Glossary

The committee that advises the Health Departments on written applications from practitioners for certificates which will enable them to use specific radioactive medicinal products in diagnosis, therapy or research.

An ARSAC research certificate is obtained for all trials which result in radiation exposure to subjects additional to that involved in their routine diagnostic or therapeutic management.

Means an ATMP as defined in Article 2(1) of Regulation 1394/2007 which is tested or used in a clinical trial (in accordance with Article 2(d) of Directive 2001/20/EC).

Means any of the following medicinal products for human use: a gene therapy medicinal product a somatic cell therapy medicinal product a tissue engineered product. As defined in Article 2(1) of Regulation 1394/2007.

Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Any untoward and unintended response to an investigational medicinal product related to any dose administered. Comment: All adverse events judged by either the reporting investigator or the sponsor as having a reasonable causal relationship to a medicinal product would qualify as adverse reactions. The expression ‘reasonable causal relationship’ means to convey, in general, that there is evidence or argument to suggest a causal relationship.

A technique used to prevent selection bias by concealing the allocation sequence from those assigning participants to intervention groups, until the moment of assignment. Allocation concealment prevents researchers from (unconsciously or otherwise) influencing which participants are assigned to a given intervention group.

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, analysed and accurately reported according to the protocol, sponsor’s Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

In relation to the Chief of Principal investigator in a CTIMP; a registered doctor, dentist, nurse or pharmacist. This definition does not apply for research other than CTIMPs.

An AxMP is a medicinal product used for the needs of a clinical trial as described in the protocol, but not as an investigational medicinal product.

Systematic distortion of the estimated intervention effect away from the "truth", caused by inadequacies in the design, conduct, or analysis of a trial.

The practice of keeping the trial participants, care providers, those collecting data, and sometimes even those analysing data unaware of which intervention is being administered to which participant. Blinding is intended to prevent bias on the part of study personnel. The most common application is "double-blinding", in which participants, caregivers and those assessing outcome are blinded to intervention assignment. The term "masking" may be used instead of blinding.

A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject.

In the case of a CTIMP: a) In relation to a clinical trial conducted at a single trial site, the Investigator for that site; or b) In relation to a clinical trial conducted at more than one trial site, the authorised health professional, whether or not he is an Investigator at any particular site, who takes primary responsibility for the conduct of the trial. For research other than CTIMPs: The person who takes overall responsibility for the design, conduct and reporting of a study if it is at one site; or if the study involves researchers at more than one site, the person who takes primary responsibility for the design conduct and reporting of the study whether or not that person is an Investigator at any particular site.

A clinical study in which participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. The assignments are determined by the study protocol. Participants may receive diagnostic, therapeutic, or other types of interventions. A Study Type.

Authorisation by a competent authority (MHRA in the UK) to conduct a clinical trial.

Pre-2004 Clinical Trial Arrangements: former method for approval of a clinical trial by the MHRA, now replaced by the Clinical Trials Authorisation.

For for certain 'Type A' trials notification of the trial to the MHRA is possible. Type A trials are those involving medicinal products licensed in any EU Member State if: they relate to the licensed range of indications, dosage and form; or they involve off-label use (such as in paediatrics and oncology, etc) if this off-label use is established practice and supported by sufficient published evidence and/or guidelines. See the MHRA website for further information.

A clinical trial that is within the scope of the UK Medicines for Human Use (Clinical Trials) Regulations 2004. An investigation in human subjects, other than a non-interventional trial, intended: a) to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more medicinal products, b) to identify any adverse reactions, or c) to study absorption, distribution, metabolism and excretion, with the object of ascertaining the safety and/or efficacy of those products.

Directive 2001/20/EC: On the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use.

Pre-2004 Clinical Trial Arrangements: former method for the approval of a clinical trial by the MHRA now replaced by the Clinical Trial Authorisation.

