1. Pharmacists Responsibilities in Clinical Studies Mike R Sather, PhD Crystal L Harris, PharmD February 26, 2004

2. Today’s Presentation  Rules & Regulations  Investigator’s Commitments  Pharmacy Essential Documents  Audits/Inspections  Future of Research Pharmacist

3. Rules & Regulations Governing VA Research  FDA GCP Regulations  21 CFR 54 – Financial Disclosure  21 CFR 56 – IRB  21 CFR 312 – IND  21 CFR 314 – NDA  21 CFR 812 – IDE  21 CFR 814 – PMA (premarket approval application - devices)

4. Rules & Regulations Governing VA Research  ICH GCP Guidelines  45 CFR 46 (Common Rule) – Protection of Human Subjects in federally funded research  38 CFR 17 & 18 (VA Research)  VHA Handbook 1200.5  M-2, Part VII, Chapter 6

5. M-2, Part VII - Basic Policy  Pharmacy is charged with:  Protecting the patient, staff, facility, and quality of the study.  Assuring the PI is qualified  Assuring R&D/IRB approval  Assuring informed consent obtained

6. Roles and Responsibilities in Clinical Trials - Research Team

7. The reputation of clinical research depends on all of us.

8. Investigator’s Commitment  Drugs - Form 1572  Devices – Investigator’s Signed Agreement

9. Form 1572 – The Commitment Investigator agrees to: Conduct the study in accordance with the relevant, current, protocol(s) and will only make changes in a protocol after notifying the sponsor, except when necessary to protect the safety, rights, or welfare of subjects. Personally conduct or supervise the described investigations(s).

10. Form 1572 – The Commitment Investigator agrees to: Inform any patients, or any persons used as controls, that the drugs are being used for investigational purposes and I will ensure that the requirements relating to obtaining informed consent in 21CFR Part 50 and Institutional Review Board (IRB) review and approval in 21CFR Part 56 are met. Signed copy before filling initial Rx

11. Form 1572 – The Commitment Investigator agrees to: Report adverse experiences that occur in the course of the investigation(s) in accordance with CFR 21 312.64. Read and understand the information in the investigator’s brochure, including the potential risks and side effects of the drug. Ensure that all associates, colleagues, and employees assisting in the conduct of the study(ies) are informed about their obligations in meeting the above commitments.

12. Form 1572 – The Commitment Investigator agrees to: Maintain adequate and accurate records in accordance with 21 CFR 312.62 and make those records available for inspection in accordance with 21 CFR 312.68. Drug accountability records Protect Patient and Public Safety Protect Data Integrity

13. Form 1572 – The Commitment Investigator agrees to: Ensure that an IRB that complies with the requirements of 21 CFR Part 56 will be responsible for the initial and continuing review and approval of the clinical investigation. I also agree to promptly report to the IRB all changes in the research activity and all unanticipated problems involving risks to human subjects and others. Additionally, I will not make any changes in the research without IRB approval, except where necessary to eliminate apparent immediate hazards to human subjects. Comply with all other requirements regarding the obligations of clinical investigators and all other pertinent requirements in 21 CFR Part 312. “NON – NEGOTIABLE NINE”

14. Essential Documents – Pharmacy  FDA regulations  M2 Part VII  Pharmacy Policies and Procedures

15. Essential Documents – Pharmacy  Copy of complete protocol as approved by IRB.  Investigational Drug Information Record (10-9012)  Documentation on appropriate form of IRB approval  Complete summary of dispensing & record keeping procedures & responsibilities.

16. Essential Documents – Pharmacy  Name of principal investigator & authorized prescribers of investigational drug  Copy of each patient’s informed consent ESSENTIAL DOCUMENTS

17. Inspections, Audits, Reviews…. “The meeting of this watchdog agency will come to order...”

18. GROUPS THAT PROMOTE QUALITY IN RESEARCH FDA*- Inspects IRBs & Investigators OHRP (HHS)- Inspects Research Protection Programs ORO (VA) - Inspect VA Research Programs NCQA- Accredits Research Programs AAHRPP - Accredits Research Programs Sponsor- Inspects its investigators IRB- May review Investigator records *If sponsor plans data submission to FDA

19. Recent FDA Findings Protocol Non-adherence 27% Patient Records Inadequate / Inaccurate 20% Consent Form Missing Required Elements 15% Inadequate AE reporting to sponsor 15% Poor Drug Accountability 9% Consent Obtained & Documented Improper 8% Failure to Inform IRB (AEs, Progress, etc) 7% Failure to Obtain Consent Before Procedures 2% Failure to Obtain Required IRB Approvals 2% RESULTS PUBLISHED ANNUALLY

20. Disaster Preparedness  Emergency Code Envelopes  Unblinding of patients

21. Future of Research Pharmacist

22. Research Pharmacist…… You are a member of one of the largest and most productive research program in the world……VA Research & Development

23. VA Research Pharmacist Meeting  First time gathering  Continue to network with each other  Organize annual meeting?  Training and education

24. Issues…  M2 Part VII Chapter 6  Pharmacist on R& D Committee  Pharmacy Service oversight?  ADR reporting  Agent for Investigation Drug Unblinding  Co-Pays for Investigational vs. Marketed Study Drugs  Managing study patient drop-ins  VAF 10-9012 use for marketed study drugs  Electronic versus paper documentation  Investigational Devices

25. Discussion 25