|
A Desk Top Guide to
Terms and Acronyms Associated with
Research Compliance & Assurance
RESEARCH: “A systematic
investigation designed to develop or contribute to generalizable
knowledge” [38 CFR 16.102 (d), 45 CFR 46.102 (d)] [Clinical
investigation means any experiment that involves a test article and one or
more human subjects… The terms research, clinical research, clinical study, study and clinical
investigation are deemed to be synonymous…
21 CFR 50/56] HUMAN SUBJECT: A living individual about whom an
investigator… conducting research obtains (1) data through intervention or
interaction with the individual, or (2) identifiable private information [38 CFR 16.102
(f), 45 CFR 46.102 (f)] [Human
subject… an individual who is or becomes a participant in research, either as
a recipient of the test article or as a control…. may be either a healthy
individual or a patient. …
21 CFR 50/56]
AAALAC Association for Assessment and Accreditation of Laboratory
Animal Care, International. A private, nonprofit organization that
promotes the humane treatment of animals in science through a voluntary
accreditation program. It is the
accrediting body for animal research programs recognized by the VA for VA
animal research. Website: www.aaalac.org AAMC Association of American Medical Colleges An organization whose mission is to
improve the health of the public by enhancing the effectiveness of academic
medicine. They support institutions,
organizations and individuals associated with academic medicine in: Educating the physician and the medical
scientist workforce; Discovering new medical knowledge; Developing innovative technologies for
prevention, diagnosis and treatment of disease; Providing health care services in
academic settings. Website:
www.aamc.org AE Adverse Event Any unfavorable or unintended event
associated with a research study. Must be reported to the IRB. [21 CFR 312.66] Serious Adverse Event (SAE) is any event
that results in death, life threatening situation, hospitalization or
prolonged hospitalization, disability, incapacity or a congenital
anomaly/birth defect. Unexpected Adverse Drug Reaction (ADR) is a reaction that is not consistent
in nature or severity with study application. ARENA Applied Research Ethics National Association A national service organization for professionals
concerned with issues relating to the protection of human subjects, the
humane care and treatment of animals, scientific misconduct, ethical
decision-making in healthcare, and other ethical issues pertaining to
biomedical and behavioral research. Its mission is the promotion of
networking among its members, the development of educational activities, the
resolution and/or amelioration of mutual problems, and the professional
advancement of its members in order to enhance the ethical conduct of research
and medicine. Website:
www.primr.org/arena.html A report issued by the National
Commission for the Protection of Human Subjects of Biomedical and Behavioral
Research in 1979. The report describes some basic ethical
principles and guidelines for the protection of human subjects participating
in research. The three ethical principles discussed
are: Respect for persons Beneficence Justice CFR Code of Federal
Regulations This is a codification of the general and
permanent rules published in the Federal Register by the Executive
departments and agencies of the Federal government. The Code is divided into 50 titles that
represent broad areas subject to Federal regulation. For research conducted at the VA, the
titles that would most frequently apply are 38 CFR – Department of Veterans Affairs 45 CFR – Department of Health and Human
Services 21 CFR – Food and Drug Administration Website:
www.access.gpo.gov/nara/cfr Common Rule The common federal policy for protecting
human subjects, promulgated in regulation and contained in the CFR, that
outlines the provisions regarding the review and approval of research, is
generally referred to as the “Common Rule”.
It was signed by 17 federal agencies, including the VA, which are thus
bound by it. The “Common Rule” for VA is in 38 CFR 16.
