Adverse Drug Reaction (ADR)
An unintended reaction to a drug taken at doses normally used in man
for prophylaxis, diagnosis, or therapy of disease, or for the
modification of physiological function. In clinical trials, an ADR would
include any injuries by overdosing, abuse/dependence, and unintended
interactions with other medicinal products.
Adverse Event (AE)
A negative experience encountered by an individual during the course
of a clinical trial, that is associated with the drug. An AE can include
previously undetected symptoms, or the exacerbation of a pre-existing
condition. When an AE has been determined to be related to the
investigational product, it is considered an Adverse Drug Reaction.
Adverse Event Reports
Investigator reports of all serious and adverse events, injury and
deaths given to the sponsor, the IRB and the FDA.
A renewable permit granted by the federal government to an
institution or research center to conduct clinical trials.
A virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood
component or derivative, allergenic product, or analogous product
applicable to the prevention, treatment or cure of diseases or injuries
Any technique that uses living organisms, or substances from
organisms, biological systems, or processes to make or modify a product
or process, to change plants or animals, or to develop micro-organisms
for specific uses.
The process through which one or more parties to a clinical trial are
unaware of the treatment assignments. In a single-blinded study, usually
the subjects are unaware of the treatment assignments. In a
double-blinded study, both the subjects and the investigators are
unaware of the treatment assignments. Also, in a double-blinded study,
the monitors and sometimes the data analysts are unaware. "Blinded"
studies are conducted to prevent the unintentional biases that can
affect subject data when treatment assignments are known.
Case Report Form (CRF)
A record of pertinent information collected on each subject during a
clinical trial, as outlined in the study protocol.
Certified Research Coordinator (CCRC)
CRC with >2 years experience and with certification earned by
passing required program and exam.
A systematic study designed to evaluate a product (drug, device, or
biologic) using human subjects, in the treatment, prevention, or
diagnosis of a disease or condition, as determined by the product's
benefits relative to its risks. Clinical investigations can only be
conducted with the approval of the Food and Drug Administration (FDA).
Study of drug, biologic or device in human subjects with the intent
to discover potential beneficial effects and/or determine its safety and
efficacy. Also called clinical study and clinical investigation. Note
that in this manual, this term is used in its narrow sense as used by
the FDA. Thus, it does not encompass all the research that is carried
out in the clinical setting (e.g., health services research).
Clinical Research Associate (CRA)
Person employed by the study sponsor or CRO to monitor a clinical
study at all participating sites. See also, monitor.
Clinical Research Coordinator (CRC)
Site administer for the clinical study. Duties are delegated by the
investigator. Also called research, study or healthcare coordinator, and
data manager, research nurse or protocol nurse.
Clinical Study Materials
Study supplies (i.e., study test article, laboratory supplies, case
report forms) provided by the study sponsor to the investigator.
Any investigation in human subjects intended to determine the
clinical pharmacological, pharmacokinetic, and/or other pharmacodynamic
effects of an investigational agent, and/or to identify any adverse
reactions to an investigational agent to assess the agent's safety and
1991 agreement to cover all federal-sponsored research by a common
set of regulations.
A document explaining all relevant study information to assist the
study volunteer in understanding the expectations and requirements of
participation in a clinical trial. This document is presented to and
signed by the study subject.
Contract Research Organization (CRO)
A person or an organization (commercial, academic or other)
contracted by the sponsor to perform one or more of a sponsor's
study-related duties and functions.
A comparison group of study subjects who are not treated with the
investigational agent. The subjects in this group may receive no
therapy, a different therapy, or a placebo.
This term is legally defined according to the institution. It
generally refers to recorded information regardless of form. Most
institutions hold title to data while researchers have rights to access
The process of handling the data gathered during a clinical trial.
May also refer to the department responsible for managing data entry and
database generation and/or maintenance.
Intentionally misleading or withholding information about nature of
Declaration of Helsinki
A series of guidelines adopted by the 18th World Medical
Assembly in Helsinki, Finland in 1964. The Declaration addresses ethical
issues for physicians conducting biomedical research involving human
subjects. Recommendations include the procedures required to ensure
subject safety in clinical trials, including informed consent and Ethics
Refers to the characteristics of study participants, including sex,
age, family medical history, and other characteristics relevant to the
study in which they are enrolled.
An instrument, apparatus, implement, machine, contrivance, implant,
in vitro reagent, or other similar or related article, including
any component, part or accessory, which is intended for use in the
diagnosis, cure, treatment or prevention of disease. A device does not
achieve its intended purpose through chemical action in the body and is
not dependent upon being metabolized to achieve its purpose.
All forms of records that describe or document study methods, conduct
and results, including any adverse events and actions taken.
The design of a study in which neither the investigator or the
subject knows which medication (or placebo) the subject is receiving.
As defined by the Food, Drug and Cosmetic Act, drugs are "articles
(other than food) intended for the use in the diagnosis, cure,
mitigation, treatment, or prevention of disease in man or other animals,
or to affect the structure or any function of the body of man or other
A finished dosage form (e.g. tablet, capsule, or solution) that
contains the active drug ingredient usually combined with inactive
Drug or Device Accountability Records (DAR)
Required documentation for material accountability, quantity used and
left over, and date of disposal.