A term used to describe The Medicines for Human Use (Clinical Trials) Regulations (SI 2004 1031) and its amendments. A brief description of each of the statutory instruments and their relationship with the European Directives can be accessed here.

Where two or more organisations share a significant interest in a study, they may elect to act as co-sponsors. See the Sponsorship Principles document for further details.

Provides a simple and secure mechanism for exchange of information between applicants and regulatory agencies via one platform.

An investigational or marketed product (i.e. active control) or placebo, used as a reference in a clinical trial.

Each member state in the European Economic Area has appointed a competent authority to perform certain functions required by Directive (2001/20/EC). The MHRA (the UK’s licensing authority established under the Medicines Act 1968) is the competent authority in the UK.

A service organisation that provides support to the pharmaceutical and biotechnology industries (and other organisations) in the form of research services outsourced on a contract basis.

The groups being compared in the randomized trial. Also referred to as "study groups", "treatment groups", "the arms" of a trial, or by individual terms such as treatment and control groups.

A type of clinical trial in which observations made during the trial are compared to a standard (called the control). The control may be observations from a group of participants in the same trial or observations from outside the trial (for example, from an earlier trial, called a "historical control").

The Coordinated System for gaining NHS Permission in England which is: a) a service to Investigators which facilitates set up and approval for research in the NHS b) a standardised process by which NHS organisations provide NHS permission for research. Also sometimes used informally to refer to the information system which supports the process.

A 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.

A list of appropriately qualified persons to whom the investigator has delegated significant trial related duties. Sponsors/host organisations will usually provide a template for the Delegation Log and researchers should check with their NHS R&D office if any ‘preferred template’ is available. If no default document is available, a template can be found on the Transcelerate website.   

The common format for annual safety reports on investigational drugs in the ICH regions under ICH guideline E2F.

Pre-2004 Clinical Trial Arrangements: former method for the approval of a clinical trial by the MHRA now replaced by the Clinical Trial Authorisation.

A trial where the investigators and the subjects included in the trial (healthy volunteers or patients) do not know which interventions / treatments have been assigned.

A measure of whether the medicinal product has its intended effect.

The key standards that people who want to participate in a clinical study must meet or the characteristics that they must have. These include inclusion criteria and exclusion criteria. For example, a study might only accept participants who are above or below certain ages.

In clinical studies where endpoints are complex to assess and/or include subjective components or the study cannot be blinded, an Endpoint Adjudication Committee, consisting of clinical experts in a specific clinical area, might be set up to harmonise and standardise endpoint assessment and to determine whether the endpoints meet protocol-specified criteria. In order to allow for an unbiased endpoint assessment the members of such a committee should be blinded to treatment assignment. Endpoint Adjudication Committees are, for example, widely used in the assessment of radiological endpoints.

The act of admitting a participant into a trial. Participants should be enrolled only after study personnel have confirmed that all the eligibility criteria have been met. Formal enrolment must occur before randomised assignment.

The essential documents relating to a clinical trial are those which enable both the conduct of the clinical trial and the quality of the data produced to be evaluated; and show whether the trial is, or has been, conducted in accordance with the applicable regulatory requirements.

The website providing the public with information held in the EU clinical trial database, EudraCT. It provides the public with information on clinical trials which have been authorised in the EEA and also those which are part of a PIP (Paediatric Investigation Plan). It gives users the ability to search for information on any paediatric clinical trial and any adult clinical trial recorded in EudraCT.

Part of the EudraVigilance data processing network and management system to facilitate the electronic reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs) as required by Directive 2001/20/EC.

The European Commission is the executive body of the European Union, responsible for proposing legislation, implementing decisions, and day-to-day running of the EU.

The European Medicines Agency is a decentralised agency of the European Union, located in London. The Agency is responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the European Union.

The European Clinical Trials Database of all clinical trials administered by the European Medicines Agency. It is mandatory for sponsors to post clinical trial summary results in EudraCT following the end of a trial.

