Good Clinical Practice – An introduction for Investigators

Good Clinical Practice – An introduction for Investigators Lena Pettersson Lead Research Management & Governance (RM&G) Manager West Anglia CLRN West Anglia Comprehensive Local Research Network Aims  Brief overview of Good Clinical Practice (GCP) and its regulations  Responsible parties according to GCP  Responsibilities of the investigator  A reality check – overview of most important tasks  Get the message across of the importance of formal GCP training West Anglia Comprehensive Local Research Network Definition GCP Good Clinical Practice is a set of internationally recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects. Compliance with this good practice provides assurance that the rights, safety and wellbeing of trial subjects are protected and that the results of the clinical trials are credible. (EU Directive 2001/20/EC) West Anglia Comprehensive Local Research Network A bit of history  Declaration of Helsinki  ICH – International Conference of Harmonisation 1996  European Directive 2001  Statutory Instruments in each EU member state. West Anglia Comprehensive Local Research Network UK Clinical Trials Regulations, i.e. the Law  The Medicines for Human Use (Clinical Trials) regulations 2004 (ST 1031).  The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (ST 1928)  The Medicines for Human Use (Clinical Trials) Amendment (No 2) Regulations 2006 (ST 2984)  The Medicines for Human Use (Clinical Trials) and Blood Safety and Quality (Amendment) Regulations 2008 (ST 941)  The Medicines for Human Use (Miscellaneous Amendments) Regulations 2009 (ST 1164) West Anglia Comprehensive Local Research Network Other regulations and guidance documents      Data Protection Act 1998 Medical Devices Regulations 2002 The Human Tissue Act 2004 Mental Capacity Act 2005 Research Governance Framework for Health and Social Care 2005 West Anglia Comprehensive Local Research Network Main responsible parties  Competent Authority (Medicines and Healthcare products Regulatory Agency, MHRA)  The Sponsor  The Investigator  Authorising bodies, e.g. Research Ethics Committees (RECs), NIGB (former PIAG) and GTAC. West Anglia Comprehensive Local Research Network Definition of a Sponsor An individual, company, institution or organisation which takes responsibility for the initiation, management and/or financing of a clinical trial (EU Directive 2001/20/EC) West Anglia Comprehensive Local Research Network Definition of an Investigator … a doctor or a person following a profession agreed in the Member State for investigations because of the scientific background and the experience in patient care it requires. (EU Directive 2001/20/EC) West Anglia Comprehensive Local Research Network Responsibility of Investigators  The Investigator is responsible for the conduct of a clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the leader responsible for the team and may be called Principal Investigator (PI). (EU Directive 2001/20/EC) West Anglia Comprehensive Local Research Network Chief Investigator  The Chief Investigator (CI) is the person responsible for the conduct of a clinical trial at all trial sites in a multicentre study or a single centre study The CI ensures the trial is conducted according to all UK regulations and guidelines and works in co-operation with the PIs at each trial to ensure the same.  West Anglia Comprehensive Local Research Network Responsibilities of Investigators according to ICH GCP guidelines section 4 : 1. 2. Qualifications and Agreements Adequate Resources 3. 4. 5. 6. 7. 8. 9. Medical Care of trial subjects Compliance with Protocol Randomisation Procedures & Un blinding Premature termination or suspension of a trial Communication with EC Investigational product Informed Consent 10. 11. 12. 13. Records and Reports Progress reports Safety Reporting Final report by the investigator West Anglia Comprehensive Local Research Network Qualifications  To conduct a clinical trial, the investigator(s) should be qualified by education, training and experience to assume responsibility for the proper conduct of the trial.  The PI should meet all the qualifications specified by the applicable regulatory requirements.  The PI should provide evidence of such qualifications through up-to-date CV (signed and dated) and/or other documents requested by Sponsor, Ethics Committee & Regulatory Authority West Anglia Comprehensive Local Research Network  The PI can delegate (not abdicate) some of the duties/responsibilities to other members of the team.  These members need to be appropriately qualified and trained for that task.  