**STATEMENT**

**OF**

**JOHN H. MATHER, M.D.,**

**CHIEF OFFICER,**

**OFFICE OF RESEARCH COMPLIANCE AND ASSURANCE**

**DEPARTMENT OF VETERANS AFFAIRS**

**ON**

# OVERSIGHT OF RESEARCH AND OTHER ISSUES

**BEFORE THE**

**SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS**

**AND THE**

**SUBCOMMITTEE ON HEALTH**

**OF THE**

**COMMITTEE ON VETERANS' AFFAIRS**

**U.S. HOUSE OF REPRESENTATIVES**

# MAY 16, 2002

**\*\*\*\*\***

Mr. Chairman and Members of the Subcommittees, thank you for the
opportunity to appear before you to discuss the activities of the Office
of Research Compliance and Assurance (ORCA) and, in particular, its role
and responsibilities in the protection of human research subjects in the
Veterans Health Administration (VHA). Further, this will provide an
update on the scope, structure, philosophy, and product lines of ORCA
since this committee's oversight hearings of April 21, 1999, and
September 28, 2000.

**Scope**

The scope of ORCA is defined in the Mission statement, which is in
accordance with the commitment made to the Congress in 1999:

> The Office of Research Compliance and Assurance (ORCA) serves as the
> primary VHA component in advising the Under Secretary for Health on
> all matters affecting the integrity of research in the protection of
> human subjects and animals, promoting enhancements in the ethical
> conduct of research in conformance with regulations and policies and
> investigating any allegations of research improprieties and research
> misconduct.

ORCA reports directly to and serves as the primary advisor to the Under
Secretary for Health on all matters affecting the integrity of VHA
research related to compliance and assurance. ORCA advocates and
promotes the application of continuous quality improvement to enhance
the ongoing protection of human subjects enrolled in research and
welfare of animals used in research. Further, in circumstances involving
allegations of potential research impropriety and research misconduct,
this office conducts the necessary investigations, and prepares
recommendations for remedial and corrective actions. This scope of
responsibility is codified in VHA Directive 1058, "Responsibilities of
the Office of Research Compliance and Assurance," issued May 23, 2001.

Important to ORCA and the VA are the connections made through ongoing
collaboration with the various other federal departments and agencies,
and non-governmental organizations that are responsible for the issues
under ORCA's purview. ORCA has close working relationships with the
Office for Human Research Protections (OHRP), the Food and Drug
Administration (FDA), the Office for Laboratory Animal Welfare (OLAW)
and the Office of Research Integrity (ORI), all located in the
Department of Health and Human Services. Vitally important relationships
with these organizations have helped to ensure that the VA is conducting
its activities in a consistent and ethical manner. There is much more
that can and will be done to build upon these productive relationships.

Structure

The structure of ORCA includes a central office and five regional
offices. The central office is responsible for the overall
accomplishment of its mission, while providing direction, guidance and
oversight to its five field-based units that routinely perform their
delegated operational roles and responsibilities. The central office has
eight (8) full time staff; and the four (4) fully activated regional
offices are each staffed with four full time staff. Recruitments for the
fifth regional office are currently in process.

Each regional office covers a geographical area that encompasses between
three and six Veterans Integrated Service Networks (VISNs) and provides
support and services on the full scope of ORCA's activities to about 25
VA medical centers (VAMCs) and VA Health care Systems (HCSs). The
original four regional offices have been fully staffed since September
2001, and the fifth regional office, which will serve the VAMCs in the
three VISNs in the Northeast, will be completely activated by the end of
this fiscal year. Each regional office is developing an expertise in a
particular area so that it can be an authoritative resource throughout
ORCA. For example, in the Southern regional office in Decatur, GA, we
have a veterinarian on the staff who collaborates with the VA's chief
veterinarian, located at the same VAMC, while the Mid-Atlantic regional
office in Washington DC is developing an emphasis in the area of
research safety. While the preponderance of ORCA's activities have so
far been related to human subject protections, the areas of animal
welfare and research safety need to be given greater attention. Also,
research misconduct oversight is rapidly evolving as a major issue with
the implementation of the new Federal Research Misconduct Policy and the
publication in the April 30,2002 Federal Register, that the VA has
adopted this policy.