Comparable regulations for DHHS are 45 CFR 46 Subpart A & for FDA
are 21 CR 50 and 56. Co-Op Study VA Cooperative
Study A multi-center, centrally coordinated
clinical trial funded by VA R&D Cooperative Studies Program (122). It is a program that allows for flexible
proposal development by investigators supported by an extensive network of
professional biostatisticians, health economists, pharmacists, programmers,
and administrators. Multi-center studies require IRB and
R&D approval at each site of the study. Website:
www.va.gov/resdev/csp.htm FDA Food and Drug
Administration Regulates products, drugs, devices
biologics and food/color additives (collectively known as FDA-regulated test
articles). Regulates clinical investigations,
defined as: Involves use of a test article One or more human subjects Has the authority to suspend clinical
trials and/or disqualify clinical investigators not in compliance with FDA
regulations. Website:
www.fda.gov A formal agreement, which outlines an
institution’s commitment to conduct its research projects in an ethically
sound manner and to protect the welfare of the human subjects. Federal policy requires this for all
institutions ‘engaged’ in federally supported human subjects research. [45 CFR 46, section 103(a)] This replaces the OHRP MPA
(Multiple Project Assurance). OHRP and ORCA are working together so
that the FWA number assigned to a VAMC will function for both OHRP and the
VA. HRPP Human Research Protection Program The systematic and comprehensive approach
by an organization to ensure human subject protection in all research. The implementation of any part of the
program may be delegated to specific committees, individuals or entities
(i.e., academic affiliate or another VAMC) by the organization. IACUC Institutional Animal Care and Use Committee The local committee, at every VA medical
center with a research program involving the use of live vertebrate animals,
responsible for assuring compliance with animal research regulations and
guidelines. In
the VA system, the IACUC reports to the R&D Committee as a subcommittee. Website: http://www.iacuc.org IDE Investigational Device Exemption A FDA requirement for any new device that
is not commercially or generally available and is to be used in a clinical
investigation.New medical
products not yet been approved for marketing by the FDA require a special
status so they can be legally shipped for the purpose of conducting clinical
investigations to establish safety and efficacy. An approved investigational
device exemption (IDE) permits a device to be shipped to conduct clinical
investigations of that device. [21 CFR 812] IND Investigational New Drug Application A FDA requirement for any new drug,
antibiotic drug or biological drug that is used in a clinical
investigation. IND is an investigational new drug application
and is synonymous with “Notice of Claimed Investigational Exemption for a New
Drug,” given so the drug can be legally shipped. Investigational new drug (or investigational drug) means a new
drug or biological drug used in a clinical investigation. An investigational drug must have an IND
before it can be shipped. May also be required of an existing drug
being evaluated for a new indication, dose or route of administration. [21 CFR 312] Informed Consent A document that provides a summary of a
medical research trial and explains to a potential subject their rights as a
participant. Basic elements of Informed Consent [38 CFR
16.116a, 45 CFR Part 46.116a and 21
CFR Part 50.25a] Statement that the study involves
research; explanation of purposes of the research and expected duration of
subject’s participation; description of procedures to be followed and
identification of any procedures which are experimental. Description of risks or discomforts to
subjects. Description of benefits to subjects or to
others. Disclosure of alternative procedures, if
appropriate. Description of the extent to which
confidentiality will be maintained.(FDA requires statement that they may
inspect records.) Explanation of whom to contact if
questions arise about: a) the
research; b) the subject’s rights; or c) whom to contact if research related
injury occurs. For research involving more than minimal
risk, explanation as to whether compensation and medical treatments are
available if injury occurs Statement that participation is
voluntary, that refusal to participate involves no penalty or loss of
benefits, and that subjects may discontinue at any time. Additional elements of Informed Consent
(supplied when appropriate [38 CFR
16.116b, 45 CFR Part 46.116b and 21
CFR Part 50.25b] 1. A
statement that the particular treatment or procedure may involve risks to the
subject (or to the embryo or fetus, if the subject is or may become pregnant)
which are currently unforeseeable. 2. Anticipated
circumstances under which the subject's participation may be terminated by
the investigator without regard to the subject's consent. 3. Any
additional costs to the subject that may result from participation in the
research. 4. The
consequences of a subject's decision to withdraw from the research and
procedures for orderly termination of participation by the subject. 5. A
statement that significant new findings developed during the course of the
research which may relate to the subject's willingness to continue
participation will be provided to the subject 6. The
approximate number of subjects involved in the study. IRB Institutional Review Board A committee established by law that
oversees all research involving human subjects at an institution. The IRB is legally viewed as the protector
of integrity and ethical standards of all research and has the authority to
enforce these standards. The main function of the IRB review are
to assure that: Risks are minimized and are reasonable in
relation to anticipated benefits. There is voluntary informed consent. Rights and welfare of subjects are
protected. Membership must include at least: Five (5) members, of diverse backgrounds. One member not affiliated with the
institution. One member whose primary concerns are in
scientific areas. One member whose primary concerns are in
nonscientific areas. The IRB has the authority to: approve, disprove or modify conduct continuing review observe/verify changes suspend or terminate approval The IRB’s determination is final! The institution or institutional officials
cannot over rule. In the VA system, the IRB is the Human
Subjects Subcommittee of the Research & Development Committee.
