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Studiu Clinic EN-EN PDF
Studiu Clinic EN-EN PDF
Glossary Terms
CDISC Glossary Project
510(k). Premarket Notification (PMN)
Arthur Gertel, Project Leader Johnson PRD; Arthur Gertel, Beardsworth
required for certain medical devices. See
Glossary Project Core Team: Consulting; Stephen A. Raymond, PHT
http://www.fda.gov/cdrh/510k Corporation; Theresa Quinn, Lockheed
Patricia Beers Block, Liaison from the
home.html Office of Science & Health, FDA; Martin; Erin Muhlbradt, PhD, Lockheed
Helle-Mai Gawrylewski, Johnson and Martin
21 CFR 314.3; Guidance to Industry the original record. An audit trail of chance rather than bias. The study
and FDA Staff (10/08/2003)] facilitates the reconstruction of the groups should be compared at baseline
history of such actions relating to the for important demographic and clinical
electronic record. [after ICH E6, CSUICI] characteristics. Baseline data may be
arm. A planned sequence of elements, especially valuable when the outcome
typically equivalent to a treatment measure can also be measured at the
group. [SDTM] See element. back translation (natural start of the trial. [CONSORT Statement]
language). The process of translating
a document that was translated from
assessment. A measurement, one language to another back to the baseline imbalance. Systematic
evaluation, or judgment for a study original language. Used to ensure that error in creating intervention groups,
variable pertaining to the status of consent forms, surveys, and other such that they differ with respect to
a subject. NOTE: Assessments are clinical trial documents will be clear and prognosis. That is, the groups differ
usually measured at a certain time, accurate in the translated form. in measured or unmeasured baseline
and usually are not compounded characteristics because of the way
significantly by combining several participants were selected or assigned.
simultaneous measurements to form background material. Information NOTE: Also used to mean that the
a derived assessment (e.g., BMI) or pertinent to the understanding of participants are not representative
a result of statistical analysis. See a protocol. NOTE: Examples include of the population of all possible
variable; outcome, endpoint; the term investigator brochure, literature participants. [ICH E9]
assessment is intended to invoke some review, history, rationale, or other
degree of evaluation or judgment documentation that places a study in
concerning subject status. context or presents critical features. Bayesian approaches. Approaches
[PR Project] to data analysis that provide a posterior
probability distribution for some
attribute (n). In data modeling, parameter (e.g., treatment effect),
refers to specific items of data that can balanced study. Trial in which a derived from the observed data and
be collected for a class. particular type of subject is equally a prior probability distribution for the
represented in each study group. parameter. The posterior distribution
is then used as the basis for statistical
audit. A systematic and independent inference. [ICH E9 Glossary]
examination of trial-related activities bandwidth. An indicator of the
and documents to determine whether throughput (speed) of data flow on
the evaluated trial-related activities were a transmission path; the width of Bayesian statistics. Statistical
conducted and the data were recorded, the range of frequencies on which a approach named for Thomas Bayes
analyzed, and accurately reported transmission medium carries electronic (1701–1761) that has among
according to the protocol, sponsor’s signals. All digital and analog signal its features giving a subjective
standard operating procedures (SOPs), channels have a bandwidth. interpretation to probability, accepting
good clinical practice (GCP), and the the idea that it is possible to talk
applicable regulatory requirement(s). about the probability of hypotheses
[ICH E6 Glossary] baseline assessment. Assessment being true and of parameters having
of subjects as they enter a trial and particular values.
before they receive any treatment.
audit certificate. Document that
certifies that an audit has taken place beta error. Probability of showing
(at an investigative site, CRO, or clinical baseline characteristics. no significant difference when a true
research department of a pharm Demographic, clinical, and other difference exists; a false acceptance
aceutical company). [ICH E6 Glossary] data collected for each participant at of the null hypothesis. See also Type 2
the beginning of the trial before the error. [AMA Manual of Style]
intervention is administered. NOTE:
audit report. A written evaluation by Randomized, controlled trials aim
the auditor of the results of the audit. to compare groups of participants bias. Situation or condition that
[Modified from ICH E6 Glossary] that differ only with respect to the causes a result to depart from the true
intervention (treatment). Although value in a consistent direction. Bias
proper random assignment prevents refers to defects in study design or
audit trail. A process that captures selection bias, it does not guarantee measurement. [AMA Manual of Style.
details such as additions, deletions, that the groups are equivalent at See also ICH E9, CONSORT Statement]
or alterations of information in an baseline. Any differences in baseline
electronic record without obliterating characteristics are, however, the result
bioanalytical assays. Methods for blinded study. A study in which the the time of a medication’s known
quantitative measurement of a drug, subject, the investigator, or anyone biological activity.