Specific criteria which are defined within the study protocol that expressly exclude specific individuals from participating in a study. The reasons for considering exclusion can range from safety issues, potential difficulties in management of particular participants or the need to control variables within the study. Exclusion criteria must always be defended ethically to guard against discrimination.

An agreement between an organisation and relevant external parties for example between an organisation and a research organisation. External agreements may be required to confirm issues such as: indemnity, intellectual property, roles and responsibilities, data protection, confidentiality, financial and termination issues, standards of service and where applicable regulatory obligations.

A process of periodic contact with participants enrolled in the trial for the purpose of administering the assigned intervention(s), modifying the course of intervention(s), observing the effects of the intervention(s), or for data collection.

The competent authority for the regulation of food and drugs in the United States of America.

Organisation providing funding for a study (through agreements, grants or donations to an authorised member of the employing and/ or care organisation). The main funder typically has a key role in scientific quality assurance. In any case, it remains responsible for securing value for money.

The Gene Therapy Advisory Committee is the national ethics committee for clinical trials involving medicinal products for gene therapy under Regulation 14(5).

GDPR refers to requirements in both the EU General Data Protection Regulation and the UK Data Protection Act 2018 (ratified 23 May 2018). The HRA website defines key terms in the legislation.

The extent to which the findings of a clinical trial can be reliably extrapolated from the subjects who participated in the trial to a broader patient population and a broader range of clinical settings.

Good Clinical Practice is a set of internationally recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects.

Good Manufacturing Practice (GMP) is that part of quality assurance which ensures that medicinal products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorisation (MA) or product specification.

A policy document has been written by the UK Health Departments describing what is expected from the research ethics committees that review research proposals relating to areas of the UK Health Department's responsibility. It also explains when review by these committees is required. It can be downloaded from the Department of Health’s Publications Policy and Guidance web page.

An NHS organisation established to protect and promote the interests of patients and the public in health research. The National Research Ethics Service (NRES) is now part of the HRA.

In a trial, a statement relating to the possible different effect of the interventions on an outcome. The null hypothesis of no such effect is amenable to explicit statistical evaluation by a hypothesis test, which generates a P value.

An adult unable by virtue of physical or mental incapacity to give informed consent.

Specific criteria which are defined within the study protocol that expressly include specific individuals to participate in a study e.g. individuals within a certain age range, with a specific condition, etc.

Insurance or indemnity includes provision for meeting losses or liabilities— a) under a scheme established under— i) section 21 of the National Health Service and Community Care Act 1990 (schemes for meeting losses and liabilities etc. of certain health service bodies in England and Wales)(d), ii) section 85B of the National Health Service (Scotland) Act 1978 (schemes for meeting losses and liabilities etc. of certain health service bodies in Scotland)(e), or iii) Article 24 of the Health and Personal Social Services (Northern Ireland) Order 1991(schemes for meeting losses and liabilities etc. of certain health service bodies in Northern Ireland)(f), or b) in accordance with guidance issued by— i) the Secretary of State, ii) the Scottish Ministers, iii) the National Assembly for Wales, or iv) the Department for Health, Social Services and Public Safety, As to the arrangements to be adopted by health service bodies for meeting the costs arising from clinical negligence (known as NHS Indemnity).

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. For CTIMPs: A person gives informed consent to take part only if his/her decision: a) is given freely after that person is informed of the nature, significance, implications and risks of the trial; and b) either— i) is evidenced in writing, dated and signed, or otherwise marked, by that person so as to indicate his consent, or ii) if the person is unable to sign or to mark a document so as to indicate his consent, is given orally in the presence of at least one witness and recorded in writing.

The act by a competent authority of conducting an official review of documents, facilities, records, quality assurance arrangements, and any other resources that are deemed by the competent authority 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 organisation's facilities, or at other establishments which the competent authority sees fit to inspect. In the UK, the MHRA's Good Clinical Practice (GCP) Inspectorate is part of the Inspection, Standards and Enforcement Division of the MHRA.

