Part VI: Glossary of Terms
Last revised on 1 February 2003
Most entries in this Glossary are from either the Code of Federal Regulations, Title 45, Part 46 or from the following freely available government publication: US Department of Health and Human Services, Public Health Service, National Institutes of Health, Office of Extramural Research, Office for Human Research Protection.
abuse-liablePharmacological substances that have the potential for creating abusive dependency. Abuse-liable substances can include both illicit drugs (e.g., heroin) and licit drugs (e.g., methamphetamines).
ACSMSee: American College of Sports Medicine
adverse effectAny undesirable and unintended, although not necessarily unexpected, result of therapy or other intervention (e.g., headache following spinal tap or intestinal bleeding associated with aspirin therapy).
adverse eventAny occurrence of an adverse effect; any adverse finding (including a sign, symptom, or abnormal assessment (e.g., lab, EKG)); any report regarding the quality, safety, or performance of a medical product; or any other unfavorable outcome that affects a human subject detrimentally, or that worsens, as a result of their participation in a study.
American College of Sports Medicine (ACSM)a sport-related organization of persons from a wide variety of occupations: sport science doctors, physiologists, researchers, coaches, trainers, and other practitioners and instructors. The ACSM's Mission Statement is to "promote and integrate scientific research, education, and practical applications of sports medicine and exercise science to maintain and enhance physical performance, fitness, health, and quality of life."
assuranceA formal written, binding commitment that is submitted to a federal agency in which an institution promises to comply with applicable regulations governing research with human subjects and stipulates the procedures through which compliance will be achieved.
authorized institutional officialAn officer of an institution with the authority to speak for and legally commit the institution to adherence to the requirements of the federal regulations regarding the involvement of human subjects in biomedical and behavioral research.
behavioralThe scope and diversity of research areas in the behavioral and social sciences is quite broad. Some research is readily applicable to human affairs; other studies may broaden understanding without any apparent or immediate application. Some research is designed to test hypotheses derived from theory; other research is primarily descriptive. Still other research may be directed at evaluating an intervention or social program. Behavioral research involving human subjects generates data by means of questionnaires, observation, studies of existing records, and experimental designs involving exposure to some type of stimulus or intervention.
beneficenceAn 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.
biological(1) Of or related to life or to living organisms; (2) A drug derived from a biological source.
biomedicalBiomedical research employs many methods and research designs. Studies designed to evaluate the safety, effectiveness, or usefulness of an intervention include research on therapies (e.g., drugs, diet, exercise, surgical interventions, or medical devices), diagnostic procedures (e.g., CAT scans or prenatal diagnosis through amniocentesis, chorionic villi testing, and fetoscopy), and preventive measures (e.g., vaccines, diet, or fluoridated toothpaste). Research on normal human functioning and development can include studies of the human body while exercising, fasting, feeding, sleeping, or learning, or responding to such things as stress or sensory stimulation. Subjects of some biomedical studies engage in ordinary tasks while measurement of physiological and bodily functions are made. Some biomedical studies, particularly those conducted to evaluate new therapies or treatments, use such rigorous experimental methods as random assignment to treatment and control groups.
case-control studyA study comparing persons with a given condition or disease (the cases) and persons without the condition or disease (the controls) with respect to antecedent factors (See also: retrospective studies.).
childrenPersons who have not attained the legal age for consent to treatment or procedures involved in the research, as determined under the applicable law of the jurisdiction in which the research will be conducted [45 CFR 46.402(a)].
CDCCenters for Disease Control and Prevention; an agency within the Public Health Service, Department of Health and Human Services.
cognitively impairedHaving either a psychiatric disorder (e.g., psychosis, neurosis, personality or behavior disorders, or dementia) or a developmental disorder (e.g., mental retardation) that affects cognitive or emotional functions to the extent that capacity for judgment and reasoning is significantly diminished. Others, including persons under the influence of or dependent on drugs or alcohol, those suffering from degenerative diseases affecting the brain, terminally ill patients, and persons with severely disabling physical handicaps, may also be compromised in their ability to make decisions in their best interests.
cohortA group of subjects initially identified as having one or more characteristics in common who are followed over time. In social science research, this term may refer to any group of persons who are born at about the same time and share common historical or cultural experiences.