drug metabolites, or chemicals in assessing the outcome is unaware of
biological fluids. the treatment assignment(s). NOTE:
Blinding is used to reduce the potential case history. An adequate and
for bias. [Modified ICH E6 Glossary] See accurate record prepared and maintained
bioavailability. Rate and extent also blinding/masking, double-blind by an investigator that records all
to which a drug is absorbed or is study, single-blind study, triple-blind observations and other data pertinent
otherwise available to the treatment study; contrast with open-label or to the investigation on each individual
site in the body. unblinded study. administered the investigational drug
(device or other therapy) or employed
as a control in the investigation. NOTE:
bioequivalence. Scientific basis blinding. A procedure to limit Case histories include the case report
on which drugs with the same active bias by preventing subjects and/or forms and supporting data including,
ingredient(s) are compared. NOTE: study personnel from identifying for example, signed and dated consent
To be considered bioequivalent, the which treatments or procedures forms and medical records including, for
bioavailability of two products must are administered, or from learning example, progress notes of the physician,
not differ significantly when the two the results of tests and measures the individual’s hospital chart(s), and
products are given in studies at the undertaken as part of a clinical the nurses’ notes. The case history for
same dosage under similar conditions. investigation. NOTE: Masking, while each individual shall document that
often used synonymously with blinding, informed consent was obtained prior
usually denotes concealing the specific to participation in the study. [21 CFR
biological marker. See biomarker. study intervention used. [from ICH E9] 312.62b]
The term masking is often preferred to
blinding in the field of ophthalmology.
Biologics Licensing Application case record form. See case report
[from AMA Manual of Style]. See also
(BLA). An application to FDA for form.
blinding, double-blind study, masking,
a license to market a new biologic
single-blind study, triple-blind study.
product in the United States.
Contrast with open-label and/or
unblinded study. case report form (CRF). 1. A
printed, optical, or electronic document
biomarker. A characteristic that is designed to record all of the protocol-
objectively measured and evaluated required information to be reported to
as an indicator of normal biological branch. Point within a study design
where there is an allocation of subject the sponsor for each trial subject. 2.
processes, pathogenic processes, A record of clinical study observations
or pharmacologic responses to a subsets to particular procedures or
treatment groups. and other information that a study
therapeutic intervention. [Biomarker protocol designates must be completed
definitions working group] for each subject. NOTE: In common
brand name. See proprietary name. usage, CRF can refer to either a CRF
Synonyms: trade name; proprietary page, which denotes a group of one
biostatistics. Branch of statistics or more data items linked together for
applied to the analysis of biological name. [SPL]
collection and display, or a casebook,
phenomena. which includes the entire group of CRF
browser. Computer program that pages on which a set of clinical study
runs on the user’s desktop computer observations and other information
blind review. Checking and
and is used to navigate the World Wide can be or have been collected, or
assessing data prior to breaking the
Web. See also Web browser. the information actually collected by
blind, for the purpose of finalizing the
completion of such CRF pages for
planned analysis. [Modified ICH E9]
a subject in a clinical study [ICH E6
cache. Storage area on a computer’s Glossary]. See also CRF (paper).
blinded (masked) medications. hard drive where the browser stores
Products that appear identical in size, (for a limited time) Web pages and/or
case report tabulations (CRT). In
shape, color, flavor, and other attributes graphic elements.
a paper submission, listings of data that
to make it very difficult for subjects
may be organized by domain (type of
and investigators (or anyone assessing
data) or by subject. See also eCRT.
the outcome) to determine which carry-over effect. Effects of
medication is being administered. treatment that persist after treatment
has been stopped, sometimes beyond
categorical data. Data evaluated is usually an entity that represents a clinical document architecture.
by sorting values (for example, severe, person, place, or thing. Specification for the structure and
moderate, and mild) into various semantics of “clinical documents” for
categories. the purpose of exchange. [HL7; SPL]
clean database. A set of reviewed
data in which errors have been resolved
causality assessment. An to meet QA requirements for error rate clinical document. A documentation
evaluation performed by a medical and in which measurements and other of clinical observations and services.
professional concerning the likelihood values are provided in acceptable units; NOTE: An electronic document should
that a therapy or product under study database that is ready to be locked. See incorporate the following characteristics:
caused or contributed to an adverse also database lock, clean file. persistence, stewardship, potential for
event. authentication, wholeness, and human
readability. [SPL]
clean file. When all data cleaning is
CDISC Standard (The). CDISC term completed and database is ready for
for a proposed uniform CDISC standard quality review and unblinding. clinical efficacy. Power or capacity
intended to address the full life-cycle to produce a desired effect (i.e.,
of a clinical trial including protocol appropriate pharmacological activity in
representation, capture of source data, client. A program that makes a a specified indication) in humans. [SQA]
submission, and archiving using a set of service request of another program,
fully integrated and consistent models, usually running on a server, that fulfills
terms, and controlled vocabularies the request. Web browsers (such as clinical encounter. Contact
derived from the current set of CDISC Netscape Navigator and Microsoft between subject/patient and healthcare
standards. Explorer) are clients that request HTML practitioner/researcher, during which
files from Web servers. an assessment or activity is performed.
