Academic Research Organization
Adverse Drug Experience
Adverse Drug Reaction
Adverse Event
Code of Federal Regulations
Case Report Form
Contract Research Organization
Data and Safety Monitoring Board
Food and Drug Administration
Good Clinical Practice
Good Laboratory Practice
Good Manufacturing Practice
lnternational Conference on Harmonization
Investigational Device Exemption
Investigational New Drug Application
Institutional Review Board
NEW Drug Application
Principal Investigator
Serious Adverse Event
Site Management Organization
Standard Operating Procedure


Academic Research Organization (ARO)
An academic organization that sponsors a trial or is contracted by the sponsor to perform one or more of a sponsor’s trial-related activities, including but not limited to: protocol development and design, recruitment of investigators, study management and coordination, monitoring, data management, and statistical analysis. An ARO uses academic leaders and/or clinicians to provide leadership and may be affiliated with an academic institution.
Adverse Drug Reaction (ADR)
A response to an investigational drug that occurs at any dose and is noxious and unintended. A response to a marketed drug that is noxious, unintended, and that occurs at doses normally used for prophylaxis, diagnosis, therapy, or for modification of physiological function. Adverse drug reactions can be expected or unexpected.
Adverse Event (AE)
Any unfavorable change that may affect a subject during or after a clinical trial; the change is not necessarily caused by the investigational product. Includes physical signs and symptoms, abnormal laboratory findings, changes in vital signs, a new condition or illness, or the worsening of a condition or illness that was present before product use. Also called adverse experience. When a causal relationship has been established between a product and the AE, the AE is referred to as an adverse drug reaction (causal relationship with a drug) or an adverse device effect (causal relationship with a medical device).
See Protocol Amendment.
An agreement to participate in clinical research. Assent may be required from children who are of adequate age and emotional maturity to understand the concept of the study but are incapable of grasping all the details of the study.
A legally binding written document that requires a public or private institution to comply with applicable federal minimum standards for the protection of human subjects in research.
An independent and systematic review of study data, associated records, protocol procedures, study conduct, and interim or final study reports to determine whether the information is accurate and whether the study has been carried out in compliance with the protocol, standard operating procedures, good clinical practice, and applicable regulations. Sponsors may conduct internal audits, audits of AROs/CROs designated to perform sponsor responsibilities, and audits of investigative sites participating in a clinical trial. Audits may also be performed to review manufacturing practices, laboratory processes, and storage facilities.
Audit Trail
Documentation of events that allows auditors to identify the original source of the data and track the path of changes made to the original documentation.
Belmont Report
Report issued by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report identifies basic ethical principles for the conduct of clinical research.
A valued, favorable, or desired outcome.
A procedure in which one or more parties in a clinical trial are kept unaware of the treatment assignments. In a single-blind study, the subjects are unaware of the treatment assignments, while in a double-blind study, the subjects, investigators, and study personnel are unaware of the treatment assignments. In case of emergencies that require knowledge of the treatment assignment, mechanisms exist to unblind the code, commonly called breaking the blind. An open or open label study has no blinding of the subject or the study staff.
Case Report Form (CRF)
A printed, optical, or electronic document used to record protocol-required information for each subject in the study.
Causality Assessment
A determination of whether an adverse event may have been caused by or related to an investigational product. Examples of categories for causality include: (1) not a reasonable possibility-it is unlikely the adverse event was caused by the investigational product, and (2) a reasonable possibility-the adverse event may have been caused by the investigational product. Further categorization sometimes includes (1) unrelated, (2) remotely related, (3) possibly related, (4) probably related, and (5) definitely related.
Children (in clinical research)
Individuals who are under the legal age to give consent for participation in a clinical research study. The assent of children who are considered of adequate age and emotional maturity may be required for study participation. Specific legal age is determined under the applicable laws in the jurisdiction where the research isbeing conducted.
Clinical Trial
Systematic study conducted in human subjects.
Clinical Trial Agreement
A letter outlining the terms of the contract between the sponsor and the University. Contents of a letter of agreement usually include the terms of the study, including the start and anticipated end of the study, payment methods, data confidentiality, publishing requirements, and product liability issues.
Code of Federal Regulations (CFR)
An annually revised documentation of the general and permanent rules published in the Federal Register. The code is divided into 50 titles that represent broad areas subject to federal regulations. Title 21 of the CFR includes most of the regulations affecting the discovery, development, approval, and marketing of drugs and devices.
Assigning data such as adverse events and medications to categories. This allows data to be grouped and retrieved for analysis. Codes may be a group of letters, numbers, or symbols with associated rules for usage.
Adherence to protocol requirements, standards of good clinical practice, and applicable regulations.
Prevention of unauthorized disclosure of a sponsor’s proprietary information or of a subject’s identity and personal medical information.