collaborating entitiesEntities engaged in human subjects research by virtue of subject accrual, transfer of identifiable information, and/or in exchange of something of value, such as material support (e.g., money, drugs, or identifiable specimens, coauthorship, intellectual property, or credits).
compensationPayment or medical care provided to subjects injured in research; does not refer to payment (remuneration) for participation in research. (Compare: remuneration.)
competenceTechnically, a legal term, used to denote 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. (See also: incompetence, incapacity.)
confidentialityPertains 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.
conflict of interestA conflict of interest occurs when an IRB member is in a position to advance the IRB member's own interest or that of the IRB member's family or others to the potential detriment of any human subject involved in the research under review.
consentSee: informed consent.
continuing reviewThe Department of Health and Human Services (HHS) Regulations, 45 CFR 46, require at Section 46.109(e) that "an IRB shall conduct continuing review at intervals appropriate to the degree of risk, but not less than once per year " Continuing review must be substantive and meaningful. Review by the convened IRB, with recorded vote, is required unless the research is otherwise appropriate for expedited review under Section 46.110.
contractAn agreement; as used here, an agreement that a specific research activity will be performed at the request, and under the direction, of the agency providing the funds. Research performed under contract is more closely controlled by the agency than research performed under a grant. (Compare: grant.)
control (subjects) or controlsSubject(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 study. Control conditions may be concurrent (occurring more or less simultaneously with the condition under study) or historical (preceding the condition under study). When the present condition of subjects is compared with their own condition on a prior regimen or treatment, the study is considered historically controlled.
contraindicatedDisadvantageous, perhaps dangerous; a treatment that should not be used in certain individuals or conditions due to risks (e.g., a drug may be contraindicated for pregnant women and persons with high blood pressure).
cooperative protocol research program (CPRP)Programs involving multi-protocol, multi-site research, in which data from standardized protocols are pooled across institutions. These protocols, conducted or sponsored by DHHS, are approved and monitored by DHHS Protocol Review Committees that are recognized by OHRP as satisfactorily addressing the quality of human subject protections.
cooperative research projectsResearch projects covered by 45 CFR 46 that involve more than one institution. In the conduct of cooperative research projects, each institution is responsible for safeguarding the rights and welfare of human subjects and for complying with federal policy [45 CFR 46.114].
correlation coefficientA statistical index of the degree of relationship between two variables. Values of correlation coefficients range from -1.00 through zero to +1.00. A correlation coefficient of 0.00 indicates no relationship between the variables. Correlations approaching -1.00 or +1.00 indicate strong relationships between the variables. However, causal inferences about the relationship between two variables can never be made on the basis of correlation coefficients, no matter how strong a relationship is indicated.
CPRPSee: cooperative protocol research program.
cross-over designA type of clinical trial in which each subject experiences, at different times, both the experimental and control therapy. For example, half of the subjects might be randomly assigned first to the control group and then to the experimental intervention, while the other half would have the sequence reversed.
data and safety monitoring boardA committee of scientists, physicians, statisticians, and others that collects and analyzes data during the course of a clinical trial to monitor for adverse effects and other trends (such as an indication that one treatment is significantly better than another, particularly when one arm of the trial involves a placebo control) that would warrant modification or termination of the trial or notification of subjects about new information that might affect their willingness to continue in the trial.
dead fetusAn expelled
or delivered fetus that exhibits no heartbeat,
spontaneous respiratory activity, spontaneous movement of
voluntary muscles, or pulsation of
the umbilical cord (if still attached) [45 CFR 46.203(f)].
Generally, some organs, tissues, and cells (referred to collectively
as fetal tissue) remain alive for varying periods of time
after the total organism is dead.
debriefingGiving subjects previously undisclosed information about the research project following completion of their participation in research. (Note that this usage, which occurs within the behavioral sciences, departs from standard English, in which debriefing is obtaining rather than imparting information.)
