Adverse Device Effect (ADE)
Adverse event related to the use of an investigational medical device. Note: This definition includes adverse events resulting from insufficient or inadequate Instructions for Use, deployment, implantation, installation, or operation, or any malfunction of the investigational medical device. This definition includes any event resulting from use error or from intentional misuse of the investigational medical device.
Note: Three definitions taken from two sources are provided here. Use the definition appropriate to your trial.
1. National Clinical Trials Governance Framework
An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An adverse event is an incident that results, or could have resulted, in harm to a patient or consumer. An unintended near miss is a type of adverse event. See also near miss.
2. NHMRC Safety monitoring and reporting in clinical trials involving therapeutic goods - Definition used for Investigational medicinal product trials
Any untoward medical occurrence in a patient or clinical trial participant administered a medicinal product and that does not necessarily have a causal relationship with this treatment.
3. NHMRC Safety monitoring and reporting in clinical trials involving therapeutic goods - Definition used for Investigational medical device trials
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in participants, users or other persons, whether or not related to the investigational medical device. Note: This definition includes events related to the investigational medical device or the comparator. This definition includes events related to the procedures involved. For users or other persons, this definition is restricted to events related to investigational medical devices.
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 possibility of a causal relationship to an investigational medicinal product would qualify as adverse reactions.
Approving authorities are public or private legal entities (institutions or organisations) where trials are conducted.
A senior member of the clinical trial team designated and supervised by the investigator at a trial site to perform trial-related procedures and/or to make important trial-related decisions. Associates, residents, research fellows, clinical research coordinators may be called an Associate Investigator.
A systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data recorded, analysed and accurately reported according to the protocol, sponsor’s standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirements(s). In the case of investigator-initiated trials, auditing activities are usually undertaken by the sponsor institution’s Research Governance Office.
Australian Code for the Responsible Conduct of Research
A principles-based document that articulates the broad principles and responsibilities that underpin the conduct of Australian research.
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Carers are people who provide unpaid care and support to family members and friends who have a disability, mental illness, chronic condition, terminal illness, an alcohol or other drug issue or who are frail aged.
Caring may include help and support in any of the daily activities of the person being cared for. It may include physical and personal care and assistance such as dressing, lifting, showering, feeding or providing transport. Commonly, carers are responsible for the management of medications. Carers provide emotional, social or financial support. Caring may also involve helping the person they are caring for to be organised, reminding them to attend appointments and dealing with emergencies.
CAPA (Corrective and Preventive Action) Owner
An individual who ensures that a corrective and or preventive action(s) is managed, documented, completed, modified and verified as effective.
Centralised monitoring is a remote evaluation of accumulating data, performed in a timely manner, supported by appropriately qualified and trained persons, eg data managers and biostatisticians. Provides additional monitoring capabilities to on-site monitoring that can complement and reduce the extent and/or frequency of on-site monitoring and help distinguish between reliable data and potentially unreliable data.
Review of the accumulating data may include statistical analyses and can be used to:
- Identify missing data, inconsistent data, data outliers, unexpected lack of variability and protocol deviations
- examine data trends such as the range, consistency, and variability of data within and across sites
- evaluate for systematic or significant errors in data collection and reporting at a site or across sites; or potential data manipulation or data integrity problems
- analyse site characteristics and performance metrics
- select sites and/or processes for targeted on-site monitoring
A copy (irrespective of the type of media used) of the original record that has been verified (ie, 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.
Chief Executive Officer (CEO)
The CEO (or equivalent) is required to support a culture within their organisation of responsible clinical trial practice and ensuring their staff are aware of their responsibilities. The role is responsible for ensuring all clinical trials undertaken within their organisation complies with the requirements of national and local legislation and ensures appropriate research governance, personnel, systems and structures are in place.
Clinical governance is an integrated component of corporate governance of health service organisations. It ensures that everyone – from frontline clinicians to managers and members of governing bodies, such as boards – is accountable to patients and the community for assuring the delivery of safe, effective and high-quality services. Clinical governance systems provide confidence to the community and the healthcare organisation that systems are in place to deliver safe high-quality health care.
Clinical registries are used to record diagnoses of a particular condition or health service/product specific and include surgical registries or disease registries. Clinical registries are also used for Registry-Randomised Controlled Trials (rRCT). They may exist independently of the trial or be established alongside a specific registry trial, according to the associated protocol.