Contact may be physical or virtual.
certified copy. A copy of original [CDISC]
clinical benefit. A therapeutic
information that has been verified
intervention may be said to confer
as indicated by a dated signature,
clinical benefit if it prolongs life,
as an exact copy having all of the clinical investigation. See clinical
improves function, and/or improves the
same attributes and information as trial, clinical study. NOTE: Increased
way a subject feels.
the original. NOTE: The copy may be usage of investigation or study in the
verified by dated signature or by a U.S. rather than “trial,” may reflect
validated electronic process. A certified clinical clarification. A query the appearance of the term in FDA
copy of a source document may serve resolution received from the sponsor regulations concerning clinical research
as a source for a clinical investigation. activities.
staff (medical monitors, DSMB
See also source data, source. [After
monitoring board, etc.). See also self-
CSUICI]
evident change. clinical pharmacology. Science
that deals with the characteristics,
Certified IRB Professional (CIP). clinical data. Data pertaining to effects, properties, reactions, and uses
Certification awarded to persons the medical well-being or status of a of drugs, particularly their therapeutic
who satisfy the educational and patient or subject. value in humans, including their
employment requirements and pass an toxicology, safety, pharmacodynamics,
examination conducted by the Applied and pharmacokinetics (ADME).
Research Ethics National Association clinical development plan.
(ARENA), the membership division of A document that describes the
Public Responsibility in Medicine and collection of clinical studies that are clinical protocol. See protocol.
Research (PRIM&R). to be performed in sequence, or
in parallel, with a particular active
substance, device, procedure, or clinical research and
class. A definition of objects with treatment strategy, typically with the development. The testing of a
properties (attributes, methods, intention of submitting them as part drug compound in humans primarily
relationships) that all objects in the of an application for a marketing done to determine its safety and
class have in common. [HL7, 2001] In authorization. NOTE: The plan should pharmacological effectiveness. Clinical
data modeling, a class defines a set of have appropriate decision points and development is done in phases, which
objects that share the same attributes, allow modification as knowledge progress from very tightly controlled
relationships, and semantics. A class accumulates. [from ICH E9] See also dosing of a small number of subjects to
development plan.
comparative study. One in which believed to encompass the “true” value which a variable (for example, a rating
the investigative drug is compared with high probability (usually 95%). scale) measures what it is supposed to
against another product, either active The confidence interval is expressed in measure. [ICH E9 Glossary]
drug or placebo. the same units as the estimate. Wider
intervals indicate lower precision;
narrow intervals, greater precision. contingent subject trial contact.
comparator (product). An [CONSORT Statement] Planned response to an anticipated
investigational or marketed product but conditional event in a clinical trial.
(i.e., active control), or placebo, used [CDISC Trial Design Project]
as a reference in a clinical trial. [ICH E6 confidentiality. Prevention of
Glossary] See also control. disclosure to other than authorized
individuals of a sponsor’s proprietary contract research organization
information or of a subject’s identity. (CRO). A person or an organization
Competent Authority (CA). [ICH E6 Glossary] (commercial, academic, or other)
The regulatory body charged with contracted by the sponsor to perform
monitoring compliance with the one or more of a sponsor’s trial-related
national statutes and regulations of confirmatory trial. Phase 3 trial duties and functions. [ICH E6 Glossary]
European Member States. during which the previously revealed
actions of a therapeutic intervention
are confirmed. NOTE: Procedures in contract. A written, dated, and
complete file. File for which all data confirmatory trials should be set firmly in signed agreement between two or
cleaning is complete and database is advance. Compare to exploratory trial. more involved parties that sets out
ready for quality review and unblinding. any arrangements on delegation and
distribution of tasks and obligations
conformity assessment. The
completion. 1. Subject completion: and, if appropriate, on financial
process by which compliance with
the case where a subject ceases active the EMEA’s Essential Requirements is matters. The protocol may serve as the
participation in a trial because the assessed. See also Notified Body. basis of a contract. [ICH E6 Glossary]
subject has, or is presumed to have,
followed all appropriate conditions
of a protocol. 2. Study completion: consent form. Document used control (of electronic records).
according to the study protocol, the during the informed consent process To prepare and maintain case histories
point at which all protocol-required that is the basis for explaining to and other records for regulated clinical
activities have been executed. potential subjects the risks and investigations. NOTE: Control is often
[Modified EU CTD] potential benefits of a study and the used as a casual synonym for the terms
rights and responsibilities of the parties in 21 CFR 312.62 requiring investigative
involved. NOTE: The informed consent sites to prepare, maintain, and retain
compliance (in relation to document provides a summary of a adequate and accurate case histories.
trials). Adherence to trial-related clinical trial (including its purpose, the
requirements, good clinical practice treatment procedures and schedule,
(GCP) requirements, and the applicable potential risks and benefits, alternatives control group. The group of
regulatory requirements. [Modified ICH to participation, etc.) and explains an subjects in a controlled study that
E6 Glossary] individual’s rights as a subject. It is
receives no treatment, a standard
designed to begin the informed consent
treatment, or a placebo. [21 CFR
process, which consists of conversations
computer application. See between the subject and the research 314.126] See also controls.
application. team. If the individual then decides to
enter the trial, s/he gives her/his official
control(s). 1. Comparator against
consent by signing the document.
concept. Discrete notion having a single Synonym: informed consent form; see which the study treatment is evaluated
meaning. In a controlled vocabulary a also informed consent. [e.g., concurrent (placebo, no
concept is mapped to one or more of the treatment, dose-response, active), and
words that convey its meaning. external (historical, published literature)]
consumer safety officer (CSO). 2. Computer: processes or operations
FDA official who coordinates the intended to ensure authenticity,
confidence interval. A measure of review process of various applications.