Declaration of HelsinkiA code of ethics for clinical research approved by the World Medical Association in 1964 and widely adopted by medical associations in various countries. It was revised in 1975 and 1989.
departmental review bodiesCommittees or persons representing a UIUC department involved in human subjects research, and which are delegated the authority to review applications for such research if it is minimal risk and is not externally funded.
descriptive studyAny study that is not truly experimental (e.g., quasi-experimental studies, correlational studies, record reviews, case histories, and observational studies).
device (medical)See: medical device.
emancipated minorA legal status conferred upon persons who have not yet attained the age of legal competency as defined by state law (for such purposes as consenting to medical care), but who are entitled to treatment as if they had by virtue of assuming adult responsibilities such as being self-supporting and not living at home, marriage, or procreation. (See also: mature minor.)
embryoEarly stages of a developing organism, broadly used to refer to stages immediately following fertilization of an egg through implantation and very early pregnancy (i.e., from conception to the eighth week of pregnancy). (See also: fetus.)
equitableFair or just;
used in the context of selection of subjects to indicate that
the benefits and burdens of research
are fairly distributed.
ethics advisory boardAn interdisciplinary group that advises the Secretary, HHS, on general policy matters and on research proposals (or classes of proposals) that pose ethical problems.
ethnographic researchEthnography is the study of people and their culture. Ethnographic research, also called fieldwork, involves observation of and interaction with the persons or group being studied in the group's own environment, often for long periods of time. (See also: fieldwork.)
exculpatoryClearing or tending to clear from alleged fault or guilt. Statements of informed consent may not include exculpatory language that would justify, excuse, or clear an investigator from alleged fault or guilt (in the case of an adverse event), or through which the subject waives their legal rights [45 CFR 46.116].
expanded availabilityPolicy and procedure that permits individuals who have serious or life-threatening diseases for which there are no alternative therapies to have access to investigational drugs and devices that may be beneficial to them. Examples of expanded availability mechanisms include treatment INDs, parallel track, and open study protocols.
expedited reviewReview of proposed research by the IRB chair or a designated voting member or group of voting members rather than by the entire IRB. Federal rules permit expedited review for certain kinds of research involving no more than minimal risk and for minor changes in approved research.
experimentalTerm often used to denote a therapy (drug, device, procedure) that is unproved or not yet scientifically validated with respect to safety and efficacy. A procedure may be considered "experimental" without necessarily being part of a formal study (research) to evaluate its usefulness. (See also: research.)
Experimental studyA true experimental study is one in which subjects are randomly assigned to groups that experience carefully controlled interventions manipulated by the experimenter according to a strict logic allowing causal inference about the effects of the interventions under investigation. (See also: quasi-experimental study.)
FDAFood and Drug Administration;
an agency of the federal government established by Congress
in 1912 and presently part of the Department
of Health and Human Services.
Federal Policy (the)The federal policy that provides regulations for the involvement of human subjects in research. The Policy applies to all research involving human subjects conducted, supported, or otherwise subject to regulation by any federal department or agency that takes appropriate administrative action to make the Policy applicable to such research. (Also known as the "Common Rule.")
fetal materialThe placenta, amniotic fluid, fetal membranes, and umbilical cord.
fetusThe product of conception from the time of implantation until delivery. If the delivered or expelled fetus is viable, it is designated an infant [45 CFR 46.203(c)]. The term "fetus" generally refers to later phases of development; the term "embryo" is usually used for earlier phases of development. (See also: embryo.)
fieldworkBehavioral, social, or anthropological research involving the study of persons or groups in their own environment and without manipulation for research purposes (distinguished from laboratory or controlled settings). (See also: ethnographic research.)
510(k) deviceA medical device that is considered substantially equivalent to a device that was or is being legally marketed. A sponsor planning to market such a device must submit notification to the FDA 90 days in advance of placing the device on the market. If the FDA concurs with the sponsor, the device may then be marketed. 510(k) is the section of the Food, Drug and Cosmetic Act that describes premarket notification; hence the designation "510(k) device."
Food and Drug AdministrationSee: FDA.
45 CFR 46See: Title 45 Code of Federal Regulations Part 46.
full board reviewReview of proposed research at a convened meeting at which a majority of the membership of the IRB is present, including at least one member whose primary concerns are in nonscientific areas. For the research to be approved, it must receive the approval of a majority of those members present at the meeting.
general controlsCertain FDA statutory provisions designed to control the safety of marketed drugs and devices. The general controls include provisions on adulteration, misbranding, banned devices, good manufacturing practices, notification and record keeping, and other sections of the Medical Device Amendments to the Food, Drug and Cosmetic Act [21 U.S. Code §360(c) (Food, Drug and Cosmetic Act §513)].