Clinical study report
A written description of a trial of any therapeutic, prophylactic, or diagnostic agent conducted in human participants, in which the clinical and statistical description, presentations, and analyses are fully integrated into a single report and provided to the applicable regulatory agency(ies) to support marketing applications. The report should meet the standards of the International Conference of Harmonisation (ICH): Guideline for Structure and Content of Clinical Study Reports.
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 trials include but are not limited to:
- Surgical and medical treatments and procedures
- Experimental drugs and diagnostics
- Biological products
- Medical devices
- Health-related service changes
- Health-related preventative strategies
- Health-related educational interventions
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 CTX scheme is appropriate for trials where the approving 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 governance office review
Clinical trial ‘governance’ is the term used for institutional review or site-specific assessment (SSA). From a broader perspective, ethics-approval forms part of the overall governance framework that ensures the compliance, accountability and transparency of research activity at a site.
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 approving ethics committee has enough scientific and technical expertise to review the proposed use of the unapproved therapeutic good(s). The majority of investigator-initiated trials would be in this category.
Clinical Trial Research Agreement
An agreement between the trial sponsor and trial site. Sets out the terms of the partnership including financial arrangements, budgetary milestones, insurance arranges, intellectual property and publications.
Clinical trial team
The clinical trial team includes individuals, identified by the investigator, who are responsible for study coordination, data collection and data management. Members of the clinical trial team may also be called the research coordinator, study coordinator, research nurse, study nurse or sub-investigator, clinical trial pharmacist and may have various roles in the clinical trial including:
- Participant recruitment and enrolment
- Obtaining consent from prospective participants, meet with research participants, and collect and record information from research participants
- Maintain consistent study implementation
- Data management, and to ensure integrity
- Dispensing and administering the investigational product
- Compliance with regulatory and reporting requirements.
Clinical trial workforce
The clinical workforce includes, but is not limited to: trial investigators, trial sub-investigators, clinical trial pharmacists, trial managers, trial coordinators HREC Executive Officers, Site Specific Assessment Officers, research office staff.
Collaborative Research Group
An academic and/or non-commercial collaborative research group responsible for sponsoring, initiating, managing, developing and coordinating a study.
An agreement used when confidential information will be shared or received from an external organisation. It binds the receiving party to maintaining the confidential nature of the information.
A person who has used, or may potentially use, health services, or is a carer for a patient using health services. A healthcare consumer may also act as a consumer representative, to provide a consumer perspective, contribute consumer experiences, advocate for the interests of current and potential health service users, and take part in decision-making processes.
The sponsor will require contracts to be finalised and signed before the contracted activity commences. Examples of contracts required for investigator-initiated trials include:
- Service provider agreements with individuals/organisations contracted to perform sponsor’s trial-related duties or functions, eg external laboratories, Clinical Research Organisations (CRO), courier service provider
- Clinical Trial Research Agreement (CTRA) with each participating trial site
- Funding agreements with external funders, eg NHMRC, pharmaceutical company providing drugs
- Data Transfer Agreement with collaborators seeking to re-use the clinical trial data
- Sponsorship Agreement (such as a 'Certificate of Sponsorship') between investigator and sponsoring institution
Contract research organisation (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.
Coordinating Principal Investigator (CPI)
If a study is conducted at more than one study site, the Principal Investigator taking overall responsibility for the study and for the coordination across all sites is known as the Coordinating Principal Investigator (CPI). The Principal Investigator at each site will retain responsibility for the conduct of the study at their site.
Corrective and Preventive Action (CAPA)
A Corrective and Preventive Action (CAPA) 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
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Data refers to bits of information in their raw form. Data can refer to raw data, cleaned data, transformed data, summary data and metadata (data about data). It can also refer to research outputs and outcomes. (See National Statement, Chapter 3.1, Element 4). Note: Information generally refers to data that have been interpreted, analysed or contextualized.
An individual or a group of researchers from a third party seeking access to data from a Sponsor-Investigator.
