A
Adverse Event (AE)
Any harm or untoward medical occurrence in a research participant administered a medical product, medical treatment or procedure even if it does not necessarily have a causal relationship with the product, treatment, or procedure. An adverse event can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medical product, medical treatment or procedure whether or not considered to be related.
[FDA: 21CFR 312.32]
Applicable Clinical Trial
- For any trials of drugs and biologics: controlled clinical investigations, other than Phase I investigations, of a product subject to FDA regulation.
- For trials of biomedical devices: controlled trials with health outcomes of devices subject to FDA regulation, other than small feasibility studies, and pediatric post-market surveillance.
Audit
A systematic and independent examination of trial-related activities and records performedby the sponsor, service provider (including Contract Research Organization (CRO)), orinstitution to determine whether the evaluated trial-related activities were conducted and the data were recorded, analyzed, and accurately reported according to the protocol, applicable Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).
[ICH GCP E6(R3)]
Audit Trail
Metadata records that allow the appropriate evaluation of the course of events by capturing details on actions (manual or automated) performed relating to information and data collection and, where applicable, to activities in computerised systems. The audit trail should show activities, initial entry and changes to data fields or records, by whom, when and, where applicable, why. In computerised systems, the audit trail should be secure, computer-generated and time stamped.
[ICH GCP E6(R3)]
C
Cancer-related study
A study that meets one or more of the following characteristics:
- Funded by NCI; or
- Primary site of a multi-site trial has classified the study as cancer or cancer-related; or
- The trial cohort will include both patients with a cancer diagnosis and others without a cancer diagnosis AND includes a primary or secondary analysis of the portion of the cohort with a cancer diagnosis; or
- Research of secondary conditions related to cancer treatment in patients with a cancer diagnosis who have received that treatment; or
- Cancer prevention studies that specifically include a primary outcome of cancer diagnosis;
- BMT not related to cancer treatment.
Case Report Form (CRF)
A data acquisition tool designed to record protocol-required information to be reported by the investigator to the sponsor on each trial participant (see Data Acqusition Tool).
[ICH GCP E6(R3)]
Clinical Research Staff
Individuals involved in the design, conduct, and/or reporting of a clinical trial and to whom an investigator delegates study-related duties.
Code of Federal Regulations
The Code of Federal Regulations (CFR) annual edition is the codification of the general and permanent rules published in the Federal Register by the departments and agencies of the [United States] Federal Government.
Co-investigator
An individual involved with the program director/principal investigator (PD/PI) in the scientific development or execution of a project supported by the National Institutes of Health (NIH).
Compliance (in relation to trials)
Adherence to the trial-related requirements, GCP requirements and the applicable regulatory requirements.
[ICH GCP E6(R3)]
Consortium Clinical Trial
A cancer or cancer-related clinical trial (that meets NCI reporting requirements) and is conducted by a Consortium member or affiliate member
Consortium PI
Principal Investigator who is a member or affiliate member of the Cancer Consortium and is the responsible leader of the team for a study conducted by a group of individuals at a study site.
Consortium Study Coordinator (CSC) Training Curriculum
A collection of online training modules developed by the Clinical Research Support (CRS) Training Program to establish foundational training for Consortium clinical research staff.
Corrective and Preventive Action Plan (CAPA)
A formal written document which outlines a strategy for correcting and/or eliminating a problem that has been identified and taking steps to prevent it from occurring in the future.
D
Data Acquisition Tool (DAT)
A paper or electronic tool designed to collect data and associated metadata from a data originator in a clinical trial according to the protocol and to report the data to the sponsor. The data originator may be a human (e.g., the participant or trial staff), a machine (e.g.,wearables and sensors) or a computer system from which the electronic transfer of data from one system to another has been undertaken (e.g., extraction of data from an electronic health record or laboratory system).
[ICH GCP E6(R3)]
Data and Safety Monitoring Board (DSMB)
An independent data monitoring committee that may be established by the sponsor to periodically assess the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial.
Data and Safety Monitoring Committee (DSMC)
A Cancer Consortium committee that reviews safety- and compliance-related study data for ongoing investigator-initiated clinical trials with a drug, device, or biological agent.
Delegation of Authority Log (DoA)
A mechanism for contemporaneously tracking appropriately qualified individuals to whom the investigator has delegated significant trial-related roles and responsibilities.
Digital Signature
An electronic signature based upon cryptographic methods of originator authentication, computed by using a set of rules and a set of parameters such that the identity of the signer and the integrity of the data can be verified.
Drug Master File (DMF)
Submissions to FDA used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products.
E
Electronic Record
Any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.
Electronic Signature
A computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual's handwritten signature.
Epic
An electronic medical record system that includes registration, scheduling, financial clearance, charge capture, and billing capabilities.
Essential Documents
See Essential Records.
