Adverse Event (AE), (article C.05.001, Health Canada) – 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.
Adverse Event (AE), (ICH/GCP 1.2) – 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 unfavorable 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 (see the ICH Guidance for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).
Adverse Drug Reaction (ADR), (ICH/GCP 1.1) – 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).
Audit, (ICH/GCP 1.6) – 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).
Biologic, (Health Canada) – A drug that is prepared using a biological starting material or source material (e.g. derived from a microorganism, virus, animal, human, or plant), and using for example, either conventional manufacturing methods, recombinant DNA technology, and/or other novel approaches. Some examples of biologics include vaccines, blood and its derivatives, certain hormones and enzymes, recombinant DNA products, gene therapies, and transgenics. Biologics make up one large category of drugs; the other major category of drugs is pharmaceuticals, or synthetic drugs, made from chemicals.
Blinding/Masking, (ICH/GCP 1.10) – A procedure in which one or more parties to the trial are kept unaware (blinded) 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) (triple blind) being unaware of the treatment assignment(s).
Clinical Trial, (Art. C.05.001, Health Canada) – An investigation in respect of a drug for use in humans that involves human subjects and that is intended to discover or verify the clinical, pharmacological or pharmacodynamic effects of the drug, identify any adverse events in respect of the drug, study the absorption, distribution, metabolism and excretion of the drug, or ascertain the safety or efficacy of the drug.
Clinical Trial/Study, (ICH/GCP 1.12) – 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, 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, Multicentre, (ICH/GCP 1.40) – A clinical trial, conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator.
Case Report Form (CRF), (ICH/GCP 1.11) – A printed, optical, or electronic document designed to record all of the protocol required information on each trial subject to be reported to the sponsor.
Confidentiality, (ICH/GCP 1.16) – Prevention of disclosure of a sponsor’s proprietary information or of a subject’s identity to other than the authorized individuals.
Compliance (in relation to trials), (ICH/GCP 1.15) – Adherence to all trial-related requirements, Good Clinical Practice (GCP) requirements, and the applicable regulatory requirements.
Comparator (Product), (ICH/GCP 1.14) – An investigational or marketed product (active control), or placebo, used as a reference in a clinical trial.
Contract, (ICH/GCP 1.17) – 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), (ICH/GCP 1.20) – 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.
Clinical Trial/Clinical Study Report, (ICH/GCP 1.13) – A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects, in which clinical and statistical description, presentations, and analyses are fully integrated into a single report.
Drug, (Article C.05.001, Health Canada) – A drug for human use that is to be tested in a clinical trial.
Documentation, (ICH/GCP 1.22) – All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records, and scans, x-rays, and lectrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.
Essential Documents, (ICH/GCP 1.23) – Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced (see 8. Essential Documents for the Conduct of a Clinical Trial).
Good Clinical Practice (GCP), (ICH/GCP 1.24) – Standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.
Good Clinical Practices, (Article C.05.001, Health Canada) – Good clinical practices means generally accepted clinical practices that are designed to ensure the protection of the rights, safety and well-being of clinical trail subjects and other persons, and the good clinical practices referred to.
Investigational Product, (ICH/GCP 1.33) – 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.
ICH – International Conference on Harmonization, (www.ich.org) – joint initiative involving both regulators and industry as equal partners in the scientific and technical discussions of the testing procedures which are required to ensure and assess the safety, quality and efficacy of medicines.
Investigator / Institution, (ICH/GCP 1.35) – An expression meaning “the investigator and/or institution, where required by the applicable regulatory requirements”.
Investigator’s Brochure, (ICH/GCP 1.36) – 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 Brochure, (Article C.05.001, Health Canada) – Investigator’s brochure means, in respect of a drug, a document containing the preclinical and clinical data on the drug that are described in paragraph C.05.005
Interim Clinical Study Report, (ICH/GCP 1.32) – A report of intermediate results and their evaluation based on analyses performed during the course of a trial.
Institution (medical), (ICH/GCP 1.30) – Any public or private entity or agency or medical or dental facility where clinical trials are conducted.
Inspection, (ICH/GCP 1.29) – The act of conducting an official review of documents by a regulatory authority(ies), on 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).
Institutional Review Board (IRB), (ICH, GCP 1.31) – 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.
IRB Approval, (ICH/GCP 1.5) – 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.
Independent DataSafety Monitoring Committee (DSMC), (ICH/GCP 1.25) – 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.
Informed Consent, (ICH/GCP 1.28) – 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.
Impartial Witness, (ICH/GCP 1.26) – 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.
Legally Acceptable Representative (LAR), (ICH/GCP 1.37) – 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.
Monitoring, (ICH/GCP 1.38) – 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).
Opinion (in relation to Independent Ethics Committee), (ICH/GCP 1.42) – The judgment and/or the advice, provided by an Independent Ethics Committee (IEC).