"expressed in theories, principles, and statements of
relationships" that can be widely applied to our experiences
[the Belmont Report]. The term
"generalizable knowledge" is used to distinguish
the results of research from the results
of nonresearch activities such as "practice" activities.
"For the most part, the term 'practice' refers to interventions
that are designed solely to enhance the well-being of an individual
patient or client. By contrast, the term "research" designates
an activity designed to test an hypothesis, permit conclusions
to be drawn, and thereby to develop or contribute to generalizable
knowledge [the Belmont Report]."
genetic screeningTests to identify persons who have an inherited predisposition to a certain phenotype or who are at risk of producing offspring with inherited diseases or disorders.
grantFinancial support provided for research study designed and proposed by the principal investigator(s). The granting agency exercises no direct control over the conduct of approved research supported by a grant. (Compare: contract.)
guardianAn individual who is authorized under applicable state or local law to give permission on behalf of a child to general medical care [45 CFR 46.402(3)].
Health and Human ServicesSee: DHHS.
Helsinki DeclarationSee: Declaration of Helsinki.
Hippocratic OathAn oath of ethical professional behavior sworn by some new physicians and attributed to Hippocrates, a Greek physician of about the Fifth Century BC. A central tenet of the oath is "do no harm." Excerpts from the oath: "I swear that...I will follow that system of regimen which, according to my ability and judgment, I consider for the benefit of my patients, and abstain from whatever is deleterious and mischievous. I will give no deadly medicine to any one if asked, nor suggest any such counsel Into whatever houses I enter, I will go into them for the benefit of the sick, and will abstain from every voluntary act of mischief and corruption .Whatever, in connection with my professional practice, or not in connection with it, I see or hear in the life of men, which ought not to be spoken of I will not divulge, as all such should be kept secret."
historical controlsControl subjects (followed at some time in the past or for whom data are available through records) who are used for comparison with subjects being treated concurrently. The study is considered historically controlled when the present condition of subjects is compared with their own condition on a prior regimen or treatment.
HIVSee: human immunodeficiency virus.
human immunodeficiency virusThe virus that causes acquired immune deficiency syndrome (AIDS).
human in vitro fertilizationAny fertilization involving human sperm and ova that occurs outside the human body.
Human subjectsIndividuals whose physiologic or behavioral characteristics and responses are the object of study in a research project. Under the federal regulations, human subjects are defined as: living individual(s) about whom an investigator conducting research obtains: (1) data through intervention or interaction with the individual; or (2) identifiable private information.
IDESee: Investigational Device Exemptions.
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.
Often used as a synonym for incompetence. (See also: incompetence.)
incompetenceTechnically, a legal term meaning inability to manage one's own affairs. Often used as a synonym for incapacity. (See also: incapacity.)
INDSee: Investigational New Drug.
informed consentA 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. In giving informed consent, subjects may not waive or appear to waive any of their legal rights, or release or appear to release the investigator, the sponsor, the institution or agents thereof from liability for negligence [Federal Policy §116; 21 CFR 50.20 and 50.25].
in loco parentisIn the place of a parent; instead of a parent; charged with a parent's rights, duties, and responsibilities.
institution (2)A residential facility that provides food, shelter, and professional services (including treatment, skilled nursing, intermediate or long-term care, and custodial or residential care). Examples include general, mental, or chronic disease hospitals; inpatient community mental health centers; halfway houses and nursing homes; alcohol and drug addiction treatment centers; homes for the aged or dependent, residential schools for the mentally or physically handicapped; and homes for dependent and neglected children.