ORCA has established a Field Advisory Committee that meets twice a year
to advise on the implementation of its programs. It is composed of VA
staff across the full spectrum of operations and research, including
representatives from VISNs and VAMCs, such as Associate Chiefs of Staff
for Research and Development, Administrative Officers for Research, and
Research Compliance Officers.

Philosophy

From the beginning, ORCA has set for itself a course that seeks to
promote continuous quality improvement in the responsible conduct of
research. Since ORCA is not an entity that has the authority to
'regulate', it is forging a different paradigm. ORCA's philosophy for
oversight has been described as the ACE approach. This balanced approach
is embodied in the acronym ACE, which refers to ORCA's need to create a
culture of Assurance/Assessment, being a Counselor/Cop, and acting as
Educator/Enforcer.

Another key feature has been the interest in developing an emphasis on
preventative measures rather than a reliance on the after-the-fact
investigation of research improprieties. Research improprieties are
violations of the regulations, which the VA has adopted, that govern the
responsible conduct of research. These include the "Common Rule" (Title
38 CFR Part 16), various FDA regulations, and certain State regulations
for the protection of human subjects enrolled in research. There are
also a number of federal regulations that pertain to the welfare of
animals, research safety, and the recently promulgated research
misconduct policy.

The ongoing intent of ORCA is to continue to shift the philosophy of
compliance from a reactive to a [proactive]{.underline} mode, wherever
possible. ORCA's [reactive]{.underline} mode of retrospectively
conducting inquiries into allegations of research improprieties will
continue as post hoc "for cause" reviews, very similar to those of the
Office of the Medical Inspector in its review of allegations of
improprieties in clinical situations. Nonetheless, ORCA seeks to
emphasize a prospective approach to oversight and surveillance that
increasingly relies on prevention of regulatory non-compliance. This
requires continuing education that logically will result in a reduced
need for remedial education and training.

Product Lines

In accordance with ORCA's scope and derived from its philosophy of
proactive operations, ORCA has four primary and four secondary product
lines.

The four primary product lines are: 1) Administration of the Assurances
Program, 2) Prospective Compliance, 3) Reactive Compliance, and 4) the
Training, Education and Development (TED) activity.

The four secondary product lines are: 1) Management of the Adverse
Event-Serious Adverse Event processes, 2) Promotion of the Research
Compliance Officer (RCO) concept, 3) Liaison with the VA National Ethics
Center, and 4) Liaison with the VA Office of Research and Development
regarding management of the Human Research Protection Program (HRPP)
accreditation contract with the National Committee for Quality Assurance
(NCQA).

Primary Product Lines

In March 2000 ORCA assumed responsibility from the Office of Research
and Development for the VA Multiple Project Assurance (MPA) contracts
for the protection of human subjects. This contract, required by the
"Common Rule" is a written document that a VA facility prepares so that
it commits itself to fulfill all of the requirements of the federal
regulations and VA operational policies and procedures in the protection
of human subjects. Today, 111 VAMCs have these "Assurances". At about 40
sites, of the 111, the VAMC, or HCS, rely on the academic affiliate's
Institutional Review Board (IRB) to review research protocols to ensure
compliance with the provisions of the "Common Rule" and other pertinent
regulations.

Since early in 2001, ORCA has worked closely with OHRP to implement a
new Federal-Wide Assurance (FWA) program, which is designed to simplify
the assurance process. This collaboration with OHRP has worked well, and
we have almost completed the conversion of the VA MPA contracts to this
new FWA process. Further, ORCA, under this overall FWA schema, has
developed and issued guidance for two sorts of Memoranda of
Understanding (MOU). The first set of MOUs allows VAMCs with relatively
small research programs to partner with VAMCs having much larger
programs and a mature Human Research Protections Program (HRPP). This
will enable these smaller programs to capitalize on some economies of
scale. Additionally, ORCA has provided VAMCs with guidance and a
template for a second MOU between a VAMC and its Academic affiliate,
where the VAMC relies upon the affiliate's IRB. These MOUs are important
for VAMCs to complete, as they are required by the standards for the
accreditation of a HRPP sponsored by the NCQA.