The dose of an investigational agent that produces the outcome
considered "effective," as defined in the study protocol. This could
mean a cure of the disease in question or simply the mitigation of
A product's ability to produce beneficial effects on the duration or
course of a disease. Efficacy is measured by evaluating the clinical and
statistical results of clinical tests.
An independent group of both medical and non-medical professionals
who are responsible for verifying the integrity of a study and ensuring
the safety, integrity, and human rights of the study participants.
Refers to the characteristics that would prevent a subject from
participating in a clinical trial, as outlined in the study protocol.
Family Educational Rights and Privacy Act (FERPA)
Covers rights of parents of school children regarding reviewing,
amending and disclosing educational records.
Food and Drug Administration (FDA)
Within the Department of Health and Human Services. Enforces Food,
Drug and Cosmetics Act and related federal public health laws. Grants
IND, IDE, PMA and NDA approvals.
Food Drug and Cosmetic Act (FD & C Act )
States only drugs, biologics and devices proven safe and effective
can be marketed.
FDA Form 1572
A list of commitments and requirements by the FDA for each
investigator performing drug/biologics studies. Also referred to as a
statement of the investigator.
The mixture of chemicals and/or biological substances and excipients
used to prepare dosage forms.
A medicinal product with the same active ingredient, but not
necessarily the same inactive ingredients as a brand-name drug. A
generic drug may only be marketed after the original drug's patent has
Good Clinical Practice (GCP)
International ethical and scientific quality standard for designing,
conducting, monitoring, recording, auditing, analyzing and reporting
studies. Insures that the data reported is credible and accurate, and
that subject's rights and confidentiality are protected.
A patient or healthy individual participating in a research study. A
living individual about whom an investigator obtains private information
or data through intervention or interaction.
A list of criteria that must be met by all study subjects.
The voluntary verification of a patient's willingness to participate
in a clinical trial, along with the documentation thereof. This
verification is requested only after complete, objective information has
been given about the trial, including an explanation of the study's
objectives, potential benefits, risks and inconveniences, alternative
therapies available, and of the subject's rights and responsibilities in
accordance with the current revision of the Declaration of Helsinki.
Location of research. Retains ultimate responsibility for human
subject regulation compliance.
Institutional Review Board (IRB)
An independent group of professionals designated to review and
approve the clinical protocol, informed consent forms, study
advertisements, and patient brochures, to ensure that the study is safe
and effective for human participation. It is also the IRB's
responsibility to ensure that the study adheres to the FDA's
Investigational New Drug Application (IND)
The petition through which a drug sponsor requests the FDA to allow
human testing of its drug product.
Investigational Device Exemption (IDE)
Exemption from FD & C Act to study investigational medical devices.
A medical professional, usually a physician but may also be a nurse,
pharmacist or other health care professional, under whose direction an
investigational drug is administered or dispensed. A principal
investigator is responsible for the overall conduct of the clinical
trial at his/her site.
Relevant clinical and non-clinical data compiled on the
investigational drug, biologic or device being studied.
In Vitro Testing
Non-clinical testing conducted in an artificial environment such as a
test tube or culture medium.
In Vivo Testing
Testing conducted in living animal and human systems.
A study conducted over a long period of time.
An FDA program designed to monitor adverse events (AE) from drugs
marketed in the U.S. Through the MedWatch program, health professionals
may report AEs voluntarily to the FDA. Drug manufacturers are required
to report all AEs brought to their attention.
Person employed by the sponsor or CRO who reviews study records to
determine that a study is being conducted in accordance with the
protocol. A monitor's duties may include, but are not limited to,
helping to plan and initiate a study, and assessing the conduct of
studies. Monitors work with the clinical research coordinator to check
all data and documentation from the study. See also CRA.
Reviewing a clinical study, ensuring conduct, proper records and
reports are performed as stated in the clinical protocol, standard
operating procedures, GCP and by regulatory requirements.
Multiple Project Assurance
Permit given to institution for multiple federally funded research
grants for a specified period of time. States institution retains
responsibility for all research involving humans and that the
institution must have an established IRB.
National Research Act
Act created by the National Commission for Protection of Human
Subjects of Biomedical and Behavioral Research in 1974 and mandated
review of studies by institutional review boards and subject protection
by informed consent.
National Institutes of Health (NIH)
Agency within DHHS that provides funding for research, conducts
studies and funds multi-site national studies.
New Drug Application (NDA)
The compilation of all non-clinical, clinical, pharmacological,
pharmacokinetic and stability information required about a drug by the
FDA in order to approve the drug for marketing in the U.S.
As a result of the medical experimentation conducted by Nazis during
World War II, the U.S. Military Tribunal in Nuremberg in 1947 set forth
a code of medical ethics for researchers conducting clinical trials. The
code is designed to protect the safety and integrity of study
The unauthorized use of a drug for a purpose other than that approved
of by the FDA.
Office for Human Research Protection (OHRP)
A federal government agency that issues Assurances and overseas
compliance of regulatory guidelines by research institutions.