Institutional Review BoardA specially constituted review body established or designated by an entity to protect the welfare of human subjects recruited to participate in biomedical or behavioral research.
institutionalized cognitively impairedPersons who are confined, either voluntarily or involuntarily, in a facility for the care of the mentally or otherwise disabled (e.g., a psychiatric hospital, home, or school for the retarded).
interactionIncludes "communication or interpersonal contact between investigator and subject" [45 CFR 46.102(f)(2)].
interventionIncludes "both physical procedures by which data are gathered (for example, venipuncture), and manipulations for the subject or the subject's environment that are performed for research purposes" [45 CFR 46.102(f)(2)].
investigational device exemptions (IDE)Exemptions from certain regulations found in the Medical Device Amendments that allow shipment of unapproved devices for use in clinical investigations [21 CFR 812.20].
investigational new drug or deviceA
drug or device permitted by FDA
to be tested in humans but not yet determined to be safe and
effective for a particular use in the general population and
not yet licensed for marketing.
investigatorIn clinical trials, an individual who actually conducts an investigation [21 CFR 312.3]. Any interventions (e.g., drugs) involved in the study are administered to subjects under the immediate direction of the investigator. (See also: principal investigator.)
in vitroLiterally, "in glass" or "test tube;" used to refer to processes that are carried out outside the living body, usually in the laboratory, as distinguished from in vivo.
In vivoLiterally, "in the living body;" processes, such as the absorption of a drug by the human body, carried out in the living body rather than in a laboratory (in vitro).
IRBSee: Institutional Review Board.
justiceAn 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 representativeA person authorized either by statute or by court appointment to make decisions on behalf of another person. In human subjects research, 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.
major modificationA significant change to a protocol where subjects would be engaging in activities not previously approved during the review process or where there is an increased level of risk to the physical, emotional, or psychological well-being of participants, especially in relation to the loss of confidentiality.
masked study designsStudy designs comparing two or more interventions in which either the investigators, the subjects, or some combination thereof do not know the treatment group assignments of individual subjects. Sometimes called "blind" study designs. (See also: double-masked design; single-masked design.)
mature minorSomeone who has not reached adulthood (as defined by state law) but who may be treated as an adult for certain purposes (e.g., consenting to medical care). Note that a mature minor is not necessarily an emancipated minor. (See also: emancipated minor.)
medical deviceA diagnostic or therapeutic article that does not achieve any of its principal intended purpose through chemical action within or on the body. Such devices include diagnostic test kits, crutches, electrodes, pacemakers, arterial grafts, intraocular lenses, and orthopedic pins or other orthopedic equipment.
Medical device amendments (MDA)Amendments
to the Federal Food, Drug and Cosmetic Act passed in 1976
to regulate the distribution of medical
devices and diagnostic products.
mental disability(ies)See: cognitively impaired.
mentally disabledSee: cognitively impaired.
METSee: metabolic equivalent.
metabolic equivalentThe oxygen cost of energy expenditure measured at supine rest (1 MET = 3.5 ml O2 per kg of body weight per minute); multiples of MET are used to estimate the oxygen cost of activity, e.g., 3 to 5 METs for light work; more than 9 METs for heavy work [Stedman's Medical Dictionary, 26th ed.]
minimal riskA risk is minimal where the probability and magnitude of harm or discomfort anticipated in the proposed 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. For example, the risk of drawing a small amount of blood from a healthy individual for research purposes is no greater than the risk of doing so as part of routine physical examination. The definition of minimal risk for research involving prisoners differs somewhat from that given for noninstitutionalized adults. [See 45 CFR 46.303(d)]
minor modificationProtocol modifications that might include minor wording changes in the consent form, changes in compensation, time of participation, or subject recruitment, or the use of a new investigation site that is not materially different from a previously approved site. There may also be changes to other parameters whereby the investigator provides the subjects with more accurate information as a result of additional experience with the protocol.
multiple project assuranceA formal document filed with OHRP that outlines specifically how an IRB will comply with DHHS regulations for the protection of human subjects (45 CFR 46), in accordance with the federal policy.
National CommissionNational Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. An interdisciplinary advisory body, established by Congressional legislation in 1974, which was in existence until 1978, and which issued a series of reports and recommendations on ethical issues in research and medicine, many of which are now embodied in federal regulations.
National Institutes of HealthSee: NIH.
NDASee: new drug application.
NIAAANational Institute on Alcohol Abuse and Alcoholism; an institute in NIH.
NIDANational Institute on
Drug Abuse; an institute in NIH.
