Glossary
Adaptive; as in ‘adaptive trial’ or ‘adaptive design’
An adaptive trial is a trial where aspects of the trial design may be modified, typically based on analysis of accumulated data at interim analyses. Can be either Bayesian or frequentist. See interim analysis. General overviews of adaptive trial designs, including common design types, can be found in Berry (2012), Park et al. (2018), and Pallmann et al. (2018). For a clinician-focused primer on design consideration, see Thorland et al. (2018). For an overview of methodological considerations, see Granholm et al. (2022). Berry et al. (2010) provide a comprehensive handbook on adaptive trials using Bayesian methods in particular.
For a regulators perspective, see US Food and Drug Administration (2010, 2018, 2020, 2022). Wason et al. (2019) provide an insightful commentary on when adaptive designs are not useful.
Adaptive Platform Trial Design
A clinical trial setup allowing for the adjustment of treatments being tested—such as adding new ones or removing ineffective ones—based on ongoing results.
Adverse Event
Any untoward medical occurrence in a patient or clinical trial participant administered a medicinal product or other intervention. It does not necessarily have a causal relationship with this treatment.
Adverse Reaction (AR)
Any untoward and unintended response to an investigational medicinal product related to any dose administered.
Auditor
An independent person or organisation who performs a systematic and independent examination of research related activities and documents to determine whether trial related activities, documentation, and data management have been conducted according to the protocol, GCP and applicable regulatory requirements.
Basket Trial
The US Food and Drug Administration (2022) define a basket trial as a:
[...] trial [that] involves a single investigational drug or drug combination that is studied across multiple populations defined by disease, histology, number of prior therapies, genetic or other biomarkers, or demographic characteristics.
Note that, more generally, the intervention does not necessarily need to be a drug and could conceivably be any type of intervention.
Bayesian Analysis
A statistical method that updates the probability for a hypothesis as more evidence becomes available.
Case Report Form (CRF)
Data collection tool used to record all the protocol required information to be reported to the sponsor on each research/trial participant. The CRF may be paper or electronic.
Central Trial Coordinating Team
A group of MCRI researchers (at the Sponsor-level) organised to coordinate the planning, development, operations and conduct of an MCRI-sponsored, Investigator-Initiated, clinical trial.
Clinical Epidemiology and Biostatistics Unit (CEBU)
CEBU specialises in biostatistics, epidemiological methods and data management. The group is jointly supported by MCRI and the University of Melbourne's Department of Paediatrics to provide expertise and support in these areas to all researchers on the Melbourne Children's campus.
Clinical Monitoring Plan (CMP)
In accordance with the Integrated Addendum to ICH E6 (R1) Guideline for Good Clinical Practice E6 (R2) Section 5.18.7 (that was formerly adopted by the TGA with annotations on 8 February 2018), the Sponsor should develop a monitoring plan that is tailored to the specific human subject protection and data integrity risks of the trial. This plan must describe the monitoring strategy, the monitoring responsibilities of all the parties involved, the various monitoring methods to be used, and the rationale for their use.
Certified Copy
A copy (irrespective of the type of media used) of the original record that has been verified (i.e., by a dated signature or by generation through a validated process) to have the same information, including data that describe the context, content, and structure, as the original.
Central Trial Coordinating Centre
A group of MCRI researchers organised to coordinate the planning, development, operations and conduct of an MCRI-sponsored IIT, multi-centre, clinical trial.
Clinical Research Coordinator
A research worker who works at a clinical research site under the immediate direction of a Principal Investigator, whose research activities are conducted under Good Clinical Practice guidelines. May also be called a research coordinator, study coordinator or (for clinical trials research) a clinical trial coordinator.
Clinical Research Development Office (CRDO)
CRDO provides education and training to facilitate and increase capacity for clinical and public health research across the Melbourne Children's campus. This includes the development and implementation of Standard Operating Procedures and templates to enable researchers to conduct high quality research.
Clinical Trial
The World Health Organization (WHO) definition for a clinical trial is: 'any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes'.
Clinical Trial Approval (CTA)
Formally known as Clinical Trial Exemption (CTX), one of two schemes used by the Therapeutic Goods Administration (TGA) to authorise the supply of unapproved therapeutic goods, including medicines, medical devices, and biologicals, to participants participating in clinical trials in Australia.