the precision of an estimated value. integrity, and confidentiality of
The interval represents the range of electronic records. NOTE: The protocol
values, consistent with the data, that is content validity. The extent to incorporates scientific rationale for
selection of comparator and describes
by the responsible authority or data data item. A named component of data quality. A dimension of data
that represents a high value should a data element. Usually the smallest contributing its trustworthiness and
be cryptographically protected if it is component [ANSI]. See also data pertaining to accuracy, sensitivity,
vulnerable to unauthorized disclosure model, data element. validity, and suitability to purpose.
or undetected modification during Key elements of data quality include
transmission or while in storage. attributability, legibility (decipherable,
[from Federal Information Processing data management conventions. unambiguous), contemporaneousness,
Standards (FIPS) Publication 46-2] Procedures and policies for data originality (i.e., not duplicated),
management (e.g., documented accuracy, precision, completeness,
procedure(s) for resolving self-evident consistency (logical, not out of range).
data entry. Human input of data changes). [ICH E6] See self-evident NOTE: Scientists may reasonably trust
into a structured, computerized format change. data that are accurate (high quality) that
using an interface such as a keyboard, have also been reviewed by investigators
pen-based tablet, or voice recognition. and protected from unauthorized
NOTE: Although data capture is data management. Tasks alteration (high integrity). See also
often used synonymously, capture associated with the entry, transfer, ALCOA, data integrity.
implies direct entry of original source and/or preparation of source data
data into an electronic record rather and derived items for entry into a
than transcription (entry) from paper clinical trial database. NOTE: Data data security. Degree to which
source. Contrast with data acquisition, management could include database data are protected from the risk of
electronic data capture; direct entry. creation, data entry, review, coding, accidental or malicious alteration or
See data collection. data editing, data QC, locking, or destruction and from unauthorized
archiving; it typically does not include access or disclosure. [FDA]
source data capture.
data integrity. A dimension of
data contributing to trustworthiness data selection criteria. The rules
and pertaining to the systems and data model. Unambiguous, by which particular data are selected
processes for data capture, correction, formally stated, expression of items, and/or transferred between the
maintenance, transmission, and the relationship among items, and point of care and the patient record;
retention. Key elements of data the structure of the data in a certain subsequently, from the patient record
integrity include security, privacy, problem area or context of use. A to the database; and from database to
access controls, a continuous pedigree data model uses symbolic conventions inclusion in sub-population analyses.
from capture to archive, stability (of agreed to represent content so that
values, of attribution), protection content does not lose its intended
against loss or destruction, ease of meaning when communicated. data transformations. Algorithmic
review by users responsible for data operations on data or data sets to
quality, proper operation and validation achieve a meaningful set of derived
of systems, training of users. NOTE: In data monitoring. Process by data for analysis. [ADaM] See also
clinical research the FDA requires that which clinical data are examined for derived variable.
data relied on to determine safety and completeness, consistency, and accuracy.
efficacy of therapeutic interventions be
trustworthy and establishes guidance data type. Data types define the
and regulations concerning practices data monitoring committee structural format of the data carried
and system requirements needed to (DMC). Group of individuals with in the attribute and influence the set
promote an acceptable level of data pertinent expertise that reviews on of allowable values an attribute may
integrity. [FDA, CSUICI, IEEE]. Compare a regular basis accumulating data assume. [HL7]
with data quality. from an ongoing clinical trial. The
DMC advises the sponsor regarding
the continuing safety of current data validation. 1. Checking data
data integrity verification. Process participants and those yet to be for correctness and/or compliance
of manually supervised verification of recruited, as well as the continuing with applicable standards, rules,
data for internal consistency. validity and scientific merit of the trial. and conventions. 2. Process used
NOTE: A DMC can stop a trial if it to determine if data are inaccurate,
finds toxicities or if treatment is proved incomplete, or unreasonable. The
data interchange. Transfer
beneficial. [After FDA guidance on process may include format checks,
of information between two or
establishment and operation of clinical completeness checks, check key tests,
more parties, which maintains the
trial data monitoring committees] reasonableness checks, and limit
integrity of the contents of the data
checks. [1. FDA. 2. ISO]
for the purpose intended. See also
interoperability.
data listing. Set of observations demographic data. Characteristics direct access. Permission to examine,
organized by domain. of subjects or study populations, which analyze, verify, and reproduce
include such information as age, sex, any records and reports that are
family history of the disease or condition important to evaluation of a clinical
database. A collection of data or for which they are being treated, and trial. NOTE: The party (e.g., domestic
information, typically organized for other characteristics relevant to the and foreign regulatory authorities,
ease and speed of search and retrieval. study in which they are participating. sponsor’s monitors and auditors)
with direct access should take all
reasonable precautions within the
database lock. Action taken to dependent variable. Outcomes constraints of the applicable regulatory
prevent further changes to a clinical that are measured in an experiment requirement(s) to maintain the
trial database. NOTE: Locking of a and that are expected to change as a confidentiality of subjects’ identities
database is done after review, query result of an experimental manipulation and sponsor’s proprietary information.