NIHNational Institutes of Health: a federal agency within the Public Health Service, DHHS, comprising 21 institutes and centers. It is responsible for carrying out and supporting biomedical and behavioral research.
nonaffiliated memberMember of an Institutional Review Board who has no ties to the parent institution, its staff, or faculty. This individual is usually from the local community (e.g., minister, business person, attorney, teacher, homemaker).
nontherapeutic researchResearch that has no likelihood or intent of producing a diagnostic, preventive, or therapeutic benefit to the current subjects, although it may benefit subjects with a similar condition in the future.
nonviable fetusAn expelled or delivered fetus which, although it is living, cannot possibly survive to the point of sustaining life independently, even with the support of available medical therapy [45 CFR 46.203 (d) and (e)]. Although it may be presumed that an expelled or delivered fetus is nonviable at a gestational age less than 20 weeks and weight less than 500 grams [Federal Register 40 (August 8, 1975): 33552], a specific determination as to viability must be made by a physician in each instance. (See also: viable infant.)
normal volunteersVolunteer subjects used to study normal physiology and behavior or who do not have the condition under study in a particular protocol, used as comparisons with subjects who do have the condition. "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.
null hypothesisThe proposition, to be tested statistically, that the experimental intervention has "no effect," meaning that the treatment and control groups will not differ as a result of the intervention. Investigators usually hope that the data will demonstrate some effect from the intervention, thereby allowing the investigator to reject the null hypothesis.
Nuremberg CodeA code of research ethics developed during the trials of Nazi war criminals following World War II and widely adopted as a standard during the 1950s and 1960s for protecting human subjects.
Office for Human Research Protections (OHRP)New name for the OPRR after it was moved out of the NIH and directly under the purview of the DHHS in June 2000; this office is currently responsible for implementing DHHS regulations governing human subjects research.
Office For Protection From Research Risks (OPRR)The office that, until June 2000, was within the National Institutes of Health, an agency of the Public Health Service, Department of Health and Human Services, and responsible for implementing DHHS regulations (45 CFR Part 46) governing research involving human subjects.
OHRPSee: Office for Human Research Protections.
OPRRSee: Office for Protection from Research Risks.
parentA child's adoptive or biological parent [45 CFR 46.402(d)].
phase 1, 2, 3, 4 drug trialsDifferent 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 drug trialPhase 1 trials include the initial introduction of an investigational new drug into humans. These studies are typically conducted with healthy volunteers; sometimes, where the drug is intended for use in patients with a particular disease, however, 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. The total number of subjects involved in Phase 1 investigations is generally in the range of 20-80.
phase 2 drug trialPhase
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.
Phase 3 drug trialPhase 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 and 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 patient-subjects.
Phase 4 drug trialConcurrent with marketing approval, FDA may seek agreement from the sponsor to conduct certain postmarketing (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 [21 CFR §312.85].Public Health Service. Part of the US Department of Health and Human Services, it includes FDA, NIH, CDC, SAMHSA, and HRSA.
placeboA 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 actual power of a drug.
placentaA membranous, highly vascularized organ of metabolic interchange between a fetus and its mother; partly of embryonic origin and partly of maternal origin [Stedman's Medical Dictionary, 26th ed.].
pregnancyThe 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 would presume that a living fetus was present until evidence to the contrary was 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.
premarket approvalProcess of scientific and regulatory review by the FDA to ensure the safety and effectiveness of Class III devices.
principal investigatorThe scientist or scholar with primary responsibility for the design and conduct of a research project. (See also: investigator.)
prisonerAn individual involuntarily confined in a penal institution, including persons: (1) sentenced under a criminal or civil statue; (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 incarceration in a penal institution [45 CFR 46.303(c)].
privateAffecting or belonging to private individuals rather than to the general public for public use or consumption.
prophylacticPreventive or protective; a drug, vaccine, regimen, or device designed to prevent, or provide protection against, a given disease or disorder.
prospective studiesStudies designed to observe outcomes or events that occur subsequent to the identification of the group of subjects to be studied. Prospective studies need not involve manipulation or intervention but may be purely observational or involve only the collection of data.
protocolThe 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.
radioactive drugAny substance defined as a drug in §201(b)(1) of the Federal Food, Drug and Cosmetic Act that exhibits spontaneous disintegration of unstable nuclei with the emission of nuclear particles or photons [21 CFR 310.3(n)]. Included are any nonradioactive reagent kit or nuclide generator that is intended to be used in the preparation of a radioactive drug and "radioactive biological products," as defined in 21 CFR 600.3(ee). Drugs such as carbon-containing compounds or potassium-containing salts containing trace quantities of naturally occurring radionuclides are not considered radioactive drugs.
