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Adverse Drug Reaction (ADR)
In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established, all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. The phrase responses to a medicinal product means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out.
Regarding marketed medicinal products: a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function. (See the ICH Guidance for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting.) -
Adverse Event (AE)
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Any adverse occurrence in the health of a clinical trial subject who is administered a drug, that may or may not be caused by the administration of the drug, and includes an adverse drug reaction. -
Amendment (to the protocol)
See Protocol Amendment. -
Applicable Regulatory Requirement(s)
Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products. Canadian regulatory requirements are based on Division 5 and Guidelines for Clinical Practice. -
Approval (in relation to Institutional Review Boards)
The affirmative decision of the IRB that the clinical trial has been reviewed and may be conducted at the institution site within the constraints set forth by the IRB, the institution, Good Clinical Practice (GCP), and the applicable regulatory requirements. -
Audit
A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor's standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s). -
Audit Certificate
A declaration of confirmation by the auditor that an audit has taken place. -
Audit Report
A written evaluation by the sponsor's auditor of the results of the audit. -
Audit Trail
Documentation that allows reconstruction of the course of events. -
Bias
A predetermined perception or a condition that affects the results or a condition that affects the results or the interpretation of a study, such that it no longer is in agreement with the truth. -
Biologics
Any virus, therapeutic serum, toxin, antitoxin, or analogous product applicable to the prevention, treatment or cure of diseases or injuries of man. -
Blinding/Masking
A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single-blinding usually refers to the subject(s) being unaware, and double-blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s). -
Case Report Form (CRF)
A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial. -
Clinical Trial/Study
Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are synonymous. -
Clinical Trial/Study Report
A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects, in which the clinical and statistical description, presentations, and analyses are fully integrated into a single report. (See the ICH Guidance for Structure and Content of Clinical Study Reports.) -
Clinical Research Associate (CRA)
A CRA is employed by the study sponsor to ensure regulatory compliance at the research site and to perform other clinical trial related activities for the sponsor. -
Cohort
A population or group of participants or healthy people who are followed over time. These individuals share common attributes relevant to the research question being evaluated. -
Co-Investigator
See sub-investigator. -
Comparator (Product)
An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial. -
Compliance (in relation to trials)
Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements, and the applicable regulatory requirements. -
Confidentiality
Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of a subject's identity. -
Contract
A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract. -
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 trial-related duties and functions -
Coordinating Committee
A committee that a sponsor may organize to coordinate the conduct of a multicentre trial. -
Coordinating Investigator
An investigator assigned the responsibility for the coordination of investigators at different centres participating in a multicentre trial. -
Cross-Over
A study design where each patient, in random order, is treated with all the preparations being used in a study. -
Dangerous Goods
Dangerous goods are articles or substances which are capable of posing a significant risk to health, safety or to property when transported by air. Shippers of diagnostic specimens where a relatively low probability exists that infectious substances are present must comply with Dangerous Goods Regulations Packing Instructions. The shipper must also ensure that shipments are prepared in such a manner that they arrive at the destination in good condition and that they present no hazard to persons or animals during shipment. -
Dose Comparison
When different doses of a medication are studied over a period of time. -
Double Blind
Neither the participant nor the Investigator is aware of which treatment the participant is receiving. A double-blind design is generally considered to provide the most reliable data from a clinical trial. This type of clinical trial, however, is usually more complicated to initiate and conduct than single-blind or open-label trials. -
Direct Access
Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsor's monitors and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects' identities and sponsor's proprietary information. -
Documentation
All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records, and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken. -
Drop Out
A patient who doesn’t complete the study in accordance with the protocol. -
Double Dummy
A technique used for blinding when two comparative drugs cannot be made to look identical. An identical placebo of each drug is then manufactured and all patients receive tablets of both drugs – an active tablet of Drug A and an inactive tablet of Drug B. -
Efficacy
A relative concept referring to the ability of a medicine to elicit a beneficial clinical effect. This may be measured or evaluated using objective or subjective parameters, and in terms ranging from global impressions, to highly precise measurements. Efficacy is assessed at one or more levels of organization and may be extrapolated to other levels. -
End-Point
An indicator measured in a participant or biological sample to assess safety, efficacy, or another trial objective. Some endpoints are derived from primary endpoints (e.g. cardiac output is derived from stroke volume and heart rate). Synonyms include outcome, variable, parameter, marker and measure. -
Essential Documents
Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced. (See Essential Documents for the Conduct of a Clinical Trial.) -
