analysis of hrpp & rdcp routine reviews calendar year 2010

Analysis of HRPP & RDCP Routine Reviews

Calendar Year 2010

Frequent FindingsAileen Ward and Bob Brooks

HRPP 201Orlando FloridaMarch 24, 2010

Routine Reviews

• Overview of the Human Research Protection Program (HRPP) and Research & Development Program (RDCP) Reviews

• Review of Frequent Findings • Visit RCO SharePoint Site for document

Office of Research Oversight

• Public Law 108-170 (38 USC §7307)– Created VHA Office of Research Oversight– Reports directly to Under Secretary for Health– Chief Officer has statutory authority to halt research

• ORO findings must be reported to House and Senate Veterans Affairs Committee– Quarterly and Annual Reports to Congress– Copies of ORO Reports

Routine Reviews 2010

• 57 HRPP and RDCP Routine Reviews (RR)– 51 in 2009

• 36 VAMC RR of HRPP/RDCP– 28 in 2009


• 11 ACUP (Animal Care & Use Program)• 5 RSSP (Research Safety & Security Prg)• 17 RIPP (Res Information Protection Prg• 4 BSL-3 (Biosafety Level) • 5 For Cause Reviews (FCR)


• 21 RR included both HRPP & RDCP simultaneously– 1 w/o findings– 2009 almost all were simultaneous reviews

• 11 RR were HRPP alone– 1 w/o findings

• 4 RR were RDCP alone

Routine Reviews 2010Most Frequently Cited Concerns (All ROs)

“Top 10 in 2010”RDCP1. The R&DC did not fully satisfy the requirements for annual

reviews of subcommittees and research programs. (76%-19/25)

2. R&DC policies and procedures contained information that was outdated or inconsistent with current VHA policies. (72%-18/25)

3. The R&DC did not maintain SOPs or other written procedures for all recurring processes. (56%-14/25)

4. The R&DC and ACOS/R&D did not fully satisfy the requirements of annual quality assurance (QA) reviews of publications, scopes of practice, and CRADAs. (40%-10/25)

5. The R&DC membership roster was outdated or did not identify the primary member(s) for whom each alternate member may substitute. R&DC meeting minutes did not indicate the name of primary member whom the alternate member is replacing. (36%- 9/25)


“Top 10 in 2010” continued

HRPP1. IRB policies and procedures contained information that was

outdated or inconsistent with current VHA policies. (53%-17/32)2. Research personnel and/or oversight committee members did

not complete required training. (38%-12/32)

3. Research personnel conducted research without a research scope of practice and/or current scopes of practice for all non-privileged research personnel were not retained in the Research Office. (38%-12/32)

4. The ISO and PO did not thoroughly review research protocols and document their reviews. (31%-10/32)

5. The informed consent document (ICD or VA Form 10-1086) approved by the IRB did not contain all required elements. (25%-8/32)

1. The R&DC did not fully satisfy the requirements for annual reviews of subcommittees and research programs

Review of R&DC meeting minutes and interview with ACOS/R&D and the R&DC Vice Chair revealed that R&DC conducted annual reviews of the VAMC IRB, IACUC, and SRS, but not the VA Central IRB and affiliate IBC. In addition, R&DC did not submit a summary of its review and evaluation of the VAMC R&DC subcommittees to MCD


The RDC did not conduct annual assessments that systematically evaluated the research program. For example the following areas were not evaluated:– HRPP and IRB Performance– ACUP and IACUC Performance– The Research Safety Program and SRS

Committee Performance


Incomplete annual evaluations of subcommittees.

The RDC annual evaluations of the IACUC and IRB lack required elements .

Specifically, the annual evaluation does not include:a status review of credentialing and training; budget and space; or review of support staff, quality improvement activities, compliance issues, and goals for the next year.



The RDC annual evaluations of the IACUC and IRB lack required elements .

The annual evaluation of the IACUC lacks: evaluation of the inspection reports; review of the composition and membership of the committee; or consideration of budget, space, support staff, training, quality improvement activities; or review of compliance issues and goals for next year.



….some required elements of these evaluations have not been carried out…. As examples, the evaluation of the IACUC does not include consideration of budget, space, or goals for the year, and the evaluation of the SRS does not include consideration of security issues or planned training.


