Presentation on theme: "Research Ethics & Governance"— Presentation transcript:
1 Research Ethics & Governance Claire DaffernQuality Assurance ManagerClinical Trials Unit
2 In this session: NHS research governance Ethical & legal frameworks for researchPrinciples of Good Clinical PracticeHow to obtain approvals to commence a research project
3 Declaration of Helsinki widely regarded as the cornerstone document of human research ethics KEY principles:Respect for the individualInformed consentRisks and benefitsEthics reviewProduced by the World Medical Association (WMA) – not legally binding but considered to be the ‘cornerstone document in relation to human research ethics.Declaration of Helsinki 1st published in 1964 – developed from the Nuremburg Code which came about after the Nuremburg war trialsMajor points;Respect for the individualThe right to make informed decisions (consent; both initially and during the course of the trial)The subject's welfare must always take precedence over the interests of science and societyEthical considerations must always take precedence over laws and regulations5 updates
4 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
5 Amendment 2006 UK Regulations 2004 EU Directive 2001/20/EU ICH GCP – basis of EU Directive – each member state obliged to transpose the Directive into law – so a few discrepancies between member states – Directive is currently under revision and will eventually be re-issued as a Regulation i.e. will be the same across whole of Europe.Amendment 2006
6 Key changesCompliance with the principles of GCP is now a legal requirement for all IMP trialsNew regulatory approval system – via MHRA (UK Competent Authority)Mandatory GCP and GMP inspectionsNational REC with specific timescales for reviewRegulatory approval for phase I trialsAdditional constraints for trials involving vulnerable subjectsIMP trials to be registered on EUDRACT databaseManufacturing of IMP only at licensed sites under GMP conditions
7 If yes = EU Directive = ICH GCP Which Guidelines?If yes = EU Directive = ICH GCPIf no = MRC GCP
8 NHS Research Governance Framework 2005 Sets out the broad principle of good research governance for health and social carebrings together general principles of good practicerefers to the law on clinical trials involving medicinesseeks to promote improvements in research quality
9 Health and social care research is not the province of a single discipline, profession or organisation and nosingle 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.54 pages
10 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.”All work undertaken within CTU is based on the principles of Good Clinical Practice.Good Clinical Practice is defined as "a standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected“ (ICH GCP).SUBJECT PROTECTION MOST IMPORTANTQUALITY STANDARDApplicable to the whole of the clinical trial/clinical research process - affects everyone involved: subjects, investigators and AZ employees.
11 GCP Guidelines include: 13 Principles of Good PracticeDefinition of Responsibilities (Ethics Committees, Investigators & Sponsors)Protocol – what should be includedInvestigator Brochure – information relating to the IMP in useEssential Documents – how trial data should be managed
13 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).
14 Principle 2Before 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.SponsorMRECDMECRISK ASSESSMENTMHRATSCRISKBENEFITSOP 18
15 Principle 3The rights, safety and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.123SOP 17
16 Principle 4The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.i.e. get as much background information as possible to justify the need for the trial
17 Principle 5 SOPs 4, 8 & 9 TEMPLATE Clinical trials should be scientifically sound and described in a clear, detailed protocol.SOPs 4, 8 & 9TEMPLATE
18 Principle 6A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB) / independent ethics committee (IEC) approval / favourable opinion.SOPs 5, 6 & 29
19 Principle 7The 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.CurriculumVitaeJBrown07/04/07MRC-GCP: situations where it would be appropriate for other healthcare professionals, such as midwives etc. to be responsible for patient care.
20 Principle 8Each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective task(s).PersonalDevelopmentFolderInduction documentationJob descriptionFull CV – signed and datedInternal training (incl SOPs) recordsExternal training recordsPublicationsNameResponsibilitiesInitalsSignSOP 24
21 Principle 9Freely 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”20Elementslisted in GCPSOP 7MinorsIncapacitatedMRC-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.
22 Principle 10All clinical trial information should be recorded, handled and stored in a way that allows its accurate reporting, interpretation and verification.XTrial Master FileSite Master FileSOP 11Age (yrs)
23 Principle 11The confidentiality of records that could identify subjects should be protected by privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).SOP 15
24 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.InvestigatorSubjectSponsorSOP 27
25 SOPs Monitoring Principle 13 Audits SOPs 18, 19 & 25 Systems with procedures that assure the quality of every aspect of the trial should be implemented.SOPsMonitoringAuditsSOP 19 – Quality ControlProcedures to ensure the trial is being conducted as intended i.e. to protocolEspecially important during recruitment and data collection phasesSOPs 18, 19 & 25
27 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 trialEducational ResearchLaboratoryNon-clinical interventionSponsorClinical InterventionsNHS patientsSOP 3University involvementClinical InterventionCommercially FundedA sponsor is a company, institution, organisation or individual which takes responsibility for the quality and delivery of the research.A sponsor is required for all research within the NHS and all trial involving IMPs.If your trial requires a sponsor, you must have a formal letter from your sponsor before any work can commence. The ethics committee will require proof of sponsorship – so it’s a good idea to start this process as early as possible.The CI is responsible for ensuring sponsorship arrangements are in place – for UoW CI’s, contact REGM in WMS in first instance.For the University of Warwick to act as your sponsor, apply via WMS research Ethics & Governance Office
28 Insurance SOP 10 Invasive? Insurance Non-negligent cover? The University of Warwick has Clinical Trials Insurance cover in place,provided by HDI GerlingThe policy covers most trials at Warwick, but there are multiple criteria wherea referral to the insurers is required. Including (but not limited to):Studies where blood-products will be testedStudies 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 5SOP 10Other referral criteria are stated – check SOP 10 for full detailsList on slide is not all of the criteria – need to check the SOP
29 Randomised Controlled? APPROVALSYesApply forISRCTNRandomised Controlled?££YesApply forEUDRACTIs it a drug trial?YesSubmit viaIRASApprovals
30 IRAS Integrated Research Application System 1 FormEthicsARSACMHRANIGBGTACNOMSR&DAn integrated system that brings together the information requirements for a range of permissions and approvals. It streamlines the application process by allowing you to enter study information in one place without duplication in separate application forms for each type of account.
31 Randomised Controlled? APPROVALSYesApply forISRCTNRandomised Controlled?££YesApply forEUDRACTIs it a drug trial?60 daysApprovals via IRASYesMain EthicsSOP 6Site ApprovalsR&DSubmit toMHRAMHRA – 45 days for type B + C trials. 14 days for type A (low risk trials) – see SOP 5SOP 5££45 daysARSACCAGNOMSGTAC
32 } University Research Support Services via HR Funder CONTRACTS Co-SponsorUniversity ResearchSupport ServicesSubcontractsSitesStaffHonoraryContractsvia HR
33 Before First Subject enters Letter of Sponsorship agreementInsurance CertificateWritten Ethics ApprovalWritten R&D / PCT ApprovalWritten Regulatory Approval (for CTIMPs)ARSAC Certificate/other approvalsSigned agreement by all partiesCV of CI/PI at sites
34 Warwick CTU web site For further information, go to: Section entitled ‘Conducting a Clinical trial’ includes:Current SOPsLinks to UoW Research Code of PracticeLinks to legislationAnd a step by step guide to running a trial, split into sections:Initial PlanningSet-upDuring the TrialAfter the Trial