The generic term used by the Food & Drugs Administration (FDA) in the United States for independent ethics committees that have been formally designated to review and monitor biomedical research involving human subjects.

The online application system used to apply for most permissions and approvals for research in health and social care in the UK.

IP can be described as the novel or previously undescribed tangible output of any intellectual activity. It has an owner and can be bought, sold or licensed and must be adequately protected. It can include inventions, industrial processes, software, data, written works, designs and images.

Interactive Response Technology (IRT) is software that enables activities such as randomisation into clinical trial and dispensing medications in a blinded trial. Examples include telephone based Interactive Voice Response Systems (IVRS) or internet based, Interactive Web Response Systems (IWRS). These technologies are also used in other trial management activities.

An analysis comparing intervention groups undertaken at any time before the formal completion of the trial, usually before recruitment is complete. Often used with "stopping rules" so that a trial can be stopped if participants are being put at risk unnecessarily. Timing and frequency of interim analyses should be specified in the protocol.

An agreement between an organisation and relevant internal parties. Examples include: Agreements, memoranda or documentation between a ' R&D Office' and clinical and non-clinical support services in order to facilitate engagement and internal authorisation from named support service leads. Agreements between a Principal Investigator / Chief Investigator and support service or stakeholders within an organisation. Agreements between the organisation and relevant party for resources who require an honorary research contract or letter of access. These agreements may be in the form of a standardised document or email format.

The ICMJE is a group of general medical journal editors whose participants meet annually and fund their work on the Uniform Requirements for Manuscripts.

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use is a joint initiative involving both regulators and research-based industry focusing on the technical requirements for medicinal products containing new drugs to establish common standards for clinical trials.

A simple numeric system for the unique identification of randomised controlled trials worldwide. The randomly generated number is unique to a registered trial, thereby ensuring that the trial can be simply and unambiguously tracked throughout its lifecycle. The ISRCTN Register also accepts registration of other forms of studies designed to assess the efficacy of health-care interventions.

A process or action that is the focus of a clinical study. This can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include non-invasive approaches such as surveys, education, and interviews.

A clinical study in which participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. The assignments are determined by the study protocol. Participants may receive diagnostic, therapeutic, or other types of interventions.

A pharmaceutical form of an active substance or placebo being tested, or to be tested, or used, or to be used, as a reference in a Clinical Trial, and includes a medicinal product which has a marketing authorisation but is, for the purposes of the trial - a) used or assembled (formulated or packaged) in a way different from the form of the product authorised under the authorisation, b) used for an indication not included in the summary of product characteristics under the authorisation for that product, or c) used to gain further information about the form of that product as authorised under the authorisation.

The IMPD includes summaries of information related to the quality, manufacture and control of any IMP (including reference product and placebo), and data from non-clinical and clinical studies.

The Investigator Site File contains all essential documents held by Principal Investigator(s) conducting a trial which individually and collectively permit the evaluation of the conduct of a trial and the quality of the data produced.

A document containing a summary of the clinical and non-clinical data relating to an investigational medicinal product which are relevant to the study of the product in human subjects.  Guidance on when an Investigator's Brochure is required can be accessed from the Trial Supplies station.

INVOLVE is a national advisory group that supports greater public involvement in NHS, public health and social care research. INVOLVE is funded by and part of the National Institute of Health Research (NIHR).

Where two or more organisations share a significant interest in a study, they may elect to act as joint-sponsors. See Sponsorship Principles document for further details.

A person who gives written informed consent on behalf of a vulnerable subject in a CTIMP as defined in Schedule 1, Part 1 (2) of The Medicines for Human Use (Clinical Trials) Regulations, as amended.

If the main sponsor of a clinical trial with a medicinal product is not based in the European Economic Area (EEA), for example, an American or Japanese company, it is a statutory requirement to appoint a legal representative based in the EEA for the purposes of the trial.