Federal Drug Administration (FDA)
The federal agency responsible for regulating the sale of food, drugs and cosmetics in the -
Good Clinical Practice (GCP)
A standard by which clinical trials are designed, implemented and reported so that there is a public assurance that the data are credible and that the rights, integrity and confidentiality of participants are protected. -
Good Manufacturing Practice (GMP)
That part of the pharmaceutical quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate for their intended use and as required by the product specification. -
Impartial Witness
A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject or the subject's legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject. -
Incidence rate
The rate of occurrence of new cases of a disease, adverse reaction, or other event in a given population at risk -
Investigational New Drug, a -
Independent Data-Monitoring Committee (IDMC) (Data and Safety Monitoring Board, Monitoring Committee, Data Monitoring Committee)
An independent data-monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial. -
Independent Ethics Committee (IEC) - In Canada we use “REB”
An independent body (a review board or a committee, institutional, regional, national, or supranational), constituted of medical professionals and non-medical members, whose responsibility it is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, reviewing and approving/providing favourable opinion on, the trial protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial subjects.
The legal status, composition, function, operations and regulatory requirements pertaining to Independent Ethics Committees may differ among countries, but should allow the Independent Ethics Committee to act in agreement with GCP as described in this guidance document. -
Informed Consent
A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject's decision to participate. Informed consent is documented by means of a written, signed and dated informed consent form. -
Inspection
The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor's and/or contract research organization's (CRO's) facilities, or at other establishments deemed appropriate by the regulatory authority(ies). -
Institution (medical)
Any public or private entity or agency or medical or dental facility where clinical trials are conducted. -
Institutional Review Board (IRB) – in Canada we use “REB”
An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trial protocol and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects. -
Intention to Treat or Intent to Treat
An analysis where all randomized patients are included in the final analysis regardless of whether they completed the study correctly or not. -
Interim Analysis
A planned or unplanned analysis of the results while the study is still ongoing. -
Interim Clinical Trial/Study Report
A report of intermediate results and their evaluation based on analyses performed during the course of a trial. -
(Principal) Investigator (PI)
A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator. -
Investigational Product
A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use -
Investigator's Brochure
A compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of the investigational product(s) in human subjects. -
Investigator’s File
A hard copy of all the essential documents according to GCPs, correspondence and other documentation as required by the sponsor. This documentation is not part of the CRF. -
Legally Acceptable Representative
An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject's participation in the clinical trial. -
Literally an “after analysis,” an analysis covering several differing studies that follow the same basic fundamentals, which are later combined and analyzed together. -
Monitor
A person appointed by the sponsor or Contract Research Organization (CRO) to be responsible to the sponsor or CRO for the monitoring and reporting on the progress of the trial and for the verification of data. The monitor must have the appropriate qualifications and experience to provide knowledgeable supervision of the particular trial. Trained technical assistants may help the monitor in collection of documentation and subsequent processing. -
Monitoring
The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s). -
Monitoring Report
A written report from the monitor to the sponsor after each site visit and/or other trial-related communication according to the sponsor's SOPs. -
Multicentre Trial
A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator. -
NDA
New Drug Application, an application for registration of a drug in the -
Nonclinical Study
Biomedical studies not performed on human subjects. -
Nonsignificant risk Device
Includes crutches, knee braces and blood pressure devices. They do not: penetrate the skin, ocular cavity, mucous membrane or urethra. -
Original Medical Record
See Source Documents. -
Pharmacodynamics
The processes of the body's responses resulting from treatment with a medicine or compound. The processes include pharmacological, biochemical, physiological, and therapeutic effects. The pharmacodynamics of a response to treatment are presented with the scientific and/or clinical language of the disciplines involved in detecting, measuring and describing the effects. -
Pharmacokinetics
The processes of absorption, distribution, metabolism and excretion of compounds and medicines. -
Prevalence
The total number of people in a population that are affected with a particular disease at a given time. This term is expressed as the rate of all cases (e.g., the prevalence of disease X is Y participants per 100,000 population) at a given point or period of time. -
Prospective
A group of people (a cohort) is assembled, none of whom have experienced the outcome of interest. On entry to the study, people in the cohort are classified according to these characteristics that might be related to outcome. These people are then followed over time to see which of them experience the outcome. A prospective study implies the forward direction in which participants are pursued. Other names for such studies are: longitudinal (emphasizing that participants are followed over time); incidence (calling attention to the basic measure of disease events over time). -
Protocol
A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents. Throughout the ICH GCP Guidance the term protocol refers to protocol and protocol amendments. -
Protocol Amendment
A written description of a change(s) to or formal clarification of a protocol.
