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 Research Terms/Definitions

These are just the beginnings of a list of Research terms and definitions. The list will slowly be expanded as time goes on.

Directory

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

A
 

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 

AAHRPP:  The Association for the Accreditation of Human Research Protection Programs

The organization that the Department of Veterans Affairs has contracted with to provide its 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 has been in place since 2/26/2002.

                                                                                   Website:  www.aahrpp.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

Adverse Event (AE): Any reaction or undesirable event that occurs in conjunction with the use of a drug, biologic product, diagnostic agent, medical device, experimental procedure, or even accepted medical treatment (if part of a research protocol), whether or not the event is considered related to the drug treatment or procedures.  Such events may be psychological, emotional, social and/or physical and include any illness, sign, symptom, or clinically significant laboratory test abnormality that has appeared or worsened during the course of the experimental study regardless of causal relationship to the drugs and procedures under study.  

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

Assent:  A child's affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent.                 
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 C

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

Children:  Persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted.

Coercion:  Coercion occurs when an overt or implicit threat of harm is intentionally presented by one person to another in order to obtain compliance.  For example, an investigator might tell a prospective subject that he or she will lose access to needed health services if he or she does not participate in the research.  This would be considered coercion.

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.

Compassionate use:  the provision of investigational drugs outside of an ongoing clinical trial to a limited number of patients who are desperately ill and for whom no standard alternative therapies are available.

Confidentiality:  a condition in which information is shared or released in a controlled manner so that information is not made available or disclosed to unauthorized individuals, entities or processes.

Conflict of Interest:  Any situation in which financial or personal obligations may compromise or present the appearance of compromising an individual’s or group’s professional judgment in conducting, reviewing, or reporting research.  Conflicts of interest may arise because of the intellectual property involved in many research discoveries or industry-academic partnerships, from financial incentives pharmaceutical or biotech companies may offer researchers or physicians for conducting trials or enrolling subjects, or due to particular role relationships.

Continuing Review: The IRB is required to review all non-exempt research projects at intervals appropriate to the degree of risk, but not less than once a year.

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D

Data Safety Monitoring Board (DSMB):  A group of experts that advise study sponsors and investigators.  The members of the DSMB serve in an individual capacity and provide their expertise and recommendations.  

Disability:  The substantial disruption of a person’s ability to conduct normal life functions.

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 E

Emergency use: A life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval.

Ethics: There are three major ethical codes that provide general ethical guidelines for the responsible conduct of research in the United States and which provide the basis for the HHS/FDA regulations on the protection of human research participants. Most institutions use the Belmont Report, Declaration of Helsinki and the Nuremberg Code.
 

Belmont Report: A report consisting of ethical principles and guidelines for protection of human research participants in research. It was issued April 18, 1979, by the National Commission for the Protection of Human Research participants of Biomedical and Behavioral Research.

Declaration of Helsinki: An international ethical code first issued in 1964 by the 18thWorld Medical Assembly in Helsinki, Finland. The Declaration contains 12 basic principles which are similar to the Nuremberg Code but represent an expansion of what constitutes acceptable research and the ethical responsibilities of investigators. Unlike the Nuremberg Code, the Declaration of Helsinki addresses the need for peer review (i.e., IRB review). It is interesting to note that the FDA will not accept foreign data unless the studies in which such data are generated are conducted in compliance with the Declaration of Helsinki (21 CFR 312.20, 46 Fed Reg 8953, Tuesday, January 17, 1981). 

Nuremberg Code: An international ethical code published in 1947 which established standards for the conduct of research involving human beings. It arose out of the Nuremberg War Crimes Trial, where 23 Nazis were charged with crimes against humanity that involved murderous pseudo medical experimentation. Twenty of the individuals charged were physicians.

Exempt:  The project is exempt from all Federal Regulations but since it is still human subject research it must be submitted to ORI for a determination that the research is exempt and approval.

Expedited Review: This means the project must receive review by the IRB chair or an experienced voting member or group of experienced voting members designated by the IRB chair rather than the entire IRB.

Expired Protocols: If the IRB has not re-approved a research study by the study's current expiration date, the research is no longer approved. While all research activities must stop, including recruitment, enrollment, interventions, interactions, and data analysis.  If an investigator believes that currently enrolled participants will be harmed by stopping interventions, the investigator must provide a list of such subjects and the reasons why participation in the research should continue.  The IRB chair, and in the case of VA research the IRB chair in consultation with the VA Medical Director, will determine which participants may continue because of an over-riding safety concern or ethical issue involved such that it was in the best interests of the individual participant to continue participating in the research interventions or interactions.  Under no circumstances will investigators be allowed to enroll new participants into expired research.  The expiration will be lifted when and if the protocol is re-approved by the IRB.

