Version 1.0_01 December 2023
This glossary applies to the terms found in the documents on the Division of Microbiology and Infectious Diseases Quality Management System.
A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z
A
Abbreviated Device Exemption (IDE)
Refers to abbreviated requirements for non-significant risk (NSR) device studies under 21 CFR 812.2(b). Abbreviated requirements address labeling, IRB approval, informed consent, monitoring, records, reports, and prohibition against promotion. The submission of progress or final reports to the FDA is not a requirement. Definition source: FDA, https://www.fda.gov/media/75459/download.
Adverse Event
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product (see the ICH Guidance for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Agreement
A legally binding mutual understanding that is negotiated through offers, acceptances, and exchanges of consideration to address the responsibilities and obligations of the involved parties. At NIAID, no funding is exchanged under an Agreement (unless under an approved CRADA or Contract). Definition source: NIH/NIAID, https://www.niaid.nih.gov/research/dmid-clinical-research-agreements.
Aliquot
Equal fractions of the entire specimen. Definition source: NIAID/DMID.
Applicable Regulatory Requirement
Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Assessment
A systematic evaluation process of collecting and analyzing data to determine the current, historical or projected compliance of an organization to a standard. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Audit (in relation to clinical trial/research study)
A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor’s standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Audit (non-specific)
A systematic, independent and documented process for obtaining objective evidence and evaluating it objectively to determine the extent to which the audit criteria are fulfilled. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Audit Certificate
A declaration of confirmation by the auditor that an audit has taken place. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Audit Conclusion
Outcome of an audit, after consideration of the audit objectives and all audit findings. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Audit Criteria
Set of policies, procedures or requirements used as a reference against which objective evidence is compared. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Audit Finding(s)
Results of the evaluation of the collected audit evidence against audit criteria. If the audit criteria are selected from statutory requirements or regulatory requirements, the audit finding can be called compliance or non-compliance. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Audit Plan
Description of the activities and arrangements for an audit. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Audit Recommendation
Comment(s) provided by an Auditor that identifies an opportunity for improvement in a process or approach that is not a violation of a regulation, standard, or NIH/NIAID/DMID requirement. Definition source: NIH/NIAID/DMID.
Audit Report
A written evaluation by the sponsor’s auditor of the results of the audit. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Audit Scope
Extent and boundaries of an audit. The audit scope generally includes a description of the physical locations, organizational units, activities and processes. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Audit Team
One or more persons conducting an audit, supported if needed by technical experts. One auditor or the audit team is appointed as the team leader. The audit team can include auditors-in-training. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Audit Trails
Processes that capture details such as additions, deletions, or alterations of information in an electronic record without obscuring the original record. Audit trails facilitate the reconstruction of the course of such details relating to the electronic record. Audit trails typically capture each change itself, the individual making the change, the data and time of the change and, when applicable, the reason or reasons for the change. Definition source: FDA Draft Guidance Electronic Systems, Records, Signatures, https://www.fda.gov/media/166215/download.
Auditee
Organization being audited. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Auditor
Person who conducts an audit. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
B
Blinding/Masking
A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single blinding usually refers to the subject(s) being unaware, and double¬ blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s). Definition source: E6R2, https://www.fda.gov/media/93884/download.
C
Certificate of Analysis (COA)
A summary of tests and results for manufactured drug and biological products demonstrating release of the lot, which includes tests of sterility, identity, strength, quality, and purity to ensure conformity with specifications. The COA includes the lot/batch number, test method, date tested, specifications, results and signature of the individual authorized to release the product. Definition source: FDA- Q7 GMP, https://www.fda.gov/media/71518/download.
Certified Copy
A copy (irrespective of the type of media used) of the original record that has been verified 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. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Clinical Hold
A clinical hold is an order issued by the FDA to the applicant to delay a proposed clinical investigation or to suspend an ongoing investigation. A clinical hold may be designated either a complete clinical hold or a partial clinical hold. FDA, https://www.fda.gov/media/72548/download.
Clinical Quality Management Plan (CQMP)
A written description of the quality control (QC) and quality assurance (QA) procedures, roles and responsibilities, scope, sample size, and frequency of these activities to ensure a level of quality in clinical research activities. Synonymous terms found in funding agreements may include ‘quality assurance and quality control procedures’ or ‘quality management plan’.
- Single site: A site-specific CQMP developed by a site and its sub-contractor(s) (as applicable) conducting a single protocol or multiple protocols.
- Protocol specific: A single protocol-specific CQMP centrally developed and disseminated to all sites for consistent implementation across multiple sites. Definition source: NIAID/DMID.
Clinical Research
See "Human Subjects Research".
