# Presentation: 706197

## Pharmacists Responsibilities in Clinical Studies

- Mike R Sather, PhD
- Crystal L Harris, PharmD
- February 26, 2004

## Today’s Presentation

- Rules & Regulations
- Investigator’s Commitments
- Pharmacy Essential Documents
- Audits/Inspections
- Future of Research Pharmacist

## 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)

## 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

## 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

## Roles and Responsibilities in   Clinical Trials - Research Team

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

## Investigator’s Commitment

- Drugs - Form 1572
- Devices – Investigator’s Signed Agreement

## 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).

## 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

## 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.

## 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

## 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”***

## Essential Documents – Pharmacy

- FDA regulations
- M2 Part VII
- Pharmacy Policies and Procedures

## 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.

## Essential Documents – Pharmacy 

- Name of principal investigator & authorized prescribers of investigational drug
- Copy of each patient’s informed consent

**                         **

**ESSENTIAL**
**        ****DOCUMENTS**
**                         **

## Inspections, Audits, Reviews....

**“****The meeting of this watchdog agency will come to order . . .”**

## 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****** ***

**Notes:**
So let’s look at the groups that help us assure quality in research and may visit us in a  trial-------<READ SLIDE
FDA visits are possible only in IND or IDE trials and even then occur only at key sites in key trials (“PIVOTAL”)
OHRP visits – possible, but generally only in conjunction with an audit of the research operation of an entire facility
NCQA(National Committee for Quality Assurance) – this group is invited like JCAHO and which recently joined with JCAHO to review entire research program at a VAMC.  The Research Office, IRB, Pharmacy and a few selected investigators are visited during the NCQA visit.
AAHRPP – (Association for the 
. Of Human Research)yet another organization similar to NCQA providing voluntary accreditation
and is an arm of PRIM&R (Public Responsibility in Medicine & Research)             Read slide from sponsor down
      ----those listed above the first redline we think of as external inspectors;
         - those below the second red line line we consider to be internal bodies 
	we want you to be very aware of potential external inspections and reviews 
Each group listed is concerned with quality research: some focus more on partnering , mentoring, providing resources, serving as educators and others place a greater emphasis on identifying  problems/deficiencies like...........next slide.....identifying  Scientific Misconduct

## 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****** ***

## Disaster Preparedness

- Emergency Code Envelopes
- Unblinding of patients

## Future of Research Pharmacist

## Research Pharmacist......

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

## VA Research Pharmacist Meeting

- First time gathering
- Continue to network with each other
- Organize annual meeting?
- Training and education

## 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

## 
Discussion

- Discussion