Appendix II: Glossary

**A very expanded glossary for use in informed consent can be found at a
website maintained by University of California at Davis:**

<http://ovcr.ucdavis.edu/HumanSubjects/HSDefinitions/HSGlossary.htm>

# A. Lay Language for Informed Consent

+-----------------------------------------------------------------------+
|   --------------- --------------------------------------------------- |
|   **Term**        **Definition**                                      |
|                                                                       |
|   acute           new, recent, sudden                                 |
|                                                                       |
|   adverse effect  side effect                                         |
|                                                                       |
|   assay           lab test                                            |
|                                                                       |
|   benign          not malignant, usually without serious consequences |
|                                                                       |
|   bolus           an amount given all at once                         |
|                                                                       |
|   carcinogenic    Capable of causing cancer                           |
|                                                                       |
|   catheter        a tube for withdrawing or introducing fluids        |
|                                                                       |
|   chronic         continuing for a long time                          |
|                                                                       |
|   clinical trial  an experiment with patients                         |
|                                                                       |
|   controlled      a study in which the experimental procedures are    |
|   trial           compared to standard (accepted) treatments or       |
|                   procedures                                          |
|                                                                       |
|   culture         test for infection, or organisms that could cause   |
|                   infection                                           |
|                                                                       |
|   double blind    study in which neither the investigators nor the    |
|                   subjects know which intervention the subject is     |
|                   receiving                                           |
|                                                                       |
|   dysplasia       abnormal cells                                      |
|                                                                       |
|   edema           increased fluid                                     |
|                                                                       |
|   efficacy        effectiveness                                       |
|                                                                       |
|   extravasate     to leak outside of a blood vessel                   |
|                                                                       |
|   hematoma        a bruise, a black and blue mark                     |
|                                                                       |
|   heparin lock    needle placed in the arm with blood thinner to keep |
|                   the blood from clotting                             |
|                                                                       |
|   monitor         check on, keep track of, watch carefully            |
|                                                                       |
|   morbidity       undesired result or complication                    |
|                                                                       |
|   mortality       death or death rate                                 |
|                                                                       |
|   necrosis        death of tissue                                     |
|                                                                       |
|   oncology        the study of tumors or cancer                       |
|                                                                       |
|   percutaneous    through the skin                                    |
|                                                                       |
|   placebo         a substance of no medical value, an inactive        |
|                   substance                                           |
|                                                                       |
|   PRN             as needed                                           |
|                                                                       |
|   protocol        plan of study                                       |
|                                                                       |
|   random          by chance, like the flip of a coin                  |
|                                                                       |
|   relapse         the return of a disease                             |
|                                                                       |
|   retrospective   looking back over past experience                   |
|   --------------- --------------------------------------------------- |
+-----------------------------------------------------------------------+

B. Frequently Used Terms

**Adverse Event (AE)** -- An undesirable and unintended, although not
necessarily unexpected, result arising during the course of a research
protocol.

**Adverse Event Report** -- Report to appropriate institutional
officials about adverse events.

**Advertising** -- One mechanism or method used by researchers to
recruit subjects for research studies.

**Alternatives** -- Options that exist for a subject who is thinking
about participating in research.

**ARENA** -- Applied Research Ethics National Association: a membership
organization for individuals interested in ethical issues relating to
medicine and research.

**Assent** -- Agreement by an individual not competent to give legally
valid informed consent to participate in research (e.g., a child).

**Assurance** -- A formal written, binding commitment that is submitted
to a federal agency in which an institution promises to comply with
regulations governing the protection of human subjects in research.
Assurance is the word used in the Federal Policy (Common Rule).

**Authorized Institutional Official** -- See "Institutional Official."

**Autonomy** -- See "Respect for Persons."

**Belmont Report** -- A statement of basic ethical principles governing
research involving human subjects issued in 1978 by the National
Commission for the Protection of Human Subjects of Biomedical and
Behavioral Research.

**Beneficence** -- An ethical principle discussed in the Belmont Report
that entails an obligation to protect persons from harm. The principle
of beneficence can be expressed in two general rules: (1) do not harm;
and (2) protect from harm by maximizing possible benefits and minimizing
possible risks of harm.