ORO’s review of R&DC meeting minutes and its interviews with personnel did not provide evidence of comprehensive oversight reviews that would have fully satisfied these requirements.

1. The R&DC did not fully satisfy the requirements for annual reviews of subcommittees and

research programs.

VHA Handbook 1200.01 §9 stipulates that the R&DC is responsible for:b(5) Reviewing and evaluating all R&D subcommittees both within the

VA facility and at external entities that function in lieu of R&D subcommittees….

A summary of these reviews and evaluations must be sent to the medical center Director annually; andc(2) Review of subcommittee activities including: (a) Annual reviews of the Research Safety and Security Program

(including planned training, compliance, security issues, etc.); (b) The Animal Care and Use Program (including inspection reports,

IACUC composition, IACUC arrangements, budgets, space, support staff, training, quality improvement activities, compliance issues, and goals for the next year); and

(c) The Human Research Protection Program (including IRB composition or IRB arrangements, credentialing and training status report, budget, space , support staff, quality improvement activities, compliance issues, and goals for the next year).

2. R&DC policies and procedures con-tained information that was outdated or inconsistent with current VHA policies.

The R&DC did not develop procedures that allow the Committee to hold unscheduled meetings in response to emergent issues.

Specifically, the R&DC SOP stated that R&DC may use an expedited review process when the R&DC Chair deems it appropriate.

R&DC minutes reflect that an expedited review process was used on several occasions.


• http://vaww.vha.vaco.portal.va.gov/sites/ORO/RCO/FAQs/Forms/AllItems.aspx). Question: Can a Research and Development Committee (R&DC) give approval contingent on Institutional Review Board (IRB) approval?

Response: No. R&DC review may not occur until all the relevant subcommittee approvals occur. Because there is no provision for expedited R&DC review under Veterans Health Administration (VHA) policy, there is no mechanism for implementing an R&DC contingent approval process.


The SOPs state that:

Electronic voting will occur in the event a quorum is lost or when important business requires action prior to the R&DC meeting. Electronic voting approval requires that a quorum of votes be received electronically and that more than 50 percent of the votes cast are for approval.


However, VHA Handbook 1200.01 §11 stipulates that:

If physical presence is not possible, a [R&DC] member may be considered through teleconferencing or videoconferencing.

Thus, VHA Handbook 1200.01 includes no provision for electronic voting.


The SOPs state that “The Executive Career Field (ECF) Performance Plan states that the RCO will serve as a non-voting member on the Institutional Review Board (IRB), Institutional Animal Care and Use Committee (IACUC), Biosafety Committee, and Research and Development Committee (R&DC).”


The cited ECF Performance Plan was for FY2009. The recently released VHA Handbook 1058.01 (dated May 21, 2010) §4.t stipulates that “In addition to conducting required audits, the RCO may serve as a nonvoting consultant, ….

The RCO may not serve as a voting or non-voting member of these committees.” (See also ORD Guidance at: http://www.research.va.gov/pride/policy/Guidance-RCO-committee.pdf)


…it was stated that “records must be maintained for a minimum of 5 years.”

However, VHA Handbook 1200.05 §7.j stipulates that “The required records, including the investigator’s research records, must be retained until disposition instructions are approved by the National Archives and Records Administrations and are published in VHA’s Records Control Schedule (RCS 10-1).” (1200.01 §12.b)


VHA Handbook 1200.01 §12b stipulates that ‘Records are the property of VA and the policy for record retention is outlined in VHA Records Control Schedule (RCS) 10-1.’ Likewise, VHA Handbook 1200.05 §26h stipulates that ‘The required records, including the investigator’s research records, must be retained until disposition instructions are approved by the National Archives and Records Administration and are published in VHA’s RCS 10-1.


The ACOS/R&D who will also serve as the Executive Secretary, and 2. Chairpersons of the subcommittees …. are the R&DC ex officio members with vote.”


However, VHA Handbook 1200.01 §13.f(1) requires that ACOS/R&D be an ex-officio, non-voting member of R&DC and functions as Executive Secretary of the R&D Committee

3. The R&DC did not maintain SOPs or other written procedures for all

recurring processes.

ORO noted that the R&DC SOP did not include written procedures for some recurring processes, such as responsibilities of the ACOS/R, R&DC, and R&DC evaluation of its subcommittees.



VHA Handbook 1200.01 §11.e requires that R&DC SOPs must be maintained for all recurring processes.