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F

FDA:   Food and Drug Administration
Regulates products, drugs, devices biologics and food/color additives (collectively known as FDA-regulated test articles).
Regulates clinical investigations involving participants, where "clinical investigation" is defined as:

• Any use of a drug, other than the use of an approved drug in the course of medical practice.

• Any use of a medical device other than the use of an approved medical device in the course of medical practice. 

• Any activity in which data will be submitted to or held for inspection by FDA.

Participant is defined as:

• An individual who is or becomes a participant in a clinical investigation, either as a recipient of the test article or as a control.  A participant may be either a healthy human or a patient.

• Or in the case of a medical device: A human who participates in a clinical investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control.  A participant may be in normal health or may have a medical condition or disease.

                                                                                   Website:  www.fda.gov

FWA:  Federal Wide Assurance
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.

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 G

Guardian:  An individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care.

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H

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.

HUD: Humanitarian Use Device

A HUD is a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year.

Human subject: Living individual(s) about whom an investigator conducting research obtains: (1) data through intervention or interaction with the individual; or (2) identifiable private information [Federal Policy 46 CFR §46.102(f)].  Under FDA regulations a human subject is defined as [FDA regulations 21 CFR §50.3(g), 21 CFR §56.102(e), 21 CFR §812.3(p):

• An individual who is or becomes a participant in research, either as a recipient of the test article or as a control.  A participant may be either a healthy human or a patient.

• Or in the case of a medical device: A human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control.  A participant may be in normal health or may have a medical condition or disease.

Intervention includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. Interaction includes communication or interpersonal contact between investigator and subject. Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects.

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I

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
An FDA requirement for use of any medical device to be used in a clinical investigation, unless exempt.  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]

Identifiable:  The identity of the individual is or may readily be ascertained by the investigator or associated with the information.

IND:   Investigational New Drug Application
An FDA requirement for any drug or biological product used in a clinical investigation, unless exempt.  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.  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: Prospective subjects must be given sufficient information about the research and its risks and benefits to reach an informed decision as to whether they will voluntarily participate.  Investigators must obtain the informed consent of prospective subjects before they can be included in research, unless waived by the IRB.  

IRB approval: the determination of the IRB that the research has been reviewed and may be conducted at an institution within the constraints set forth by institutional and federal requirements.  An IRB shall have the authority to suspend research that is not being conducted in accordance with the IRB's requirements.

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 functions of IRB review are to assure that the regulations are met and the rights and welfare of participants is protected.

The IRB has the authority to

• approve, disprove or modify

• conduct continuing review

• observe/verify changes

• suspend or terminate approval

The institution or institutional officials cannot approve research that has not been approved by the IRB.  In the VA system, the IRB is the Human Subjects Subcommittee of the Research & Development Committee. (Note:  The R&D cannot approve research that has not been approved by 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]

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 L

Legally Authorized Representative: Legally authorized representative means an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedure(s) involved in the research.  This definition is the same for DHHS and FDA.

• For VAMC Research:  A legally authorized representative is an individual or body authorized under applicable law to provide permission on behalf of a prospective subject to the subject's participation in the procedure(s) involved in the research. A legally authorized representative includes not only a person appointed as a health care agent under a Durable Power of Attorney for Health Care (DPAHC), a court appointed guardian of the person, but also next-of-kin in the following order of priority unless otherwise specified by applicable state law: spouse, adult child (18 years of age or older), parent, adult sibling (18 years of age or older), grandparent, or adult grandchild (18 years of age or older).

Life-threatening adverse experience:  An adverse experience that places the patient or subject at immediate risk of death from the reaction as it occurred.

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 M

MAP:  Multi Assessment Program*
A prospective, not a for-cause, on-site review.
Scope of a MAP encompasses 4 area

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.

Minimal risk:  The probability and magnitude of harm or discomfort in the research are not greater in and of themselves than those encountered in daily life or during the performance of routine physical or psychological examinations or tests.  In the case of research involving prisoners as participants, minimal risk is the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons.

Misconduct:  A serious deviation from accepted practice in carrying out research, or in reporting the results of research; or material failure to comply with Federal requirements affecting specific aspects of the conduct of research (e.g., the protection of human subjects and the welfare of laboratory animals).

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N

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

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O

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

Oral History:  The Oral History Association defines oral history as “a method of gathering and preserving historical information through recorded interviews with participants in past events and ways of life.”

Website:  www.alpha.dickinson.edu/oha

ORO:  Office of Research Oversight

Serves as the primary VHA office in advising the Under Secretary for Health on all matters of compliance and assurance regarding human subjects protections, animal welfare, research safety, and research misconduct.
                                                                                     Website:  www1.va.gov/oro

Orphan Drug:  An orphan drug is one for a disease which affects less than 200,000 Americans, or less than 5 per 10,000 people in a community.

