research ethics & governance claire daffern quality assurance manager clinical trials unit
DESCRIPTION
Research Ethics & Governance Claire Daffern Quality Assurance Manager Clinical Trials Unit. NHS research governance Ethical & legal frameworks for research Principles of Good Clinical Practice How to obtain approvals to commence a research project. In this session:. - PowerPoint PPT PresentationTRANSCRIPT
In this session:• NHS research governance• Ethical & legal frameworks for research• Principles of Good Clinical Practice• How to obtain approvals to commence a research project
Declaration of Helsinkiwidely regarded as the cornerstone document of human research ethics
KEY principles:•Respect for the individual•Informed consent•Risks and benefits•Ethics review
5 updates
Development of Good Clinical Practice
1964 Declaration of Helsinki1981 FDA regulations1986 ABPI regulations1989 Nordic guidelines1989 MHW Japan guidelines1990/1 EU guidelines/directives1992 WHO guidelines1996 ICH GCP guidelines1998 MRC GCP guidelines
EU Directive2001/20/EU
UK Regulations 2004
Amendment 2006
Key changes•Compliance with the principles of GCP is now a legal requirement for all IMP trials•New regulatory approval system – via MHRA (UK Competent Authority)•Mandatory GCP and GMP inspections•National REC with specific timescales for review•Regulatory approval for phase I trials•Additional constraints for trials involving vulnerable subjects•IMP trials to be registered on EUDRACT database•Manufacturing of IMP only at licensed sites under GMP conditions
Which Guidelines?
If yes = EU Directive = ICH GCPIf no = MRC GCP
NHS Research Governance Framework 2005• Sets out the broad principle of good research
governance for health and social care• brings together general principles of good
practice• refers to the law on clinical trials involving
medicines• seeks to promote improvements in research
quality
Health and social care research is not the province of a single discipline, profession or organisation and no single document adequately captures the full range of legislation, standards and good practice guidelines that apply to this body of work.
The framework covers five domains:• ethics;• science;• information;• health, safety and employment;• finance and intellectual property.
For each domain the framework stipulates:• requirements in legislation and regulations;• standards required by the Department of Health;• other established principles of good practice from recognised international and national authorities and professional organisations.
Good Clinical Practice is …
“international ethical and scientific quality standard for designing, conducting, recording and reporting trials that
involve the participation of human subjects”
“assurance that the rights, safety and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and that
the clinical trial data is credible.”
GCP Guidelines include:
• 13 Principles of Good Practice• Definition of Responsibilities (Ethics
Committees, Investigators & Sponsors)• Protocol – what should be included• Investigator Brochure – information
relating to the IMP in use• Essential Documents – how trial data
should be managed
Principle 1Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with GCP and the applicable regulatory requirement(s).
Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risk.
RISK ASSESSMENT
DMECMREC
MHRA TSC
Principle 2
Sponsor
RISK BENEFIT
The rights, safety and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.
Principle 3
The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.
Principle 4
Clinical trials should be scientifically sound and described in a clear, detailed protocol.
Principle 5
A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB) / independent ethics committee (IEC) approval / favourable opinion.
Principle 6
The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.
Principle 7
Curriculum
VitaeCurriculum
Vitae
JBrow
n
07/04
/07
MRC-GCP: situations where it would be appropriate for other healthcare professionals, such as midwives etc. to be responsible for patient care.
Each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective task(s).
Principle 8
PersonalDevelopmentFolder
1. Induction documentation2. Job description3. Full CV – signed and dated4. Internal training (incl SOPs) records5. External training records6. Publications
Name Responsibilities Initals Sign
Freely given informed consent should be obtained from every subject prior to clinical trial participation.
“taken freely after being duly informed of its nature,
significance, implications and risks”
20Elements
listed in GCP
Principle 9
Minors Incapacitated
MRC-GCP: situations do exist in which fully informed consent may not be possible. In these cases, procedures agreed in existing guidelines should
be followed, provided favourable EC opinion given.
X
All clinical trial information should be recorded, handled and stored in a way that allows its accurate reporting, interpretation and verification.
Trial Master FileSite Master File
Principle 10
Age (yrs)
Age (yrs)
Age (yrs)
The confidentiality of records that could identify subjects should be protected by privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
Principle 11
Principle 12Investigational products should be manufactured, handled and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol.
InvestigatorInvestigator
Subject
Sponsor
Systems with procedures that assure the quality of every aspect of the trial should be implemented.
Principle 13
MonitoringSOP
s
Educational ResearchLaboratoryNon-clinical intervention
Clinical InterventionsNHS patients
University involvementClinical Intervention
Commercially Funded
Sponsor
SponsorshipICH GCP defines a Sponsor as: An individual, company institution or organisation which takes responsibility for the initiation, management, and/or financing of a clinical trial
For the University of Warwick to act as your sponsor, apply via WMS research Ethics & Governance [email protected]
Invasive?
Non-negligent cover?Insurance
Insurance
The University of Warwick has Clinical Trials Insurance cover in place, provided by HDI Gerling
The policy covers most trials at Warwick, but there are multiple criteria where a referral to the insurers is required. Including (but not limited to):
Studies where blood-products will be tested Studies with a planned duration of more than 8 yearsStudies in which pregnant women are involvedAny trial to be conducted outside of the UKStudies involving children under the age of 5
Randomised Controlled?Apply forISRCTN
Yes
APPROVALS
££
Is it a drug trial?Apply for
EUDRACTYes
ApprovalsSubmit via
IRASYes
IRASIntegrated Research Application System
ARSAC
Ethics
NOMSR&D
MHRA
https://www.myresearchproject.org.uk/ GTAC
NIGB
Randomised Controlled?Apply forISRCTN
Yes
APPROVALS
££
Is it a drug trial?Apply for
EUDRACTYes
Submit toMHRA45 days
££
ARSAC
Approvals via IRASMain Ethics
Yes60 days
Site Approvals R&D
GTACNOMSCAG
CONTRACTS
Funder
Sites
Staff
} University ResearchSupport Services
Co-Sponsor
HonoraryContracts
Subcontracts
via HR
Before First Subject enters
Letter of Sponsorship agreement
Insurance Certificate
Written Ethics Approval
Written R&D / PCT Approval
Written Regulatory Approval (for CTIMPs)
ARSAC Certificate/other approvals
Signed agreement by all parties
CV of CI/PI at sites
Warwick CTU web siteFor further information, go to:http://www2.warwick.ac.uk/fac/med/research/hscience/ctu/Section entitled ‘Conducting a Clinical trial’ includes:o Current SOPso Links to UoW Research Code of Practiceo Links to legislationo And a step by step guide to running a trial, split into sections:
Initial Planning Set-up During the Trial After the Trial