The CTA scheme is appropriate for trials where the reviewing ethics committee does not have access to the appropriate scientific and technical expertise to review the trial under the CTN scheme. It is generally used for high risk or novel treatments, such as gene therapy, where there is no or limited knowledge of safety.
Clinical Trial Notification (CTN)
One of two schemes used by the Therapeutic Goods Administration (TGA) to authorise the supply of unapproved therapeutic goods, including medicines, medical devices, and biologicals, to participants participating in clinical trials in Australia.
The CTN scheme is appropriate for trials where the reviewing ethics committee has enough scientific and technical expertise to review the proposed use of the unapproved therapeutic good(s). Most investigator-initiated trials would be in this category.
Clinical Trial of an Investigational Medicinal Product (CTIMP)
A Clinical Trial of an Investigational Medicinal Product (CTIMP) is a study that looks at the safety or efficacy of a medicine/foodstuff/placebo in humans, as defined by the Medicines for Human Use (Clinical Trials) Regulations 2004.
Clinical Trial Research Agreement
An agreement between the Sponsor and a participating site that sets out the rights and obligations of each party in relation to the conduct of a clinical trial.
Cluster randomisation
When treatment is randomly allocated to groups (or clusters), rather than individuals. Used as the basis for cluster randomised trials including stepped-wedge and cluster cross-over designs. In a cluster randomised trial, the ’unit of analysis’ typically refers to the level at which the data are analysed. For example, the ’unit of analysis’ may be at the individual level, but in some cases outcomes may be analysed at the cluster level.
Collaborative Research Group
An academic and/or non-commercial collaborative research group responsible for sponsoring, initiating, managing, developing, and coordinating a research study/trial.
Concurrently Randomised Controls
Participants in a clinical trial assigned to a control or comparison group at the same time as others are assigned to the experimental or treatment group.
Control
A group of participants that does not receive the experimental treatment being tested. This group may receive no treatment, a standard treatment, or a placebo to compare the effects of the experimental treatment against.
Consumer
Patients and potential patients, carers, and people who use health care services. Consumers can also be people who represent the views and interests of a consumer organisation, a community, or a wider constituency.
Contract Research Organisation (CRO)
An organisation (commercial, academic or other) providing a service used by either the sponsor or the investigator to fulfil trial-related activities.
Core (Master) Protocol
Also known as a ‘master protocol’. A document that details the central aims of a trial along with core trial endpoints, decision rules, estimands, and trial governance structures that will be consistent throughout the design and across different domains. Typically used in platform, umbrella, and basket trials. Ideally immutable over time, although subject to change with appropriate approvals from ethical, research, and funding bodies. The core protocol is typically supplemented by appendices that describe specific aspects of the trial, facilitate design adaptations, typically including a statistical appendix, a continually updated and version controlled implementation guide for scheduled analyses, and statistical analysis plans that are implemented when a terminal analysis is required. See recent regulatory guidelines (US Food and Drug Administration, 2020).
Corrective and Preventive Action Plan
A Corrective and Preventive Action (CAPA) plan is a quality system plan and incorporates:
- Identifying the issue, including scope and impact
- Identifying the root cause of the issue – how/why it occurred
- Identifying actions to prevent recurrence of the issue (corrective action) or, identify actions to prevent an issue from occurring (preventive action)
- Documenting that the corrective actions/preventive actions were completed
- Documenting that the corrective/preventive action has resolved the problem
Critical to Quality (CTQ) Factors
A basic set of factors relevant to ensuring study quality identified for each study. They are attributes of a study whose integrity is fundamental to the protection of study participants, the reliability and interpretability of the study results, and the decisions made based on the study results. They are considered to be critical because if their integrity was undermined by errors of design or conduct, the reliability or ethics of decision-making based on the results of the study would also be undermined.
Data Safety Monitoring Board (DSMB)
An independent and multi-disciplinary group established by the trial sponsor to review, at intervals, accumulating trial data, in order to monitor the progress of a trial and to make recommendations on whether to continue, modify or stop the trial for safety or ethical reasons.