The legal representative:

• may be an individual person or a representative of a corporate entity
• does not have to be a legally qualified person
• should be willing to act as the agent of the sponsor in the event of any legal proceedings instituted in the EEA (for example, for service of legal documents)
• should be established and contactable at an address in the EEA
• does not assume any of the legal liabilities of the sponsor(s) for the trial by virtue of the role of legal representative and does not therefore require insurance or indemnity to meet such liabilities, but may in some cases enter into specific contractual arrangements to undertake some or all of the statutory duties of the sponsor in relation to the trial, in which case the legal representative would also be regarded as a co-sponsor and would then require insurance or indemnity cover.

Letters of access enable NHS employees or staff with an honorary clinical contract (e.g. clinical academics) with one NHS organisation to conduct research in another NHS organisation.

A medicinal product may only be placed on the market in the European Economic Area (EEA) when a marketing authorisation has been issued by the competent authority of a Member State (or EEA country) for its own territory (national authorisation) or when an authorisation has been granted in accordance with Regulation (EC) No 726/2004 for the entire Community (a Community authorisation).

The entity that has been granted a Marketing Authorisation. Marketing Authorisation Holders must be established within the EEA.

Any instrument, apparatus, implement, machine, appliance, implant, software, material, or other similar or related article

a) intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the specific purpose(s) of

1. diagnosis, prevention, monitoring, treatment or alleviation of disease,
2. diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury,
3. investigation, replacement, modification, or support of the anatomy or of a physiological process,
4. supporting or sustaining life,
5. control of conception,
6. disinfection of medical devices, and

b) which does not achieve its primary intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its intended function by such means.

The MHRA is the competent authority for the UK in relation to the Directive 2001/20/EC and the Clinical Trials Regulations, and for Medical Devices, the competent authority in relation to the Medical Devices Regulations 2002.

Provides a statutory framework to empower and protect vulnerable people who are not able to make their own decisions. It makes it clear who can take decisions, in which situations, and how they should go about this.

The research provisions of the Mental Capacity Act 2005 do not apply to the conduct of CTIMPs.

In relation to a CTIMP, defined in ‘The Medicines for Human Use (Clinical Trials) Regulations’ as a person under the age of 16.

An individual who undertakes monitoring activities for a trial.

The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted and recorded in accordance with the protocol, Standard Operating Guidelines (SOP’s), 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 trial/study conducted at more than one site.

An independent statutory body that was responsible for Section 251 of the NHS Act 2006 in England and Wales; and reviewed applications for use of identifiable data where consent was not practicable. From April 2013 this function will transfer to the Health Research Authority (HRA) who will convene a Confidentiality Advisory Group (CAG) to perform this function.

The National Research Ethics Service (NRES) is the core function of the Health Research Authority (HRA) and provides help and leadership for NHS Research Ethics Committees (RECs) by co-ordinating the development of operational and infrastructure arrangements in support of their work.

NHS Permission for research (formerly known as R&D Approval) confirms that appropriate checks have been made and that clinical negligence will be covered by NHS indemnity schemes or by independent contractors' professional indemnity insurance during the course of the research. In addition, where the staff of an NHS organisation were responsible for designing the study, NHS permission confirms that indemnity is provided for harm arising from the design of the study.

NHS permission for research ensures that:

• The organisation is aware of the potential impact of the research in terms of risks and resources.
• The organisation has made the necessary arrangements to support the activity.
• All the activities for which the organisation is responsible are compliant with the law.
• The organisation accepts vicarious liability for the activities of staff for which it is responsible.

Letter confirming that NHS Permission has been given and the study can commence. Similar terms are used for the permission letter issued in other UK countries.

The responsible person / team acting on behalf of the organisation in matters relating to R&D management. The NHS R&D Office may delegate some of its functions to other parties.

NB. Where a trial is run without NHS involvement, the term NHS R&D office may often be replaced with the term ‘sponsor’s office’.