ORCA created and then initiated the prospective compliance product line
in September 2001. An ORCA working group, the members drawn from staff
at VAMC research programs, has guided the preparation of a Multi
Assessment Program or MAP. This MAP has two components: 1) a Self
Assessment instrument, and 2) an On-Site review process. The MAP
Self-Assessment instrument incorporates checklists for the full scope of
ORCA's four areas of responsibility. This instrument includes an
introduction to Self Assessment and provides a full list of websites
that VAMCs can access to assist them in completing Self Assessments.
ORCA has incorporated and distributed the checklist for the HRPP into
compact disc (CDROM) containing a compendium of all of the regulations
and guidance pertinent to the protection of human subjects. This
compendium, also posted on the ORCA website, has cross-linked references
to all of the regulations, checklists and accreditation standards for a
HRPP mandated by the VA and other federal agencies, including OHRP and
FDA. It contains more than 150 documents and they are completely
cross-linked to the regulatory source: clicking the internet hyperlink
promptly displays the section of the rule or guidance being cited.

During their site visits ORCA's regional office staff orient each VAMC
to the MAP Self Assessment process, and provide a list of NCQA's
accreditation standards for an HRPP that go beyond the minimum
regulatory requirements. The VAMC is also provided written guidance on
how to complete a MAP Self Assessment. Research staffs are encouraged to
consult with the staff of the VAMC's Quality Assurance Office to assist
in conducting a MAP Self Assessment. The ORCA regional office offers to
return to do an On-Site MAP review when the VAMC has completed its MAP
Self Assessment or before, if the VAMC invites ORCA to return. This MAP
is a voluntary program and increasingly VAMCs are recognizing its
benefit. Wherever possible, the regional office provides training and
education on any subject pertinent to ORCA's mission, requested by the
VAMC.

The reactive compliance product line has always been a fundamental ORCA
activity. Whenever a VAMC reports a potential or actual research
impropriety or ORCA receives a notification from other sources, such as
OHRP or the FDA, the ORCA regional office is responsible for follow-up
and assistance with the resolution of the issue. The inquiry may be
handled by telephone or exchange of correspondence; in some instances
the regional office conducts a limited fact finding visit, an on-site
Focus Review. If there are more serious systematic problems ORCA selects
a Special Inquiry Force Team (SIFT) for an on-site review that lasts for
several days. The process follows the general methods involved in
performing a root cause analysis. The SIFT team conducts its work
according to a written charter and files its report and recommendations
with ORCA central office. The Under Secretary for Health signs and
issues the final report and ORCA monitors Action Plans until all of the
recommendations have been fully implemented. ORCA then closes the SIFT
review with a written notification to conclude the process and after all
of the recommendations have been satisfactorily implemented.

ORCA has conducted ten (10) SIFT reviews, two of which are in active
status. Among the eight (8) that have now been closed out, one VAMC was
in serious regulatory non-compliance, and ORCA placed restrictions on
its "Assurance", that took almost a year to resolve. ORCA confers with
OHRP when issuing a restriction on a VAMC's "Assurance". The problems
ORCA has identified in the SIFT reviews are comparable to, if not
identical to, the problems that have been identified by OHRP.

