Glossary

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 18^th 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.