The R&DC Handbook and SOPs did not describe recurring processes. For example,

“Administrative Review” and the PO/ISO review and documentation process were not described as required by VA policy.



VHA Handbook 1200.01 §11.e stipulates that ‘Standard operating procedures or other written procedures must be maintained for all recurring processes. These processes include, but are not limited to, communication with the Medical Center Director, the COS, investigators, and committees or subcommittees.

4. The R&DC and ACOS/R&D did not fully satisfy the requirements of annual

quality assurance reviews of publications, scopes of practice, and CRADAs.The R&DC did not conduct effective oversight of the research program and make appropriate recommendations to the MCD. Specifically, the VAMC provided no documentation that the R&DC conducted annual evaluations that assessed:ACOS/R&D quality assurance reports including annual assessments of publications, employees involved in human subjects research, and Cooperative Research and Development Agreements (CRADAs), and other agreements in support of the research program.


quality assurance reviews of publications, scopes of practice, and CRADAs.

…the ACOS/R did not conduct an annual quality assurance (QA) review of research staff scopes of practice.


quality assurance reviews of publications, scopes of practice, and CRADAs

Review of R&DC meeting minutes and interview with ACOS/R&D and the R&DC Chair revealed that …neither R&DC nor ACOS/R&D conducted any of the required annual quality assurance reviews.


quality assurance (QA) reviews of publications, scopes of practice, and CRADAs.

VHA Handbook 1200.01 §7.c., 7.d., and 7.f. require the ACOS/R&D to conduct annual QA reviews of publications assessing the acknowledgement of VA support and affiliation; annual QA review of resarch employees regarding scopes of practice and their credentialing and privileges; and annual QA review of CRADA and other agreements in support of the research program.


quality assurance (QA) reviews of publications, scopes of practice, and CRADAs.

9.c.(1)In fulfilling its responsibilities….the R&DC needs to rely on a variety of information sources including:(1) Quality assurance activities, reports to the committee by the ACOS/R&D, AO/R&D, or other research staff members, subcommittee reports…..

5. The R&DC membership roster was outdated or did not identify the primary

member(s) for whom each alternate member may substitute. R&DC meeting minutes did not indicate the name of primary member whom the alternate

member is replacing.The VAMC did not have the roster of the SRS committee on site; the RDC roster provided to ORO did not specify the voting status of each member , and the date of membership for the RCO is not accurate.

The VAMC RDC roster provided to ORO does not identify whom the alternate member may replace.



member is replacing.

The RDC membership roster did not indicate the primary members whom the alternate members might substitute or were replacing.




The membership rosters that were provided to ORO were outdated, listing members that were no longer VA employees or no longer members of the committees. …The RDC roster lists two persons who are no longer RDC members. None of the rosters were dated so that correct and current membership for a specific point in time could not be verified.




VHA Handbook 1200.01 §12.a stipulates that ‘The adequate documentation of all of the activities of the R&DC must be maintained, including but not limited to, the following….(3) Membership lists for the R&DC and all R&DC subcommittees.’




VHA Handbook 1200.01 §13.c(6) stipulates that ‘The R&DC membership roster must identify the primary member(s) for whom each alternate member may substitute.’




§11.c(1) …and ‘If an alternate is present in place of a voting member, the minutes need to indicate this fact and name who the alternate member is replacing.

1. IRB policies and procedures contained information that was outdated or

inconsistent with current VHA policies.The criteria and timelines for reporting research events in the VAMC IRB SOP are not consistent with VHA Handbook 1058.01 For example, the VAMC SOP requires that when the RCO determines that non-compliance is serious or continuing, a report is to be filed within 10 days to the IRB, the ACOS/R, and the MCD. The VAMC IRB SOP does not accurately reflect procedures or timelines to evaluate the unanticipated problem or SAE as described in the Handbook.


inconsistent with current VHA policies.

VHA Handbook 1058.01 § 6.a.(4)(b) establishes the required timeline at 5 business days. In addition, VHA Handbook 1058.01 § 6 and Appendix B § 11-13 establishes criteria and timelines for IRB evaluations, determinations and reporting requirements for unanticipated problems and SAEs. The VAMC IRB SOP does not accurately reflect procedures or timelines to evaluate the unanticipated problem or SAE as described in the Handbook.


inconsistent with current VHA policies. ….page XXX stated that “The IRB Coordinator serves as the alternate voting IRB, non-scientific, and affiliated member.”