Clinical Study Report (CSR)
A written description of a trial/study conducted in human subjects, in which all clinical and statistical descriptions, presentations, and analyses for all endpoints are fully integrated into a single report.
- Interim CSR: The document containing the analyses for the majority (minimum of primary and secondary) of the study endpoints.
- Addendum CSR: A document that includes data or analysis of study endpoints not presented in an interim CSR.
- CSR Amendment: A subsequent version of the CSR (including interim or addendum) that contains corrections or revisions to results in the previous version. CSR amendments will be version controlled. Definition source: FDA, https://www.fda.gov/media/71271/download.
Clinical Trial
A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. Definition source: NIH, https://grants.nih.gov/policy/clinical-trials/definition.htm.
Clinical Trials Agreement (CTA)
An Agreement that legally binds the parties (usually NIAID and a manufacturer of an investigational product) to responsibilities and obligations in the conduct of a clinical study. NIH/NIAID, https://www.niaid.nih.gov/research/dmid-clinical-research-agreements.
ClinicalTrials.gov
Web-based resource that provides patients, their family members, health care professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions. The Web site is maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH). Information on ClinicalTrials.gov is provided and updated by the sponsor or principal investigator of the clinical study. Studies are generally submitted to the Web site (that is, registered) when they begin, and the information on the site is updated throughout the study. In some cases, results of the study are submitted after the study ends. This Web site and database of clinical studies is commonly referred to as a "registry and results database." Definition source: NIH, https://clinicaltrials.gov/.
Combination Products
Combination product is a product composed of any combination of a drug and a device; a biological product and a device; a drug and a biological product; or a drug, device, and a biological product. Definition source: FDA, https://www.fda.gov/media/106799/download#:~:text=1.,%2D%E2%80%90entity%E2%80%9D%20combination%20product%5D%3B.
Completion of the Clinical Trial
The clinical trial is complete when all data analyses under the Protocol have been performed and the Clinical Study Report (CSR) has been submitted to the FDA. Definition source: NIH/NIAID, https://clinregs.niaid.nih.gov/country/united-states#progress_reporting.
Compliance (in relation to trials)
Adherence to all the trial-related requirements, good clinical practice (GCP) requirements, and the applicable regulatory requirements. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Conformity
Fulfilment of a requirement. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Contract
A legal instrument by which a non-Federal entity purchases property or services needed to carry out the project or program under a federal award. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Contract Research Organization (CRO)
A CRO is an organization that provides clinical trial management services for Sponsors. Definition source: NIAID/DMID.
Contractor
An entity that receives a contract. May also refer to employee(s) of that entity. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Controlled Document
A document that must undergo formal review and approval within the electronic Quality Management System (eQMS) to ensure authorized creation, edits/revisions, versioning, distribution, and archival. Definition source: NIH/NIAID/DMID.
Coordinating Committee
A committee that a sponsor may organize to coordinate the conduct of a multicenter trial. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Corrective Action
A solution meant to reduce or eliminate an identified problem. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Corrective and Preventive Action (CAPA) Plan
A written plan to document identification of a problem, action(s) taken to eliminate the cause of the problem, identify the root cause of the problem, action(s) taken to correct the root cause of the problem, and actions taken to prevent recurrence of the problem. Definition source: FDA, https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-guides/corrective-and-preventive-actions-capa.
Critical Reagents
Critical Reagents are requisite components of an assay that have direct impact on assay performance. Examples of critical reagents are reference standards, antibodies, recombinant proteins, cell lines, and quality controls. Definition source: FDA, https://www.fda.gov/files/drugs/published/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf.
D
Data Management Plan (DMP)
A written document that describes the data a sponsor expects to acquire or generate during the course of a research study; how the sponsor intends to manage, describe, analyze, and store said data; and what mechanisms will be used at the end of the study to preserve and share the research data. Definition source: FDA Guidance-Decentralized Clinical Trials, https://www.fda.gov/media/167696/download.
Data Safety Monitoring Board (DSMB)
A formal, independent board of experts including investigators and biostatisticians that advise study investigators regarding the safety progression of a study. In general, NIH requires the establishment of DSMBs for multi-site clinical trials involving interventions that entail potential risk to the participants and for all Phase III clinical trials. As necessary, a DSMB may be appropriate for Phase I and Phase II or other clinical trials if the studies are blinded (masked), employ high-risk interventions, or involve vulnerable populations. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Deviation (in relation to DMID QMS)
Departure from an approved instruction, procedure, established standard, or specification. Deviations may be planned or unplanned. Definition source: NIH/NIAID/DMID.
Digital Signatures
Electronic signatures 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. Definition source: FDA Draft Guidance Electronic Systems, Records, Signatures, https://www.fda.gov/media/166215/download.
