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.
Assurance
A renewable permit granted by the federal government to an institution
or research center to conduct clinical trials.
Biologic
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
of man.
Biotechnology
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.
Blinding
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.
Clinical Investigation
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).
Clinical Research
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.
Clinical Trial
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 efficacy.
Common Rule
1991 agreement to cover all federal-sponsored research by a common
set of regulations.
Consent Form
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.
Control Group
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.
Data
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 data.
Data Management
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.
Deception
Intentionally misleading or withholding information about nature
of experiment.
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 Committee reviews.
Demographic Data
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.
Device
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.
Documentation
All forms of records that describe or document study methods, conduct
and results, including any adverse events and actions taken.
Double-Blind
The design of a study in which neither the investigator or the
subject knows which medication (or placebo) the subject is receiving.
Drug
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
animals."
Drug Product
A finished dosage form (e.g. tablet, capsule, or solution) that
contains the active drug ingredient usually combined with inactive
ingredients.
Drug or Device Accountability Records (DAR)
Required documentation for material accountability, quantity used
and left over, and date of disposal.
Effective Dose
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 symptoms.
Efficacy
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.
Ethics Committee
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.
Exclusion Criteria
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.
Formulation
The mixture of chemicals and/or biological substances and excipients
used to prepare dosage forms.
Generic Drug
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 expired.
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.
Human Subject
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.
Inclusion Criteria
A list of criteria that must be met by all study subjects.
Informed Consent
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.
Institution
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 regulations.
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.
Investigator
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.
Investigator's Brochure
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.
Longitudinal Study
A study conducted over a long period of time.
MedWatch Program
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.
Monitor
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.
Monitoring
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.
Nuremberg Code
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 participants.
Off Label
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.
Open-Label Study
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.
Orphan Drug
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.
Over-the-Counter (OTC)
Drugs available for purchase without a physician's prescription.
Patient
Individual seeking medical care.
Pharmacoeconomics
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 metabolism.
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.
Pivotal Study
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 possible, double-blind.
Placebo
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.
Pre-Clinical Testing
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.
Protocol
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.
Protocol Amendment
Changes or clarifications made in writing to the original protocol.
Quality Assurance
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.
Randomization
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.
Recruitment
Act of enrolling subjects with the proper inclusion criteria.
Recruitment Period
Time allowed to recruit all subjects for a study.
Regulatory Affairs
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.
Research
Systematic investigation designed to develop or contribute to generalizable
knowledge. Includes Clinical Research.
Research Team
Investigator, subinvestigator and clinical research coordinator
involved with study.
Risk-Benefit Ratio
Risk to individual subject vs. potential benefits. Also called
Risk-Benefit Analysis.
Safety Reports
FDA report required by investigator for any serious and unexpected
adverse experience.
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."
Source Data
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.
Source Documentation
Location where information is first recorded including original
documents, data and records.
Sponsor
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.
Standard Treatment
The currently accepted treatment or intervention considered to
be effective in the treatment of a specific disease or condition.
Sub-investigator
Helps design and conduct investigation at a study site.
Subject/Study Subject
Participant in a study. See "Human Subject."
Telephone Report
Notification via telephone to the FDA of unexpected fatal or life
threatening advent associated with a clinical study.
Treatment IND
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 program.
Unexpected Adverse Drug Reaction
A reaction that is not consistent in nature or severity with study
application.
Vulnerable Subjects
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).
Well-being
Subject's physical and mental soundness.
Withdrawal Application
Investigator/sponsor letter to FDA requesting application withdrawal
when no additional work is envisioned.