Essential Records
Essential records are the documents and data (and relevant metadata), in any format, associated with a clinical trial that facilitate the ongoing management of the trial and collectively allow the evaluation of the methods used, the factors affecting a trial, and the actions taken during the trial conduct to determine the reliability of the trial results produced and the verification that the trial was conducted in accordance with GCP and applicable regulatory requirements.
[ICH GCP E6(R3)]
Expanded Access
The use of an investigational drug outside of a clinical trial to treat a patient with a serious or immediately life-threatening disease or condition who has no comparable or satisfactory alternative treatment options.
FDA Inspections
Fred Hutch has hosted numerous successful FDA Bioresearch Monitoring inspections of Clinical Investigators in association with commercial marketing applications. Resources include:
- Online FDA inspection training modules for investigators and staff
- Guidelines and SOPs for inspection preparation, conduct, and follow-up
- Experienced regulatory affairs support throughout the inspection process
G
Good Clinical Practice (GCP)
A standard for the planning, initiating, performing, recording, oversight, evaluation, analysis, and reporting of clinical trials that provides assurance that the data and reported results are reliable and that the rights, safety and well-being of trial participants are protected.
[ICH GCP E6(R3)]
H
Handwritten Signature
The scripted name or legal mark of an individual handwritten by that individual and executed or adopted with the present intention to authenticate a writing in a permanent form. The act of signing with a writing or marking instrument such as a pen or stylus is preserved. The scripted name or legal mark, while conventionally applied to paper, may also be applied to other devices that capture the name or mark.
Human Subjects Protection (HSP)
A collective term for the federal, state, and local policies, procedures, and ethical considerations that protect the rights and welfare of human beings who participate in research as the subjects of that research.
Human Subjects Radiation Approval Committee (HSRAC)
A centralized body to review and approve applications to use radiation in human subjects research.
I
IND Safety Report
A report issued by the sponsor of an IND to notify the FDA and all participating investigators about newly discovered, potential serious risks of an investigational product. Sometimes referred to as third party safety report, Medwatch report (referring to the FDA form used for reporting), or CIOMS report (referring to the Council for International Organizations of Medical Sciences form used for reporting). Reported information may include serious and unexpected suspected adverse reactions (SUSARs) or other important safety information.
Informed Consent Form
A document which provides information to a potential subject in order to allow the individual to make an informed decision about participation in a clinical trial.
Informed Consent
A process by which a participant or their legally acceptable representative voluntarily confirms their willingness to participate in a trial after having been informed and been provided with the opportunity to discuss all aspects of the trial that are relevant to the participant’s decision to participate.
[ICH GCP E6(R3)]
Institutional Review Board (IRB)
An independent body (a review board or a committee, institutional, regional, national or supranational, constituted of medical professionals and non-medical members whose responsibility it is to ensure the protection of the rights, safety and well-being of human participants involved in a trial and to provide public assurance of that protection by, among other things, reviewing and approving/providing favourable opinion on the trial protocol, the suitability of the investigator(s), the facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial participants.
[ICH GCP E6(R3)]
Institution-Sponsored IND (ISI) Program Staff
An IND application for which Fred Hutch assumes all responsibilities of an IND sponsor outlined in the Code of Federal Regulations. ISIs are managed by staff within the CRS Clinical Research Regulatory and Compliance group.
Institution-Sponsored IND (ISI) Program Staff
Clinical Research Support personnel responsible for regulatory activities associated with ISI studies.
Institution-Sponsored IND Medical Monitor
The faculty member who reviews and approves protocols, amendments, and safety information on behalf of the committee.
Institution-Sponsored IND Oversight Committee (ISIOC)
The committee that oversees and manages Fred Hutch’s rights and responsibilities when acting as the sponsor of an IND under 21 CFR Part 312 and the Guideline for Good Clinical Practice (ICH E6 [R2]).
Interim Monitoring Visit (IMV)
A visit conducted by a monitor to review source documents and study-related materials, and to ensure protocol and regulatory compliance. This visit takes place during the conduct of the study.
Investigational New Drug Application (IND)
A set of information provided to, reviewed by, and updated for the FDA in accordance with 21 CFR Part 312. An active IND permits use of an unapproved drug (or use of an approved drug used in a way that significantly increases risk) in clinical trials.
Investigator
A person responsible for the conduct of the clinical trial, including the trial participants for whom that person has responsibility during the conduct of the trial. If a trial is conducted by a team of individuals, the investigator is the responsible leader of the team and may be called the principal investigator.
[ICH GCP E6(R3)]
Investigator-Initiated Trial (IIT)
A clinical trial in which the investigator conceives the research and develops the protocol.
Investigator's Brochure (IB)
A compilation of the clinical and nonclinical data on the investigational product(s) that is relevant to the study of the investigational product(s) in human participants.