Direct Access
Permission to examine, analyse and verify records that are important to the evaluation of a clinical trial and may be performed on-site or remotely. Any party (e.g., domestic and foreign regulatory authorities, sponsor’s monitors and auditors) with direct access should take reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of participants’ identities and their data and sponsor’s proprietary information.
Domain
A set of mutually exclusive and competing interventions that share a common clinical mode of action or clinical context of use.
Domain-specific Appendix (DSA)
An appendix to a core or master-protocol document describing the protocol relating to a given domain of a multifactorial platform trial.
Embedding
The process of integrating research activities within routine patient care, e.g. one or more of screening, recruitment, delivery of intervention, and data collection.
Estimated
Specific definition of the quantity of interest in a research study. Defining an estimand entails providing details on five attributes: intervention condition(s), population, outcome, population-level summary and postrandomisation events (also known as intercurrent events).
Essential Documents
Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced. These documents serve to demonstrate the compliance of the Investigator, Sponsor and monitor with the standards of Good Clinical Practice (GCP) and with all applicable regulatory requirements. Filing essential documents at the Sponsor site and participating trial sites also assists with the successful management of the trial.
Food and Drug Administration (FDA)
A department of the United States of America’s federal government responsible for the control and supervision of food safety, tobacco products, dietary supplements, medications, vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, animal foods & feed, and veterinary products.
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 participants are protected.
Good Manufacturing Practice (GMP)
A set of principles and procedures that when followed helps ensure that therapeutic goods are of high quality.
A basic tenet of GMP is that:
- quality cannot be tested into a batch of product
- quality must be built into each batch of product during all stages of the manufacturing process.
Human Research Ethics Committee (HREC)
A body which reviews research proposals involving human participants to ensure that they are ethically acceptable and in accordance with relevant standards and guidelines. The National Statement requires that all research proposals involving human participants be reviewed and approved by an HREC and sets out the requirements for the composition of an HREC.
Inclusion and Exclusion criteria
- Inclusion criteria - A list of conditions, that individuals must meet, in order to be eligible to participate in the study.
- Exclusion criteria - A list of conditions, any of which will exclude the person from participating in the study.
International Conference on Harmonisation (ICH)
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is unique in bringing together the regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of drug registration.
Interim Analysis
An analysis conducted over the course of an ongoing trial using the data accumulated so far. Results can be used to implement a priori decision rules and potentially modify the conduct of the trial. See also ‘scheduled analysis’.
Intervention/Treatment
A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include non-invasive approaches, such as education or modifying diet and exercise.
Investigational New Drug Application (IND)
An IND is a request for authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans. Such authorization must be secured prior to interstate shipment and administration of any new drug or biological product that is not the subject of an approved New Drug Application or Biologics/Product License Application (21 CFR 312).
Investigator
A person responsible for the conduct of the clinical trial at a trial site. There are four types of Investigator roles used to describe Investigators with different levels of responsibility for the conduct of clinical trials. These are described below.
Associate Investigator
Any individual member of the clinical trial team designated and supervised by the Principal 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). May also be referred to as sub-investigator.
Coordinating Principal Investigator (CPI)
If a study is conducted at more than one study site, the Principal Investigator taking the additional responsibility for coordination of the study across all sites in a region is known as the Coordinating Principal Investigator (CPI). This role applies to externally sponsored studies where the Sponsor may be a collaborative research group, commercial Sponsor or an institution. The Principal Investigator at each site will retain responsibility for the conduct of the study at their site.
Principal Investigator
The PI is the person responsible, individually or as a leader of the clinical trial team at a site, for the conduct of a clinical trial at that site. As such, the PI supports a culture of responsible clinical trial conduct in their health service organisation in their field of practice and, is responsible for adequately supervising his or her clinical trial team.
The PI must conduct the clinical trial in accordance with the approved clinical trial protocol and ensure adequate clinical cover is provided for the trial and ensure compliance with the trial protocol.
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 participant. The term does not include any person other than an individual (eg, 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.
Investigational Medicinal Product (IMP)
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 authorisation 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.
Investigational Medical Device (IMD)
A device that is the subject of a clinical study designed to evaluate the effectiveness and/or safety of the device.
Investigator-Initiated Trials (IITs)
A clinical trial which is initiated and organised by an Investigator i.e. an individual rather than a collaborative group, company, or organisation. In these cases, the Investigator will take on the role of the trial sponsor and will then be responsible for the extensive GCP and regulatory requirements associated with both the management and conduct of the trial.