Contract Research Organization (CRO)
An organization contracted by the sponsor to perform one or more of a sponsor’s trial-related activities, including but not limited to: protocol development and design, recruitment of investigators, study management and coordination, monitoring, data management, and statistical analysis. Compare to Academic Research Organization (ARO).
Consent Form
See Informed Consent.
Control Group
The group of patients who receive the standard treatment (no treatment or placebo) and who are compared to the group of patients receiving the investigational treatment.
Curriculum Vitae (CV)
A summary of an investigator’s education, training, and experience; similar to a resume.
Data and Safety Monitoring Board (DSMB)
An independent committee of clinicians, statisticians, ethicists, and other specialists who assess the progress of a trial, its safety, and its efficacy at specified intervals. The committee can make recommendations that a study be continued, modified, or stopped based on the data reviewed.
Data Forms
Forms used to record patient data from original source documents. Including but not, limited to: case report forms, enrollment forms, serious adverse event forms, and follow-up forms. Also referred to as patient data forms.
Declaration of Helsinki
A statement of ethical principles developed by the 18th World Medical Assembly, Helsinki, Finland, June 1964, to provide guidance to physicians who practice biomedical research involving human subjects. The declaration sets forth the requirements for the ethical treatment of patients and research volunteers. It mandates obtaining informed consent and stresses the overriding importance of the subjects’ needs as individuals over the needs of science and society. The basic thrust of the Declaration of Helsinki is incorporated in the Code of Federal Regulations (21 ยง CFR 312).
Double-Blind Study
See Blinding.
Drug Accountability
Records of the receipt and disposition of investigational drug supplies.
Eligibility Criteria
Rules for selecting subjects to participate in a clinical trial. Participants must meet all of the inclusion criteria for trial entry and not have any of the exclusion criteria.
An indicator measured to assess the effect of a treatment or therapy-an assessment of safety, efficacy, or another study objective. Also called outcome, variable, parameter, marker, and measure.
The state resulting from the presumed equality of the study treatments. In this situation, an investigator may be uncertain about which study treatment would be more beneficial for a patient.
Exclusion Criteria
Rules of eligibility that exclude an individual from participation in a study.
Expedited Adverse Event Reporting
Reporting of adverse events designated by the protocol/sponsor to the FDA within specified time frames.
Federal Register
A weekly publication that identifies proposed and approved regulations.
Food and Drug Administration (FDA)
A division of the Department of Health and Human Services responsible for assuring the safety and efficacy of pharmaceuticals, biological products, and medical devices, and the safety of foods and cosmetics. Primary FDA offices are located in Rockville, Maryland; the internet address is
Form FDA 1571
The Investigational New Drug (IND) application form that is completed and submitted by the sponsor as part of the IND application.
Form FDA 1572
This Statement of Investigator form must be completed by all investigators participating in a clinical trial when an Investigational New Drug (IND) application is being submitted or an existing IND is being updated. By signing this form, the investigator agrees to comply with all regulations pertaining to clinical research. The completed and signed form is submitted to the sponsor, who in turn submits it to the FDA.
Good Clinical Practice (GCP)
The standards for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials. These standards provide assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.
Good Laboratory Practice (GLP)
Regulations found in Title 21, Part 58, that apply to clinical laboratories performing analyses for clinical trials. Key provisions of Good Laboratory Practice regulations are requirements for creating a quality assurance unit; developing standard operating procedures; analyzing of the investigational product for concentration, uniformity, and stability; and the maintaining, calibrating, and standardizing instruments.
Good Manufacturing Practice (GMP)
Regulations found in Title 21, Parts 210, 211, and 820. GMP regulations describe the methods, equipment, facilities, and controls required for producing products, devices, and food. The regulations apply to clinical research when pharmaceutical products and medical devices are manufactured and tested, and they apply to any drug product intended for administration to humans or animals, including products still in developmental stages.
Written principles and practices pertaining to applying the regulations. Although guidelines are an accepted standard of practice, they are not enforceable by law. FDA guidelines are applicable in the United States while International Conference on Harmonization (ICH) guidelines reflect an international movement to standardize practices across nationalborders.
Inclusion Criteria
Rules of eligibility that an individual must meet in order to participate in a clinical study. See Eligibility Criteria.
Informed Consent
A process by which a subject voluntarily confirms his or her willingness to participate in a clinical trial after having been informed of all aspects relevant to the subject’s decision to participate. The Declaration of Helsinki states that in any human research, each potential subject must be adequately informed of the aims, methods, anticipated benefits, potential hazards, and discomforts that study participation might entail. Informed consent is typically documented via a written, signed, and dated consent form.
An official review by regulatory authorities of documents, facilities, records, and other study-related resources. Inspections may be carried out at investigative sites, at the facilities of the sponsor, at organizations performing sponsor-delegated activities, or at other establishments deemed appropriate by the authorities performing the inspection.