Direct Access
Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsor's monitors, and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects' identities and sponsor's proprietary information. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Document
Information and the medium on which it is contained. Example: Record, specification, procedure document, drawing, report, standard. The medium can be paper, magnetic, electronic, or optical computer disc, photograph or master sample, or combination thereof. A set of documents, for example specifications and records, is frequently called “documentation”. Some requirements (e.g., the requirement to be readable) relate to all types of documents. However, there can be different requirements for specifications (e.g., the requirement to be revision controlled) and for records (e.g., the requirement to be retrievable). Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Document Types
A set of rules that specify the structure of a document and the tags (e.g., macros) used to define the structure that can be used to validate whether a document is well formed (e.g., Policy, Standard Operating Procedure, Guidance, Manual, etc.). Definition source: NIH/NIAID/DMID.
Documentation (in relation to clinical trials/studies)
All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records, and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken. Definition source: E6R2, https://www.fda.gov/media/93884/download.
E
Effective Date
Is an "as of date", meaning the date upon which a Policy or Standard Operating Procedure (SOP) becomes active after approval. The date is typically to occur after the date of approval (e.g., 2 weeks, 30 days) to allow time for staff training. Definition source: NIH/NIAID/DMID.
Effective Departure Date
The last day the employee is participating in activities in support of DMID (e.g. the last day of email and phone access). This may differ from employment severance date (e.g. terminal leave, etc.). Definition source: NIAID/DMID.
Effective Document
An approved QMS document (e.g., Policy or SOP) that becomes active upon conclusion of the specified training period (e.g.,30 days). Effective documents are controlled documents. Definition source: NIH/NIAID/DMID.
Electronic Quality Management System (eQMS)
Software program that automates and centralizes Quality Management System (QMS) processes and procedures required to achieve effective quality management. Definition source: NIH/NIAID/DMID.
Electronic Records
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. Definition source: FDA Draft Guidance Electronic Systems, Records, Signatures, https://www.fda.gov/media/166215/download.
Electronic Signatures
Computer data compilation of any symbol or series of symbols executed, adopted, or authorized by individuals to be the legally binding equivalent of the individuals’ handwritten signatures. FDA Draft Guidance Electronic Systems, Records, Signatures, https://www.fda.gov/media/166215/download.
Electronic Systems
Systems, including hardware and software, that produce electronic records. Definition source: FDA, https://www.fda.gov/media/166215/download.
Essential Document Collection Organization (EDCO)
The organization responsible for the collection, review, acceptance of essential documents from the trial site. Definition source: NIH/NIAID/DMID.
Essential Documents
Documents that individually and collectively permit evaluation of the conduct of a study and the quality of the data produced (see section 8. "Essential Documents for the Conduct of a Clinical Trial"). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Event
Occurrence or change of a particular set of circumstances. An event can be one or more occurrences and can have several causes. An event can consist of something not happening. An event can sometimes be referred to as an “incident” or “accident”. An event without consequences can also be referred to as a “near miss”, “incident”, “near hit” or “close call”. Definition source: ISO Guide 73:2009, https://www.iso.org/obp/ui/#iso:std:iso:guide:73:ed-1:v1:en.
External Quality Assessment (EQA)
EQA is defined as a system for objectively checking the laboratory’s performance using an external agency. Definition source: WHO, https://www.who.int/publications/m/item/overview-of-external-quality-assessment-eqa.
F
Federal-Wide Assurance
is the only type of new assurance of compliance accepted and approved by OHRP for institutions engaged in non-exempt human subjects research conducted or supported by HHS. Under an FWA, an institution commits to HHS that it will comply with the requirements set forth in 45 CFR 46, as well as the terms of assurance. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Form
A document type used to capture and record information. Definition source: NIH/NIAID/DMID.
G
Good Clinical Practice (GCP)
A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Guidance
A DMID document type that describes DMID best practices associated with a standard, procedure, or expectation that is a reflected in a rule or requirement, therefore, compliance with such documents is enforceable by DMID. Definition source: NIH/NIAID/DMID.
H
Human Subject Research
A human subject is "a living individual about whom an investigator (whether professional or student) conducting research: Obtains information or biospecimens; or through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens." Definition source: Title 45 CFR 46, https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46/subpart-A/section-46.102.