Data Sharing Statement
As of 1 July 2018, manuscripts submitted to ICMJE journals that report the results of clinical trials must contain a data sharing statement. Data sharing statements must indicate the following:
- Whether individual de-identified participant data (including data dictionaries) will be shared
- What data in particular will be shared
- Whether additional, related documents will be available (eg, study protocol, statistical analysis plan, etc.)
- When the data will become available and for how long
- By what access criteria data will be shared (including with whom, for what types of analyses, and by what mechanism)
Data Transfer Agreement
The Data Transfer Agreement (DTA) is a binding legal agreement which must be executed by the individual/third party requesting access to the data (Data Requester) and the sponsoring institution prior to the transfer of data.
The DTA sets out the obligations of the Data Requester in relation to storage and use of the data. It describes the terms and conditions which must be agreed to prior to the release of data.
Delegation of duties log
An essential document used to demonstrate that the site Principal Investigator (PI) has authorised appropriately trained and qualified individuals to undertake certain trial-related tasks. May be combined with the site staff signature log. Should clearly state the name of the person, their role and the activities they are delegated by the PI as well as being signed and dated by the PI prior to the activity being undertaken by the individual.
Any breach, divergence or departure from the requirements of Good Clinical Practice or the clinical trial protocol.
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety or performance. Device deficiencies include malfunctions, use errors, and inadequate labelling.
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Electronic Medical Record (EMR)
EMRs are digital versions of the notes and information collected by and for the clinicians in that office, clinic, or hospital and are mostly used by providers for diagnosis and treatment.
EMRs are more valuable than paper records because they enable providers to track data over time, identify patients for preventive visits and screenings, monitor patients, and improve health care quality.
Ethical Review Manager (ERM)
The Ethical Review Manager (ERM) is an information management system for all ethics and research governance, throughout the life of a research project. The system is used for:
- All ethics applications
- All research governance applications
- All post-approval reports
- Data management
- Data reporting and metrics
- Document management
- Audit trail
Participants who have provided informed consent, have been screened for study eligibility and have been deemed eligible are considered enrolled in the study, except in clinical trials where participants are considered enrolled only after they have been assigned to the intervention.
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. The International Conference of Harmonisation GCP provides a minimum list of essential documents required to evaluate a study in Section 8 of the guideline. This list should be supplemented or may be reduced where justified based on the importance and relevance of the specific documents to the trial.
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General Data Protection Regulation (GDPR)
The EU General Data Protection Regulation (GDPR) replaces the Data Protection Directive 95/46/ED and was designed to harmonise data privacy laws across Europe, to protect and empower all EU citizens’ data privacy and to reshape the way organisations across the region approach data privacy.
Good Clinical Practice (GCP)
A standard for the design, conduct, performance, monitoring, auditing, recording, analysis 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.
The current GCP guideline is referred to as the Integrated addendum to ICH E6 (R1): Guideline for Good Clinical Practice ICH E6 (R2).
The Australian regulatory agency, the Therapeutic Goods Administration (TGA) has adopted this version of GCP but with some variations, TGA: ICH Guideline for Good Clinical Practice.
A set of relationships and responsibilities established by a health service organisation between its executive, workforce and stakeholders (including patients and consumers).
Governance incorporates the processes, customs, policy directives, laws and conventions affecting the way an organisation is directed, administered or controlled. Governance arrangements provide the structure for setting the corporate objectives (social, fiscal, legal and HR) of the organisation and the means to achieve the objectives. They also specify the mechanisms for monitoring performance.
Effective governance provides a clear statement of individual accountabilities within the organisation to help align the roles, interests and actions of the different participants in the organisation to achieve the organisation’s objectives. In the National Safety and Quality Health Service (NSQHS) Standards (second edition) governance includes both corporate and clinical governance.
The governing body is a board, chief executive officer, organisation owner, partnership or other highest level of governance (individual or group of individuals) that has ultimate responsibility for strategic and operational decisions affecting safety and quality in a health service organisation.
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Health care is the prevention, treatment and management of illness and injury, and the preservation of mental and physical wellbeing through the services offered by clinicians, such as medical, nursing and allied health professionals.
Healthcare record includes a record of the patient’s medical history, treatment notes, observations, correspondence, investigations, test results, photographs, prescription records and medication charts for an episode of care.