The fourth primary product line is the training, education and
development (TED) activity. ORCA has an ongoing working group for this
TED activity and the Under Secretary for Health has annually approved
the strategic plan for these TED activities. The TED working group has
provided guidance in several basic and developmental activities. ORCA
has a web site \[www.va.gov/ORCA\] that continues to grow in importance
as a vehicle for identifying important education and training resources.
Copies of all of ORCA's fifty or so Information Letters, the ten ALERTS
on critical issues, and the minutes of ORCA's Bimonthly Teleconferences
are all posted on the website. The website is regularly updated. Also
appearing on the website is a Best Practices guidance document n how a
VAMC can prepare a standard operating procedures manual for its IRB.
ORCA originally issued this as a CD, and we have had many requests for
copies from interested parties beyond the VA. The TED working group has
also identified sources for training and education of investigators in
human subjects protection as required by VA's Office of Research and
Development and National Institutes of Heath (NIH). Through
collaborative arrangements with several academic institutions that are
involved in a project known as CITI (Collaborative IRB Training
Initiative), we were able to assist in the preparation of a specific
module on research protections in the Department of Veterans Affairs.
This CITI program is an optional training vehicle for investigators to
be certified in human subjects protection. In addition, all VAMC
Directors must complete three training modules on their responsibilities
under the FWA that they all sign. Recently, ORCA has, in conjunction
with OHRP, begun to distribute CDs to VAMCs and training manuals
prepared by the main professional association, Public Responsibility in
Medicine and Research (PRIM&R). These are intended for use by
investigators and other research staff to help them understand the
ethical foundations of the regulatory requirements for the responsible
and ethical conduct of research involving human subjects.

ORCA has also presented a VA DAY at the Annual PRIM&R meeting for the
past two years and will continue to support these annual forums. In
partnership with OHRP and the FDA, ORCA is sponsoring joint conferences
and seminars on the protection of human subjects, which occur about six
times a year. ORCA's regional offices take the lead for the VA on the
seminar's planning committees. Further, over the past year, ORCA has
worked with the VISN leadership to conduct one-day intensive seminars on
the various requirements for the responsible conduct of research. The
faculty for these seminars, which are targeted for VA's senior
executives routinely include representatives from OHRP and FDA. These
seminars have broad representation from the leadership of the VISNs and
their VAMCs. These seminars, almost complete now, have been well
received and the materials distributed are current.

While TED activities assist VA personnel in understanding the
responsible conduct of research within the research enterprise, ORCA has
not forgotten the veteran who is or might participate in VA research.
ORCA has developed a brochure, "I'm a veteran. Should I participate in
research?" which was recently unveiled April 10 by the Under Secretary
for Health at the bi-monthly meeting of the Veterans' Services
Organizations (VSOs). This brochure will help veterans understand their
rights as research volunteers and help them decide if they want to
participate in a research protocol. ORCA will widely distribute the
brochures this month throughout the VA and to the VSOs. The brochure
indicates where veterans can make local contact with those knowledgeable
about VA research at a VAMC and what it means to volunteer.

Secondary Product Lines

As regards to the four secondary product lines some particular comments
are needed to clarify ORCA's role. Management of the Adverse
Event/Serious Adverse Event processes was assigned to ORCA in March
2000. Dr. David Weber, Deputy Chief Officer, ORCA, has taken the lead
for administering this process and is continuing to bring some 'common
sense' to this difficult and complex issue. He processes all serious and
unexpected adverse events reported to ORCA, in accordance with
regulations and the additional guidance ORCA has provided in its
Information Letters. For the past several months he has participated in
a working group, under the aegis of OHRP with representation from
several other departments and agencies. He chairs an ORCA working group
that is charged with simplifying the adverse events reporting issues for
research. Further, guidance will soon be provided, which will harmonize
with the directions taken by OHRP and, in particular, FDA.

ORCA has been promoting the concept of dedicated quality assurance staff
for research activities. About five years ago, VISN \# 7 established a
Research Assurance and Compliance Officer (RACO) for its research
product line, and since then other VISNs have established RACOs, and,
some VAMCs have established Research Compliance Officers (RCOs). These
individuals play a role in quality assurance and quality improvement
management, monitoring compliance with regulations for the responsible
conduct of research. These individuals have performed a number of
functions such as "audits" of research protocols, routine monitoring of
the IRB activities and the conduct of education and training activities.
ORCA's Field Advisory Committee recently established a subcommittee to
document the level of activity within VAMCs and the VISNs and ascertain
what ORCA can do to assist in the further development of these RACO and
RCO positions.

ORCA, early on in its existence, established a close liaison with the VA
National Ethics Center for the purposes of collaborating on matters
concerning the ethical conduct of research. A member of ORCA's central
office staff serves on the VA's Ethics Advisory Committee, administered
by this Center. It has been addressing a number of important issues
related to research, especially in regard to clarification of some
important definitions of what should be included under the umbrella of
human subjects research.