Institutional Review Board (IRB)
A board, committee, or other group that reviews and approves clinical studies at an investigative site. The primary responsibility of the committee is to ensure the protection of the rights and welfare of study participants. Also called Independent Review Committee, Ethics Committee, Human Protection Committee.
International Conference on Harmonization (ICH)
A committee established to develop a unified standard for the European Union, Japan, and the United States, and to facilitate the mutual acceptance of clinical data by regulatory authorities in these jurisdictions.
Investigational Device Exemption (IDE)
Exemption from certain regulatory requirements that apply to commercially distributed medical devices in order to allow manufacturers to distribute devices that are intended solely for investigational use on human subjects. An approved IDE application permits a device that would otherwise be subject to marketing clearance to be lawfully shipped for use in a clinical study.
Investigational New Drug (IND) Application
An application that sponsors must submit to the FDA before beginning studies of an investigational drug in humans. An IND is an application for exemption from the laws that prevent the distribution and use of pharmaceutical agents that have not been approved for use by the FDA. The IND should describe the plan for treatment, previous human experience with the investigational drug, the structural formula, animal test results, and manufacturing information. Also called the Notice of Claimed Investigational Exemption for a New Drug.
Investigational New Drug (IND) Safety Report
A report issued by the sponsor of an investigational product when a safety issue arises. The report is submitted to the FDA and to investigators participating in the clinical trial.
Investigative Site
The location where a study is being conducted. Site locations include physicians’ offices, hospitals, and outpatient clinics. Also known as study site.
An individual who conducts a clinical study and directs the use, administration, and distribution of the investigational agent to a subject. When a team of individuals at a specific location conducts an investigation, the investigator is the responsible leader of the group. The investigator holds regulatory responsibility for the conduct of the trial at the investigative site. A co-investigator is an individual who shares equal responsibility in conducting the trial at a site.
Investigator-Directed Inspection
An FDA inspection that focuses on the work of an investigator rather than on a specific study. This may be an extension of a study-directed inspection and may result from problems encountered during, or questions arising from, a study-directed inspection. Formerly referred to as for-cause inspection; also see Inspection.
Investigator’s Brochure
A brochure compiled by the sponsor providing all known information about the test article or investigational agent. It includes the formulation of the investigational agent, pharmacology, toxicology, pharmacokinetics, safety and effectiveness data, possible side effects, and risks. Both pre-clinical and clinical data are included. Also called investigator’s drug brochure and investigational drug brochure.
Letter of Indemnification
A legal document indicating protection or exemption from liability. The letter of indemnification usually protects the investigator and investigative site from claims by the study participant that harm was caused as a result of participation in the clinical trial. It does not, however, protect the investigator from claims resulting from negligence on the part of the investigator.
An individual selected by a sponsor to oversee the progress of a clinical investigation. Activities often include site visits to ensure that the investigator is fulfilling the responsibilities set forth in the Code of Federal Regulations, that the data submitted are accurate and complete, and that regulatory requirements pertaining to protocol compliance, adverse event reporting, lRB review and approval, and informed consent are met. Also known as Clinical Research Associate (CRA) and Clinical Trial Monitor (CTM).
Overseeing the progress of a clinical trial to ensure that it is conducted, recorded, and reported according to the protocol, standard operating procedures, good clinical practice guidelines, and applicable regulations.
New Drug Application (NDA)
An application submitted to the FDA requesting approval to market a new drug for human use. The contents of the NDA are provided to demonstrate the safety and efficacy of the investigational drug. The application contains information about the class of the drug, the scientific rationale for the drug, its intended use, and the potential clinical benefits. A summary of the clinical data collected is included with the results of the statistical analyses of the clinical trials.
Nuremberg Code
A code of ethics developed from the Nuremberg Military Tribunal’s decision in the case of the US versus Karl Brandt, et al. The Code includes ten conditions delineating permissible medical experimentation on human subjects. According to this code, human experimentation is justified only if its results benefit society and if it is carried out in accord with the basic principles that “satisfy moral, ethical, and legal concepts.”
Open-Label Study
A study in which the treatment assignment is not blinded to the subjects or study personnel.
Agreement of parents or guardians of a child or ward to participate in clinical research.
Phases of Pharmaceutical Clinical Trials
Clinical trials are often categorized into four general phases. Test articles may be evaluated in two or more phases simultaneously in different trials, and some trials may overlap two phases. Phase I -The first stage of testing in humans is to determine safety, duration of action and pharmacologic effect (how the drug is absorbed, distributed, metabolized, and excreted). Subjects are usually healthy volunteers, but may be patients with diseases such as cancer or AIDS. Phase II -To demonstrate safety and efficacy, studies are performed on a small group of subjects (100-300) with the target disease. Phase III – To provide conclusive evidence of safety and effectiveness for a specific indication, studies are performed on a larger subject group (several hundred to several thousand) with the target disease. Phase IV – Toestablish long-term safety and efficacy, studies are performed after FDA approval.