Investigator Site File (ISF)
Filing repository controlled by the site Principal Investigator. It is held at the trial site and contains all the essential documents necessary for the site trial team to conduct the trial as well as the essential documents that individually and collectively permit evaluation of the conduct of the trial at the site and the quality of the data produced.
Investigator’s Brochure (IB)
The document containing a summary of the clinical and non-clinical data relating to an investigational medicinal product that are relevant to the study of the product in humans.
Legal Representative
A Legal Representative is an individual or legal entity established within the European Union that is designated to act on behalf of a non-EU sponsor for regulatory matters related to clinical trials. This role is crucial for ensuring that clinical trials meet the regulatory requirements set by the EU, including submission to National Competent Authorities and Ethics Committees.
Sponsors conducting clinical trials in the European Union without a registered European Economic Area (EEA), must appoint an EEA-based legal representative as per EU Clinical Trial Regulation. This requirement covers clinical trials involving medicinal products and medical devices. This representative acts as the point of contact with EU authorities, ensuring that the study complies with local laws and regulations.
Low / Negligible Risk (LNR)
Negligible Risk:
Research in which there is no foreseeable risk of harm or discomfort, and any foreseeable risk is of inconvenience only.
Low Risk:
Research in which the only foreseeable risk is one of discomfort.
Manual of Procedures (MOP)
A handbook which supplements the protocol to guide a study’s conduct and facilitate consistency in protocol implementation and data collection across participants and clinical sites. Also commonly known as Manual of Operations (MOO).
Melbourne Children’s
The campus encompassing all staff from The Royal Children’s Hospital, Murdoch Children’s Research Institute and Department of Paediatrics University of Melbourne who initiate or carry out research under one or more of these institutional affiliations.
Melbourne Children’s Trials Centre (MCTC)
Melbourne Children’s Trials Centre (MCTC) is a collaboration between the Royal Children’s Hospital, The Murdoch Children’s Research Institute, The Royal Children’s Hospital Foundation and The University of Melbourne. This Centre brings together expertise in research, clinical practice, and education and incorporates anyone who initiates or carries out research under one or more of these institutional affiliations.
Monitor
A person appointed by the Sponsor to undertake the role of monitoring for the trial. Monitors should be appropriately trained and should have the scientific and/or clinical knowledge needed to monitor the trial adequately.
Monitoring
The act of overseeing the progress of a clinical trial and of ensuring that the clinical trial is conducted, recorded and reported in accordance with the protocol, SOPs, GCP and the applicable regulatory requirement(s).
Multi-arm, multi-stage (MAMS)
A common name for an adaptive trial with more than 2 arms where data are used to evaluate pre-specified decision rules at different successive interim analyses.
Murdoch Children’s Research Institute (MCRI)
An Australian paediatric medical research institute located in Melbourne, Victoria, affiliated with the Royal Children's Hospital and the University of Melbourne. The institute has six research themes: cellular biology, clinical sciences, genetics, infection and immunity, population health, and data science.
National Health and Medical Research Council (NHMRC)
An independent statutory body within the portfolio of the Australian Minister for Health and Ageing responsible for allocating funding for, and directing, health and medical research, ethics and advice.
Non-Compliance Report Form
Used by sites participating in MCRI-sponsored IITs to report non-compliance with protocol or GCP to the Sponsor-Investigator/CPI when their assessment suggests a serious breach has occurred.
Non-Compliance Review Form
Used by Sponsor-Investigator/CPI to review non-compliance report Forms submitted by participating sites. This form documents the review and assessment of whether the Sponsor-Investigator/CPI determines the non-compliance to meet the definition of a serious breach.
Non-Concurrently Randomised Controls
Participants assigned to a control group before the introduction of participants to a new treatment group within a trial.
Participant
A participant is a person that is the subject of the research.
Participant Information and Consent Form (PICF)
The PICF provides information about research and its requirements so that the prospective participant can decide if they wish to take part in the research. In general, this includes the purpose, methods, demands, risks, and benefits of the research. It must provide information to participants in a concise format that they are likely to understand. It must be participant centred.