ORCA has a direct liaison with the HRPP accreditation program sponsored
by National Committee for Quality Assurance (NCQA) and under contract
with the VA, through the Office of Research and Development. Until just
recently, ORCA has acted in a general advisory capacity, offering its
ideas and suggestions. Now that the contractor for this accreditation
program, the NCQA, has begun to notify VAMCs it has surveyed of their
accreditation statuses, the level of activity for ORCA has significantly
increased. NCQA has made determinations of accreditation status at
eleven (11) of the 23 sites it has surveyed and has issued notices of
"Not Accredited" at three (3) VAMCs and "Accredited with Conditions" at
the other eight VAMCs.

These accreditation determinations have been of great concern. ORCA
makes immediate contact with the VAMCs that are "Not Accredited" to make
a preliminary assessment of the situation. Within 48 hours a Focus
Review team, of one or two ORCA staff, is on-site to make a better
assessment as to whether human subjects enrolled in the research
protocols are adequately protected and determine, as far as possible,
whether there has been any medical harm. Also, an evaluation is made as
to whether there is any serious or egregious non-compliance with the
regulations that are designed to protect human subjects at the VAMC. If
so, ORCA may immediately suspend or restrict the VAMC's "Assurance". So
far, the three completed Focus Review reports are reassuring, but they
are insufficient to make a complete determination of the extent and
magnitude of possible regulatory non-compliance.

Each of these VAMCs that received notification of "Not Accredited" were
surveyed several months ago by NCQA, and all of them have sent NCQA
letters of intent to appeal, within 30 day limit. Filing an appeal with
NCQA "freezes" the notification until the NCQA's Appeals Panel considers
additional information provided by the VAMC and renders a final
decision. ORCA needs in depth and current information about the HRPP
activities and has created a Systematic Post-Accreditation Review
(SP-AR) to address the situations at VAMCs when NCQA gives a "Not
Accredited" designation. ORCA conducts a SP-AR review at the VAMC, the
week after the VAMC files its appeal documents with NCQA. The charter
for a SP-AR defines the purpose for these on-site reviews performed by a
team of several ORCA staff and peer research administrators. The SP-AR
is expected to assess the full scope and significance of the issues that
relate to the performance of the VAMC's HRPP. The SP-AR report,
including recommendations, is available two weeks after the team
completes its on-site review. The first SP-AR report is due the end of
this week.

During the course of the on-site review, serious and egregious
non-compliance with the regulations that protect human research subjects
may become apparent. If so, ORCA may issue a suspension or restriction
on the VAMC's "Assurance". While no SP-AR reports have been completed,
ORCA has issued a restriction on the "Assurance" at one VAMC that was
"Not Accredited" for serious, but not egregious, non-compliance with
several provisions of the "Common Rule". When the SP-AR report is
completed ORCA decides on the next steps and elicits an Action Plan from
the VAMC that has to substantially address the recommendations. Other
notifications will need to be made, as appropriate, to other regulatory
agencies such as OHRP and FDA. Eventually, when the Recommendations have
all been fully implemented to ORCA's satisfaction, the Office of
Research and Development will be notified. This will signal that
consideration might be given to a new review of the VAMC's HRPP through
the NCQA accreditation program.

Conclusion.

In summary, in the three years since the Under Secretary for Health
announced the establishment of this office, ORCA has exerted
considerable time, thought and energy to defining its scope, creating
its structure, articulating its philosophy, and delineating its product
lines. The 'die has been cast' to firmly establish ORCA as the primary
office within the VA for oversight of the VA research enterprise in
regard to the responsible conduct of research. This role and
responsibility has to be fulfilled in collaboration with the other VA
offices, the relevant other federal departments and agencies, and
non-governmental organizations. Over the next few years the foundation
that has been established in ORCA will allow for the construction of an
even more robust research enterprise where the rights of human subjects
will be continuously protected.

Again, I appreciate the invitation to discuss these important issues
with you, and I will be pleased to try and answer any questions you
might have.