**Benefit** -- A valued or desired outcome; an advantage.

**Certificate of Confidentiality** -- A Certificate of Confidentiality
protects the compelled release of identifiable information about
research subjects in any legal proceeding. These documents are issued by
the DHHS and can be requested for all research, regardless of funding
source \[42 USC 241(d)\]. VA does not issue its own Certificates of
Confidentiality.

**Certification** -- The human subject regulations, in certain parts
require the Institutional Review Board (IRB) to provide a
"certification" to the government. For example, see the prisoner
regulations at 45 CFR Part 46, Subpart C.

**Chair** -- The person who leads the activities of the IRB.

**Children** -- Persons who are minors as defined by law.

**Clinical Investigation** -- Any experiment that involves a test
article and one or more human subjects that is subject to Food and Drug
Administration (FDA) requirements for research or marketing permits \[21
CFR Part 50.3(c) and 56.102(c)\].

**Clinical Trial** -- A controlled study involving human subjects
designed to contribute to generalizable knowledge about the safety
and/or effectiveness of an intervention or treatment.

**Coercion** -- The act of inducing or pressuring an individual to
consent to participate in research or to stay in research.

**Cognitive Impairment** -- Some disorder that affects cognitive or
emotional functions to the extent that capacity for judgment and
reasoning is significantly diminished.

**Common Rule** -- The short description of the Federal Policy for the
Protection of Human Subjects in Research \[56 FR 29003\].

**Compensation** -- Refers to payment or other benefits that will be
given to subjects who volunteer to participate in research protocols.

**Competence** -- The capacity to act on one's own behalf; the ability
to understand information presented; to appreciate the consequences of
acting or not acting on that information, and to make a choice.

**Confidentiality** -- Pertains to the treatment of information that an
individual has disclosed in a relationship of trust and with the
expectation that it will not be divulged to others without permission in
ways that are inconsistent with the understanding of the original
disclosure.

**Consent** -- Agreement to do something. Informed consent is agreement
to do something based upon a complete understanding of that task.

**Control** -- Subject(s) used for comparison who are not given a
treatment under study or who do not have a given condition, background,
or risk factor that is the object of the study.

**Continuing Review** -- The regulatory requirement that the
Institutional Review Board (IRB) review research at intervals not
greater than one year. The IRB may review research at more frequent
intervals \[45 CFR 46.109(e); 21 CFR 56.109(f)\].

**Data and Safety Monitoring Board (DSMB)** -- A group of people who
monitor a clinical trial for adverse events and other trends. The Data
and Safety Monitoring Board looks for any information that might warrant
modification or termination of the trial or notification of subjects
about new information that might affect their willingness to continue in
the trial.

**Deception Study** -- A research study that incorporates in the design
a technique for intentionally misleading a human subject during the
course of the study to obtain certain results. The subject is debriefed
after the study ends or after their participation ends.

**Declaration of Helsinki** -- A code of ethics for clinical research
approved by the World Medical Association. It has been widely adopted by
medical associations worldwide and has been revised numerous times.

**DHHS** -- Acronym for U.S. Department of Health and Human Services.

**DSMB** -- Acronym for Data and Safety Monitoring Board.

**Emancipated Minor** -- Defined by law, this refers to the legal status
of a person who has not yet attained the age of legal competency but who
is entitled to adult status for certain matters.

**Embryo** -- Early stages of a developing organism, broadly used to
refer to stages immediately following fertilization of an egg through
implantation and very early pregnancy.

**Exemptions** -- The Federal Policy for the Protection of Human
Subjects contains six exemptions. Research falling under one of these
exemptions is not required to undergo IRB review and the investigator is
not required to abide by the requirements for obtaining information
consent \[See 45 CFR 46.101(b)\]. FDA regulations contain an exemption
from IRB review requirements for the emergency use of a test article
\[21 CFR 56.104(c)\] and for certain taste and food quality evaluations
and consumer acceptance studies \[21 CFR 56.104(d)\].