Pharmacovigilance
Process of ongoing monitoring of the safety profile, combined with the ongoing assessment and evaluation of the risk-benefit of medicines. The process is important to identify adverse reactions/adverse device effects and changes in the known safety profile.
Placebo
A treatment with no therapeutic effect, used as a control in testing new drugs.
Platform trial
A trial design that allows multiple interventions within one or more domains across one or more subgroups of participants, that is governed centrally using a core protocol.
Population
Comprises all those who meet the eligibility criteria (i.e. fulfil the inclusion criteria and exclusion criteria). Not necessarily only the trial participants.
Pragmatic Real-World Evaluation
A type of clinical study designed to test the effectiveness of interventions in real-life routine practice conditions, rather than under controlled clinical trial conditions.
Protocol
A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial.
Protocol Deviation
A protocol deviation is any breach, divergence or departure from the requirements of GCP or the clinical trial protocol.
Pseudonymisation
Replacing information which could be used to identify an individual with a pseudonym / value which does not allow the individual to be directly identified. This is distinct from anonymisation as it is usually possible to identify the subject of pseudonymised data by analysing the underlying or related data.
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 GCP and the applicable regulatory requirement(s).
Quality Control (QC)
The operational techniques and activities undertaken to verify that the requirements for quality of the trial-related activities have been fulfilled.
Quality by Design
A systematic approach to development that begins with predefined objectives and emphasises product and process understanding and process control, based on sound science and quality risk management.
Randomisation
Means by which trial participants are randomly allocated to treatment.
Response adaptive randomisation (RAR)
A randomisation procedure that uses past intervention assignments and participants responses to alter the probability of allocation to different intervention arms/regimens. Typically favours better performing arms/regimens at the time the calculation is made. Can either be ‘between participant’ or ‘within-participant’:
· Between-participant Individuals are randomised only once, however that randomisation depends on the observed outcomes of other individuals. Includes group-sequential, multi-arm, multi-stage designs, and response adaptive randomisation.
· Within-participant Individuals are randomised, with fixed probability, to multiple treatments sequentially over time, possibly depending on their observed histories. Includes sequential multiple assignment randomised trial designs and some N-of-1 studies.
Recruitment
Recruitment of participants for a research project (known as a study) is the process where people are identified and contacted for further discussion, provide informed consent, are screened and (where eligible) enrolled in a study.
Reference Safety Information (RSI)
The information contained in either an investigator’s brochure or an approved Australian Product Information (or another country’s equivalent) that contains the information used to determine what adverse reactions are to be considered “expected” adverse reactions. It will also contain information on the frequency and nature of those adverse reactions.
Registry trial
A pragmatic trial that uses clinical registries as an efficient and low-cost platform for case records, data collection, randomisation, and follow-up.
Repurposed Drugs
Medications that are already approved for one condition but are being tested for effectiveness against another condition.
Research Ethics and Governance Office (REG)
REG supports the HREC and institutional research governance processes at MCRI.
Research Governance Office (RGO)
The Office or coordinated function within Melbourne Children's which is responsible for assessing the site-specific aspects of research applications, make a recommendation to the CEO / delegate as to whether a research project should be granted authorisation at that site, and overseeing that authorised research at the site meets appropriate standards (research governance).
Royal Children’s Hospital (RCH)
The Royal Children’s Hospital is major specialist paediatric hospital in Victoria, the Royal Children's Hospital provides a full range of clinical services, tertiary care, as well as health promotion and prevention programs for children and young people. Its campus partners are the Murdoch Children's Research Institute and The University of Melbourne Department of Paediatrics, which are based on site at the hospital.
Statistical Analysis Plan (SAP)
A defined outline of the planned statistical methods for the analyses for a clinical trial which provides details on the scope of planned analyses, population definitions and methodology. It may be integrated into the Protocol or exist as a separate document.
Serious Adverse Event (SAE)
An adverse event is defined as serious if it:
· results in death
· is life-threatening
· requires hospitalisation or prolongation of existing hospitalisation
· results in persistent or significant disability or incapacity
· is a congenital anomaly or birth defect
Other important medical events will be considered an SAE when, based upon appropriate medical judgment, they may jeopardise the research participant safety and may require medical or surgical intervention to prevent one of the outcomes listed in the above definition. This can include diagnosis of cancer.