However, VHA Handbook 1200.05 §12.j stipulates that “R&D Administration officials including, but not limited to the ACOS for R&D and the AO for R&D, may not serve as voting members of the IRB.” This prohibition extends to IRB Coordinators/Administrators.


inconsistent with current VHA policies.On page XXX regarding the storage and dispensing of Investigational Devices and Drugs, it was stated that “The investigator is responsible for storage, security and dispensing of investigational devices and drugs.”


inconsistent with current VHA policies.VHA Handbook 1108.04 stipulates that: Regardless of the source, all investigational drugs must be delivered to the Pharmacy Service and/or Research Service Investigational Pharmacy for receipt, storage, security, dispensing, distribution, and disposition. All investigational drugs must remain under the direction of Pharmacy Service.” (§7a)


inconsistent with current VHA policies.VHA Handbook 1108.04 stipulates that:

The Chief, Pharmacy Service, or Chief (Manager) for the Research Service Investigational Pharmacist may delegate in writing the custody of investigational drugs stored outside the pharmacy to the PI.” (§6a) Thus, in order for the investigator to store and dispense investigational drugs, the Chief of Pharmacy must delegate this authority to the investigator in writing.



The VA IRB SOP statement, “The costs of the non-veteran participants must be absorbed by the study’s sponsoring agency. No costs would be covered by the VA for these participants,”



VHA Handbook 1200.05 32.a.(3)(a)Pursuant to 38 CFR 17.102, subjects in VA-approved research cannot be charged, nor can their insurance be billed, for research-related interventions or procedures (e.g., tests, drugs, clinic visits, hospital admissions, transportation) that are required by the protocol. If medical services are furnished to a person who is not eligible for medical services as a Veteran, the medical care appropriation will be reimbursed from the research appropriation.



The IRB approval letter stated that: “Research records must be retained for three years after completion of the research, if the study involves medical treatment; it is recommended that the records be retained for eight years.”

2. Research personnel and/or oversight committee members did not complete

required training.ORO noted that three active research personnel did not maintain mandatory training requirements.

Review of Personnel Training Records revealed that 17 out of 239 active research study personnel (7.1%) lapsed in their required trainings.

Review of training records revealed that the records were accurate and up-to-date. However, 14 out of 117 active research study personnel (12%) lapsed in their required trainings.

2. Research personnel and/or oversight committee members did not complete

required training.VHA Handbook 1200.05 stipulates that “The local research office maintains accurate, up-to-date records regarding the mandatory training and credentialing of investigators and other research staff in the protection of human research subjects” (§5.a(6)); and that“The IRB must determine that the PI and all other investigators of the proposed research activity have met all current educational requirements for the protection of human research subjects as mandated by the facility’s Assurance, VA ORD, . . .” (§7.a(10).[§61.a.2]

3. Research personnel conducted research without a research scope of practice and/or current scopes of practice for

all non-privileged research personnel were not retained in the Research Office.

The VAMC Research Office was unable to produce documentation of active research staff and their required training.



VHA Handbook 1200.05 § 5.a(6) requires the local Research Office to maintain accurate, up-to-date records regarding the mandatory training and credentialing of investigators and other appropriate research staff in the protection of human research subjects. [§61.a.2]



Scope of Practice statements not required for all personnel.

The VAMC IRB SOP only requires Scopes of Practice for persons designated as “Others to Assist,” and does not require them for co-investigators and PIs.

3. Research personnel conducted

research without a research scope of practice….

VHA Directive 1200 § 4 (c)(9)(a) states that a research Scope of Practice Statement or Functional Statement must be defined for all individuals conducting VA research, including individuals who do not function as healthcare providers. If the individual holds clinical privileges at the facility and the research responsibilities and duties match the clinical privileges, the Functional Statement may be used in lieu of a Scope of Practice Statement. If there are additional responsibilities and duties, these should be included in a Scope of Practice Statement along with a copy of the clinical privileges.[§62.c]

4. The ISO and PO did not thoroughly review research protocols and document

their reviews.

ISO/PO Review protocols not documented.

ISO carried out protocol reviews but did not have a formal mechanism to document the results of these reviews.