I
Independent Data Monitoring Committee (IDMC)
An independent data monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial. May also be referred to as Data and Safety Monitoring Board (DSMB), Monitoring Committee (MC), Data Monitoring Committee (DMC). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Independent Ethics Committee (IEC)
An independent body (a review board or a committee, institutional, regional, national, or supranational), constituted of medical professionals and non-medical members, whose responsibility it is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, reviewing and approving/providing favorable opinion on the trial protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial subjects. The legal status, composition, function, operations and regulatory requirements pertaining to Independent Ethics Committees may differ among countries but should allow the Independent Ethics Committee to act in agreement with GCP as described in this guidance. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Informed Consent (IC)
A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject's decision to participate. Informed consent is documented by means of a written, signed, and dated informed consent form (ICF). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Inspection
The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor's and/or contract research organization's (CROs) facilities, or at other establishments deemed appropriate by the regulatory authority(ies). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Institutional Review Board (IRB)
An independent body constituted of medical, scientific, and nonscientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trial protocols and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Internal Audit (first party audit)
A first-party audit is an internal audit conducted within an organization by auditors who are employed by the organization being audited but who have no vested interest in the audit results of the area being audited. Definition source: ASQ, https://asq.org/quality-resources/auditing.
Intervention
As related to the definition of a clinical trial, a manipulation of the subject or subject's environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. Examples include drugs/small molecules/compounds; biologics; devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); treatment strategies; prevention strategies; and diagnostic strategies. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Investigational Device Exemption (IDE)
An IDE refers to the regulations under 21CFR 812 and allows an investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application or a Premarket Notification [510(k)] submission to FDA. An approved IDE means that the IRB (and FDA for significant risk devices) has approved the sponsor's study application and all the requirements under 21CFR 812 are met. Definition source: FDA, https://www.fda.gov/medical-devices/investigational-device-exemption-ide/ide-definitions-and-acronyms#:~:text=Investigational%20device%20exemption%20(IDE),-IDE%20refers%20to&text=An%20approved%20IDE%20means%20that,21%20CFR%20812%20are%20met.
Investigational New Drug Application (IND)
Is a formal application submitted to the Food and Drug Administration (FDA) by a clinical study sponsor requesting authorization to administer an investigational drug or biological product to humans. The authorization must be secured prior to the shipment and administration of any new drug or biological product that is not subject of an approved IND or Biologics Product License Application (BLA). Definition source: FDA, https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/investigational-new-drug-applications-inds-cber-regulated-products.
Investigational Product
An investigational product is defined by DMID as any drug, biologic, device, or combination product that is provided for the study or identified in the protocol as a study product, including any diluents or placebos provided for use during the study. ‘Investigational product’ and ‘study product’ may be used interchangeably and are used in lieu of the following terms: Investigational drug (21 CFR Part 312); Investigational Device (21 CFR Part 812); Test article (21 CFR Part 50). Definition source: NIAID/DMID.
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 subjects (see section 7. “Investigator’s Brochure”). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Issue
A matter or topic of discussion or concern. Definition source: NIAID/DMID.
J
Joint Audit
Audit carried out at a single auditee by two or more auditing organizations. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
K
L
Level of Risk
Magnitude of a risk or combination of risks, expressed in terms of the combination of consequences and their likelihood. Definition source: ISO Guide 73:2009, https://www.iso.org/obp/ui/#iso:std:iso:guide:73:ed-1:v1:en.
Likelihood
Chance of something happening. In risk management terminology, the word “likelihood” is used to refer to the chance of something happening, whether defined, measured or determined objectively or subjectively, qualitatively or quantitatively, and described using general terms or mathematically [such as a probability or a frequency over a given time period]. Definition source: ISO Guide 73:2009, https://www.iso.org/obp/ui/#iso:std:iso:guide:73:ed-1:v1:en.
M
Management Review
A top management meeting held at planned intervals to review the continuing suitability and effectiveness of DMID's Quality Management System (QMS). Definition source: NIH/NIAID/DMID.
Manual (MAN)
A document type that serves as a compilation of information or instructions about specific processes and/or procedures. Definition source: NIH/NIAID/DMID.
Manual of Procedures (MOP)
A study-specific document that describes protocol-specific instructions, processes, and procedures. Definition source: NIH/NIAID/DMID.
Metric
A standard for measurement. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Monitoring
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), GCP, and the applicable regulatory requirement(s). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Monitoring Manual (MM)/Plan
The document developed on a protocol level to ensure consistency in activities to be completed during monitoring visits. The MM is equivalent to the term monitoring plan. Both terms will be used throughout this document. The plan describes the monitoring strategy, responsibilities, and methods to be used for review of data and processes. Definition source: NIAID/DMID.
Monitoring Report
A written report from the monitor to the sponsor after each site visit and/or other trial-related communication according to the sponsor's SOPs. Definition source: E6R2, https://www.fda.gov/media/93884/download.
N
Noncompliance
Failure to follow the applicable laws, regulations, or institutional policies governing the protection of human subjects in research, or the requirements or determinations of the Institutional Review Board (IRB), whether the failure is intentional or not. Definition source: NIH IRBO, https://irbo.nih.gov/confluence/display/ohsrp/Office+of+Compliance+and+Training.