The Australian Commission on Safety and Quality in Health Care separates health literacy into two components – individual health literacy and the health literacy environment. The health literacy environment is the infrastructure, policies, processes, materials, people and relationships that make up the health system, which affect the ways in which consumers access, understand, appraise and apply health-related information and services.
Health service organisation
A separately constituted health service that is responsible for implementing clinical governance, administration and financial management of a service unit or service units providing health care at the direction of the governing body. A service unit involves a group of clinicians and others working in a systematic way to deliver health care to patients. It can be in any location or setting, including pharmacies, clinics, outpatient facilities, hospitals, patients’ homes, community settings, practices and clinicians’ rooms.
Human Research Ethics Committee (HREC)
The HREC is responsible for assessing the ethical acceptability of a proposal to conduct a clinical trial within the requirements of the NHMRC: National Statement on Ethical Conduct in Human Research and relevant national and jurisdictional legislation including guardianship legislation and the roles of civil and administrative tribunals for participation of people without the capacity to provide consent.
HRECs also monitor compliance, during ongoing trial conduct for the ethical conduct of the trial, in accordance with the National Statement and provide advice on strategies to promote awareness of the ethical conduct of clinical trials and research more broadly.
Human research ethics review
A process to explore the ethical issues presented by, and implications of, a research project. Human Research Ethics Committees (HREC) play a central role in the Australian system of ethical oversight of research involving humans.
HRECs review research proposals involving human participants to ensure that they are ethically acceptable and in accordance with relevant standards and guidelines, including the NHMRC: National Statement on Ethical Conduct in Human Research.
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Details attached to data, such as name and/or contact information, that identify an individual. It may remain possible to identify an individual even after all identifiers have been removed, if a code number has been assigned and there is access to the code, or if the data or tissue can be cross-linked to other data or tissue banks.
A person, who is independent of the trial, cannot be unfairly influenced by people involved with the trial, attends the informed consent process if the participant or the participant’s legally acceptable representative cannot read, and reads the informed consent form and any other written information supplied to the participant.Coordinatoring
An incident (clinical) is an event or circumstance that resulted, or could have resulted, in unintended or unnecessary harm to a patient or consumer; or a complaint, loss or damage. An incident may also be a near miss. See also near miss.
Indemnity is a form of insurance cover for damages or loss. Indemnity is usually not applicable for investigator-initiated trials. For commercially sponsored trials, the Sponsor indemnifies the employees of the trial site against any claims made on behalf of participants for personal injury relating to their participation in the trial.
This is evidenced by a Form of Indemnity that is signed by both a representative of the Sponsor and the institution. In some cases indemnity is required for the ethics committee approving the trial.
Individual health literacy
Individual health literacy is the skills, knowledge, motivation and capacity of a consumer to access, understand, appraise and apply information to make effective decisions about health and health care, and take appropriate action.
Informed consent is a process of communication between a patient and a clinician about options for treatment, care processes or potential outcomes. This communication results in the patient’s authorisation or agreement to undergo a specific intervention or participate in planned care. The communication should ensure that the patient has an understanding of the care they will receive, all the available options and the expected outcomes, including success rates and side effects for each option.
Refers to sponsorship of investigator-initiated trials by the Investigator’s employer. This may be a hospital, university or research institute. Institutional sponsorship is not automatic but managed through an application process by the requesting Investigator. The institution may delegate many of the sponsor responsibilities to the lead Investigator (also known as the Sponsor-Investigator) but they must still have oversight of these delegated functions.
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)
A harmonisation initiative for regulators and pharmaceutical industry, originally founded in 1990 and reformed as a non-profit legal entity under Swiss Law in 2015.
The ICH develops and maintains a suite of technical guidelines, including the Good Clinical Practice (GCP) guideline, Integrated addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6 (R2). The adoption of these guidelines by national regulatory authorities across the globe contributes to:
- Prevention of unnecessary duplication of clinical trials and post market clinical evaluations
- Development and manufacturing of new medicines
- Registration and supervision of new medicines
- Reduction of unnecessary animal testing without compromising safety and effectiveness
Investigational Medical Device
An Investigational Medical Device (IMD) includes any medical device being assessed for safety or performance in a clinical investigation. Note: This includes medical devices already on the market, that are being evaluated for new intended uses, new populations, new materials or design changes.