[ICH GCP E6(R3)]
M
Medical Monitor
A physician or other qualified individual, separate from the study team, who is responsible for assessing medical and safety information and providing relevant guidance during the conduct of a clinical trial.
Monitor
An individual retained by the sponsor to verify that a trial is being conducted, recorded, and reported in accordance with the protocol, standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirements.
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).
[ICH GCP E6(R3)]
N
Noncompliance
An event, action, or activity related to human subjects research that does not adhere to the requirements of the research protocol, IRB approval, or laws and regulations governing research conduct.
Note to File (NTF)
A source document created to supplement or clarify clinical trial information in the regulatory binder or other study records, in order to present a clear description of trial activity and demonstrate appropriate study oversight.
Nuclear Medicine Radiolabeling Laboratory
Facility within the Department of Radiology at the University of Washington (UW) where radiolabeled products for clinical trials are prepared and tested in a controlled environment.
P
Principal Investigator (PI)
See Investigator.
Protocol
A document that describes the objective(s), design, methodology, statistical considerations and organisation of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents.
[ICH GCP E6(R3)]
R
Responsible Party (ClinicalTrials.gov)
The sponsor of a clinical trial (i.e., individual, corporation, agency, or other entity that initiates a clinical trial but does not personally conduct the trial); or the principal investigator (PI) of such clinical trial if so designated by a sponsor, grantee, contractor, or awardee, so long as the PI is responsible for conducting the trial, has access to and control over the data from the clinical trial, has the right to publish the results of the trial, and has the ability to meet all of the requirements under Title 42, Part 11 of the U.S. Code of Federal Regulations for the submission of clinical trial information.
S
Serious Adverse Event (SAE)
Any adverse event that results in any of the following outcomes: Death, a life-threatening adverse event (real risk of dying), inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity/or change in psychosocial status, a congenital anomaly or, requires intervention to prevent permanent impairment or damage.
[FDA:21 CFR 312.32(a)]
Site Initiation Visit (SIV)
A meeting with the PI, study team, applicable clinical site personnel, and sponsor personnel that takes place prior to the start of the clinical research study. The purpose of this meeting is to review the protocol, Investigator’s brochure, all procedures, forms, and documents related to the conduct of the study.
Source Records
Original documents or data (which includes relevant metadata) or certified copies of the original documents or data, irrespective of the media used. This may include trial participants’ medical/health records/notes/charts; data provided/entered by trial participants (e.g., electronic patient-reported outcomes (ePROs)); healthcare professionals’ records from pharmacies, laboratories and other facilities involved in the clinical trial; and data from automated instruments, such as wearables and sensors.
[ICH GCP E6(R3)]
Sponsor
An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial.
- Commercial Sponsor: A pharmaceutical company or drug or biological product manufacturer that is developing, or has developed, a product for commercial purposes (market approval or licensure or changes to product labeling) and has submitted an IND for the product.
- Funding Sponsor: An individual, company, institution, or organization that provides financial support for a clinical trial.
- IND Sponsor: An individual, company, institution, or organization responsible for submitting and maintaining an Investigational New Drug application (IND).
- Sponsor Product: An individual, company, institution, or organization that supplies a drug or biological product for use in a clinical trial.
Sponsor Records
The collection of submissions to and correspondence with FDA for an IND. Use definition with ISI program only.
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 subject. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.
[ICH GCP E6(R3)]
Sub-Investigator (Sub-I)
Any individual member of the clinical trial team designated and under the oversight of the investigator to perform significant trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows).
[ICH GCP E6(R3)]
T
Therapeutic Products Program (TPP)
A Shared Resource core within Fred Hutch that provides facilities and services in process development and manufacturing of Good Manufacturing Practice (GMP)-grade biologic and cellular therapeutic products for Phase 1 and 2 clinical trials.
Trial Master File (TMF)
A standard filing system that contains all essential documents in an organized manner allowing the conduct of a clinical trial to be reconstructed and evaluated. TMFs may be paper or electronic, or a hybrid system.
U
Unanticipated Problem
Any incident, experience, or outcome that meets all of the following criteria: a) unexpected (in terms of nature, severity, or frequency) given [i] the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and [ii] the characteristics of the subject population being studied; b) related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and c) suggests that the research places research participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.
Reference Safety Information (RSI)
Contains a cumulative list of ADRs that are expected for the investigational product being administered to participants in a clinical trial. The RSI is included in the Investigator’s Brochure or alternative documents according to applicable regulatory requirements. Refer to ICH E2F Development Safety Update Report for more information about RSI.
[ICH GCP E6(R3)]
Unexpected Adverse Event
An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator’s Brochure or alternative documents according to applicable regulatory requirements; see RSI).
[ICH GCP E6(R3)]