The ISOs and PO were only reviewing the application forms, not verifying assertions/statements made by investigators in the applications by examining the protocols, consent forms and other source documents included in review submissions. [§38]


their reviews.

The Privacy Officer and the ISO are responsible for:a. Ensuring the proposed research complies with all applicable local, VA and other Federal requirements for privacy and confidentiality, and for information security, respectively, by identifying, addressing, and mitigating potential concerns about proposed research studies, and by serving in an advisory capacity to the IRB or R&D Committee as a nonvoting member.b. Reviewing the proposed study protocol and any other relevant materials submitted with the IRB application.


their reviews.

NOTE: It is not sufficient for the Privacy Officer or ISO to review a checklist completed by the investigator, and not the study protocol and related materials themselves.

5. The informed consent document approved by the IRB did not contain all

required elements.

Lack of whom to contact for questions about the research subjects’ rights and to confirm that this is a valid VA study.

No contact is given specifically for questions about subjects’ rights or to verify the validity of the study.


required elements.

VHA Handbook 1200.05, states that informed consent documents must include an explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of research-related injury to the subject (38 CFR 16.116(a)(7). There must be at least one contact other than the investigator or study personnel. [§31.a.(11)]


required elements.

VHA Handbook 1200.05 states the investigator is responsible for: …ensuring the research team makes initial contact with the potential subject in person or by letter prior to initiating any telephone contact… The initial contact must provide a telephone number or other means that the potential subject can use to verify the study constitutes VA research. [§9.m.(1)]


required elements.

The VAMC IRB-approved informed consent forms did not contain required co-payment statement: Review of protocol files revealed that this co-payment language was not included in many IRB-approved informed consent forms.


required elements.

VHA Handbook 1200.05. Basic Element for Informed Consent stipulates that: A statement that a veteran-subject will not be required to pay for care received as a subject in a VA research project except as follows… certain veterans are required to pay co-payments for medical care and services provided by VA. Veterans receiving medical care and services from VA that are not rendered as part of the VA-approved research study, must pay any applicable co-payment for such care and services. [§32.a.(3)(b)]


required elements.

Approval of incorrect consent information about treatment for injury. 38 CFR 16 § 116(a)(6) requires the consent process include an explanation as to whether any medical treatments are available if injury occurs.

…consent document s include the statement, “In the event of physical injury resulting from your participation in this research, necessary medical treatment will be provided to you and billed as part of your medical expenses. Costs not covered by your health care insurer will be your responsibility.”


required elements.

The Common Rule at 38 CFR 16 § 116(a)(6) requires that the consent process include an explanation as to whether any medical treatments are available if injury occurs.

The VA regulation at 38 CFR 17 § 85 requires the VA to provide necessary treatment for subjects injured as a result of research participation…


“Top 9 in 2009”• R&DC oversight of research program, and performing an

annual quality review (2010)• R&DC and subcommittees performing annual on-going

reviews of all protocols• Effective systems to track protocols, staff, and subjects• System for assuring credentialing, scopes of practice, and

research-related training is effective and info is current (2010)

• Better involvement of MCD and COS in research program• Communication between IRB and other subcommittees with

R&DC, especially if IRB is at the affiliate institution• Having a registered IBC if doing rDNA research• Issues with the ISO and PO, training and protocol review

(2010)• Reporting of SAEs and SCN to ORO in a timely manner


“2005”• R&D Committee:

– Members exceed three year term limits– R&DC does not report to MCD thru ACOS/R as an ex officio

member– R&DC does not meet monthly– R&DC not reviewing IRB minutes timely

• IRB votes do not distinguish recusal from abstention– (Recused members do not count for quorum)

• IRB violates SOPs re expedited reviews and waiver of consent

• NO involvement of MCD and COS in research program

• R&DC and IRB members do not have adequate knowledge

• Informed Consent Documents do not follow SOPs


“2003-4”• Failure to Obtain Written Informed Consent• Failure to follow IRB-approved research

protocol• Beginning research prior to R&DC approval• Inadequate staff to support the HRPP program• Inadequate tracking system for protocols• Failure to maintain records for at least 3 years

after closure• Reviews of Serious Adverse Events not

documented

analysis of hrpp & rdcp routine reviews calendar year 2010

Documents

research programsthe

rdc policies

research office

research protocols

rdcpthe rdc

vamc rdc subcommittees

rdcp aloneroutine reviews

privileged research