# Presentation: 937269

## ORO’S ROUTINE REVIEW PROGRAM

**Office of Research Oversight**
**September 21, 2005**

## OUTLINE

**Mission/Responsibilities**
**Compliance Reviews**
**Regional Offices**
**Compliance Findings**

##               ORO LEGISLATION*¶ 7307. Office of Research Oversight“(a) Requirement for Office.-(1) There is in the Veterans Health Administration an Office of Research Oversight (hereinafter in this section referred to as the ‘Office’).  The Office shall advise the Under Secretary for Health on matters of compliance and assurance in human subjects protection,...........”*Public law 108 (170) signed by President 12/6/2003

## ORO MISSION

**Advise Under Secretary for Health on matters of regulatory compliance and assurance in research involving human subjects, animal welfare, research safety, and research misconduct**

## OVERSIGHT RESPONSIBILITIES

**Monitor, review, and investigate regulatory compliance and assurance in research (HSP, AW, RS, and RM) **
**Advise USH based on these findings**

## ORO COMPLIANCE ACTIVITIES

**For-Cause Reviews**
**Routine Reviews**
**BSL-3 Laboratory Inspections**
**Research Misconduct Oversight**
**Management of Assurance Program**
**Adverse Event Oversight**
**	****(substantive actions by IRB or death, HB 1058.1)**
**Compliance Information via Teleconferences, Meetings, etc.**
**Routine Monitoring and Follow-up of Compliance Issues**

## ROUTINE REVIEW PROGRAM

**Systematic and prospective review of research programs to assure adequate protection of human subjects, support for laboratory animal welfare, and research safety and security.**

## ROUTINE REVIEWS

**Directed at assurance of regulatory compliance in VHA.  Not a for-cause site visit and not an audit or an investigation.**

## ROUTINE REVIEWS

**Assessment**- review the current level of compliance with acceptable practices for the conduct of research and vigilance of institutional oversight
**Remediation**- actions recommended by ORO to address deficiencies identified by Routine Review team.

## ROUTINE REVIEWS

**4 to 6 RRs conducted by each RO/yr **
**Teams of 2-5 members for 1-5 days**
**Site visit reports**
**Facility action plans**
**ORO follow-up**

## Where Do Questions Asked in a Routine Review Come From?

## Human Subject Protections

*The Belmont Report*, *Ethical Principles and Guidelines for the Protection of Human **Subjects of Research*
- 38 CFR Part 16, *Protection of Human Subjects*
*38 CFR 17.33, Patients’ Rights*
*38 CFR 17.85, Treatment of Research-Related Injuries to Human Subjects*

## Human Subject Protections

**Veterans Health Administration (VHA) Handbook 1058.1, *****Reporting Adverse Events to the ORO***
**VHA Handbook 1200.5, *****Requirements for the Protection of Human Subjects in Research***
**VHA Handbook 1200.16,***** Off-Site Research Handbook***
**Additional VHA Memoranda and Directives related to HRP.**
**VA Manual, M-3, Part 1, Chapter 1, *****Introduction, Research and Development (R&D) Program; *****Chapter 2, *****R&D Organizational Structure; *****Chapter 3,***** R&D Function***** **

## WHAT TO REPORT TO OROMEMORANDOM

**Identifies issues VHA facilities must report to ORO as required by various Federal regulations and VHA policies. **
**	****	**
**	**_[http://www.va.gov/oro/](http://www.va.gov/oro/)_
**November 12, 2003**

## LABORATORY ANIMAL WELFARE

- Veterans Health Administration (VHA) Handbook 1200.7, *Use of Animals in Research*
- PL 99-158, *Health Research Extension Act of 1985, *Section 495:* Animals in Research*
- 7 USC, 2131-2159, 7 CFR 2.22, 2.80, and 371.2(g), *Animal Welfare Act, As Amended.*
- 9 CFR Parts 1, 2, 3, and 4, *Procedures under the Animal Welfare Act, *Department of Agriculture.

## Research Safety and Security

- VHA Handbook 1200.6, *Control of Hazardous Materials in VA Research Laboratories, *2004
- VHA Handbook 1200.8, *Safety of Personnel Engaged in Research*, 2002
- VHA Directive 2003-030,* Management of Hazardous Chemicals, *2003
- VHA Directive 2005-003. *Requirements for Submittal and Approval of Biosafety Level-3 (BSL-3) Research Laboratory Construction and Renovation, *2005

## Research Misconduct

- Veterans Health Administration (VHA) Handbook 1058.2, *Research Misconduct, *2005
- 38 CFR Part 44, *Governmentwide Debarment and Suspension (Nonprocurement).*
- 65 FR 76260, *Federal Policy on Research Misconduct,* Office of Science and Technology Policy (OSTP), 2000

## WHEN IS A RR DONE?

**RRs are usually initiated by ORO ROs. The ORO RO Director will select the VHA facilities to be reviewed.  Requests for review from facilities also** **will be considered.**

## Typical RR

_**Prior to Site Visit**_
- Scheduling
- Initial Contact
- Letter of Notification
- Pre-Site Visit Preparation

## Typical RR

_**Site Visit**_
**Entrance Briefing **
**Review Processes**
**Interview of key personnel**
**Group Meetings**
**Record/Document Review**
**Process Observation**
**Facility Inspection**
**Executive Session**
**Briefing and Exit Interview**

## Typical RR

_**After Site Visit**_
- Drafting the Report
- Finalizing the Review
- Follow-up

## ORO Regional Offices

**Northeastern**
**	****Bedford, MA**
**	****VISNs 1, 2, 3**
**Mid-Atlantic**
**	****Washington, DC**
**	****VISNs 4, 5, 6, 9, 10**
**Southern**
**	****Decatur, GA**
**	****VISNs 7, 8, 16, 17**

**Midwestern**
**	****Hines, IL**
**	****VISNs 11, 12, 15, 19, 23**
**Western**
**	****March ARB, CA**
**	****VISNs 18, 20, 21, 22**

## ORO Regional Offices

## Findings: R&D Committee

- 1.  **Terms of R&D Comm. Members exceed the three (3) year limit and a majority of members were appointed at one time.**
- M-3, Part I, Chapter 2.02 b. (5) (c) states that members “Serve terms of not more than 3 years with not less than 1 year between terms (does not apply to ex officio members).  The terms shall be staggered to provide partial change in membership annually.”