Serious Breach
A breach of Good Clinical Practice or the protocol that is likely to affect to a significant degree: a) The safety or rights of a trial participant, or b) The reliability and robustness of the data generated in the clinical trial. Note: this guidance's definition of serious breach differs from the definition in the Australian Code for the Responsible Conduct of Research and is about deviations from the requirements of Good Clinical Practice or the clinical trials protocol.
Significant Safety Issue (SSI)
A safety issue that could adversely affect the safety of participants or materially impact on the continued ethical acceptability of the trial.
Source Data
Source data is the original recording of an item of data. "All information in original records and certified copies of original records or clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial.” (Section 1.51, Notes for Guidance on Good Clinical Practice (CPMP/ICH/135/95) Annotated with TGA Comments).
Source Document
Source documents are documents which contain source data. When data is entered directly into your electronic Case Report Forms (data collection forms) or database, the Case Report Form/database becomes your source document for that information.
Sponsor
An individual, organisation or group taking on responsibility for securing the arrangements to initiate, manage and finance a study. For investigator-initiated trials, MCRI or RCH will act as the Sponsor but delegate many sponsor responsibilities to the Coordinating Principal Investigator. In this case the CPI has the role of both Sponsor and Investigator and hence the MCTC has adopted the term Sponsor-Investigator to reflect the dual role of the CPI in investigator-initiated trials.
Co-Sponsors
Multiple organisations share the funding acquisition, responsibility and conduct of the trial, potentially including pharmaceutical companies, research institutions, and government agencies. This can happen when organisations have a shared interest in the trial, for example, one as the employer of the principal investigator and another as the host institution. Each co-sponsor is accountable for their allocated responsibilities, and formal arrangements should be in place to clarify these responsibilities.
Co-sponsors divide amongst themselves both the responsibilities and the liabilities associated with sponsorship. Clinical trial applications to regulatory authorities must clearly define the set of sponsorship responsibilities taken on by each party. In the EU, the clinical trial authorisation (CTA) must clearly define the set of sponsorship responsibilities taken on by each party.
What does co-sponsorship mean in the context of an APT?
In the context of an Adaptive Platform Trial (APT), co-sponsorship means that two or more organisations jointly share responsibility for the trial, rather than a single entity. This is particularly relevant in APTs, which often involve multiple researchers, institutions, and funders collaborating to address a complex problem:
· Co-sponsorship implies that the responsibilities for the trial's initiation, management, and financing are shared among the co-sponsors.
· APTs are often conducted by collaborative networks of researchers or research institutions, like disease-focused consortia, making co-sponsorship a natural fit.
· Clear agreements between co-sponsors are crucial to delineate responsibilities and ensure a smooth trial execution. These agreements should outline who is responsible for various aspects of the trial, such as data management, safety reporting, and audits.
· Co-sponsorship can leverage the expertise and resources of multiple organisations, leading to more robust and efficient trial
Joint Sponsor
In the context of clinical trials, joint sponsors refer to partner organisations who accept joint liability for all the sponsor’s responsibilities. They are jointly and severally responsible for all the duties of the sponsor, such that all are responsible in the event of a failure of any one of the partner organisations to discharge their responsibilities.
Both organisations would have to have suitably qualified and trained staff to oversee all of the sponsor’s activities.
N.B. Most institutions that sponsor clinical trials involving IMPs have chosen to adopt sole sponsorship or co-sponsorship arrangements as they offer the greatest degree of clarity and transparency in the allocation of roles and responsibilities.
UK Universities generally do not permit co/joint sponsorship but rather will only act as a Legal Representative on behalf of MCRI providing delegation of roles and responsibilities are clearly defined and form the basis of the Agreement, e.g. University of Oxford.
Standard Operating Procedure (SOP)
Detailed, written instructions to achieve uniformity of the performance of a specific function.
Study Team
Refers to the extended group of people involved in a research study. This includes the investigator team and any additional members of staff who are involved in the set-up or conduct of the study e.g. research nurse, research assistants.
Suspected Breach
A report that is judged by the reporter as a possible serious breach but has yet to be formally confirmed as a serious breach by the Sponsor.
