# Presentation: 497920

## 
ORO On-Site Review Findings

ORO Nationwide Call 
January 9, 2008

*ORO On-Site Review Findings*
*ORO Nationwide Call *
*January 9, 2008*

*Office of Research Oversight*

## ORO Mission

- Principal Advisor to USH for ...
- Conducts Compliance Oversight of** ...**
- Protection of Human Research Subjects
- Laboratory Animal Welfare
- Research Safety and Laboratory Security
- Research Information Security
- Research Misconduct
- Debarment for Research Impropriety

*ORO Regional Offices*

**Northeastern **
- Bedford, MA
- VISNs 1, 2, 3
- Hines VAMC

**Midwestern**
- Hines, IL
- VISNs 11, 12, 15, 19, 23

**Western**
- Loma Linda, CA
- VISNs 18, 20, 21, 22

**Southern**
- Atlanta (Duluth), GA
- VISNs 7, 8, 16, 17
- WDC & Martinsburg VAMCs

**Mid-Atlantic**
- Washington, DC
- VISNs 4, 5, 6, 9, 10

## ORO Site Visits

- Site Visits (Trips to Facilities)

- 2003       2004       2005       2006       2007

- 100
- 75
- 50
- 25

**19**

**22**

**34**

**29**

**69**

## ORO Site Visits

- Site Visits (Trips to Facilities)

- 2003       2004       2005       2006       2007

- 40
- 30
- 20
- 10

**6**

**5**

**4**

**4**

**11**

**For Cause**

**13**

**17**

**30**

**25**

**58**

-   **Routine**

## ORO Site Visits

- Facilities Visited (some were visited more than once)

- 2003       2004       2005       2006       2007

- 100
- 75
- 50
- 25

**19**

**22**

**34**

**28**

**46**

## ORO Site Visits

- Program Reviews (Human, Animal, Safety etc)

- 2003       2004       2005       2006       2007

- 100
- 75
- 50
- 25

**19**

**22**

**45**

**33**

**101**

*Common Compliance Concerns**** ***

**Oversight of Research Program**
- Lack of Program Oversight by Facility Director
- Lack of Program Oversight by R&D Committee
- Role Confusion / Inappropriate Reliance on ACOS/R or AO/R
- Lack of R&D Committee Knowledge about VA and Federal Research Requirements
- Lack of R&D Committee Knowledge about Subcommittee Responsibilities, Procedures, and Current Issues of Concern
- Uncritical R&D Committee Reliance on Subcommittees
- Lag in Meeting Information Security Requirements

**Human Research Protection Program**
- Initiating Research without IRB and/or R&D Committee Approval
- Enrolling Subjects with Absent or Deficient Informed Consent
- Implementing Unapproved Protocol Changes / Deviations
- Inadequate Procedures for Reporting to IRB and/or ORO:
- Serious / Related / Unexpected Adverse Events
- Unanticipated Problems Involving Risks to Subjects/Others
- Inadequate Procedures for Reporting to Privacy Officer and/or ISO
- Unauthorized Use / Disclosure / Loss of Identifiable Patient Info
- Violations of VA Information Security Requirements
- Inappropriate “Contingent Approval” Requiring Substantive Changes
- Lack of Procedures for Conducting Protocol and IRB Audits

*Common Compliance Concerns*

**Animal Care and Use Program**
- Failure to Conduct Semi-Annual Program and Facility Review
- Failure to Implement Occupational Health and Safety Program
- Inadequate Review of Category D and E Protocols
- Inadequate Post-Surgical Care and Monitoring
- Use of Inappropriate Anesthesia Techniques
- Use of Outdated and/or Non-Pharmaceutical Grade Drugs
- Inadequate Tracking and Securing of Controlled Substance
- Inadequate Population Management and Animal Tracking
- Inadequate Training:  IACUC Members, Investigators, Caretakers
- Implementation of Unapproved Protocol Changes
- Inadequate Facility Maintenance and Temperature Control Testing

*Common Compliance Concerns*

**Research Safety Program**
- Failure to Conduct  Annual Reviews of the Research Areas and of the Chemical Hygiene Plan
- Failure to Conduct Semi-Annual Reviews of Personnel Access, Hazardous Agent Inventory, Select Agent / Toxin Exempt Quantity Logs
- Failure to Implement VHA Handbook 1200.06 (October 2005)
- Failure to Appoint a Research Safety Coordinator
- Failure to Ensure Annual Research-Specific Safety Training
- Failure to Comply with NIH rDNA and IBC Requirements
- Failure to Comply with National Standards for Eyewash Stations, Storage of Flammable Chemicals, Labeling and Containment of Hazardous Chemical Wastes

*Common Compliance Concerns*

## 
ORO Suspensions Since April 30, 2006
Smoking Cessation Study
Animal Care and Use Program
Research Safety Program
Research Information Security
Use of Affiliate IRB

**ORO Suspensions Since April 30, 2006**
- Smoking Cessation Study
- Animal Care and Use Program
- Research Safety Program
- Research Information Security
- Use of Affiliate IRB

*Common Compliance Concerns*

## ORO Findings:

HSR&D project to increase use “best practice” throughout 2 VISNs
Veteran subjects and their local, referring VA providers not informed adequately that the program involved:
Research comparing four separate approaches to intervention (intervention groups)
Assignment of participants to intervention groups based on geographic location rather than clinical factors.
Local VA providers not informed adequately about prescribed meds
Nicotine vs Bupropion (entails risks)

- HSR&D project to increase use “best practice” throughout 2 VISNs
- Veteran subjects and their local, referring VA providers not informed adequately that the program involved:
- Research comparing four separate approaches to intervention (intervention groups)
- Assignment of participants to intervention groups based on geographic location rather than clinical factors.
- Local VA providers not informed adequately about prescribed meds
- Nicotine vs Bupropion (entails risks)