radioactive drug research committee (RDRC)An institutional committee responsible for the use of radioactive drugs in human subjects for research purposes. Research involving human subjects that proposes to use radioactive drugs must meet various FDA requirements, including limitations on the pharmacological dose and the radiation dose. Furthermore, the exposure to radiation must be justified by the quality of the study and the importance of the information it seeks to obtain. The committee is also responsible for continuing review of the drug use to ensure that the research continues to comply with FDA requirements, including reporting obligations. The committee must include experts in nuclear medicine and the use of radioactive drugs, as well as other medical and scientific members [21 CFR 36.1].
radiopaque contrast agentsMaterials that stop or attenuate radiation that is passed through the body, creating an outline on film of the organ(s) being examined. Contrast agents, sometimes called "dyes," do not contain radioisotopes. When such agents are used, exposure to radiation results only from the X-ray equipment used in the examination. The chemical structure of radiopaque contrast agents can produce a variety of adverse reactions, some of which may be severeand possibly life-threateningin certain individuals.
radiopharmaceuticalsDrugs (compounds or materials) that may be labeled or tagged with a radioisotope. These materials are largely physiological or subpharmacological in action, and, in many cases, function much like materials found in the body. The principal risk associated with these materials is the consequent radiation exposure to the body or to specific organ systems when they are injected into the body.
random, randomly, random assignment, randomization, randomizedAssignment of subjects to different treatments, interventions, or conditions according to chance rather than systematically (e.g., as dictated by the standard or usual response to their condition, history, or prognosis, or according to demographic characteristics). Random assignment of subjects to conditions is an essential element of experimental research because it makes more likely the probability that differences observed between subject groups are the result of the experimental intervention.
recombinant DNA technology"The ability to chop up DNA, the stuff of which genes are made, and move the pieces, [which] permits the direct examination of the human genome," and the identification of the genetic components of a wide variety of disorders [Holtzman (1989), p. 1]. Recombinant DNA technology is also used to develop diagnostic screens and tests, as well as drugs and biologics for treating diseases with genetic components.
remAcronym for Roentgen Equivalent in Man; the unit of measurement for a dose of an ionizing radiation that produces the same biological effect as a unit of absorbed does (1 rad) of ordinary X-rays. One millirem is equal to 1/1000 of a rem.
remunerationPayment for participation in research. (Note: It is wise to confine use of the term "compensation" to payment or provision of care for research-related injuries.) (Compare: compensation.)
researchA systematic investigation (i.e., the gathering and analysis of information) designed to develop or contribute to generalizable knowledge.
Responsible Project Investigator (RPI)A nonvisiting member of UIUC faculty or staff who takes ultimate responsibility for the protection of the subjects and the conduct of the human subjects research described on his or her IRB application.
retrospective studiesResearch conducted by reviewing records from the past (e.g., birth and death certificates, medical records, school records, or employment records) or by obtaining information about past events elicited through interviews or surveys. Case control studies are an example of this type of research.
riskThe probability of harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study. Both the probability and magnitude of possible harm may vary from minimal to significant. Federal regulations define only "minimal risk." (See also: minimal risk.)
SAMHSASubstance Abuse and Mental Health Services Administration; includes the Center for Substance Abuse Prevention, the Center for Substance Abuse Treatment and the Center on Mental Health Services. Previously the Alcohol, Drug Abuse, and Mental Health Administration (ADAMHA). (See also: ADAMHA.)
scientific review groupA group of highly regarded experts in a given field, convened by NIH to advise NIH on the scientific merit of applications for research grants and contracts. Scientific review groups are also required to review the ethical aspects of proposed involvement of human subjects. Various kinds of scientific review groups exist, and are known by different names in different institutes of the NIH (e.g., Study Sections, Initial Review Groups, Contract Review Committees, or Technical Evaluation Committees).
secretaryA US Cabinet Officer. In the context of DHHS-conducted or -supported research, usually refers to the Secretary of Health and Human Services.
serious adverse eventAny adverse experience occurring at any dose or level of participation that results in any of the following outcomes: death, a life-threatening experience, hospitalization or prolongation of existing hospitalization, a persistent or significant disability or capacity, or a congenital anomaly or birth defect.
significant risk deviceAn investigational medical device that presents a potential for serious risk to the health, safety, or welfare of the subject.
