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 ICH Topic E 2a - 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. (see ICH Topic E 2a: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting )
A written description of a change(s) to or formal clarification of a protocol.
Applicable Regulatory Requirement(s)
Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products.
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.
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).
A declaration of confirmation by the auditor that an audit has taken place.
A written evaluation by the sponsor's auditor of the results of the audit.
Documentation that allows reconstruction of the course of events.
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).
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.
Committee for Medicinal Products for Human Use-CHMP
The Committee for Medicinal Products for Human Use (CHMP) is responsible for preparing the Agency's opinions (EMA) on all questions concerning medicinal products for human use, in accordance with Regulation (EC) No 726/2004.
An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial.
See Regulatory Authorities
Compliance (in relation to trials)
Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements, and the applicable regulatory requirements.
Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of a subject's identity.
Contract (in relation to trials)
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 trial protocol may also serve as the basis of a contract.
A committee that a sponsor may organize to coordinate the conduct of a multicentre trial.
An investigator assigned the responsibility for the coordination of investigators at different centres participating in a multicentre trial (few countries use the word 'chief investigator').
CRF-Case Report Form
A paper or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject, including adverse events.
Contract Research Organization (CRO)
A person or an organisation (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor's trial-related duties and functions.
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.
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.
Ethics Committee (EC) - Independent Ethics Committee (IEC)
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.
EMA-European Medicines Agency
The European Medicines Agency (EMA) is a decentralised body of the European Union with its headquarters in London. The EMA deals with the evaluation of medicinal products and is responsible for the protection and promotion of human and animal health.
Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced.
EudraCT is the European Clinical Trials Database of all clinical trials which commenced in the European Community from 1 May 2004 onwards. This database has been established in accordance with Directive 2001/20/EC. At the moment only the EMA and national regulatory authorities have direct access.
EudraVigilance is a data processing network and management system for reporting and evaluating suspected adverse reactions during the development and following the marketing authorisation of medicinal products in the European Economic Area (EEA).
Good Clinical Practice (GCP)
A 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 Manufacturing Practice (GMP)
Good Manufacturing Practice (GMP) is defined as "That part of Quality Assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use." The principles and guidelines for GMP are stated in two Directives; Directive 2003/94/EC for medicinal products and investigational medicinal products for human use and Directive 91/412/EEC concerning veterinary medicinal products.
ICH - International Conference on Harmonisation
The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a unique project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of product registration.
A clinical trial/study initiated by an investigator. Generally this study is non-commercial which means that there is no participation by the pharmaceutical industry (see also Sponsor-Investigator and non-commercial clinical trial).
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.
Independent Ethics Committee (IEC)
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 guideline. (see ICH Topic E 6 (R1): Guideline for Good Clinical Practice (ICH-Guideline for Good Clinical Practice )
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.
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.
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)
Any public or private entity or agency or medical or dental facility where clinical trials are conducted.
Institutional Review Board (IRB)
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.
Interim Clinical Trial/Study Report
A report of intermediate results and their evaluation based on analyses performed during the course of a trial.
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.
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.
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.
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.
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).
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.
A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator.
Biomedical studies not performed on human subjects.
Non commercial clinical trial
According to Directive 2001/20/EC clinical trials are non-commercial if they are conducted by researchers without the participation of the pharmaceutical industry.
Opinion (in relation to Independent Ethics Committee)
The judgement and/or the advice provided by an Independent Ethics Committee (IEC).
Paediatric Committee - PDCO
The PDCO is a scientific Committee of the European Medicines Agency. The main responsibility of the PDCO is to assess the content of paediatric investigation plans and to adopt opinions on them in accordance with Regulation (EC) 1901/2006 (so-called Paediatric Regulation) as amended. This includes the assessment of applications for a full or partial waiver and assessment of applications for deferrals.
Paediatric Investigational Plan - PiP
A paediatric investigation plan is a development plan aimed at ensuring that the necessary data are obtained through studies in children, when it is safe to do so, to support the authorisation of the medicine for children. The plan should be submitted by pharmaceutical companies to the Paediatric Committee, which is responsible for agreement or refusal of the plan.The paediatric investigation plan includes a description of the studies and of the measures to adapt the way the medicine is presented (formulation) to make its use more acceptable in children. For example, children cannot swallow big tablets, so a syrup may be more appropriate. (source: EMA)
A person participating in a clinical trial (see subject/trial subject).
Phase I studies are small trials (with 20-80 participants) and the first test of a drug in humans (see also: ICH Topic E 8 General Considerations for Clinical Trials ).
In Phase II studies the drug or treatment is given to a larger group of people to see the effectiveness, benefits and side effects. Participants with diseases can be included (see also: ICH Topic E 8 General Considerations for Clinical Trials ).
Phase III studies are usually larger scale controlled trials.
Commonly used treatments/drugs are compared to the new treatments/drugs. Phase III studies often are placebo-controlled (see also: ICH Topic E 8 General Considerations for Clinical Trials ).
Phase IV studies are post-marketing studies. These clinical trials are often conducted to gather information on the drug's effect in various populations as well as to find out what the long term risks and benefits are (see also: ICH Topic E 8 General Considerations for Clinical Trials ).
If a trial is conducted by a team of individuals at a trial site, the investigator responsible for the team may be called the principal investigator according to Directive 2001/20/EC (see coordinating investigator).
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.
A written description of a change(s) to or formal clarification of a protocol.
Paediatric use marketing authorisation - Puma
means a marketing authorisation granted in respect of a medicinal product for human use which is not protected by a supplementary protection certificate under Regulation (EEC) No 1768/92 or by a patent which qualifies for the granting of the supplementary
protection certificate, covering exclusively therapeutic indications which are relevant for use in the paediatric population, or subsets thereof, including the appropriate strength, pharmaceutical form or route of administration for that product.
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.
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.
Bodies having the power to regulate. In the ICH GCP guideline 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.
Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)
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.
(see ICH Topic E 2a: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting )
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).
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 © EMEA 2006 12 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).
An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial.
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.
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.
An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control.
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.
Supplementary Protection Certificate (SPC)
In the EU a Supplementary Protection Certificate (SPC) is an extension of a patent under a specific, different set of right. The extension of a patent is possible e.g. for medicinal products under the conditions of the Paediatric Regulation (EC) 1901/2006.
A term in pharmacovigilance which stands for 'Suspected Unexpected Serious Adverse Reaction'. According to Directive 2001/20/EC (and the implemented national legislation) SUSARs have to be reported to the competent authorities and Independent Ethics Committees by the sponsor.
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 ICH Topic E 2a: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting )
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 © EMEA 2006 13 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)
The physical and mental integrity of the subjects participating in a clinical trial.
- ICH Topic E 6 (R1): Guideline for Good Clinical Practice (ICH-Guideline for Good Clinical Practice)
- ICH Topic E 2a: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting
- ICH Topic E 8: General Considerations for Clinical Trials
- EMA - http://www.ema.europa.eu/