**Expedited Review** -- Review of proposed research by the IRB chair or
a designated voting member or group of voting members rather than by the
entire convened IRB. Federal regulations permit expedited review for:
(1) certain kinds of research involving no more than minimal risk and
that fall within a category listed on the November 9, 1998 Federal
Register \[63 FR 60364\]; and, (2) for minor changes in previously
approved research \[45 CFR 46.110; 21 CFR 56.110\].

**Experiment** -- Generally, this refers to an intervention or
interaction that is unproven and not yet scientifically validated.

**FDA** -- Acronym for the Food and Drug Administration, a component of
DHHS.

**Federal Policy** -- Another short reference, along with the phrase
"Common Rule," for the Federal Policy for the Protection of Human
Subjects in Research \[56 FR 28003\].

**Federal Register** -- The government's publication in which final and
proposed rules or notices are published.

**Fetus** -- The product of conception from the time of implantation
until delivery. Refer to Subpart B of 45 CFR Part 46 for specific
findings that are required for research involving fetuses.

**FR** -- Acronym for Federal Register.

**Full Board Review** -- Review of proposed research at a convened
meeting of the IRB, at which a majority of the membership of the IRB are
present, including at least one member whose primary concerns are in a
nonscientific area \[45 CFR 46.109; 21 CFR 56.108\].

**Grant** -- Financial support provided for a research study designed
and proposed by the principal investigator. May be public or private
funds.

**Guardian** -- An individual who is authorized under applicable state
or local law to give permission on behalf of another person to
participate in research.

**Helsinki Declaration** -- See Declaration of Helsinki.

**Human in Vitro Fertilization** -- Any fertilization involving human
sperm and ova that occurs outside the human body.

**Human Protections Administrator** -- An individual who has
responsibility for day-to-day operation and implementation of the
institution's program for protecting human subjects. The institutional
title and duties of the Human Protections Administrator may vary widely
from institution to institution. For example, an institutional
compliance officer, head IRB administrator, or some other individual
might fill this role, depending upon the nature of the institution. In
VA this position may be the ACOS/R&D, the A/O, or the IRB Administrator.
In any case, the Human Protections Administrator should have detailed
knowledge of institutional protection mechanisms and be readily
available for consultation with federal officials and institutional
personnel. The IRB Chairperson should not serve as the Human Protections
Administrator.

**Human Subject** -- An individual who is the object of study in a
research project. Under the Federal Policy (Common Rule), human subject
means a living individual about whom an investigator conducting research
obtains: (1) data through intervention or interaction with the
individual; or (2) identifiable private information \[45 CFR
46.102(f)\]. Under FDA regulations, "human subject" means an individual
who is or becomes a participant in research, either as a recipient of
the test article or as a control. A subject may be either a healthy
individual or a patient \[21 CFR 50.3(g) and 56.102(e)\].

**IDE** -- Acronym for Investigational Device Exemption.

**IEC** -- Acronym for Independent Ethics Committee.

**Incapacity** -- Refers to a person's mental status and means inability
to understand information presented, to appreciate the consequences of
acting (or not acting) on that information, and to make a choice.

**Inclusion Criteria** -- The criteria that establish whether a person
is eligible to participate in a clinical trial.

**Incompetence** -- A legal term meaning inability to manage one's own
affairs.

**IND** -- Acronym for Investigational New Drug Application.

**Independent Ethics Committee (IEC)** -- The equivalent of an IRB under
the International Conference on Harmonization Guidelines for Good
Clinical Practice.

**Informed Consent** -- A person's voluntary agreement, based upon
adequate knowledge and understanding of relevant information, to
participate in research or to undergo a diagnostic, therapeutic, or
preventive procedure.

**Institution** -- Any public or private entity or agency (including
federal, state, and other agencies) \[45 CFR 46.102(b); and, 21 CFR
50.3(h) and 56.102(f)\].

**Institutional Review Board (IRB)** -- A review body established by
regulation to protect the welfare of human subjects recruited to
participate in research.

**Institutional Official** -- The individual at an institution who is
responsible for ensuring the effective administration and implementation
of the institution's system for the protection of human subjects.