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P

Parent:  A child's biological or adoptive parent.

Permission:  The agreement of parent(s) or guardian to the participation of their child or ward in research.

Phase I, II, III, and IV Drug Trials:

• Phase I (One) Drug Trials.  Phase 1 drug trials include the initial introduction of an investigational new drug into humans. These studies are typically closely monitored and are conducted with a small group of healthy volunteers (20-80); sometimes, where the drug is intended for use in patients with a particular disease, however, such patients may participate as subjects.

• Phase II (Two) Drug Trials.  Phase 2 trials include controlled clinical studies conducted to evaluate the drug’s effectiveness for a particular indication in patients with the disease or condition under study, and to determine the common short-term side effects and risks associated with the drug. These studies are typically well controlled, closely monitored, and conducted with a larger number of subjects (100-300). 

• Phase III (Three) Drug Trials.  Phase 3 drug trials involve the administration of a new drug to a larger number of patients in different clinical settings to determine its safety, effectiveness, and appropriate dosage. They are performed after preliminary evidence of effectiveness has been obtained, and are intended to gather necessary additional information about effectiveness and safety for evaluating the overall benefit-risk relationship of the drug, and to provide an adequate basis for physician labeling.  These studies are conducted with large groups of subjects (1,000-3,000).

• Phase IV (Four) Drug Trials.  Concurrent with marketing approval, the FDA may seek agreement from the sponsor to conduct certain post-marketing (Phase 4) studies to delineate additional information about the drug’s risks, benefits, and optimal use. These studies could include, but would not be limited to, studying different doses or schedules of administration than were used in Phase 2 studies, use of the drug in other patient populations or other stages of the disease, or use of the drug over a longer period of time.

Privacy:  Having control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with others.

Protocol: The formal design or plan of an experiment or research activity; specifically, the plan submitted to an IRB for review and to an agency for research support. The protocol includes a description of the research design or methodology to be employed, the eligibility requirements for prospective subjects and controls, the treatment regimen(s), and the proposed methods of analysis that will be performed on the collected data.

Physician: is defined, in this document, as anyone with a doctorate-level health science degree (M.D., D.O., O.D., DMD, DPM, PhD., etc.).

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.
                                                                                   Website: www.primr.org

Principal Investigator: The scientist or scholar with responsibility for the design and conduct of a research project.

Prisoner:  An individual involuntarily confined or detained in a penal institution.

Private information:  Information about behavior that occurs in a context which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).

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 R

Research: A systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalized knowledge, or a clinical investigation.  Under FDA regulations research is defined as any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the Food and Drug Administration.

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.
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.

Research Participant:  A living individual about whom an investigator conducting a systematic investigation, designed to develop or contribute to generalized knowledge obtains data through intervention or interaction with the individual, or identifiable private information.

• An individual who is or becomes a participant in a clinical investigation, either as a recipient of the test article or as a control.  A participant may be either a healthy human or a patient; or in the case of a medical device, a human who participates in a clinical investigation, either as an individual on whom or on whose specimen an investigational device is used or as a control.  A participant may be in the normal health or may have a medical condition or disease.

Risk: The possibility of suffering harm or loss.  A risk may be known or unknown.

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S

Serious Adverse Event: Defined as events that are fatal, life-threatening, permanently disabling, or require inpatient hospitalization or prolong an ongoing hospitalization.  Congenital anomalies/birth defects in the offspring of a subject, cancers, or overdoses are also considered serious events.

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.)

Subjects (Human):  See: Human Subjects.

Suspended Protocols: Suspension of IRB approval: An action taken by the IRB to temporarily or permanently withdraw approval for some or all research activities short of permanently withdrawing approval for all research activities.

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 T

Terminated Protocols: Termination of IRB approval: An action taken by the IRB to permanently withdraw approval for all research activities.

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U

Undue Influence: Undue influence often occurs through an offer of an excessive or inappropriate reward or other overture in order to obtain compliance.  For example, an investigator might promise psychology students extra credit if they participate in the research.  If that is the only way a student can earn extra credit, then the investigator is unduly influencing potential subjects.  If, however, the investigator offers comparable non-research alternatives for earning extra credit, the possibility of undue influence is minimized.

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 V

Viable fetus:  The fetus, after delivery, is able to survive to the point of independently maintaining heartbeat and respiration, given the benefit of available medical therapy.  If the fetus is viable, it is a child and may be involved in research to the extent permissible.

Voluntarism:  Is the expression of authentic choice in the  absence of coercion.

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