1. Good Clinical Practice (GCP) UKTMN 6 th June 2006

2. What is GCP? Good Clinical Practice (GCP) 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)

3. GCP principles summary (1) Rights, safety & well being of subjects prevail over interests of science and society Individuals involved in trial should be qualified by education, training and experience to perform his/her tasks Trials shall be scientifically sound and guided by ethical principles in all their aspects Necessary procedures to secure the quality of every aspect of the trial shall be complied with

4. GCP principles summary (2) Available non-clinical and clinical information on an IMP shall be adequate to support the trial Conducted according to Helsinki Declaration (1996) Protocol shall provide inclusion and exclusion criteria, monitoring and publication policy Investigator/sponsor shall consider all relevant guidance Information recorded, handled and stored to allow accurate reporting, interpretation and verification and confidentiality of subjects’ records

5. GCP compliance ICH GCP section 5.18.3 allows individual researchers to assess the needs of their trial and apply GCP appropriately ‘central monitoring in conjunction with procedures such as investigators’ training and meetings and extensive written guidance can assure appropriate conduct of the trial in accordance with GCP.’ On-site monitoring not compulsory

6. Who must comply with GCP? All individuals involved in any aspect of the trial must be suitably ‘qualified’ to be able to comply with GCP. Sponsors/CIs are responsible for ensuring that all staff are able to comply with GCP.

7. What counts as qualified? According to GCP each individual involved in conducting a trial ‘shall be qualified by education, training, and experience to perform his or her respective task(s)’ (GCP – principle 8) Education Training Experience There is no GCP ‘qualification’

8. Education Individuals must be educated to be able to competently perform their specific trial task. –Clinicians must be clinically qualified –Statisticians must be qualified –Managers must be appropriately educated

9. Training There are a variety of courses and seminars currently available –Employer induction courses –Industry courses –E-learning (Institute of Clinical Research) –Private courses (usually run by freelance consultant) –Host institution courses –Trial specific workshops –Investigators meetings

10. Experience On-the-job learning –Discovering what is required –Doing the job (sometimes wrongly) –Cascading information and knowledge through teams/units –Talking to other trialists

11. Rationale and documentation As there is no formal qualification it is essential to keep up to date records of training. Describe the rationale for the methods of GCP ‘training’ used in the trial Document courses/seminars/meetings attended by staff on a training file Keep it up to date

12. Approvals and permissions Ethics committee approval Clinical Trials Authorisation (IMPs) R & D permission Sponsor approval

13. Trial Master File Essential documents are defined as documents which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced and should be retained in the Trial Master File Documents to be contained in the Master File will vary according to the trial Trial Master File should be held at the principal site by the Chief Investigator or at the Co-ordinating Centre Investigator’s Site Files are held by the Principle Investigators at sites and contains copies of the essential documents, local approvals, signed consent forms and completed data forms.

14. Standard Operating Procedures There should be a written description of all trial management systems and conventions. This documentation forms the operating procedures, often referred to as Standard Operating Procedures (SOPs). SOPS are usually generic to the Trials Unit or Institution. A trial specific operating procedure must be developed for each trial. These may be called MOPs (Modified Operating Procedures) or TSOPs (Trial Specific Operating Procedures).

15. Trial monitoring ICH-GCP Extent and Nature of Monitoring The sponsor should ensure that the trials are adequately monitored. The sponsor should determine the appropriate extent and nature of monitoring. The determination of the extent and nature of monitoring should be based on considerations such as the objective, purpose, design, complexity, blinding, size,and endpoints of the trial. In general there is a need for on- site monitoring, before, during, and after the trial; however, in exceptional circumstances the sponsor may determine that central monitoring in conjunction with procedures such as investigators’ training and meetings, and extensive written guidance can assure appropriate conduct of the trial in accordance with GCP. Statistically controlled sampling may be an acceptable method for selecting the data to be verified. 5.18.3

16. Informed consent Informed consent – personal autonomy ‘…a competent individual should have the right to determine those discretionary risks he/she is willing to accept for whatever benefits he/she perceives may result.’ Weil WB. Informing and Consenting In Silverman W. Where’s the evidence? OUP 1997

17. Informed consent Following the second world war and the Nuremberg trials, the Nuremberg Code and Declaration of Helsinki was agreed worldwide as a charter to protect people/patients against human experimentation Up until 1995 USA, Japan and Europe worked to different standards in the conduct of clinical trials 1995 ICH-GCP was implemented – a global standard 2001 EU Directive set out regulations for clinical trials of medicines conducted within the EU 2004 (May) the UK implemented the Directive and the UK Regulations became law

18. Consent Ethics committee must approve all information given to the trial participant Statements to comply with Data Protection Act must also be included in the PIL Consent forms and patient information leaflets must take into account recent legislation SOPs required describing who is authorised to conduct consent procedure Centre personnel who participate in the consent procedure should be listed on the delegation log, provide CVs and be trained!!

19. Consent Decision time: confusing ICH states ‘ample time to decide’ The Directive does not state any time-frame ‘6-day rule’ in Ireland (being revised in 2006) UK has no time -frame

20. Consent procedures Given freely Face to face Telephone Watch Listen Learn What works well? Share

21. Safety reporting Adverse events (annual) Serious Adverse Events (SAEs) (within 7 days) Serious Adverse Reactions (SARs) (within 7 days) Suspected Unexpected Serious Adverse Reactions (SUSARs) (expedited)

22. Expedited reporting Fatal or life threatening SUSARS: not later than 7 days after the person responsible for pharmacovigilance received information that the case fulfilled the criteria for a fatal or life threatening SUSAR, and any follow up information within a further 8 days. All other SUSARs: not later than 15 days after the sponsor for pharmacovigilance had information that the case fulfilled the criteria for a SUSAR.

23. Archiving Essential documents NOT used in a regulatory submission must be retained for at least FIVE years after the end of the trial Destruction of essential documents and a record of the destruction must also be retained for a further FIVE years Local R&D offices may also impose a retention period

24. Good Clinical Practice in Practice Be pragmatic in your approach to GCP Use your Rick Assessment to justify your approach Document the rationale behind the decisions Be brave