**Investigational Device Exemption (IDE)** -- Exemptions from certain
regulations found in the FDA, Medical Device Amendments that allow
shipment of unapproved devices for use in clinical investigations \[21
CFR 812.20\].

**Investigational New Drug Application (IND)** -- An application to
conduct a clinical investigation involving a drug not yet determined by
the Food and Drug Administration to be safe and effective for a
particular use in the general population and not yet licensed for
marketing \[21 CFR 312.1\].

**Investigator** -- The individual who actually conducts a research
investigation \[21 CFR 50.3(d) and 56.102(h)\].

**IRB** -- Acronym for Institutional Review Board.

**Justice** -- An ethical principle discussed in the Belmont Report
requiring fairness in distribution of burdens and benefits; often
expressed in terms of treating persons of similar circumstances or
characteristics similarly.

**Legally Authorized Representative (LAR)** -- The person authorized by
law to consent to something on behalf of another person. For research
purposes, only select states permit a LAR to consent for research
participation \[45 CFR 46.102(c); 21 CFR 50.3(e)\].

**Medical College of Wisconsin IRB (MCWIRB)** -- An IRB Listserve
maintained by the Medical College of Wisconsin that is widely used and
can be found at http://www.mcwirb.org.

**Member** -- A person who is listed on the roster of an IRB as a voting
participant in IRB deliberations and actions.

**Minimal Risk (Federal Policy, DHHS Subpart A, and FDA)** -- The
probability and magnitude of harm or discomfort anticipated in the
research are not greater in and of themselves than those ordinarily
encountered in daily life or during the performance of routine physical
or psychological examinations or tests \[45 CFR 46.102(i); and, 21 CFR
50.3(k) and 56.102(j)\].

**Minimal Risk (DHHS Subpart C - prisoners)** -- 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 \[45 CFR 46. 303(d)\].

**Monitoring** -- A mechanism for keeping track of any part of the
research process: data analysis, recruitment of subjects, informed
consent process, to ensure its compliance with Institutional Review
Board dictates and the federal regulations.

**National Bioethics Advisory Commission (NBAC)** -- A Presidentially
appointed commission that issues reports and makes recommendations
relating to the protection of human subjects in research.

**NIH** -- Acronym for National Institutes of Health.

**Non-Affiliated Member** -- Member of an IRB who has no ties (and whose
immediate family members have no ties) to the parent institution, its
staff, or faculty. This individual is usually from the local community
\[45 CFR 46.107(d); and 21 CFR 56.107(d)\].

**Non-Scientist** -- Member of an IRB who does not have a scientific
background, but may be affiliated with the institution \[45 CFR
46.107(c); and, 21 CFR 56.107(c)\]. At least one non-scientist member
must be present at convened meetings to approve research \[45 CFR
46.108(b); and, 21 CFR 46.108(c)\].

**Normal Volunteers** -- Volunteer subjects in a research study who do
not have the condition under study. The 1993 Office for Protection from
Research Risks (OPRR) Guidebook defines normal volunteers as follows:
"Normal" may not mean normal in all respects. For example, patients with
broken legs (if not on medication that will affect the results) may
serve as normal volunteers in studies of metabolism, cognitive
development, and the like. Similarly, patients with heart disease but
without diabetes may be the "normals" in a study of diabetes complicated
by heart disease \[OPRR IRB Guidebook, 1993, G-9\].

**Notice of Proposed Rule-Making (NPRM)** -- Pursuant to the
Administrative Procedure Act, the government must typically issue a
notice of a proposed rule before it issues the final rule. This affords
the public the opportunity to comment on contemplated government action.

**Nuremberg Code** -- A code of research ethics developed during the
trials of Nazi war criminals following World War II and widely
recognized as a standard during the 1950s and 1960s for protecting human
subjects.

**Oral Consent** -- Typically refers to informed consent that is
obtained from a subject without use of a written informed consent
document.

**Office for Human Research Protections (OHRP)** -- An office within the
DHHS that was created in June of 2000. OHRP is responsible for the
implementation of the DHHS regulations \[45 CFR Part 46\] governing the
protection of human subjects in research.