Investigational Medicinal Product
An Investigational Medicinal Product (IMP) is 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, a new patient group or when used to gain further information about an approved used. Note: This definition includes biologicals used as medicinal products.
The Investigational Product (IP) includes any product, or intervention being investigated, tested or used as a placebo or reference point in a clinical trial. This includes 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. The sponsor or their delegate, is responsible for the provision and maintenance of the IP.
An Investigator is an individual responsible for the conduct of a study, ensuring that the study complies with TGA: Guideline for Good Clinical Practice.
Investigator’s Brochure or Investigational Brochure (IB)
Compilation of the clinical and non-clinical data available on the experimental products intended for use in the clinical trial in question. It provides trial organisers and staff with an understanding of the rationale of the trial, in order to inform their compliance with the protocol requirements. The information enables a risk/benefit assessment of the appropriateness of the proposed trial, of vital importance to HREC considerations.
Investigator site file (ISF)
The investigator site file is the section of the trial master file (TMF) 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.
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Jurisdictional requirements are those systematically developed statements from state and territory governments about appropriate healthcare or service delivery for specific circumstances. Jurisdictional requirements encompass a number of types of documents from state and territory governments, including legislation, regulations, guidelines, policies, directives and circulars. Terms used for each document may vary by state and territory.
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Manual of Procedures (MOP)
A document that outlines the details of how to operationalise the protocol and conduct all study-specific procedures. The Manual of Procedures (MOP) ensures accuracy and consistency in study implementation across study participants, study sites and research staff.
Marketing Authorisation Holder
A person, or organisation, who has been granted approval by the Therapeutic Goods Administration (TGA) to supply a therapeutic good in Australia, and, in most cases, involves entry on the Australian Register of Therapeutic Goods (ARTG).
Material Transfer Agreement
An agreement that covers the provision of tangible materials from one institution to an other. It covers both biological and non-biological materials. It grants the recipient a license to use the material and ensures both parties understand how the materials can be used.
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.
A monitor’s qualifications should be documented. They should be thoroughly familiar with the investigational product(s), the protocol, written informed consent form and any other written information provided to participants, the Sponsor SOPs (both institutional-level and trial-specific), Good Clinical Practice (GCP), and the applicable regulatory requirements.
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 requirements.
The Sponsor may choose on-site monitoring, a combination of on-site and centralised, or where justified, centralised monitoring alone. On-site monitoring may also be supported by remote monitoring.
The sponsor should develop a risk-based monitoring plan that is tailored to the protocol. The plan should describe the monitoring strategy, the monitoring responsibilities of all the parties involved, the monitoring methods to be used, and the rationale for their use.
The plan should emphasise the monitoring of critical data and processes. Particular attention should be given to those aspects of the trial that are not routine clinical practice and that require additional training.
Monitoring visit report
The monitor should provide a written report of all monitoring activities, both on-site, centralised and remote, to the sponsor in a timely manner for review and follow up. The results of monitoring activities should be documented in sufficient detail to allow verification of compliance with the monitoring plan. Reports of centralised monitoring activities should be regular and may be independent from site visits.
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National Mutual Acceptance (NMA)
The NMA is a national system for mutual acceptance of scientific and ethical review of multi-centre human research projects conducted in publicly funded health services across jurisdictions. All states and territories participate in NMA. Single ethical and scientific review for a multi-centre human research project can be provided across the six participating states and territories.
The scope of NMA includes any form of human research as defined in the NHMRC: National Statement on Ethical Conduct in Human Research for which an application must be made to a Human Research Ethics Committee (HREC).
Near miss is an incident or potential incident that was averted and did not cause harm, but had the potential to do so.
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On-site monitoring is performed by the monitor at the trial site.
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A participant is a clinical trial subject (see trial subject) patient or consumer who is enrolled to participate in a clinical trial.
Participant Information and Consent Form (PICF)
The PICF provides information about a clinical trial to prospective participants and a mechanism for obtaining their written consent to participate. The information should include details such as the trial’s purpose, duration, required procedures, risks and potential benefits.
A patient is a person who is receiving care in a health service organisation.
Patient safety is the prevention of errors and adverse effects on patients associated with health care.
Information or an opinion about an identified individual, or an individual who is reasonably identifiable:
- Whether the information or opinion is true or not
- Whether the information or opinion is recorded in a material form or not.