The PI needs to maintain a Delegation log of persons to who he/she has delegated significant trial-related duties.  CVs and job descriptions needed for members of the team outlining qualifications, training and experience. West Anglia Comprehensive Local Research Network Adequate Resources  The PI should be able to properly conduct and complete the trial safely within the agreed trial time, i.e. :     demonstrate a potential for recruiting patients have sufficient time ensure all staff are qualified and trained facilities are appropriate to carry out the protocol  The PI should demonstrate ability for recruiting the required number of suitable subjects within the agreed time  The PI must adhere to inclusion and exclusion criteria  The PI must keep a log of no of subjects screened, recruited and withdrawn West Anglia Comprehensive Local Research Network Have sufficient time  for regular meetings with monitor  to identify and screen suitable patients  to interview patients  to meet frequently with trial team  to complete paperwork  to meet auditors and inspectors West Anglia Comprehensive Local Research Network Adequate facilities Equipment should meet the criteria for SCAM:     Suitable for its intended use Calibrated and Checked Available Maintained Document and record! If it isn't written down it hasn’t happened! Remember support departments! West Anglia Comprehensive Local Research Network Informed Consent A process by which a subject voluntarily confirms his/her willingness to participate in a trial after having been informed of all relevant aspects of the trial  Four parts;     invitation to participate, appropriate time to decide (usually at least 24 hrs), exchange of information formal agreement signed West Anglia Comprehensive Local Research Network Capacity to consent/competency Legal position of High Court in England that an adult has the capacity to consent if he or she can:  Understand and retain information relevant to the decision in question  Believe that information  Weigh that information in the balance to arrive at a choice  Emergency, Paediatrics, Young adults, Vulnerable groups and Altered Mental Capacity West Anglia Comprehensive Local Research Network Patient safety and Safety reporting  Shared responsibility of the Sponsor and the Investigator  Pharmacovigilance = reporting of adverse events       AE – adverse event SAE – serious adverse event AR – adverse reaction UAR – unexpected adverse reaction SAR – serious adverse reaction SUSAR – suspected unexpected serious adverse reaction West Anglia Comprehensive Local Research Network SAE – Serious Adverse Event  Need to be reported to the Sponsor within 24hrs of learning of the event;  Results in death  Is life-threatening  Requires patient hospitalisation or prolongation of existing hospitalisation  Results in persistent or significant disability or incapacity  Is a congenital anomaly/birth defect West Anglia Comprehensive Local Research Network Other timelines  Sponsor reports life-threatening or fatal SUSARs to MHRA and REC within 7 days with a follow-up report within a further 8 days  Sponsor reports all other SUSARs to MHRA and REC within 15 days of becoming aware of the event.  Annual safety reports are sent to MHRA and main ethics committee  Commercial Sponsors send 6 monthly safety reports West Anglia Comprehensive Local Research Network  Research Governance Framework requires the investigator to notify Trusts of patient safety incidents. Be aware of Trust policy.  NHS trusts are responsible for reporting patient safety incidents to the National Patient Safety Agency West Anglia Comprehensive Local Research Network Example MHRA inspection findings  Inappropriate delegation  No formal study training of staff  Pharmacy staff not trained/inappropriate storage of IMP  Consent forms not signed correctly or by wrong person  No formal procedure for emergencies or emergency un-blinding of IMP West Anglia Comprehensive Local Research Network Due diligence Regulation 51 Medicines for Human Use (Clinical Trials) Regulations 2004 “A person does not commit an offence under these Regulations if he took all reasonable precautions and exercised all due diligence to avoid the commission of that offence”  If it isn’t in writing, it is just a rumour!  Confirm, Document, File. West Anglia Comprehensive Local Research Network Useful websites www.mhra.gov.uk www.ich.org www.nres.npsa.nhs.uk www.myresearchproject.org.uk www.ct-toolkit.ac.uk www.west-anglia.crncc.nihr.ac.uk The West Anglia Comprehensive Local Research Network is part of the National Institute for Health Research and the UK Clinical Research Network West Anglia Comprehensive Local Research Network