Suspected Unexpected Serious Adverse Reaction (SUSAR)
This is a serious adverse event:
- Where there is at least a reasonable possibility of a causal relationship between an intervention and an adverse event (in other words the relationship of the SAE to the trial drug/device/other intervention cannot be ruled out)
and
- That is unexpected, meaning that the nature or severity of the reaction is not consistent with the known scientific information (e.g. Investigator’s Brochure for an unapproved investigational product or product information document or similar for an approved, marketed product)
Therapeutic Good
In relation to the evaluation, assessment and monitoring done by the TGA, therapeutic goods are broadly defined as products for use in humans in connection with:
- preventing, diagnosing, curing, or alleviating a disease, ailment, defect, or injury
- influencing inhibiting or modifying a physiological process
- testing the susceptibility of persons to a disease or ailment
- influencing, controlling, or preventing conception
- test for pregnancy
This includes things that are:
- used as an ingredient or component in the manufacture of therapeutic goods
- used to replace or modify of parts of the anatomy
Therapeutic Goods Administration (TGA)
The Therapeutic Goods Administration (TGA) is Australia's regulatory authority for therapeutic goods.
Third Party Suspected Breach Report Form
Form used by sites to directly notify the reviewing HREC of a suspected serious breach. Use of this form is uncommon but is used if the Sponsor disagrees with the site assessment that a serious breach has occurred.
Traditional Trial
Often used to refer to standard 2 arm, parallel group, randomised clinical trials.
Trial Coordinator/Trial Manager
A Trial Coordinator/Trial Manager has a significant role in the management of the clinical trial at the Sponsor level and provides leadership in clinical trial activities to ensure that the trial is completed within budget, on time and of the highest quality. A Trial Coordinator/Manager is responsible for managing the planning, implementation, and tracking of the clinical monitoring process, administration, and start-up of the clinical trial at the participating site and maintaining an overview of the conduct of the trial at sites. Some common roles and responsibilities performed by the Trial Coordinator/Manager include:
- Participate in protocol development, CRF design and clinical study report writing
- Guide in the creation and development of important study documents and manuals
- Conduct feasibility assessments
- Develop study budgets
- Oversee participant recruitment
- Oversee overall trial conduct
- Ensure compliance of site-staff with the trials Standard Operating Procedures
- Ensures compliance to all regulatory requirements both at a local and international level
- Ensures compliance to all data protection requirements both at a local and international level
- Ensures compliance to all safety reporting requirements both at a local and international level
- Conduct team meetings and site-staff training programs
- Overall responsibility of the trial
- Supervise in-house clinical trial staff
Trial Master File (TMF)
Filing repository controlled by the Sponsor/Sponsor-Investigator. It is the collection of essential documents that allows the Sponsor responsibilities for the conduct of the clinical trial, the integrity of the trial data and the compliance of the trial with Good Clinical Practice (GCP) to be evaluated.
Trial Management Group (TMG)
The TMG is a group of key people at the coordinating or principal site who oversee the day-to-day conduct and progress of a clinical trial, including safety oversight activities and/or acting on advice from other individual(s) or group(s) providing safety oversight. For many investigator-initiated trials, the TMG performs the role of a TSC (see below) and/or the DSMB.
Trial Site
The location(s) at or from where trial-related activities are conducted under the investigator’s/institution’s supervision.
Trial Steering Committee (TSC)
Most commonly used in commercial trials and large international non‑commercial trials, a TSC is appointed by the sponsor to provide independent expert oversight for the trial. The TSC may include investigators, other experts not otherwise involved in the trial and, usually, representatives of the sponsor. Although blinded, the TSC acts as a body that takes responsibility for the scientific integrity of the protocol and the assessment of study quality and conduct.
Unexpected Adverse Reaction (UAR)
An adverse reaction, the nature or severity of which is not consistent with the Reference Safety Information (RSI).
Urgent Safety Measure (USM)
A measure required to be taken to eliminate an immediate hazard to a participant’s health or safety.
Quality Assurance (QA)
Covers all policies and systematic activities implemented within a quality system. QA ensures that data are recorded, analysed, and recoded in accordance with the protocol and GCP. The use of GCP guidelines ensures ethical and scientific quality standards for the design, conduct, recording, and reporting of HREC approved clinical trials that involve research participants.