Phase I clinical trials involve the first administration of the medicine to humans, usually to small numbers of healthy volunteers. Phase I trials determine the safety of the medicine, how it works and how well it is tolerated and are usually undertaken in specially equipped centres.
Phase II clinical trials are normally the first trials of the medicine in patients suffering the condition for which the medicine is intended. The principal aim of Phase II clinical trials is to determine effectiveness and safety.
Phase III clinical trials involve greater numbers of patients and are undertaken for the purpose of determining whether the medicine confers clinical benefit in the disease/s for which effectiveness was demonstrated in Phase II clinical trials. They also determine the nature and likelihood of any side effects.
Phase IV clinical trials are those clinical trials undertaken after the medicine has been approved for the treatment of a particular disease. Phase IV clinical trials are undertaken to compare a new medicine to a wider range of existing therapies and interventions, as well as to further investigate the use of medicines in the normal clinical setting of the disease as opposed to the conditions under which the trial was conducted.
Principal Investigator (PI)
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.
Policy is a set of principles that reflect the organisation’s mission and direction. All procedures and protocols are linked to a policy statement.
The evaluation of generalised characteristics prior to consent and screening to initially determine eligibility (following ethical and governance approval of the study). The characteristics may be determined from the medical record or other sources as appropriate to the study (including self-referrals by potential participants), but not via any procedures undertaken specifically for the study.
Procedure is the set of instructions to make policies and protocols operational, which are specific to an organisation.
A process is a series of actions or steps taken to achieve a particular goal.
A Program is an initiative, or series of initiatives, designed to deal with a particular issue, with resources, a time frame, objectives and deliverables allocated to it.
The approved Australian summary of the scientific information relevant to the safe and effective use of a prescription medicine.
Note: In a trial in which the IMP is an approved product, the Product Information may replace the investigator’s brochure. If the conditions of use differ from those authorised, the PI should be supplemented with a summary of relevant clinical and non-clinical data that supports the use of the IMP in the trial.
A detailed clinical trial plan that includes the purpose and procedures of the research and who can be part of the trial. The protocol provides the rationale, design, methodology for the trial conduct, who may participate in a trial, the length of a trial and the schedule of tests, procedures, medications and dosages, method of analysis, monitoring of data safety and quality. The sponsor of the trial is responsible for the protocol.
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Quality improvement is the combined efforts of the workforce and others – including consumers, patients and their families, researchers, planners and educators – to make changes that will lead to better patient outcomes (health), better system performance (care) and better professional development. Quality improvement activities may be undertaken in sequence, intermittently or on a continual basis.
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The process where people are identified and contacted for further discussion (where potentially eligible), provide informed consent and 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 adverse reactions and on the frequency and nature of those adverse reactions.
Registry trials are clinical trials that combine conventional trial methodology with registry systems to produce real-world clinical evidence. Registry trials, otherwise known as pragmatic trials, include registry-based randomised controlled trials (RRCT).
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 organisation’s (CRO’s) facilities, or at other establishments deemed appropriate by the regulatory authority)ies). Inspections may be routine or for-cause.
During a routine inspection, inspectors will select a number of clinical trials in order to get an understanding of the work carried out by the sponsor and examine how the organisation’s trial procedures support compliance with Good Clinical Practice (GCP) and are applied in practice. Inspections may also be trial-specific, especially pivotal or key-decision making trials that are to be submitted in support of a marketing application or to significantly alter clinical practice.
Remote monitoring is the activity of accessing trial data electronically, away from the trial site. The monitor needs remote access to the electronic case report form and/or the investigator site file.
Research includes investigation undertaken to gain knowledge and understanding or to train researchers.
Research Collaborative Agreement
An agreement used to set out the terms of a collaboration between two or more institutions. For example when two institutions are involved in developing the trial protocol or sharing other Sponsor responsibilities.
Research Governance Office (RGO)
The Research Governance Office or Research Office at the institution or organisation where the trial is conducted (ie trial site). The RGO acts as the approving authority at site level and is responsible for overseeing the site assessment and authorisation process.