*Smoking Cessation Study*

## ORO Findings:
Systemic lack of IACUC and R&D Committee oversight
Semi-Annual Program Review and Facility Self-Assessment not completed
No comprehensive Occupational Safety & Health Program
No mechanisms to ensure proper training prior to handling animals
No mechanisms for tracking animal census and linking to protocols
No population management mechanisms
VMO lacked access to certain labs
VMA lacked control over animal procurement
VMO lacked any input into budget, including per diem charges
VMO perceived investigators to be disrespectful of regulatory requirements and subjecting animals to danger and harm

- Systemic lack of IACUC and R&D Committee oversight
- Semi-Annual Program Review and Facility Self-Assessment not completed
- No comprehensive Occupational Safety & Health Program
- No mechanisms to ensure proper training prior to handling animals
- No mechanisms for tracking animal census and linking to protocols
- No population management mechanisms
- VMO lacked access to certain labs
- VMA lacked control over animal procurement
- VMO lacked any input into budget, including per diem charges
- VMO perceived investigators to be disrespectful of regulatory requirements and subjecting animals to danger and harm

*Animal Care and Use Program*

## ORO Findings: 

Investigators perceived VMO to be unavailable for consultation, arbitrary, and disrespectful of investigators
OSH and training requirements for access to animals not enforced
Controlled substances obtained outside VA pharmacy
Controlled substances not properly locked and tracked
Widespread use of expired drugs
Widespread use on non-pharmaceutical grade drugs
Lack of investigator and IACUC awareness of above requirements
Investigator failure to obtain IACUC approval for protocol changes
Widespread violations of veterinary standards, especially surgical
Lack of periodic HVAC temperature testing
Lack of monitoring of cage wash temperatures

- Investigators perceived VMO to be unavailable for consultation, arbitrary, and disrespectful of investigators
- OSH and training requirements for access to animals not enforced
- Controlled substances obtained outside VA pharmacy
- Controlled substances not properly locked and tracked
- Widespread use of expired drugs
- Widespread use on non-pharmaceutical grade drugs
- Lack of investigator and IACUC awareness of above requirements
- Investigator failure to obtain IACUC approval for protocol changes
- Widespread violations of veterinary standards, especially surgical
- Lack of periodic HVAC temperature testing
- Lack of monitoring of cage wash temperatures

*Animal Care and Use Program*

## ORO Findings:
Systemic failure of SRS and R&D Committee Oversight
Improper containers
Co-storage of incompatible chemicals
Flammable chemicals in unsafe cabinets
Outdated chemicals
Inoperable eyewash stations
Use of Bunsen burners in unsuited biosafety cabinets
Chemical fume hoods with clutter impeding air flow
Outdated chemical inventories
Fire code violations:
Inconsistent temperature regulation and ventilation

- Systemic failure of SRS and R&D Committee Oversight
- Improper containers
- Co-storage of incompatible chemicals
- Flammable chemicals in unsafe cabinets
- Outdated chemicals
- Inoperable eyewash stations
- Use of Bunsen burners in unsuited biosafety cabinets
- Chemical fume hoods with clutter impeding air flow
- Outdated chemical inventories
- Fire code violations:
- Inconsistent temperature regulation and ventilation

*Research Safety Program*

## ORO Findings:
Systematic failure of IRB and R&D Committee oversight
FDA terminated 3 collaborative studies involving VA, affiliate, FDA 
VA facility audits identified serious deficiencies in a number of studies
University IRBs unresponsive to audit reports
University IRBs not cognizant of VA requirements
University failed to inform facility of SAEs / noncompliance
Facility R&D Committee and Research Service:
Deficient protocol records, inventory, and tracking
Failure to identify VA research vs Affiliate research
Lack of COI monitoring and management procedures
Lack research credentialing procedures 
Lack of enforcement of training requirements

- Systematic failure of IRB and R&D Committee oversight
- FDA terminated 3 collaborative studies involving VA, affiliate, FDA
- VA facility audits identified serious deficiencies in a number of studies
- University IRBs unresponsive to audit reports
- University IRBs not cognizant of VA requirements
- University failed to inform facility of SAEs / noncompliance
- Facility R&D Committee and Research Service:
- Deficient protocol records, inventory, and tracking
- Failure to identify VA research vs Affiliate research
- Lack of COI monitoring and management procedures
- Lack research credentialing procedures
- Lack of enforcement of training requirements

*Use of Affiliate IRB*

## Office of Research Oversight

**ORO (Central Office)**
- Department of Veterans Affairs
- 811 Vermont Ave, NW, Suite 574 (10R)
- Washington, DC  20420
- 202.565.5184  fax: 202.565.9194
**ORO Mid-Atlantic Regional Office**District of Columbia VAMC
- 50 Irving Street, N.W. (10R)Washington, DC  20422202.745.8110  fax: 202.745-8538
**ORO Midwestern Regional Office**Hines VAMC
- Building 1 (10R), Room B-1035th & Roosevelt AvenuesHines, IL  60141708. 202.7254  fax: 708.202.7250

**ORO Northeastern Regional Office**Bedford VAMC200 Springs Road (10R)Bedford, MA  01730781.687.3850  fax: 781.687-3858
**ORO Southern Regional Office**3700 Crestwood Pkwy, NW
- Suite210 (10R)Duluth, GA  30096678.924.5762  fax: 678.924.5708
**ORO Western Regional Office**
- P.O. Box 7360
- Moreno Valley, CA  92552-7360
**Express Delivery:**
- 14560 2nd Street , Bldg. 2641, Suite B
- Riverside, CA  92518
- 909.801.5164  fax: 909.801.5176