Non-Significant Risk (NSR) Device
An investigational device that does not present a potential for serious risk to the health, safety, or welfare of a subject. IRB approval is required with an IRB risk determination of NSR. The FDA considers an NSR device study to have an approved IDE after IRB approval and must meet the abbreviated IDE requirements under 21 CFR 812.2(b). Definition source: FDA, https://www.fda.gov/media/75459/download.
O
Objective Evidence
Generally consists of records, statements of fact or other information which are relevant to the audit criteria and verifiable. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Observer
Person who accompanies the audit team but does not act as an auditor. An observer can be a member of the auditee, a regulator or other interested party who witnesses the audit. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Offboarding
The decisions and processes that occur when the employer-employee relationship ends though resignation, termination, or retirement. Definition source: NIAID/DMID.
Office of Acquisitions (OA)
NIAID Office of Acquisitions (OA) solicits, negotiates, awards, and administers biomedical and behavioral research and development (R&D) contracts, contracts in support of R&D, station support contracts, and simplified acquisitions, manages the NIAID procurement processes, develops NIAID-specific acquisition policies and procedures, provides expert business management and acquisition support. Definition source: NIH/NIAID, https://www.niaid.nih.gov/about/office-acquisitions.
P
Performance
Measurable result. Performance can relate either to quantitative or qualitative findings. Performance can relate to the management of activities, processes, products, services, systems, or organizations. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Persistent
Continuing or ongoing action or activity in opposition to a required procedure, regulation, standard or requirement. Definition source: NIAID/DMID.
Personally Identifiable Information (PII)
Information which can be used to distinguish or trace an individual’s identity, such as their name, SSN, biometric records, etc. alone, or when combined with other personal or identifying information which is linked or linkable to a specific individual, such as date and place of birth, mother’s maiden name, etc.” PII is protected by the provisions of the Privacy Act (if the record in which it is located is under the control of an agency and is contained in an authorized system of records retrieved by a personal identifier). Definition source: DHS, https://www.dhs.gov/publication/handbook-safeguarding-sensitive-personally-identifiable-information.
Planned Deviation
A temporary, pre-approved departure from an approved standard, requirement, process, or procedure. Definition source: NIH/NIAID/DMID.
Policy (POL)
A written document describing the intentions and direction of NIAID and Divisions formally expressed by its management. Definition source: NIH/NIAID/DMID.
Preventive Action (PA)
Action to eliminate the cause of a potential nonconformity or other potential undesirable situation. There can be more than one cause for a potential nonconformity. Preventive action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Privacy Incident
The loss of control, compromise, unauthorized disclosure, unauthorized acquisition, unauthorized access, or any similar term referring to situations where persons other than authorized users and for another than authorized purpose have access or potential access to PII, PHI or SI, whether physical or electronic. Definition source: DHS, https://www.dhs.gov/publication/handbook-safeguarding-sensitive-personally-identifiable-information.
Problem
An obstacle, difficulty or challenge that requires a solution. Definition source: NIAID/DMID.
Procedure
Specified way to carry out an activity or a process. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Process
Set of interrelated or interacting activities that use inputs to deliver an intended result. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Process Owner
The person who has responsibility and authority for ensuing that a process meets specified requirements and achieves objectives. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Program
A coherent assembly of plans, project activities, and supporting resources contained within an administrative framework, the purpose of which is to implement an organization's mission or some specific program-related aspect of that mission. For the NIH Grants Policy Statement, "program" refers to those NIH programs carrying out their missions through the award of grants or cooperative agreements to other organizations. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Protected Health Information (PHI)
All individually identifiable health information held or transmitted by a covered entity or its business associate, in any form or media, whether electronic, paper, or oral. Definition source: HHS, https://www.hhs.gov/hipaa/for-professionals/privacy/laws-regulations/index.html.
Protocol
Formal description and design for a specific research project. A protocol involving human subject research must be reviewed and approved by an Institutional Review Board (IRB) if the research is not exempt, and by an IRB or other designated institutional process for exempt research. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Protocol Amendment
A written description of a change(s) to or formal clarification of a protocol. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Protocol Deviation
Any change, divergence, or departure from the IRB-approved research protocol.
- Major Deviation – A deviation from the IRB-approved protocol that has, or may have the potential to, negatively impact, the rights, welfare or safety of the subject, or to substantially negatively impact the scientific integrity or validity of the study.
- Minor Deviation – A deviation that does not have the potential to negatively impact the rights, safety, or welfare of subjects or others, or the scientific integrity or validity of the study. Definition source: NIAID/DMID.