## Findings: R&D Committee

**2.  The R&D Committee reports to the Director through ACOS/R&D**
- VA Manual, M-3, P-I, Chapter 2.02.b(1) identifies the R&D Committee as responsible through the COS to the facility Director for maintaining high standards throughout the facility’s R&D Program.  (Chapter 2.02b(2)(e) further stipulates that ACOS/R&D serves as an ex officio member of the R&D Committee with a vote and functions as Executive Secretary.)

## Findings: R&D Committee

**3.  R&D Committee meets infrequently**
- M-3, Part 1, Ch 3.01(c) requires the committee to meet monthly with exception of one month in the summer

## Findings: Investigational Drug Logs 

**1.  Investigational drug logs incomplete**
- See M-2, Part VII, Chapter 6.02.d and 6.03.g (1-14).
- 2. **Research Pharmacy files show VA Form 10-9012, Investigational  Drug Information Record without signatures of Chairs of IRB and R&D Committee  and  lacking VA Form 10-1223, Report of Subcommittee on Human Studies**
- See VHA HB 1200.5, part 14.c & VHA M-2, Part VII, Chapter 6

## Findings: IRB & R&D Minutes

**1.  IRB and R&D minutes not appropriately processed**
- M-3, Part I, Chapter 3.01e requires R&D Committee to review IRB minutes and append them to the minutes of the R&D Committee. The R&D Committee minutes should be signed by the Chair and the Executive Secretary (i.e., ACOS/R&D); copies are then submitted to the facility Director and COS for review and signature [3.01d(3)].

## Findings: IRB & R&D Minutes

**2. IRB minutes do not distinguish between recusal and abstention**
- Recusal is not the equivalent of abstention; recused members do not count toward a quorum.  See 38 CFR 16.107 (e) and VHA Handbook 1200.5, paragraph 6.g

## Findings: SOPs

**1.  The SOPs for the IRB, R&D, and investigators are out of date and do not comply with relevant regulations and policies**
- Should update to include requirements from HB 1200.5., 38 CFR 16, 45 CFR 16, 38 CFR 17 (treatment of research injuries), 21 CFR 50, one of the basic FDA regulations, and 21 CFR 312 and 812

## Findings: SOPs

**2.  The IRB does not consistently follow its SOP and VA regulations for expedited review procedure & waiving documentation of informed consent.**
- Must document the findings for waiver of informed consent as required by 38 CFR 16.117 (c)

## Findings: Staff Responsibilities

**1.  The facility Director and the Chief of Staff are not involved in the oversight of the Research Program**
- See responsibilities in M-3, Part I, Chapter 2.02, paragraphs a. and b.(2)(e), Chapter 2.03, paragraph b.(3), and VHA Handbook 1200.5, paragraph 5.a.(1) and b
**2.  The role and function of the current R&D Coordinator do not conform to VA Policies**
- See M-3, Part I, Chapters 2.02 a., 2.03 b., and 3.03

## Findings: Staff Responsibilities

**3. Chairpersons of R&D and IRB Committee do not show working knowledge of duties and responsibilities of their positions**
- PRIDE; training and resource support is highly recommended
**4. The IRB Committee lacks knowledge of applicable federal regulations, VHA policies, and directives governing HRP as seen by approval of protocols without quorum and use of email voting outside of convened meeting**
- PRIDE; see 38 CFR 16.108 (b) and VHA Handbook 1200.5, paragraph 7.f

## Findings: Informed Consent Form

**1.  Review and approval of ICF do not follow SOP and VA regulations.**
- Must satisfy 38 CFR 16.116 (a), VHA HB 1200.5, Appendix C

## COMPLIANCE FINDINGS 2003-04

- -**Failure to obtain written informed consent**
- 38CFR16.116 and 117a; VHA 1200.5, App. C; CFG31, 32
- -**Failure to follow IRB approved protocol**
- 38CFR16.103.b.4.iii; VHA 1200.5, 7.c.1; CFG23

## COMPLIANCE FINDINGS 2003-04

**Failure to obtain R&D Committee approval prior to conducting research**
- 	M-3, P-1, Ch 3.01.e; VHA HB 1200.5, 7.b
**Resources and staff not adequate to support HRPP program.  Inadequate protocol/records tracking system**
- 		38CFR16.103.b.2; CFG 52

## COMPLIANCE FINDINGS 2003-04

**Failure to maintain records for at least 3 years after completion of study**
- 3 yrs in 38CFR115(b), 5 yrs in VHA HB 1200.5.8.j
**Inconsistent documentation in IRB minutes and IRB files**
- 38CFR16.115.a.1,3,4,7, and 116d
**Reviews of SAE by R&D and IRB not documented**
- 21CFR56.101(a), 21CFR.108, and 21CFR56.111.

## IN PROGRESS

- International Guidance and Policy Planning with ORD
- Multi-site IRBs Guidance and Policy Planning with ORD

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