resolution, and a determination has of the independent variable(s). [Center [ICH E6 Glossary]
been made that the database is ready for Advancement of Clinical Research]
for analysis
direct entry. Recording of data by
deployment. Readying an electronic human or automated action where an
dataset. A collection of structured clinical trial system for field use by electronic record is the original means
data in a single file. [CDISC, ODM, and providing or disseminating capture of capturing the data into an electronic
SDS] Compare with analysis dataset, devices, tokens, or passwords for users records system without a paper source
tabulation dataset. of an activated system. See activation. document. Examples are an individual
keying original observations into a
system or the automatic recording
decision rule. Succinct statement of derived variable. New variable into the system of the output from
how a decision will be reached based created as a function of existing measuring devices such as a balance
upon the expected foreseen clinical variables and/or application of that measures subject’s body weight or
benefits in terms of outcomes of the mathematical functions. See also an ECG machine. Compare with data
primary endpoint. [FDA documentation] variable, raw data. entry, data acquisition.
regulated administration of individual either A (active) and B (placebo), or A required for conduct, management,
doses. [AMA Manual of Style] (placebo) and B (active). [ICH E9] analysis, and reporting of the trial.
NOTE: FDA has recently drawn a
distinction between studies and
dosage form. Physical characteristics dropout. A subject in a clinical trial trials. Both words refer to systematic
of a drug product, (e.g., tablet, who for any reason fails to continue efforts to obtain evidence relevant to
capsule, or solution) that contains a in the trial until the last visit or regulatory authorities, but, depending
drug substance, generally—but not observation required of him/her by the on regulatory context and particularly
necessarily—in association with one study protocol. [from ICH E9] in the case of postmarketing
or more other ingredients. [21 CFR commitments, a study might not be
§314.3]. See also drug product the appropriate word for a clinical trial
drug. 1. Article other than food (prospective, controlled, randomized),
intended for use in the diagnosis, cure, but should be reserved instead for
dosage regimen. The number mitigation, treatment, or prevention surveillance, structured gathering of
of doses per given time period; the of disease; or intended to affect the information, epidemiological studies, or
elapsed time between doses (for structure or any function of the body. even animal studies [DRAFT Guidance
example, every six hours) or the time Not a device or a component, part, for Industry Postmarketing Studies
that the doses are to be given (for or accessory of a device. 2. Substance and Clinical Trials—Implementation
example, at 8 a.m. and 4 p.m. daily); recognized by an official pharmacopia of Section 505(o) of the Federal Food,
and/or the amount of a medicine (the or formulary. [from FDA Glossary of Drug, and Cosmetic Act]. Synonyms:
number of capsules, for example) to Terms, CDER] eClinical study, eClinical investigation.
be given at each specific dosing time.
[from Center for Advancement of
Clinical Research] drug development process. eCRF. 1. Auditable electronic record
The program for advancing an designed to capture information
investigational product from preclinical required by the clinical trial protocol
dosage strength. 1. Proportion of studies through approval for marketing to be reported to the sponsor on
active substance to excipient, measured following review by regulatory agencies. each trial subject. 2. A CRF in which
in units of volume or concentration. related data items and their associated
2. The strength of a drug product tells comments, notes, and signatures are
how much of the active ingredient drug product. 1. A dosage form that linked electronically. NOTE: eCRFs
is present in each dosage. [2. FDA contains an active drug ingredient or may include special display elements,
Glossary of Terms] placebo. 2. A finished dosage form as electronic edit checks, and other special
described in regulations. [SPL Glossary] properties or functions and are used for
both capture and display of the linked
dose. The amount of drug data. [FDA CSUCT]
administered to a patient or test subject dynamic HTML. Collective term for a
at one time or the total quantity combination of tags and options, style
administered. [AMA Manual of Style] sheets, and programming that allows eCRT. CRTs provided in electronic
users to create Web pages in Hypertext format for eSubmissions (electronic
Mark-up Language (HTML) that are regulatory submissions). NOTE:
double-blind study. A study in more responsive to user interaction According to FDA guidance, eCRTs are
which neither the subject nor the than previous versions of HTML. datasets provided as SAS Transport files
investigator nor the research team with accompanying documentation in
interacting with the subject or data electronic submissions. They enable
during the trial knows what treatment eCertified copy. A copy that is
reviewers to analyze each dataset for
a subject is receiving. created through application of a
each study. Each CRF domain should be
validated process that is certified
provided as a single dataset; however,
to preserve the information in the
additional datasets suitable for
double-dummy. A technique for original. NOTE: an eCertified copy of an
reproducing and confirming analyses
retaining the blind when administering eSource document can also serve as a
may also be needed. Becoming
supplies in a clinical trial, when the two source document. See source, eSource,
obsolete, being replaced by SDTM.
treatments cannot be made identical. certified copy.
Supplies are prepared for Treatment A
(active and indistinguishable placebo)
edit check. An auditable process,
and for Treatment B (active and eClinical trial. Clinical trial in
usually automated, of assessing the
indistinguishable placebo). Subjects which primarily electronic processes
then take two sets of treatment; are used to plan, collect (acquire), content of a data field against its
access, exchange, and archive data expected logical, format, range, or
enrollment (target). The number eSource. Source record that is ethnicity. Denotes social groups with
of subjects in a class or group electronic. See also source, electronic a shared history, sense of identity,
(including the total for the entire trial) record. geography, and cultural roots
intended to be enrolled in a trial.
