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1. The team, the procedures, the monitor and the Sponsor Lucy H H Parker Clinical Research Governance Manager Joint Research & Enterprise Office Training

2. The Team CI and PIs Monitor Regulatory Assurance Manager Stats. ?RN/CTA/DM Research Pharmacy Archivist Finance Support Departments IT - eCRF Joint Research & Enterprise Office Training

3. How are the studies set up? Lots of meetings! Site selection Risk Assessment (26 point risk assessment) Major issues identified and minimised Monitoring plan – agreed with all parties even if external monitor Standard RG processes – initiation, routine, close out Safety reporting Joint Research & Enterprise Office Training

4. Sponsor Joint Research & Enterprise Office Training

5. Sponsor • Sponsor takes on overall responsibility for initiation, management and/or financing of study • All clinical trials must have a designated sponsor • Must be named in the protocol • Not necessarily the funder • Typically CI employer • Can delegate responsibilities to investigators Joint Research & Enterprise Office Training

6. Sponsor Responsibilities • Quality Assurance (audits) • Quality Control (monitoring) • Contracts & Agreements • Medical Expertise • Trial Design • Trial Management, Data Handling, and Record Keeping • Investigator Selection • Allocation of Responsibilities • Compensation to Subjects and Investigators • Financing • Submission to Regulatory Authorities • Confirmation of Review by REC • Information on IMP • Manufacturing, Packaging, Labelling, and Coding of IMP • Supplying and Handling of IMP • Record Access • Safety Information • Safety Reporting • Non-compliance • Premature Termination or Suspension of a Trial • Clinical Trial/Study Reports • Multi-centre Trials ICH GCP Section 5 Joint Research & Enterprise Office Training

7. Quality Assurance (QA) versus Quality Control (QC) • QC = Quality Control = monitoring • Member of trial team • Ongoing • QA = Quality Assurance = auditing • Independent • Planned and systematic Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

8. Monitoring Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

9. What is monitoring? “The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, SOPs, GCP, and any regulatory requirements” ICH GCP Section 5.18 Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

10. Purpose of Monitoring? • Protection of rights and wellbeing of human participants • Ensure consent in place for record access • Trial data are accurate, complete and verifiable from source documents • Conduct of trial is in compliance with the currently approved protocol, GCP, and all applicable regulatory requirements ICH GCP Section 5.18.1 Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

11. Qualities of a Good Monitor? • Appropriately trained • Adequate scientific and/or clinical knowledge • Documented with training logs and CVs • Thoroughly familiar with: • IMP • Protocol • Consent form • Sponsor & trial SOPs • GCP • Knowledge of local laws, regulations, customs & local language • ICH GCP Section 5.18.2 Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

12. Extent and Nature of monitoring • Monitoring should be proportionate to: • Objective • Purpose • Design • Blinding • Size and complexity • Outcome measures • Risks ICH GCP Section 5.18.3 Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

13. Types Of Monitoring (1) • Coordinating centre / day-to-day monitoring • Data collected are consistent with protocol • CRFs are being completed by authorised staff • No key data is missing • Data appears to be valid • Review of recruitment rate, withdrawals and losses to f/up Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

14. Types Of Monitoring (2) • Central monitoring • Determination of key eligibility criteria through collection of: • Consent forms (with agreement by participant) • Scans • Pathology reports • Statistics • Unusual patterns of data Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

15. Types Of Monitoring (3) • On-site monitoring • Staff training • Access to necessary documents • Confirm pharmacy and lab resources in place • Count study drugs • Adherence to protocol and GCP • Check medical records • Consent forms • Eligibility • SAEs, SADRs, SUSARs etc • Source Data Verification (SDV) Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

16. Data Management & Processing Data entry checks Double data entry EDC system OCR Data Entry CRF Completion Training Investigators Data cleaning & Validation Monitoring visits & SDV Post entry checks Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

17. Common queries and checks • Most common checks to identify discrepancies: • Missing values • Range checks, including lab values and normals • Logical date sequence • Header information consistent • Missing visits or pages • Visits in compliance with protocol • Inclusion/exclusion criteria met • Procedures performed in proper order • Fraud Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

18. Post Entry Checks Post 1. Data manager cleans & validates database 8. Corrections entered in database 2. Problems such as missing values or inconsistencies No 7. Query forms with resolution sent back to data manager Yes Data validated 6. Monitor checks query resolutions 3.Queries addressed to the PI via paper query forms 5. Query resolutions put on query form 4. PI resolves queries Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

19. Ensuring the Quality of the Data MONITORING & AUDITS Joint Research & Enterprise Office Training Joint Research & Enterprise Office Training

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