Protocol, (Article C.05.001, Health Canada) – A document that describes the objectives, design, methodology, statistical considerations and organization of a clinical trial.
Protocol, (ICH/GCP 1.44) – 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, (ICH/GCP 1.45) – A written description of a change(s) to or formal clarification of a protocol.
Person responsible for site SOPs – A member of the institutional personnel involved in clinical research is designated by the institution to complete appendix 1, Instructions Specific to the Site. He/she may participate in the SOP revision process or in the SOP annual approval process. They may also participate in the training of institutional clinical research personnel for each standard operating procedure.
Quality Assurance (QA), (ICH/GCP 1.46) – All 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 requirements.
Quality Control (QC), (ICH/GCP 1.47) – 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.
Research Ethics Board (REB), (Article C.05.001, Health Canada) – A body that is not affiliated to the sponsor, and:
a) the principal mandate of which is to approve the initiation of, and conduct periodic reviews of biomedical research, involving human subjects in order to ensure the protection of their rights, safety and well-being; and
b) that has at least five members, that has a majority of members, who are Canadian citizens or permanent residents under the Immigration and Refugee Protection Act, that is composed of both men and women and that includes at least:
· two members whose primary experience and expertise are in a scientific discipline, who have broad experience in the methods and areas of research to be approved and one of whom is from a medical discipline or, if the clinical trial is in respect of a drug to be used for dental purposes only, is from a medical or dental discipline,
· one member knowledgeable in ethics,
· one member knowledgeable in Canadian laws relevant to the biomedical research to be approved,
· one member, whose primary experience and expertise are in a non-scientific discipline, and
· one member, who is from the community or is a representative of an organization interested in the areas of research to be approved and who is not affiliated with the sponsor or the site, where the clinical trial is to be conducted.
Regulatory Authorities, (ICH/GCP 1.49) – 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 (see 1.29). These bodies are sometimes referred to as competent authorities.
Regulatory Requirement, (ICH/GCP 1.4) – Any law and regulation addressing the conduct of clinical trials of investigational products.
Radiopharmaceutical, (Health Canada) – Drugs, which are labelled with a radionuclide in tracer or therapeutic amounts, and which exhibit spontaneous disintegration of unstable nuclei with the emission of nuclear particles or photons. They can include drugs either of chemical or biological origin, which are intentionally made radioactive, as well as, kits that are used for the preparation of radiopharmaceutical and radionuclide generators. Radiopharmaceuticals are used as diagnostic or therapeutic agents, and are always prepared and administered by health care professionals; they are never self administered.
Source Data, (ICH/GCP1.51) – 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).
Source Documents, (ICH/GCP 1.52) – Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions, certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial).
Standard Operating Procedures (SOPs), (ICH/GCP 1.55) – Detailed, written instructions to achieve uniformity of the performance of a specific function.
Site standard operating procedure (SOP) – A validated site standard operating procedure is a generic SOP for which appendix 1, Instructions Specific to the Site has been completed. This site standard operating procedure has been ratified by the director of the research center and/or by institution members according to the internal procedures for the validation process. This SOP is in use in the institution.
Specific Site Instructions (QC only) – Specific instructions that outline in a detailed manner the activities related to the institution for a given standard operating procedure
Site / Trial Site, (ICH/GCP 1.59) – The location(s) where trial-related activities are actually conducted.
Sub-investigator, (ICH/GCP 1.56) – 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).
Subject / Trial Subject, (ICH/GCP 1.57) – An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control.
Sponsor, (ICH/GCP 1.53) – An individual, company, institution, or organization, which takes responsibility for the initiation, management, and/or financing of a clinical trial.
Sponsor-Investigator, (ICH/GCP 1.54) – 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 of an investigator.
Trial Flow chart – A table that illustrates and helps visualize a standard operating procedure process. The table is included in the procedure draft to facilitate understanding of the procedure.
Electronic signature, (Statutes of Canada 2000, PIPEDA) – A signature that consists of one or more letters, characters, numbers or other symbols in digital form incorporated in attached to or associated with an electronic document.
Electronic numeric signature, (MSSS, Cadre global des actifs informationnels – sécurité) – Data, appended to an electronic document, allowing the person receiving this document to know the source of the data, to attest its integrity, and to assure the transmitter adherence to the document content. We sometimes use the expression secured electronic signature.
Secure electronic signature, (Statutes of Canada 2000, PIPEDA) – An electronic signature that results from the application of a technology or process prescribed by regulations made under subsection 48 (1).
Vulnerable Subjects, (ICH/GCP 1.61) – 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.
Well-being (of the trial subjects), (ICH/GCP 1.62) – The physical and mental integrity of the subjects participating in a clinical trial.