NOTE: Target enrollments are set so
that statistical and scientific objectives eSource data (electronic European Medicines Agency
of a trial will have a likelihood of being source data). Source data captured (EMEA). The regulatory agency for
met as determined by agreement, initially into a permanent electronic the EU.
algorithm, or other specified process. record used for the reconstruction
and evaluation of a clinical study.
NOTE: “Permanent” in the context evaluable (for efficacy and
Enterprise Vocabulary Services of these definitions implies that safety). Pertains to data or subjects
(EVS). A U.S. national resource to any changes made to the electronic that meet Statistical Analysis Plan criteria
house and maintain a number of data are recorded via an audit trail. for inclusion in Efficacy/Safety datasets.
health-related glossaries and controlled [ICH, CDISC]. See also source data,
vocabularies under strict versioning. permanent data.
NOTE: Includes the CDISC Glossary. [NCI] exclusion criteria. List of
characteristics in a protocol, any one of
eSource document. The electronic
which may exclude a potential subject
epoch. Interval of time in the record used to aggregate a particular
planned conduct of a study. An epoch instance of eSource data items for from participation in a study.
is associated with a purpose (e.g., capture, transmission, storage, and/
screening, randomization, treatment, or display, and serving as a source
excretion. The act or process of
follow-up), which applies across all arms document for a clinical investigation.
of a study. NOTE: Epoch is intended as NOTE: Electronic source documents eliminating waste products from the
a standardized term to replace: period, are recorded in electronic systems body. See also ADME.
cycle, phase, stage. See also arm, visit. according to conventions (such
as those for PDF documents) that
ensure that all the fields of eSource exploratory IND study. A clinical
ePRO. PRO data initially captured data and associated contextual study that is conducted early in
electronically. NOTE: Usually ePRO information (e.g., time of capture, Phase 1; involves very limited human
data is captured as eSource. [DIA ePRO time zone, authorship, signatures, exposure and has no therapeutic
Working Group]. See also patient revisions) are linked to each other in a or diagnostic intent (e.g., screening
reported outcome, PRO, eSource. particular structure for presentation. studies, microdose studies) [FDA
The encoded specifications in the Guidance for Industry, Investigators,
electronic record thus serve the same and Reviewers: Exploratory IND Studies,
equipoise. A state in which an role as have the physical properties
investigator is uncertain about which January 2006] See also Phase 0.
of paper (binding items together).
arm of a clinical trial would be eSource documents are subject to
therapeutically superior for a patient. regulations and guidance that apply
NOTE: An investigator who has a exploratory study. Phase 1 or 2
to source documents. See also source
treatment preference or finds out that study during which the actions of a
documents. [after eSDI, CDISC]
one arm of a comparative trial offers a therapeutic intervention are assessed
clinically therapeutic advantage should and measured. NOTE: Procedures in
disclose this information to subjects essential documents. Documents exploratory studies may appropriately
participating in the trial. that individually and collectively permit be altered to expand the scope or
evaluation of the conduct of a study method of investigation. Compare to
and the quality of the data produced. confirmatory study.
equivalence trial. A trial with [ICH E6 Glossary]
the primary objective of showing
that the response to two or more extraction transformation load
treatments differs by an amount that established name. The official (ETL). A class of software applications
is clinically unimportant. NOTE: This name of a drug substance. [Food, for data extraction, transformation,
is usually demonstrated by showing Drug, and Cosmetic Act] and loading that are used to implement
that the true treatment difference is data interfaces between disparate
likely to lie between a lower and an database systems, often to populate
upper equivalence margin of clinically ethics committee. See institutional data warehouses.
acceptable differences. review board, independent ethics
committee.
health authority. Synonym for that provides markup of documents members, whose responsibility it is to
regulatory authority. NOTE: Used in the for display in a Web browser. [HL7] ensure the protection of the rights,
European Union. Contrast to XML. safety, and well-being of human
subjects involved in a trial and to
provide public assurance of that
Health Level 7 (HL7). An ANSI- hypertext. Links in a document that protection by, among other things,
accredited Standards Developing permit browsers to jump immediately reviewing and approving/providing
Organization (SDO) operating in to another document. NOTE: In most favorable opinion on the trial protocol,
the healthcare arena. NOTE: Level browsers links are displayed as colored, the suitability of the investigator(s),
7 refers to the highest level of the underlined text. facilities, and the methods and
International Standards Organization’s material to be used in obtaining and
(ISO) communications model for documenting informed consent of the
Open Systems Interconnection (OSI), hypothesis to test. In a trial, a trial subjects. NOTE: The legal status,
the application level. The application statement relating to the possible composition, function, operations, and
level addresses definition of the data different effect of the interventions regulatory requirements pertaining to
to be exchanged, the timing of the on an outcome. The null hypothesis of independent ethics committees may
interchange, and the communication of no such effect is amenable to explicit differ among countries but should allow
certain errors to the application. Level statistical evaluation by a hypothesis the independent ethics committee to
7 supports such functions as security test, which generates a P value. act in agreement with GCP as described
checks, participant identification, [CONSORT Statement] in the ICH guideline. [ICH] See also
availability checks, exchange institutional review board.