(Note: The R&D cannot override
disapproval from the IRB. A protocol
must have approval from both the IRB and the R&D to be performed at a VA
facility.) [38 CFR 16,
21 CFR 56; 45 CFR 46; VA
Manual 3, Part 1, Chapter 9] [Note: Often referred to as the Human Subjects
Subcommittee to R&D Committee] A prospective, not a for-cause, on-site
review. Scope of a MAP encompasses 4 areas: Protection of human subjects during
recruitment and participation in research Welfare of animals in research Safety of personnel involved with research Research misconduct [Note:
There is also a MAP Self-Assessment instrument.] *Under the auspices of ORCA.
A formal agreement which outlines an
institution’s commitment to conduct its research projects in an ethically
sound manner and to protect the welfare of people and animals involved in
these projects. Filed with OPRR. Must include: Statement of principles (Obsolete –
refer to FWA) Designation of IRB(s) List of members Written procedures [45 CFR Part 46.103] Note:
FDA does require written procedures, but does not require approved
assurance. The VA central office is
in the process of issuing its own assurances to all VAMC. Some VAMC’s have ‘joint’ MPA’s with their
affiliated universities. NCQA National Committee for Quality Assurance The organization that the Department of
Veterans Affairs has contracted with to develop and implement an
accreditation program for all VAMC human research protection programs. The purpose of the program is to
strengthen the protections afforded to human subjects participating in
research at a VAMC through an ongoing independent, external review. The program is in the pilot phase and
should be on line by the summer of 2001. Website:
http://www.ncqa.org NIH National Institutes of Health Agency within DHHS with both extramural
and intramural research programs that provides funding for research, conducts
studies and funds multi-site national studies. NIH is composed of many separate
institutes dealing with specific health issues, i.e. aging, cancer, heart,
etc. Website:
www.nih.gov OHRP Office of Human Research Protection formerly OPRR -Office for Protection from Research
Risk An administrative unit within the
Department of Health and Human Services (DHHS). In June 1999, on recommendation of the
advisory committee to the Director of NIH and acceptance by HHS Secretary
Donna E. Shalala, OPRR was relocated in the Office of the Secretary to elevate
its stature and effectiveness. The primary responsibility within the
federal government is for developing and implementing the policies,
procedures and regulations required to protect human subjects and animals
involved in research sponsored by HHS. OHRP provides guidance to IRB members as
well as scientists and research administrators on the complex ethical issues
relating to the use of animals and human subjects in biomedical or behavioral
research. OHRP also has a regulator role. They monitor and evaluate an institution’s
compliance with the rules governing research subjects. Furthermore, they have the authority to
investigate and, if necessary, to require corrective action or even suspend
HHS funding to an institution until the problems are resolved. Website:
www.ohrp.osophs.dhhs.gov ORCA Office of Research
Compliance and Assurance (10R) An office in VA HQ reporting directly to
the Undersecretary for Health. Conducts its operations through several
Regional Offices. Mission: to serve as the
primary VHA component in advising the USH on all matters affecting the
integrity of research in the protecting of human subjects and animals,
promoting enhancements in the ethical conduct of research in conformance with
regulations and policies investigating any allegations of research
improprieties and scientific misconduct. Assurance is ‘prospective’ ongoing
monitoring, oversight and support. Compliance is ‘retrospective’ adherence
to policies, procedures and processes. Website:
www.va.gov/orca PI Principal
Investigator (also Clinical Investigator or Investigator) Person who develops, submits to