**Office for Protection from Research Risks (OPRR)** -- Until June 2000,
this office was within the DHHS as part of the National Institutes of
Health (NIH). OPRR was responsible for the implementation of the DHHS
regulations \[45 CFR Part 46\] governing research involving human
subjects. The Office for Human Research Protections supercedes OPRR.

**Parental Permission** -- The agreement of one or both parents or a
guardian to research involving a minor \[45 CFR 46.402(c)\].

**Phase 1,2,3,4, Clinical Trials** -- Different stages of testing drugs
in humans, from first application in humans (Phase 1) through limited
and broad clinical tests (Phase 3), to postmarketing studies (Phase 4).

**Phase 1 Clinical Trials** -- Phase 1 trials include the initial
introduction of an investigational new drug into humans. These studies
are typically conducted with healthy volunteers; however, where the drug
is intended for use in patients with a particular disease, such patients
may participate as subjects. Phase 1 trials are designed to determine
the metabolic and pharmacological actions of the drug in humans, the
side effects associated with increasing doses (to establish a safe dose
range), and, if possible, to gain early evidence of effectiveness. They
are typically closely monitored. The ultimate goal of Phase 1 trials is
to obtain sufficient information about the drug's pharmacokinetics and
pharmacological effects to permit the design of well-controlled,
sufficiently valid Phase 2 studies. Other examples of Phase 1 studies
include studies of drug metabolism, structure-activity relationships,
and mechanisms of actions in humans, as well as studies in which
investigational drugs are used as research tools to explore biological
phenomena or disease processes. Typically, Phase 1 investigations
involve anywhere from 20-80 subjects \[21 CFR 312.21(a)\].

**Phase 2 Clinical 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 relatively small number of
patients, usually involving no more than several hundred subjects \[21
CFR 312.21(d)\].

**Phase 3 Clinical Trials** -- Phase 3 trials involve the administration
of a new drug to a larger number of patients in different clinical
settings to determine its safety, efficacy, 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. In Phase 3 studies, the drug is used the way it would be
administered when marketed. When these studies are completed and the
sponsor believes that the drug is safe and effective under specific
conditions, the sponsor applies to the FDA for approval to market the
drug. Phase 3 trials usually involve several hundred to several thousand
subjects \[21 CFR 312.21(c)\].

**Phase 4 Clinical Trials** -- The FDA, when it gives market approval,
may seek an agreement from the sponsor to conduct certain postmarketing
studies to ascertain 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 \[21 CFR 312.85\].

**Public Health Service (PHS)** -- A division within the DHHS. PHS
agencies include the National Institutes of Health, Centers for Disease
Control, the Indian Health Service, and the Substance Abuse and Mental
Health Services Administration.

**Placebo** -- In biomedical research, a chemically inert substance
given in the guise of medicine for its psychologically suggestive
effect; used in controlled clinical trials to determine whether
improvement and side effects may reflect imagination or anticipation
rather than the actual power of a drug. In social and behavioral
research, a condition that mimics the experimental context but does not
include the experimental manipulation under study. As in biomedical
research, the control condition is used to confirm that observed effects
are the result of the experimental manipulation rather than the research
context itself.

**Pregnancy** -- The period of time from confirmation of implantation of
a fertilized egg within the uterus until the fetus has entirely left the
uterus (i.e., has been delivered). Implantation is confirmed through a
presumptive sign of pregnancy such as missed menses or a positive
pregnancy test \[45 CFR 46.203(b)\]. This confirmation may be in error,
but, for research purposes, investigators must presume that a living
fetus is present until evidence to the contrary is clear. Although
fertilization occurs a week or more before implantation, the current
inability to detect the fertilization event or the presence of a newly
fertilized egg makes a definition of pregnancy based on implantation
necessary.

**Principal Investigator (PI)** -- The person with primary
responsibility for design and conduct of a research project.

**Public Responsibility in Medicine and Research (PRIM&R)** -- A
non-profit organization that organizes conferences, workshops, and other
activities to further the protection of human subjects in research.