mechanism negotiations, and, most
importantly, data exchange structuring. impartial witness. A person who is
independent of the trial, who cannot indication. A health problem or
be unfairly influenced by people disease that is identified as likely to be
healthcare provider. 1. One involved with the trial, who attends the benefited by a therapy being studied
who directly or indirectly administers informed consent process if the subject in clinical trials. NOTE: Where such
interventions that are designed to or the subject’s legally acceptable a benefit has been established and
improve the physical or emotional representative cannot read, and who approved by regulatory authorities, the
status of patients. 2. A person licensed, reads the informed consent form and therapy is said to be approved for such
certified, or otherwise authorized any other written information supplied an indication.
or permitted by law to administer to the subject. [ICH]
healthcare in the ordinary course of
business or practice of a profession, informed consent. An ongoing
including a healthcare facility. [1. PR inclusion criteria. The criteria in a process that provides the subject with
Project. 2. HL7] protocol that prospective subjects must explanations that will help in making
meet to be eligible for participation in educated decisions about whether to
a study. NOTE: Exclusion and inclusion begin or continue participating in a
healthy volunteer. Subject (not a criteria define the study population. trial. Informed consent is an ongoing,
patient) in a clinical trial. NOTE: Usually See also exclusion criteria. interactive process rather than a one-
healthy volunteers serve as subjects in time information session. NOTE: Under
Phase 1 trials. 21 CFR 50.20, no informed consent
independent data monitoring form may include any “language
committee (IDMC). A committee through which the subject or the
human subject. Individual who is established by the sponsor to assess representative is made to waive or
or becomes a participant in research, at intervals the progress of a clinical appear to waive any of the subject’s
either as a recipient of the test article trial, safety data, and critical efficacy legal rights, or releases or appears to
or as a control. A subject may be either variables and recommend to the release the investigator, the sponsor,
a healthy human or a patient. [21 CFR sponsor whether to continue, modify, the institution, or its agents from
50.3]. Synonym: subject/trial subject. or terminate the trial. [ICH E9] See also liability for negligence.” [ICH] See also
data monitoring committee. consent form.
Huriet Law. France’s regulations
covering the initiation and conduct of independent ethics committee inspection. The act by a regulatory
clinical trials. (IEC). An independent body (a review authority(ies) of conducting an official
board or a committee, institutional, review of documents, facilities,
regional, national, or supranational) records, and any other resources that
HyperText Markup Language constituted of medical/scientific are deemed by the authority(ies) to
(HTML). A specification of the W3C professionals and non-scientific be related to the clinical trial and
that may be located at the site of the of their compliance with the planned interoperability. Ability of two
trial, at the sponsor’s and/or contract course of treatment. The principle is or more systems or components to
research organization’s (CRO’s) intended to prevent bias caused by exchange information and to use the
facilities, or at other establishments loss of participants that may reflect information that has been exchanged.
deemed appropriate by the regulatory non- adherence to the protocol and [IEEE Standard Computer Dictionary].
authority(ies). [ICH] See also audit. disrupt baseline equivalence established See also syntactic, semantic.
by random assignment. [ICH E9; after
CONSORT Statement]
institution (medical). Any public inter-rater reliability. The property
or private entity or agency or medical of scales yielding equivalent results
or dental facility where clinical trials are interaction (qualitative and when used by different raters on
conducted. [ICH] quantitative). The situation in which different occasions. [ICH E9]
a treatment contrast (e.g., difference
between investigational product and
institutional review board (IRB). control) is dependent on another intervention. The drug, device,
An independent body constituted of factor (for example, the center). A therapy, or process under investigation
medical, scientific, and non-scientific quantitative interaction refers to the in a clinical study that is believed to have
members, whose responsibility it is to case where the magnitude of the an effect on outcomes of interest in a
ensure the protection of the rights, contrast differs at the different levels of study (e.g., health-related quality of life,
safety, and well-being of human the factor; for a qualitative interaction, efficacy, safety, pharmacoeconomics).
subjects involved in a trial by, among the direction of the contrast differs for Synonyms: therapeutic intervention,
other things, reviewing, approving, at least one level of the factor. medical product. See also: test articles;
and providing continuing review of devices; drug product; medicinal
trial protocol and of the methods and product; combination product.
material to be used in obtaining and interim analysis(es). Analysis
documenting informed consent of the comparing intervention groups at any
trial subjects. [ICH E6 1.31] Synonyms: time before the formal completion of investigational product. A
independent review board, independent the trial, usually before recruitment is pharmaceutical form of an active
ethics committee, committee for the complete. [CONSORT Statement] ingredient or placebo being tested or
protection of human subjects. used as a reference in a clinical trial,
including a product with a marketing
interim analysis schedule. The authorization when used or assembled
instrument. A means to capture time/information points at which (formulated or packaged) in a way
data (e.g., questionnaire, diary) plus interim analyses are planned. different from the approved form,
all the information and documentation or when used for an unapproved
that supports its use. NOTE: indication, or when used to gain
Generally, instruments include clearly interim clinical trial/study further information about an approved
defined methods and instructions report. A report of intermediate use. NOTE: CDISC includes test articles
for administration or responding, a results and their evaluation based on in its definition of investigational
standard format for data collection, planned analyses performed during the products. [ICH]
and well-documented methods for course of a trial. [ICH]
scoring, analysis, and interpretation
of results. [from PRO Draft Guidance] investigational treatment. An
Compare to questionnaire, survey (see internal consistency. Pertaining to intervention under investigation in a
Comments on Draft PRO Guidance, data that do not include contradictions. clinical study.