The RGO will only grant site authorisation once the trial has received ethics approval and they are satisfied that the Sponsor and site Principal Investigator have systems in place to appropriately manage quality, safety, privacy, risk management, financial management and ethical acceptability for the trial. The RGO also has responsibilities for monitoring trials to verify they the conduct of research conforms with the conditions of ethics approval and site authorisation.
Risk is the chance of something happening that will have a negative or positive impact. Risk is measured by the consequences of an event and its likelihood.
Risk assessment is the assessment, analysis and management of risks. It involves recognising which events may lead to harm in the future, and minimising their likelihood and consequence.
Risk management is the design and implementation of a program to identify and avoid or minimise risks to patients, employees, volunteers, visitors and the organisation.
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Safety culture is a commitment to safety that permeates all levels of an organisation, from the clinical workforce to executive management. Features commonly include acknowledgement of the high-risk, error-prone nature of an organisation’s activities; a blame-free environment in which individuals are able to report errors or near misses without fear of reprimand or punishment; an expectation of collaboration across all areas and levels of an organisation to seek solutions to vulnerabilities; and a willingness of the organisation to direct resources to deal with safety concerns.
A serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose results in death or is life threatening.
Scope of clinical practice
Scope of clinical practice is the extent of an individual clinician’s approved clinical practice within a particular organisation, based on the clinician’s skills, knowledge, performance and professional suitability, and the needs and service capability of the organisation.
Where the person has provided consent after being fully informed of the study, and has been found to be ineligible, either because the inclusion criteria have not been met, or an exclusion criteria has been met.
Screening involves collection of information that is in addition to clinical care, it is collected for the reason of assessing eligibility for the study. Some examples of this are: testing cognition, assessing level of physical function, taking blood samples, and requesting medication history. As such this information is always collected after consent has been obtained.
Personal information that includes information or an opinion about an individual’s:
- Racial or ethnic origin
- Political opinions or associations
- Religious or philosophical beliefs
- Trade union membership or associations
- Sexual orientation or practices
- Criminal record
- Health or genetic information
- Some aspects of biometric information
Generally, sensitive information has a higher level of privacy protection than other personal information.
Serious Adverse Device Effect (SADE)
An adverse device effect that has resulted in any of the consequences characteristic of a serious adverse event.
Serious Adverse Event (SAE)
Note: Two definitions are provided here. Depending on whether the investigational product is a medicine or a device, the definition of a serious adverse event is different. Use the definition appropriate to your trial.
- Serious Adverse Event definition for use in trials with investigational medicinal products
Any adverse event/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.
- Serious Adverse Event definition for use in trials with investigational medical devices
An adverse event that:
- Led to death
- Led to serious deterioration in the health of the participant, that either resulted in:
- A life-threatening illness or injury
- A permanent impairment of a body structure or a body function
- In-patient or prolonged hospitalisation
- Medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function
- Led to fetal distress, fetal death or a congenital abnormality or birth defect
A breach of Good Clinical Practice or the protocol that is likely to affect to a significant degree:
- The safety or rights of a trial participant
- The reliability and robustness of the data generated in the clinical trial
Note: This definition of serious breach comes from National Health and Medical Research Council (2018), Reporting of Serious Breaches of Good Clinical Practice (GCP) or the Protocol for Trials Involving Therapeutic Goods, and differs from the definition in the Australian Code for the Responsible Conduct of Research.
Agreement used when using an external service provider. For example provider of transcription/translation services, laboratory tests, courier services, trial monitoring.
Significant safety issue
A safety issue that could adversely affect the safety of participants or materially impact on the continued ethical acceptability or conduct of the trial.
A facility, location or institution (or group of institutions) that resource, conduct and manage clinical trials that come under one of the final research authorisation sign off.
A determination by an organisation that a research project to be conducted at one or more of its sites or under its auspices satisfies organisational requirements and may commence at the site/s over which it exercises its authority. Site authorisation is the outcome of the site assessment process.
Site Information Files (SIFs)
The SIF is a subsection of the Trial Master File (TMF). It contains duplicates of site-specific essential documents pertaining to participating sites.
Site-Specific Assessment (SSA)
The site governance process (separate to ethical review) completed at any time after the ethics application has been submitted for ethics review. The process is facilitated by the completion of a Site-Specific Assessment (SSA) application for each site where the research will be conducted.