Q
Quality
Degree to which a set of inherent characteristics of an object fulfils requirements. The term “quality” can be used with adjectives such as poor, good, or excellent. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Quality Assurance (QA)
All those planned and systematic actions that are established to ensure that the trial is performed, and the data are generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and the applicable regulatory requirement(s). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Quality Audit
A systematic, independent process of gathering objective evidence to determine whether audit criteria are being met. Audits are based on a sample and are independent of the system, process or product being audited, unlike verification activities, which are part of a process. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Quality Control (QC)
The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Quality Improvement
Part of quality management focused on increasing the ability to fulfil quality requirements. The quality requirements can be related to any aspect such as effectiveness, efficiency, or traceability. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Quality Management (QM)
Managing activities and resources of an organization to achieve objectives and prevent nonconformances. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Quality Management System (QMS)
Formal system that documents the structure, processes, roles, responsibilities, and procedures required to achieve effective quality management. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Quality Plan
Documented information that provides the activities or methods to be taken to achieve objectives and meet specified requirements. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Quality Policy
A documented statement of commitment or intent to be implemented to achieve quality. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Quality Tool
An instrument or technique to support and improve the activities of quality management and improvement. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Quarantine
Effective restriction of the availability of product for use until released. Definition source: NIH/NIAID/DMID.
R
Record
Document stating results achieved or providing evidence of activities performed. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Regulatory Authorities
Bodies having the power to regulate. In the ICH GCP guidance, the expression "Regulatory Authorities" includes the authorities that review submitted clinical data and those that conduct inspections. These bodies are sometimes referred to as competent authorities. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Regulatory Requirement
Obligatory requirement specified by an authority mandated by a legislative body. Definition source: ISO 9000:2015, https://www.iso.org/obp/ui/#iso:std:iso:9000:ed-4:v1:en.
Requirements
A need or expectation, generally mandatory or compulsory. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Research Grants
Major extramural research grants awarded to institutions, hospitals, and other research organizations, including small businesses, to support circumscribed research led by investigators, create developmental opportunities, and to provide research related resources under programs such as Research Careers, Research Centers, Research Projects, SBIR/STTRs, and Other Research. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Research Misconduct
Fabrication, falsification, or plagiarism in proposing, performing, or reporting research, or in reporting research results. Fabrication is making up data or results and recording or reporting them. Falsification is manipulating research materials, equipment, or processes, or changing or omitting data or results such that research is not accurately represented in the research record. Plagiarism is the appropriation of another person's ideas, processes, results, or words without giving appropriate credit. Research misconduct does not include honest error or honest differences of opinion. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Responsible Party (pertaining to ClinicalTrials.gov)
Responsible party is the term used in Title VIII of the Food and Drug Administration Amendments Act (FDAAA) of 2007 (P.L. 110-85) to refer to the entity or individual who is responsible under FDAAA for registering a clinical trial and submitting clinical trial information to ClinicalTrials.gov. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Review
Activity undertaken to determine the suitability, adequacy, and effectiveness of the subject matter to achieve established objectives. Review can be applied to a risk management framework, risk management process, risk, or control. Definition source: ISO Guide 73:2009, https://www.iso.org/obp/ui/#iso:std:iso:guide:73:ed-1:v1:en.
Risk
Combination of the probability of occurrence of harm and the severity of that harm. Definition source: ISO/IEC Guide 51:2014, https://www.iso.org/standard/53940.html.
Risk Assessment
Overall A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards. process of risk identification, risk analysis and risk evaluation. Definition source: FDA/ICH Q9, https://www.fda.gov/media/167721/download.
Risk Communication
Quality management activities communicated from the sponsor to those who are involved in or affected by such activities, to facilitate risk review and continual improvement during clinical trial execution. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Risk Control
Actions implementing risk management decisions. Definition source: ISO Guide 73:2009, https://www.fda.gov/media/93884/download.
Risk Evaluation
Comparison of the estimated risk to given risk criteria using a quantitative or qualitative scale to determine the significance of the risk. Definition source: FDA/ICH Q9, https://www.fda.gov/media/167721/download.
Risk Identification
The sponsor's recognition of risks to critical trial processes and data. Risks should be considered at both the system level (e.g., standard operating procedures, computerized systems, and personnel) and clinical trial level (e.g., trial design, data collection, and informed consent process). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Risk Management
The systematic application of quality management policies, procedures, and practices to the tasks of assessing, controlling, communicating, and reviewing risk. Definition source: FDA, https://www.fda.gov/media/167721/download.
Risk Management Framework
Set of components that provide the foundations and organizational arrangements for designing, implementing, monitoring, reviewing and continually improving risk management throughout the organization. The foundations include the policy, objectives, mandate and commitment to manage risk. The organizational arrangements include plans, relationships, accountabilities, resources, processes and activities. The risk management framework is embedded within the organization's overall strategic and operational policies and practices. Definition source: ISO Guide 73:2009, https://www.iso.org/obp/ui/#iso:std:iso:guide:73:ed-1:v1:en.
