1. Office of Research Oversight 1 ORO Research Suspensions and Other ACOS/R Concerns Tom Puglisi, PhD Local Accountability in Research April 8, 2010

2. Office of Research Oversight 2 ORO Criteria for Suspension of Research Substantive concerns about : The safety, rights, or welfare of human subjects, research personnel, or others The safety, health, or welfare of laboratory animals The effectiveness of a facility’s research protection or research oversight programs

3. Office of Research Oversight 3 ORO Research Suspensions (2006 – 2010) Multi-Site Programs or Projects: REAP (Research Enhancement Award Program) Projects –Information security and confidentiality protections Smoking Cessation Study –Subjects and providers not informed about research on 4 different intervention approaches assigned solely by site location –Providers not alerted to use of bupropion and risks/contraindications Varenicline (Chantix) – –Safety monitoring –Notification of subjects and providers concerning risks Nursing Management Implementation Study –On-site interview of VA personnel without local IRB approval

4. Office of Research Oversight 4 ORO Research Suspensions (2006 – 2010) Facility Programs: All Research (3 Facilities) Programmatic Lack of Management Controls / Infrastructure Facility could not identify all VA research projects Widely discrepant protocol inventories (ie, R&DC vs IRB or IACUC or SRS) Systematic lack of R&DC review and/or approval Inability to track project approval and expiration dates Systematic lack of documentation (ie, Research Service did not maintain protocol files)

5. Office of Research Oversight 5 ORO Research Suspensions (2006 – 2010) Facility Programs: Human Research (1 Facility) Affiliate IRB Chair and members lacked basic knowledge of Common Rule, FDA, and VA requirements IRB ignored audit findings of serious noncompliance Inadequate IRB review and oversight of research resulting in FDA suspensions Research Service lacked protocol records, tracking, etc Lack of Conflict of Interest review procedures Lack of procedures to verify credentialing and privileging Lack of procedures to verify investigator training

6. Office of Research Oversight 6 ORO Research Suspensions (2006 – 2010) Facility Programs: Animal Research (2 Facilities) Facility 1: Withdrawal of Affiliate from AAALAC Program Facility 2: Systematic failure of ACUP Oversight Program –IACUC Chair and members lacked basic knowledge of PHS Policy, UDSA, and VA requirements –Failure to complete and/or follow-up on Semi-Annual Program Reviews and Facility Assessments –Lack of Researcher Occupational Safety & Health Program –VMO lacked control over animal procurement and intake –VMO lacked access to ACORPs and animal laboratories –Lack of mechanism to track animal census and link to protocols

7. Office of Research Oversight 7 ORO Research Suspensions (2006 – 2010) Facility Programs: Animal Research (2 Facilities) Facility 2: Systematic failure of ACUP Oversight Program –Lack of population management mechanisms –Controlled substances acquired outside VA –Controlled substances stored in unlocked cabinets –Widespread use of non-pharmaceutical grade and/or expired drugs –Widespread violations of animal surgery standards –Lack of HVAC and cage wash temperature monitoring –Lack of primate technician and primate enrichment program –Chronic animal infection problems –Lack of mechanism to ensure training prior to handling animals –Multiple safety deficiencies

8. Office of Research Oversight 8 ORO Research Suspensions (2006 – 2010) Facility Programs: Research Safety (3 Facilities) Facility 1: BSL-3 Lab Suspension –Inappropriate transfer of hazardous material –Possible loss of hazardous material –Inadequate material inventory procedures Facility 2: Failure to Conduct Individual Protocol Reviews Facility 3: Systemic Failure of Safety Oversight Program –Widespread unsafe chemical storage –Multiple inoperative eye wash stations –Use of Bunsen burners in unsuited biosafety cabinets

9. Office of Research Oversight 9 ORO Research Suspensions (2006 – 2010) Facility Programs: Research Safety (2 Facilities) Facility 3: Systemic Failure of Safety Oversight Program –Improper/dated inspections of biosafety cabinets and fume hoods –Outdated chemical inventories –Multiple longstanding fire code violations –Failure to label equipment, supplies, and waste as radioactive –Failure to decontaminate abandoned laboratories –Lack of Researcher Occupational Safety & Health Program –Lack of training and supervision of laboratory personnel –Failure to correct chronic deficiencies

10. Office of Research Oversight 10 On-Site Program Reviews – Routine Inspections, Follow-Up Inspections, For-Cause Reviews (Human, Animal, Safety, BSL-3, Information Protection, R&D Oversight) CY03 CY04 CY05 CY06 CY07 CY08 CY09 125 100 75 50 25 22 40 33 95 96 107 19 Since 2006: 331 Program Reviews 9 Programmatic Suspensions

11. Office of Research Oversight 11 Deficiencies Identified – CY 2009 ORO Routine Inspections at 26 Facilities Area of Deficiency – Lack of...Percent 1.Research and Development Committee (R&DC) oversight, including annual program reviews 2.Documentation and tracking of required training, credentialing, privileging, and scope of practice 3.Effective and timely communication between affiliate Research Review Committee and VA Research Service 4.Protocol inventory controls, effective protocol tracking, and timely continuing reviews 5.Information Security Officer (ISO), and Privacy Officer protocol reviews 6.Timely reporting of adverse events and problems to ORO 7.Active involvement of Facility Leadership 65% 58% 46% 35% 27%

12. Office of Research Oversight 12 ORO Research Suspension and Other ACOS/R Concerns Tom Puglisi, PhD