A study of one or more medicinal products which have a marketing authorisation, where the following conditions are met:

• The products are prescribed in the usual manner in accordance with the terms of that authorisation
• The assignment of any patient involved in the study to a particular therapeutic strategy is not decided in advance by a protocol but falls within current practice
• The decision to prescribe a particular medicinal product is clearly separated from the decision to include the patient in the study
• No diagnostic or monitoring procedures are applied to the patients included in the study, other than those which are ordinarily applied in the course of the particular therapeutic strategy in question, and
• Epidemiological methods are to be used for the analysis of the data arising from the study.

A Non Investigational Medicinal Product (NIMP) is a medicinal product which is not classed as an IMP in a trial,  but may be taken by subjects during the trial. Examples include concomitant or rescue/escape medication  used for preventive, diagnostic or therapeutic reasons and/or medication given to ensure that adequate medical care is provided for the subject during a trial. See EU Guidance on Investigational Medicinal Products  (IMPs) and Non Investigational Products (NIMPs) (.PDF).

Trials that do not involve an Investigational Medicinal Product (IMP) as defined by the MHRA, and therefore do not fall within the scope of the Medicines for Human Use (Clinical Trials) Regulations 2004. 

A clinical study in which participants identified as belonging to study groups are assessed for biomedical or health outcomes. Participants may receive diagnostic, therapeutic, or other types of interventions, but the investigator does not assign participants to specific interventions (as in an interventional study).

Describes a clinical trial in which masking is not used. That means that all parties involved with the trial know which participants have been assigned which interventions.

A planned measurement described in the protocol that is used to determine the effect of interventions on participants in a clinical trial. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include Primary Outcome Measure and Secondary Outcome Measure.

Patient, service user, carer, relative, professional carer, other employee, or member of the public, who consents to take participate in a study. (In law, participants in clinical trials involving medicinal products or a control are referenced as subjects). See also Subject.

Organisations which refer potential participants to a research team at another organisation, but do not conduct trial related activity themselves. If activities such as consent take place, then the site would not be classed as a PIC.

A document explaining all relevant study information to assist the potential subject in understanding the expectations and requirements of participation in a clinical trial.

An active partnership between patients and the public and researchers in the research process, rather than the use of people as 'subjects' of research.

Patient and public involvement in research is often defined as doing research ‘with’ or ‘by’ people who use services rather than ‘to’, ‘about’ or ‘for’ them. This would include, for example, involvement in the choice of research topics, assisting in the design, advising on the research project or in carrying out the research.

An appropriate process of independent expert review has demonstrated that the research proposal is worthwhile, of high scientific quality and represents good value for money.

The science relating to the detection, assessment, understanding and prevention of the adverse effects of medicines.

The phases of a clinical trial can generally be categorised in the following terms:

• Phase I - Human pharmacology
• Phase II - Therapeutic exploratory
• Phase III - Therapeutic confirmatory
• Phase IV - Therapeutic use.

A control substance (a dummy treatment) that is given to people taking part in a clinical trial. It allows researchers to test for the 'placebo effect'. This is a psychological response where people feel better even though the substance they are taking has no effect. By comparing people's responses to the placebo and to the drug being tested, researchers can tell whether the drug is having any real benefit.

From Latin ‘after this’, post hoc analysis consists of looking at the data after the experiment has concluded for patterns that were not specified up front.  It is sometimes called by critics, data dredging.

For CTIMPs, the authorised health professional responsible for the conduct of that trial at a trial site, and if the trial is conducted by a team of authorised health professionals at a trial site, the Investigator is the leader responsible for that team.

For research other than CTIMPs: The person responsible, individually or a leader of the researchers at a site, for the conduct of a study at that site.

A document that describes the objective(s), design, methodology, statistical considerations and organisation of a trial. The term protocol refers to the protocol, successive versions of the protocol and protocol amendments.

All manufacturing activities will need to be conducted in a unit which has an IMP manufacturing authorisation with a named Qualified Person (QP).