Risk Management Plan
Scheme within the risk management framework specifying the approach, the management components and resources to be applied to the management of risk. Management components typically include procedures, practices, assignment of responsibilities, sequence and timing of activities. The risk management plan can be applied to a particular product, process and project, and part or whole of the organization. Definition source: ISO Guide 73:2009, https://www.iso.org/obp/ui/#iso:std:iso:guide:73:ed-1:v1:en.
Risk Matrix
Tool for ranking and displaying risks by defining ranges for consequence and likelihood. Definition source: ISO Guide 73:2009, https://www.iso.org/obp/ui/#iso:std:iso:guide:73:ed-1:v1:en.
Risk Register
Record of information about identified risks. The term “risk log” is sometimes used instead of “risk register”. Definition source: ISO Guide 73:2009, https://www.iso.org/obp/ui/#iso:std:iso:guide:73:ed-1:v1:en.
Risk Reporting
Description of the quality management approach implemented in the trial and summary of important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report (ICH E3, section 9.6 Data Quality Assurance). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Risk Review
Review or monitoring of output/results of the risk management process considering (if appropriate) new knowledge and experience about the risk. Definition source: FDA, https://www.fda.gov/media/167721/download.
Role (electronic systems/permissions)
The functions a user can perform in a system are based on the role assigned to his or her account. Definition source: NIH, https://grants.nih.gov/grants/glossary.htm.
Role (job/position)
A position or title assigned to an individual within an organization or team based on their qualifications, duties, or responsibilities. Definition source: NIH/NIAID/DMID.
Root Cause
The root cause is the core issue—the highest-level cause—that sets in motion the entire cause-and-effect reaction that ultimately leads to the problem(s). Definition source: ASQ, https://asq.org/quality-resources/root-cause-analysis#:~:text=The%20root%20cause%20is%20the,to%20uncover%20causes%20of%20problems.
Root Cause Analysis
The method of identifying the cause of a problem, solving it and preventing it from occurring again. Uncovering the correct and accurate reason(s) why something is happening or has already occurred. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary/r.
S
Safety Monitoring Board/Committee
An SOC refers to a committee of experts, independent of the trial investigators, pharmaceutical sponsor (if any) and funding agency, that periodically reviews the conduct and results of the clinical trial. Following review, the SOC makes recommendations to continue without change, continue with change, or terminate the trial. An SOC refers to either a Data and Safety Monitoring Board (DSMB) or a Safety Monitoring Committees (SMC). Definition source: NIH/NIAID/DMID.
Sensitive Information (SI)
Information for which the loss, misuse, or unauthorized access could adversely affect the national interest or the conduct of federal programs, or the privacy to which individuals are entitled under 5 U.S.C. Section 552a (the Privacy Act). Information is considered sensitive if the loss of confidentiality, integrity, or availability could be expected to have a serious, severe, or catastrophic adverse effect on organizational operations, organizational assets, or individuals. Definition source: DHS, https://www.dhs.gov/publication/handbook-safeguarding-sensitive-personally-identifiable-information.
Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)
Any untoward medical occurrence that at any dose: Results in death, Is life-threatening; Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. (See the ICH guidance for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Serious Breach
Any deviation of the approved protocol version or the clinical trial regulation that is likely to affect the safety, rights of trial participants and/or data reliability and robustness to a significant degree in a clinical trial. Definition source: EMA, https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-notification-serious-breaches-regulation-eu-no-5362014-or-clinical-trial-protocol_en.pdf.
Significant Risk (SR) Device
A device that presents a potential for serious risk to the health, safety, or welfare of a subject. Significant risk devices may include implants, devices that support or sustain human life, and devices that are substantially important in diagnosing, curing, mitigating, or treating disease or in preventing impairment to human health. Definition source: FDA, https://www.fda.gov/media/75459/download.
Site Management Organization (SMO)
An organization that provides administrative and operational support to manage clinical trial sites on behalf of clinical trial sponsors. Definition source: NIH/NIAID/DMID.
Source Data
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). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Source Document
Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial). Definition source: E6R2, https://www.fda.gov/media/93884/download.