**Prisoner** -- An individual involuntarily confined or detained in a
penal institution, including persons: (1) sentenced under a criminal or
civil statute; (2) detained pending arraignment, trial, or sentencing;
and (3) detained in other facilities (e.g., for drug detoxification or
treatment of alcoholism) under statutes or commitment procedures
providing such alternatives to criminal prosecution; or (4) incarcerated
in a penal institution \[45 CFR 46.303(c)\].

**Prisoner Representative** -- A member of an IRB who has appropriate
background and experience to represent the interests and concerns of an
individual who is involuntarily confined to an institution \[45 CFR
46.304(b)\].

**Privacy** -- Concealment from others of information about oneself.

**Protocol** -- The formal design or plan of an experiment or research
activity. 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.

**Random Assignment** -- Assignment of subjects to different treatments,
interventions, or conditions according to chance.

**Recruitment** -- The process of enrolling human subjects in research
protocols.

**Research** -- Under the Federal Policy and the DHHS Subpart A,
research is a systematic investigation designed to develop or contribute
to generalizable knowledge \[45 CFR 46.102(d)\]. Under FDA regulations,
"research" is synonymous with "clinical investigation" \[21 CFR
56.102(c)\].

**Respect for Persons** -- A principle enunciated in the Belmont Report
stating that (1) individuals should be treated as autonomous agents,
and, (2) persons with diminished autonomy are entitled to protection.

**Risk** -- The probability of harm or injury occurring as a result of
participation in a research study.

**Secretary** -- In the context of the federal regulations pertaining to
the protection of human subjects in research, refers to the head of a
federal agency \[45 CFR 46.102(a)\].

**Site Visit** -- Typically refers to a visit from a federal office to
ensure the entity is complying with federal regulations.

**Sponsor** -- Typically refers to the entity that initiates a clinical
investigation but does not actually conduct the investigation \[21 CFR
50.3(e) and 56.102(j)\].

**Sponsor-Investigator** -- An individual who both initiates and
actually conducts a clinical investigation \[21 CFR 50.3(f) and
56.102(k)\].

**Subjects** -- See "Human Subject."

**Subpart A** -- The DHHS codification of the Federal Policy for the
Protection of Human Subjects in Research is found in Subpart A of 45 CFR
Part 46.

**Subpart B** -- Subpart B of the DHHS regulations \[45 CFR Part 46\]
contains additional protections for pregnant women and fetuses that are
involved in research, and references human in vitro fertilization
research.

**Subpart C** -- Subpart C of the DHHS regulations \[45 CFR Part 46\]
contains additional protections for prisoners who are involved in
research.

**Subpart D** -- Subpart D of the DHHS regulations \[45 CFR Part 46\]
contains additional protections for children who are involved in
research.

**Surveys** -- Studies designed to obtain information from human
subjects through written questionnaires, telephone interviews,
door-to-door canvassing, or similar procedures.

**Suspension** -- Typically used in the context of a federal agency
taking action against an institution. For example, the Office for Human
Research Protections can suspend an Assurance, preventing the
institution from continuing to conduct studies supported with federal
funds.

**Test Article** -- Any drug, biological product for human use, medical
device for human use, human food additive, color additive, electronic
product subject to FDA regulations under 42 USC 262, 263b-263N \[21 CFR
50.3(j) and 56.102(e)\].

**Tuskegee** -- Often used erroneously to refer to the U.S. Public
Health Service Syphilis Study in Tuskegee, Alabama.

**Undue Influence** -- This refers to a prohibition in the Common Rule
that investigators not use unfair measures or influence to enroll
persons in research \[45 CFR 46.116\].

**Unaffiliated Member** -- See "Non-affiliated member"

**Unanticipated Problems Involving Risks to Subjects or Others** -- This
is a regulatory phrase which requires reporting of this event to the IRB
and to the government \[45 CFR 46.103(d)(5); 21 CFR 56.108(b)\].

**Voluntary** -- Free of coercion, duress, or undue influence.

**Vulnerable population** -- This is a regulatory phrase which refers to
a group of people who have some condition or situation that makes them
more susceptible to coercion or undue influence \[45 CFR 46.107(a)\].

**Waiver of Informed Consent** -- An action taken by the IRB permitting
the investigator to pursue research involving human subjects without
obtaining informed consent \[45 CFR 46.116(d)\].