An inactive agent given to a study subject instead of an active drug. To keep subjects and investigators unaware of the treatment assignment, the placebo often matches the study drug in appearance. This helps to blind the study and reduces bias based on knowledge of the treatment. Often called a sugar pill.
Pre-Clinical Trials
Animal studies that provide safety data and information about an investigational product’s activities and effects. Pre-clinical trials provide a framework for clinical trial (human) testing.
Pre-Market Approval (PMA)
A PMA application is submitted to the FDA to request approval to market a device. The FDA evaluates the safety and effectiveness of Class III devices, especially those that support or sustain human life, are of substantial importance in preventing impairment of human health, or that present a potential, unreasonable risk of illness or injury.
A document that identifies the plan or set of rules for conducting a specific clinical trial, and states the objectives, design, methodology, statistical considerations, and organization of a trial.
Protocol Amendment
A written description of changes to, or the formal clarification of, a protocol.
Quality Assurance
The planned and systematic actions that are established to ensure that a trial is conducted and data are collected and recorded according to the protocol, standards of good clinical practice, and applicable regulations.
The process of assigning trial subjects to treatment and control groups using the element of chance; random treatment assignments are performed to reduce bias.
The possibility of harm or discomfort for subjects participating in a clinical trial.
Serious Adverse Event (also Serious Adverse Experience) (SAE)
An adverse drug experience occurring at any dose that results in any of the following outcomes: (1) death, (2) a threat to the life of the subject, (3) inpatient hospitalization or prolongation of existing hospitalization, (4) persistent or significant disability/incapacity, or (5) a congenital anomaly/birth defect. Important medical events that may not result in death, be life threatening, or require hospitalization may be considered a serious adverse experience when, based upon appropriate medical judgment, they may jeopardize the patient and require medical or surgical intervention to prevent one of the outcomes listed above.
Single-Blind Study
See Blinding.
Site Coordinator
The individual at the study site who is typically responsible for the day-to-day conduct of study activities, including case report form completion, study file maintenance, investigator assistance, study drug administration, and communicating with the sponsor. Also called trial coordinator, study coordinator, research coordinator, clinical research coordinator, research nurse, and protocol nurse.
Source Documents
Original documents, data, and records from which patient case report forms are compiled. Source documents include: hospital records, clinic and office charts, laboratory and procedural reports, patient diaries, pharmacy dispensing records, and x-rays.
Source Document Verification
Process of comparing data recorded on patient case report forms with the data originally recorded on source documents.
An individual, company, institution, or organization that initiates a clinical investigation. The sponsor must comply with the responsibilities outlined in the regulations.
An individual who both initiates and conducts a clinical trial, and who directs the use, administration, and distribution of the investigational product. The obligations of a sponsor-investigator include both those of the sponsor and the investigator.
Standard Operating Procedure (SOP)
Detailed written instructions that provide a structure to ensure that activities are performed in a consistent manner.
Study-Directed Inspections
Inspections conducted periodically to determine compliance with FDA regulations. Generally, the inspections are conducted for a specific drug, device, biologic, or study as a result of a pending application for marketing approval. Also called surveillance and routine inspections.
An individual member of a clinical trial team to whom trial-related activities or procedures have been delegated by the investigator. While some sponsors ask sites to list non-physicians participating in the study in section 6 of the Form FDA 1572, the FDA regards sub-investigators as those individuals authorized by the PI to make medical judgments and decisions regarding study patients.
An individual who participates in clinical research, either as a recipient of the test article or of the control. A subject may be either a healthy human or a patient.
Determination of the study treatment administered. Unblinding should only occur when subsequent clinical treatment depends upon knowledge of the study treatment given.
Unanticipated Adverse Device Effect
Death, any life-threatening problem, or any serious adverse effect on health or safety caused by or associated with a device if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the application. Any other serious problem associated with a device that relates to the rights, safety, or welfare of subjects.
Unexpected Adverse Drug Reaction
An adverse reaction, the nature or severity of which is not consistent with the applicable product information in the investigators’ brochure for an unapproved investigational product, or on the package insert/summary of product characteristics for an approved product.
Unexpected Adverse Event
An adverse event that is unexpected for the investigational product and has not been reported in the investigator’s brochure or package insert or is an event that is being reported in greater severity or frequency than the same event previously reported.
Vulnerable Subjects
Individuals whose willingness to volunteer in a study may be unduly influenced by expectation of benefits, fear of retaliatory response, or lack of ability to understand trial-related issues. Some groups identified as vulnerable subjects are prisoners, children, unborn fetuses, homeless persons, and those incapable of giving consent.