This person ensures that an investigation medicinal product (IMP) batch is only released if there is documentation to confirm compliance with Good manufacturing Practice (or equivalent).

All those planned and systematic actions that are established to ensure that the trial is performed and the data is generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and the applicable regulatory requirement(s).

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.

An experiment in which two or more interventions, possibly including a control intervention or no intervention, are compared by being randomly allocated to participants. In most trials one intervention is assigned to each individual but sometimes assignment is to defined groups of individuals (for example, in a household) or interventions are assigned within individuals (for example, in different orders or to different parts of the body).

Committee established to provide participants, researchers, funders, sponsors, employers, care organisations and professionals with an independent opinion on the extent to which proposals for a study comply with recognised ethical standards.  For CTIMPs, the ethics committee must be one recognised by the United Kingdom Ethics Committee Authority. The REC undertaking the ethical review of an application is also known as the Main REC.

Where the term ‘ethics committees’ has been used in the Toolkit, it denotes the ethics committees in all member states that have approved a multinational clinical trial.

The UK Health Departments' Research Governance Frameworks (RGFs) documents a set of standards and principles for carrying out health related or social/community care research in the UK. It is mandatory for all research taking place in the NHS and using NHS resources. It aims to improve research and safeguard the public by:

• enhancing ethical awareness and scientific quality
• promoting good practice
• reducing adverse incidents and ensuring lessons are learned
• forestalling poor performance and misconduct.

Country specific versions of the Framework have been published: England, Scotland, Wales (PDF, 675 KB) (.PDF) and Northern Ireland (PDF, 350 KB) (.PDF).

Provides a mechanism for assuring NHS organisations of the pre-engagement checks conducted on a researcher; and other standardised procedures for handling the HR arrangements for researchers.

The NIHR has established the Research Support Service in England to help researchers develop and design high quality research proposals for submission to national, peer-reviewed funding competitions for clinical, applied health and social care research. The RSS replaces the NIHR Research Design Service (RDS) and NIHR Support Funding for Clinical Trials Units which came to an end on 30 September 2023. 

Those conducting a trial (or study).

See MRC/DH/MHRA Joint Project: The Risk-adapted Approaches to the Management of Clinical Trials of Investigational Medicinal Products (PDF, 247 KB) (.PDF) and the MHRA website for further information.

The number of participants in the trial. The intended sample size is the number of participants planned to be included in the trial, usually determined using a statistical power calculation. The sample size should be adequate to provide a high probability of detecting as significant an effect size of a given magnitude if such an effect actually exists.

The achieved sample size is the number of participants enrolled, treated or analysed in the study.

A list of corrections to the case report form that can be made by the sponsor’s data management staff without the requirement for case-by-case referral to the investigator.  For example, if a case report form page lists concomitant medications taken by a patient but the box stating ‘Are there any medications this cycle?’ is blank, the box may be ticked by the data manager. 

A list of such data correction conventions should be agreed by the investigator prior to data management activities taking place.

Any adverse event or adverse reaction that results in death, is life-threatening*, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect.

Comment:  Medical judgement should be exercised in deciding whether an adverse event/reaction should be classified as serious in other situations. Important adverse events/reactions that are not immediately life-threatening or do not result in death or hospitalisation, but may jeopardise the subject or may require intervention to prevent one of the other outcomes listed in the definition above, should also be considered serious.

* Life-threatening in the definition of a serious adverse event or serious adverse reaction refers to an event in which the subject was at risk of death at the time of the event. It does not refer to an event which hypothetically might have caused death if it were more severe.

A “serious breach” is a breach which is likely to effect to a significant degree:

a) the safety or physical or mental integrity of the subjects of the trial; or

b) the scientific value of the trial.

A communication document that makes clear what the supplier will deliver and what the organisation will ensure. It is based on the conditions of contract and specification and does not in any way replace them.

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 data may be in hard copy or electronic format.