Single-masked designTypically, a study design in which the investigator, but not the subject, knows the identity of the treatment assignment. Occasionally the subject, but not the investigator, knows the assignment. Sometimes called "single-blind design."
site visitA visit by agency officials, representatives,
or consultants to the location of a research activity to assess
the adequacy of IRB protection of human subjects or the capability of personnel to conduct the
social experimentationSystematic manipulation of, or experimentation in, social or economic systems; used in planning public policy.
sponsor (of a drug trial)A person or entity that initiates a clinical investigation of a drugusually the drug manufacturer or research institution that developed the drug. The sponsor does not actually conduct the investigation, but rather distributes the new drug to investigators and physicians for clinical trials. The drug is administered to subjects under the immediate direction of an investigator who is not also a sponsor. A clinical investigator may, however, serve as a sponsor-investigator. The sponsor assumes responsibility for investigating the new drug, including responsibility for compliance with applicable laws and regulations. The sponsor, for example, is responsible for obtaining FDA approval to conduct a trial and for reporting the results of the trial to the FDA.
sponsor-investigatorAn individual who both initiates and actually conducts, alone or with others, a clinical investigation. Corporations, agencies, or other institutions do not qualify as sponsor-investigators.
statistical significanceA determination of the probability of obtaining the particular distribution of the data on the assumption that the null hypothesis is true. Or, more simply put, the probability of coming to a false positive conclusion. If the probability is less than or equal to a predetermined value (e.g., 0.05 or 0.01), then the null hypothesis is rejected at that significance level (0.05 or 0.01).
stipulation(s)Express IRB provisions that must be satisfactorily addressed by the RPI before a human subjects research project can be approved and any involvement of human subjects in the research may begin. Under no circumstances do stipulations constitute contingent approval of the research projectapproval is neither given nor implied until the RPI has received written notice of IRB approval.
study sectionSee: scientific review group.
subjects (human)See: human subjects.
therapeutic intentThe research physician's intent to provide some benefit to improving a subject's condition (e.g., prolongation of life, shrinkage of tumor, or improved quality of life, even though cure or dramatic improvement cannot necessarily be effected.) This term is sometimes associated with Phase 1 drug studies in which potentially toxic drugs are given to an individual with the hope of inducing some improvement in the patient's condition as well as assessing the safety and pharmacology of a drug.
Title 45 of the Code of Federal RegulationsSee: 45 CFR 46.
Uniform Anatomical Gift ActLegislation adopted by all 50 States and the District of Columbia that indicates procedures for donation of all or part of a decedent's body for such activities as medical education, scientific research, and organ transplantation.
vaccineA biologic product generally made from an infectious agent or its componentsa virus, bacterium, or other microorganismthat is killed (inactive) or live-attenuated (active, although weakened). Vaccines may also be biochemically synthesized or made through recombinant DNA techniques.
variable (noun)An element or factor that the research is designed to study, either as an experimental intervention or a possible outcome (or factor affecting the outcome) of that intervention.
viableAs it pertains to a neonate, able to survive after delivery to the point of independently maintaining heartbeat and respiration. The Secretary may, from time to time, take in account medical advances and publish in the Federal Register guidelines to assist in determining whether a neonate is viable for purposes of 45 CFR 46. If a neonate is viable, then it may be included in research only to the extent permitted and in accordance with the requirements of 45 CFR 46.
Viable infantWhen referring to a delivered or expelled fetus, the term "viable infant" means likely to survive to the point of sustaining life independently, given the benefit of available medical therapy [45 CFR 46.203(d)]. This judgment is made by a physician. In accordance with DHHS regulations, the Secretary, DHHS, may publish guidelines to assist in the determination of viability. Such guidelines were published in 1975, and specify an estimated gestational age of 20 weeks or more and a body weight of 500 grams or more as indices of fetal viability [Federal Register 40 (August 8, 1975): 33552]. These indices depend on the state of present technology and may be revised periodically. (See also: nonviable fetus.)
wardA person placed by the court under the care of a guardian [Black's Law Dictionary, 5th ed.].