IRB/R&D, conducts and directs the study. Person who is ultimately responsible for
the conduct of the study. In the VA system, the PI must have at
least a 1/8 VA appointment. PRIM&R Public Responsibility in Medicine and
Research A national nonprofit organization
dedicated to educating the medical and legal professions, industry and the
public about the ethical, legal and policy dimensions of appropriate and
ethical research. IRB
101 is a comprehensive educational program that
covers the fundamentals of relevant ethical principles, federal regulations,
administrative procedures and other “best practices” that govern IRB
operations. Website:
http://www.primr.org RACO Research Assurance & Compliance Officer A VISN level person who serves as a
consultant, advisor, educator and auditor to the research services in that
VISN on research regulations and compliance issues. May also serve as the VISN contact person
for ORCA on research issues within the VISN. [Note:
VAMCs may sponsor Research Compliance Officers (RCOs)] R&D Research and Development Committee Has the responsibility to follow the
principles, objectives and functions outlined in VHA M-3, Part 1, Chapter 3, Section 3.01.
(Currently being revised and renamed VHA Handbook 1200.1). The R&D Committee is responsible for
maintaining high standards throughout the program. These standards include those assuring the scientific quality
of research projects, protection of human subjects, safety of personnel
engaged in research and animal welfare. Differs from an IRB in that it focuses
more on the scientific peer review of protocols. But, no research may be undertaken without its review and
approval. The IRB and IACUC are sub-committees of
the R&D. (ie. Protocols must have IRB and R&D
approval before they may begin.) Website:
http://www.va.gov/resdev Research Misconduct Research misconduct is
defined as fabrication, falsification, or plagiarism in proposing,
performing, or reviewing research, or in reporting research results. Fabrication
is making up data or results and recording or reporting them. Falsification
is manipulating research materials, equipment, or processes, or changing or omitting
data or results such that the research is not accurately represented in the
research record.[1] Plagiarism
is the appropriation of another person's ideas, processes, results, or words
without giving appropriate credit. Research misconduct does
not include honest error or differences of opinion. SIFT Special Inquiry
Force Team A ‘for cause’, chartered,
multidisciplinary team that goes to a facility to review records, policies
and procedures. The on-site visit generally lasts 3 days, with the final
report submitted within 30 days. SIFT’s are under the direction of ORCA. SOP Standard Operating
Procedures Detailed, written procedures for the
uniform performance of a function. For example, IRB must have and R&D
Committees should probably have written SOP’s. These must be consistent with the “Common Rule” and federal
regulations and policies pertaining to research compliance and protection of
human subjects. (Federal regulations
tell “what” to do, but not “how” to do it.
individual institutions SOP outline the “how” to do research at that
institution.) VERA Veterans Equitable Resource Allocation The mechanism used to allocate the
national VA budget among networks and facilities. There are separate components for patient care, research and
education. More details concerning VERA can be found
at: VISN Veterans Integrated
Service Networks VHA is divided into 22 networks that
provide a structural and organizational foundation for integrating services
and planning for the VA medical care system. Each network is composed of several VA
medical centers whose Chief Executive Officer reports to the Network
Director. For additional information
contact: Beth W. Gibbs, RN Research Assurance & Compliance Officer (RACO) – VISN 7 109 Bee Street phone: 843/577-5011, ext. 7399 Charleston, SC 29401 fax: 843/937-6100 e-mail: Beth.Gibbs@med.va.gov VERSION Number 1. June 18, 2001 |