Sponsor
An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Stakeholder
Any individual, group or organization that will have a significant impact on or will be significantly impacted by the quality of a specific product or service. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Standard
The metric, specification, gauge, statement, category, segment, grouping, behavior, event or physical product sample against which the outputs of a process are compared and declared acceptable or unacceptable. Also, documents that provide requirements, specifications, guidelines or characteristics that can be used to ensure that materials, products, processes and services are fit for their purpose. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Standard Operating Procedure (SOP)
Detailed, written instructions to achieve uniformity of the performance of a specific function. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Standardization
When policies and common procedures are used to manage processes throughout the system. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Statistical Analysis Plan (SAP)
A SAP is a document that contains a more technical and detailed elaboration of the principal features of the analysis described in the protocol and includes detailed procedures for executing the statistical analysis of the primary and secondary variables and other data. Definition source: FDA, https://database.ich.org/sites/default/files/E9_Guideline.pdf.
Subject Matter Expert (SME)
A Subject Matter Expert (SME) is a "person with bona fide expert knowledge about what it takes to do a particular job. First-level supervisors are normally good SMEs. Definition source: U.S. Office of Personnel Management (OPM), https://www.opm.gov/frequently-asked-questions/assessment-policy-faq/job-analysis/what-is-a-subject-matter-expert/.
Subject/Trial Subject (also referred to as study "participant")
An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control. Definition source: E6R2, https://www.fda.gov/media/93884/download.
T
Temperature Excursion
A documented event whereby a clinical product is shipped or stored at a temperature outside of its temperature range as defined in the protocol/MOP. A temperature excursion may occur in transit, at the repository, or at the site. Definition source: NIH/NIAID/DMID, https://www.niaid.nih.gov/sites/default/files/temperatureexcursions.pdf.
Templates (TMPL)
A document type that provides a consistent document structure and format for creating various document (i.e., policies, standard operating procedures, work instructions, etc.). Definition source: NIH/NIAID/DMID.
TMF Index
Functions as a table of content and navigational aide to the TMF. Definition source: Veeva, https://clinical.veevavault.help/en/lr/66019/.
TMF Plan
A written document that outlines how records for the trial will be managed and stored during and after the duration of the trial, including study specific processes and documentation for archiving and destruction. Definition source: DMID/CROMS.
Transfer of Regulatory Obligations (TORO)
When a sponsor transfers responsibility of obligations in a written agreement or contract that specifies the regulatory obligations that will be transferred from the Sponsor to a CRO or other organization and is submitted to the FDA. Definition source: DMID/NIH.
Trend
The graphical representation of a variable’s tendency, over time, to increase, decrease or remain unchanged. Definition source: ASQ, https://asq.org/quality-resources/quality-glossary.
Trial Master File (TMF)
The collection of documents and information that serves as evidence that a clinical trial is conducted in adherence with good clinical practices (GCP) and proves that the integrity of regulatory submissions data has been maintained. It is essential to allow the trial to be effectively managed by the sponsor as it allows the appropriate individuals access to the necessary trial documentation. The TMF can be in paper and/or electronic (eTMF) format. The TMF refers to all components of a Trial Master File which includes systems outside of the electronic TMF system. Definition source: NIAID/DMID.
Trial Site
The location(s) where trial-related activities are actually conducted. Definition source: E6R2, https://www.fda.gov/media/93884/download.
U
Unanticipated Problem
Any incident, experience, or outcome that meets all of the following criteria:
- unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied
- related or possibly related to participation in the research; and
- suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized. Definition source: OHRP, https://www.hhs.gov/ohrp/regulations-and-policy/guidance/reviewing-unanticipated-problems/index.html#Q1.
Unexpected Adverse Drug Reaction
An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product). (See the ICH Guidance for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). Definition source: E6R2, https://www.fda.gov/media/93884/download.
User Acceptance Testing (UAT)
A phase of testing in which users test the electronic system to ensure it can handle required tasks according to specifications. Definition source: FDA, https://www.fda.gov/media/166215/download.
V
Validation
A process of establishing and documenting that the specified requirements of an electronic system can be consistently fulfilled from design until decommissioning of the system or transition to a new system. Definition source: FDA Draft Guidance Electronic Systems, Records, Signatures, https://www.fda.gov/media/166215/download.
Validation of Computerized Systems
A process of establishing and documenting that the specified requirements of a computerized system can be consistently fulfilled from design until decommissioning of the system or transition to a new system. The approach to validation should be based on a risk assessment that takes into consideration the intended use of the system and the potential of the system to affect human subject protection and reliability of trial results. Definition source: E6R2, https://www.fda.gov/media/93884/download.
Vendor
A supplier that sells goods or services to sponsors and other regulated entities. Definition source: NIH/NIAID/DMID.
Vendor Audit
A formal external audit performed on a supplier by a customer or by a contracted organization on behalf of DMID, are subject to the rules of the contract, as the results influence purchasing decisions. Definition source: NIH/NIAID/DMID.
W
Work Instructions (WI)
A written document providing step-by-step instructions on how to perform a procedure or process in more detail. Definition source: NIH/NIAID/DMID.
X
Y