A study in which all parties, (patient, physician and study
coordinator) are informed of the drug and dose being administered. In an
open-label study, none of the participants are given placebos. These are
usually conducted with Phase I & II studies.
A designation of the FDA to indicate a therapy developed to treat a
rare disease (one which afflicts a U.S. population of less than 200,000
people). Because there are few financial incentives for drug companies
to develop therapies for diseases that afflict so few people, the U.S.
government offers additional incentives to drug companies (i.e. tax
advantages and extended marketing exclusivity) that develop these drugs.
Drugs available for purchase without a physician's prescription.
Individual seeking medical care.
The study of cost-benefit ratios of drugs with other therapies or
with similar drugs. Pharmacoeconomic studies compare various treatment
options in terms of their cost, both financial and quality-of-life. Also
referred to as "outcomes research".
Phase I Study
The first of four phases of clinical trials, Phase I studies are
designed to establish the effects of a new drug in humans. These studies
are usually conducted on small populations of healthy humans to
specifically determine a drug's toxicity, absorption, distribution and
Phase II Study
After the successful completion of phase I trials, a drug is then
tested for safety and efficacy in a slightly larger population of
individuals who are afflicted with the disease or condition for which
the drug was developed.
Phase III Study
The third and last pre-approval round of testing of a drug is
conducted on large populations of afflicted patients. Phase III studies
usually test the new drug in comparison with the standard therapy
currently being used for the disease in question. The results of these
trials usually provide the information that is included in the package
insert and labeling.
Phase IV Study
After a drug has been approved by the FDA, phase IV studies are
conducted to compare the drug to a competitor, explore additional
patient populations, or to further study any adverse events.
Usually a phase III study which presents the data that the FDA uses
to decide whether or not to approve a drug. A pivotal study will
generally be well-controlled, randomized, of adequate size, and whenever
An inactive substance designed to resemble the drug being tested. It
is used as a control to rule out any psychological effects testing may
present. Most well-designed studies include a control group which is
unwittingly taking a placebo.
Before a drug may be tested on humans, pre-clinical studies must be
conducted either in vitro but usually in vivo on animals
to determine that the drug is safe.
Protection of Pupil Rights Amendment (PPRA)
Department of Education regulation that states that surveys,
questionnaires and instructional materials for school children must be
inspected by parents/guardians.
A detailed plan that sets forth the objectives, study design, and
methodology for a clinical trial. A study protocol must be approved by
an IRB before investigational drugs may be administered to humans.
Changes or clarifications made in writing to the original protocol.
Systems and procedures designed to ensure that a study is being
performed in compliance with Good Clinical Practice (GCP) guidelines and
that the data being generated is accurate.
Study participants are usually assigned to groups in such a way that
each participant has an equal chance of being assigned to each treatment
(or control) group. Since randomization ensures that no specific
criteria are used to assign any patients to a particular group, all the
groups will be equally comparable.
Act of enrolling subjects with the proper inclusion criteria.
Time allowed to recruit all subjects for a study.
In clinical trials, the department or function that is responsible
for ensuring compliance with government regulations and interacts with
the regulatory agencies. Each drug sponsor has a regulatory affairs
department that manages the entire drug approval process.
Systematic investigation designed to develop or contribute to
generalizable knowledge. Includes Clinical Research.
Investigator, subinvestigator and clinical research coordinator
involved with study.
Risk to individual subject vs. potential benefits. Also called
FDA report required by investigator for any serious and unexpected
Serious Adverse Event (SAE)
Any adverse event (AE) that is fatal, life-threatening, permanently
disabling, or which results in hospitalization, initial or prolonged.
Single Project Assurance
Permit given to institution for single grant in compliance with
government standards. See "assurance."
All information contained in original records and certified copies of
results, observations or other facets required for the reconstruction
and evaluation of the study that is contained in source documents.
Location where information is first recorded including original
documents, data and records.
Individual, company, institution or organization taking
responsibility for initiation, management and financing of study.
Standard Operating Procedure (SOP)
Official, detailed, written instructions for the management of
clinical trials. SOPs ensure that all the functions and activities of a
clinical trial are carried out in a consistent and efficient manner.
The currently accepted treatment or intervention considered to be
effective in the treatment of a specific disease or condition.
Helps design and conduct investigation at a study site.
Participant in a study. See "Human Subject."
Notification via telephone to the FDA of unexpected fatal or life
threatening advent associated with a clinical study.
A method through which the FDA allows seriously ill patients with no
acceptable therapeutic alternative to access promising investigational
drugs still in clinical development. The drug must show "sufficient
evidence of safety and effectiveness." In recent decades many AIDs
patients have been able to access unapproved therapies through this
Unexpected Adverse Drug Reaction
A reaction that is not consistent in nature or severity with study
Group/individual that cannot give informed consent because of limited
autonomy (e.g., children, mentally ill and prisoners). Also refers to
subjects who may be unduly influenced to participate (e.g., students,
subordinates and patients).
Subject's physical and mental soundness.
For a comprehensive list of COPD Clinical Trials
Investigator/sponsor letter to FDA requesting application withdrawal
when no additional work is envisioned
For General information on clinical trials -