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Quality Assurance (QA)
All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and the applicable regulatory requirement(s). -
Quality Control (QC)
The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled. -
Randomization
The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias. -
Regulatory Authorities
Bodies having the power to regulate. In the ICH GCP guidance the expression Regulatory Authorities includes the authorities that review submitted clinical data and those that conduct inspections. These bodies are sometimes referred to as competent authorities. In -
Research Ethics Board (REB)
An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trial protocol and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects. -
Retrospective
Studies which compare the frequency of clinical findings or causal factors in a group with a group of controls. This is also known as "case control studies". A distinguishing feature of this type of study, is that cases possess the outcome of interest at the time that the clinical findings or causal factors are measured. -
Risk
A measure of (1) the probability of occurrence of harm to human health or 2) the severity of harm that may occur. Such a measure includes judgement of the acceptability of risk. Assessment of safety involves judgement, and there are numerous perspectives (participants, physicians, company, regulatory authorities) used for judging it. -
Satellite Site
A second site at which participants in a clinical trial are seen, usually by the same Investigator who sees participants at the primary site. A satellite site may be the same type of site (e.g. private office, hospital) or a different type from the primary site. -
Serious Adverse Event (SAE)
Any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect -
Significant risk device
Intended as implants and present potential for serious risk. They are intended for use in supporting or sustaining life and for use in diagnosing, curing and treating disease. -
Source Data
All information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in source documents (original records or certified copies). -
Sponsor
An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial. -
Sponsor-Investigator
An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator. -
Standard Operating Procedures (SOPs)
Detailed, written instructions to achieve uniformity of the performance of a specific function. -
Statistical Significance
This term relates to the probability that an event or difference occurred by chance alone. Thus, it is a measure of whether a difference is likely to be real, but it does not indicate whether the difference is small or large, important or trivial. The level of statistical significance depends on the number of participants studied or observations made, as well as the magnitude of difference observed. -
Study Coordinator
An appropriately experienced and qualified person who, under the direction of the investigator assists in administering the trial at the investigational site. -
Sub-investigator
Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows). (See also Investigator.) -
Subject Identification Code
A unique identifier assigned by the investigator to each trial subject to protect the subject's identity and used in lieu of the subject's name when the investigator reports adverse events and/or other trial related data. -
Subject/Trial Subject
An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control. -
Trial Site
The location(s) where trial-related activities are actually conducted. -
Unexpected Adverse Drug Reaction
An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product). (See the ICH Guidance for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting.) -
Vulnerable Subjects
Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent. -
Wash-Out
A period over which the previous treatment is discontinued, generally before start of the study treatment or between different treatments in a study. -
Well-being (of the trial subjects)
The physical and mental integrity of the subjects participating in a clinical trial. -
Withdrawals
Patients who terminate a study on the advice of the investigator.
