Research (NIHR) Coordinated System for gaining NHS Permission (CSP). • This is for NIHR portfolio studies • Reduces the need for repeat checks of eg MHRA, MREC approvals • Once one site has done the checks, they are on the system so others don’t have to do again • They give ‘approval’.

14. Trust R&D • R&D consider • Suitability of researchers • Whether other approvals in place • this is now done by CSP • Costs and agreements • Whether any impact on services • Pharmacy – during trial and after • Labs / radiology • Whether these patients over-researched

15. Clinical Trials Agreement (CTA!) • model Clinical Trial Agreement (mCTA) is contract between Sponsor and site (+/-university) commonly known as Sponsor agreement • Responsibilities etc • Costings and budget • This contract has to go from sponsor to R&D, agreed, sent back for original signature and then back to site for original signature. • This may well be the cause of delays as lots of negotiation often needed and lots of stages

16. Other considerations • Recruiting necessary staff – eg research nurse • Training of site staff • May be trial specific or general • Collection of CVs, training certificates for assessors • Delegation of duties clarified • Other departments ready • Pharmacy / labs / radiology

17. Other considerations • How are you going to recruit patients • Where are they? • Who can make first contact with them (data protection) • Ensuring systems in place • Standard Operating Procedures • Finance issues arranged • Payment to other departments • Travel/accommodation reimbursement • Storage of equipment, documentation • Enough space • Lockable

18. Thank you • Hope this has helped you to appreciate the stages of preparation involved in setting up studies at site • There may be more stages and issues for different types of research and patients • I am really sorry not to have been here.