See Reflection paper on expectations for electronic source data and data transcribed to electronic data collection tools in clinical trials (PDF, 127 KB) (.PDF).

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).

The individual, or organisation (or group of individuals or organisations) that takes on responsibility for confirming that there are proper arrangements in place to initiate, manage and monitor, and finance a study. Responsibilities are defined by the UK Policy Framework for Health and Social Care Research and by the Clinical Trials Regulations.

Where the term sponsor is used in this Toolkit, it refers to the individual, organisation or group member delegated sponsor responsibilities/functions.

Written instructions to achieve uniformity of the performance of a specific function.

A statistical analysis plan is a document that contains a more technical and detailed elaboration of the principal features of the analysis described in the protocol, and includes detailed procedures for executing the statistical analysis of the primary and secondary variables and other data.

An individual who participates in a clinical trial as either a recipient of the investigational medicinal product or a control. The preferred term for the HRA, NRES and many key trials stakeholders is 'Participant' but the term 'Subject' is referenced in law for CTIMPs. See also Participant.

A change to the terms of the approval given by either:

• the competent authority (MHRA in the UK) or the research ethics committee or;
• a change to the protocol or any other document submitted with the applications,

which significantly affects one of the following:

• the safety or physical or mental integrity of study participants
• the conduct or management of the study
• the scientific value of the study
• the quality or safety of any investigational medicinal product used in the study.

The basis of information for health professionals on how to use the medicinal product safely and effectively. They are written and updated by pharmaceutical companies and are based on their research and product knowledge. It is then checked and approved by the UK or European medicines licensing agency.

The leaflet that is included in the pack with a medicine is a patient-friendly version of this document.

An adverse reaction that is both unexpected (not consistent with the applicable product information) and also meets the definition of a Serious Adverse Event/Reaction.

View an Adverse Event flowchart (pdf, 180.98 KB) (.PDF) outlining the assessments required to determine whether a SUSAR has occurred.

The Trial Management Group normally includes those individuals responsible for the day-to-day management of the trial, such as the Chief Investigator, statistician, trial manager, research nurse, data manager. The role of the group is to monitor all aspects of the conduct and progress of the trial, ensure that the protocol is adhered to and take appropriate action to safeguard participants and the quality of the trial itself.

The Trial Master File contains all essential documents held by the sponsor/Chief Investigator which individually and collectively permits the evaluation of the conduct of a trial and the quality of the data produced.

A hospital, health centre, surgery or other establishment or facility in the UK at or from which a CTIMP, or any part of a CTIMP, is conducted.

The role of the Trial Steering Committee (TSC) is to provide the overall supervision of the trial. Ideally, the TSC should include members who are independent of the investigators, their employing organisations, funders and sponsors. The TSC should monitor trial progress and conduct and advise on scientific credibility. The TSC will consider and act, as appropriate, upon the recommendations of the Data Monitoring Committee (DMC) or equivalent and ultimately carries the responsibility for deciding whether a trial needs to be stopped on grounds of safety or efficacy.

See MRC Guidelines for GCP for Clinical Trials 1998 for terms of reference and further guidance (Appendix 3).

Trials involving medicinal products licensed in any EU Member State if:

• they relate to the licensed range of indications, dosage and form; or
• they involve off-label use (such as in paediatrics and in oncology etc.) if this off-label use is established practice and supported by sufficient published evidence and/or guidelines.

For CTIMPs: An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g. Investigator's brochure for an unauthorised investigational product or summary of product characteristics (SmPC) for an authorised product).

An appropriate measure required to be taken in order to protect the subjects of a clinical trial against any immediate hazard to their health or safety.

Please refer to the Urgent Safety Measures station for more information.

A complete NIHR research application that has been received by the NHS provider following its submission via IRAS that enables regulatory reviews by other agencies (including but not limited to Research Ethics Committee and MHRA approval) to be conducted in parallel with the work on NHS permission by the contractor.

NIHR Guidance on making an application.