The assessment helps each site decide if there are resources available to effectively conduct a research project at a nominated site. It considers risks, impacts and practices at each research location. Resources may include staff, equipment and human participant considerations. Evidence of adequate indemnity and contract arrangements (where applicable) is also reviewed.
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 verification
The act of checking the accuracy and completeness of the CRF entries against source documents to ensure that:
- All assessments have been conducted and completed in accordance with the protocol and within the specified timeframe
- The data from those assessments have been recorded in source documents
- The source data have been accurately transcribed into the CRF
- Any deviations have been identified and recorded
- All adverse events, concomitant medications and intercurrent illnesses are recorded and reported in the CRF in accordance with the protocol
- Assessments have been made by an appropriately qualified person who has been delegated that activity
Original documents, data, and records (eg, 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).
An individual, organisation or group taking on responsibility for securing the arrangements to initiate, manage and finance a study. Clinical trial sponsors can be commercial companies, collaborative research groups, government entities including health service organisations, individual investigators or universities.
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.
A standard is agreed attributes and processes designed to ensure that a product, service or method will perform consistently at a designated level.
Standard operating procedures (SOPs)
Detailed, written instructions to achieve uniformity of the performance of a specific function.
Statistical analysis plan (SAP)
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.
The Study Coordinator (also referred to as clinical trials coordinator) position liaises between the principal investigator, HREC and Site-Specific Assessment Office and works collaboratively with the governing body, clinical and non-clinical managers, clinicians, patients, trial participants, consumers and sponsors.
Departments or authorities involved in the clinical trial or research, for example: nursing, health information, pathology, interpreting services, pharmacy, tissue bank(s), radiology and medical imaging.
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)
An adverse reaction that is both serious and unexpected.
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In relation to the evaluation, assessment and monitoring done by the Therapeutic Goods Administration (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
- Testing 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 the Australian Government Department of Health agency responsible for the regulation of, supply, import, export, manufacturing and advertising of therapeutic goods in Australia.
Training is the development of knowledge and skills.
Trial feasibility assessment
The Sponsor or Sponsor-Investigator must undertake an assessment before a trial site is selected to establish if the trial can be run successfully at the site. This involves collecting information about the potential number of participants that meet the eligibility criteria, the research staff availability/expertise and any site-specific requirements. Information is assessed via questionnaires or by pre-trial selection visits.
The individual responsible for the conduct of the clinical trial at a trial site. If a clinical 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.
Trial Master File (TMF)
The TMF is the collection of essential documents that allows 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. It is normally composed of a sponsor file and an Investigator Site File and these are held, controlled and maintained by the Sponsor and site Principal Investigator, respectively. These files together are regarded as comprising the entire TMF for the trial and should be established at the beginning of the trial.
An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control.
Trial registration is the process whereby key details about the design, conduct and administration of planned clinical trials are made available on a publicly accessible database known as a clinical trial registry. The primary consideration for choice of registry is that the registry must meet the ICMJE requirement that it is either a primary register of the WHO International Clinical Trials Registry Platform (ICTRP) or ClinicalTrials.gov, which is a data provider to the WHO ICTRP.
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Unanticipated Serious Adverse Device Effect (USADE)
Serious adverse device effect which by its nature, incidence, severity or outcome has not been identified in the current version of the risk analysis report.
Unexpected Adverse Reaction (UAR)
An adverse reaction, the nature or severity of which is not consistent with the Reference Safety Information (RSI). Note: The RSI should be contained in the Investigator’s Brochure for an unapproved medicinal product or Product Information (or another country’s equivalent of the Product Information) for an approved medicinal product.
Urgent safety measure (USM)
A measure required to be taken in order to eliminate an immediate hazard to a participant’s health or safety.
Note: This type of significant safety issue can be instigated by either the investigator or sponsor and can be implemented before seeking approval from HRECs or institutions.
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The management of multiple versions of the same document.
Version control enables the user to distinguish one version of a document from another, and helps to track changes and identify when key decisions were made.
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Workforce includes all people working in a health service organisation, including clinicians, and any other employed or contracted, locum, agency, student, volunteer or peer workers. The workforce can be members of the health service organisation or medical company representatives providing technical support who have assigned roles and responsibilities for care of, administration of, support of, or involvement with, patients in the health service organisation or trial site.