April 4, 2006, by ISOQoL, p. 8).
Internet. A global system of investigator. An individual who
intention-to-treat. The principle computer networks that provides the actually conducts a clinical investigation
that asserts that the effect of a common TCP IP infrastructure for (i.e., under whose immediate direction
treatment policy can be best assessed email, the World Wide Web, and other the test article is administered or
by evaluating the basis of the intention online activities. dispensed to, or used involving
to treat a subject (i.e., the planned a subject, or, in the event of an
treatment regimen) rather than the investigation conducted by a team of
actual treatment given. NOTE: This Internet service provider (ISP). individuals, is the responsible leader
has the consequence that subjects A company that provides access to the of that team). [21 CFR 50.3] See also
allocated to a treatment group should Internet for individuals and organizations. sponsor-investigator, site investigator.
be followed up, assessed, and analyzed
as members of that group irrespective
item definition. 1. In a label. Description of a drug product/ Leiter der klinischen Prüfung.
questionnaire or form to be completed device that includes: the indication, Under the German Drug Law, the
in a clinical trial, the specification of a who should use it, adverse events, physician who is head of the clinical
question and the specification of the instructions for use, and safety investigation.
format and semantics of the response. information. NOTE: Labels must be
2. Formal specification of the properties approved by regulatory authorities.
of an item or field of data in an [FDA; SPL] Synonyms: package insert, life-threatening adverse event/
eClinical trial. [2. ODM] patient package leaflet. experience. Any adverse drug
experience that places the patient or
subject, in the view of the investigator,
item generation. Establishing the labeling (content of). All text, at immediate risk of death from the
content to be covered by the items in a tables, and figures in labeling as reaction as it occurred (i.e., it does not
PRO instrument, including generating described in regulations for a specific include a reaction that, had it occurred
item wording, evaluating the product (e.g., 21 CFR 201.56 and in a more severe form, might have
completeness of item coverage of the 201.57 for human prescription drugs; caused death). [FDA 21 CFR §312.32;
concepts of interest, and performing 201.66 for human over-the-counter ICH-E2A]
initial assessment of clarity and drugs; 21 CFR 801 for medical devices;
readability. NOTE: PRO instrument item and 21 CFR 606.122 for blood
generation is potentially incomplete products). See also structured product longitudinal study. Investigation
without patient involvement. [from label. in which data are collected from a
ISOQOL comments on PRO Draft number of subjects over a long period
Guidance] of time (a well-known example is the
laboratory (clinical). A laboratory Framingham Study).
providing analyses of samples collected
item group definition. The in clinical care or research.
specification in an eClinical trial of a mapping. In the context of
collection of items often clinically related representing or exchanging data,
to each other and useful to consider last subject out/complete (LSC/ connecting an item or symbol to a code
as an ensemble. NOTE: Item groups LPC or LSO/LPO). 1. The date and or concept. Compare with translation.
are likely to have greater granularity time when the last subject has reached
interpretation, and extrapolation. New Drug Application (NDA). null hypothesis. The assertion
Monitors work with the clinical An application to FDA for a license to that no true association or difference
research coordinator to check all data market a new drug in the United States. in the study outcome or comparison
and documentation from the trial. of interest between comparison
[from ICH E6, 5.18] See also clinical groups exists in the larger population
research associate. new safety information. With from which the study samples are
respect to a drug, information derived obtained. NOTE: A null hypothesis (for
from a clinical trial, an adverse event example,“subjects will experience no
monitoring. The act of overseeing report, a post-approval study, or peer- change in blood pressure as a result
the progress of a clinical trial and of reviewed biomedical literature; data of administration of the test product”)
ensuring that it is conducted, recorded, derived from the post-market risk is used to rule out every possibility
and reported in accordance with the identification and analysis system (REMS); except the one the researcher is
protocol, standard operating procedures or other scientific data regarding: (a) a trying to prove, and is used because
(SOPs), good clinical practice (GCP), and serious risk or unexpected serious risk most statistical methods are less
the applicable regulatory requirement(s). associated with use of the drug since able to prove something true than
[ICH E6 Glossary] the drug was approved, since the REMS to provide strong evidence that it
was required or last assessed (b) the is false. The assertion that no true
effectiveness of the approved REMS association or difference in the study
monitoring committee. See for the drug obtained since the last outcome or comparison of interest
independent data-monitoring committee. assessment of such strategy. [After 21 between comparison groups exists
CFR, Part 505-1(b)] in the larger population from which
the study samples are obtained. See
monitoring report. A written report also research hypothesis. [from AMA
from the monitor to the sponsor after n-of-1 study. A trial in which an Manual of Style]
each site visit and/or other trial-related individual subject is administered a
communication according to the treatment repeatedly over a number of
sponsor’s SOPs. [ICH] episodes to establish the treatment’s Nuremberg Code. Code of ethics,
effect in that person, often with the set forth in 1947, for conducting
order of experimental and control human medical research.
monitoring visit. A visit to a study treatments randomized.
site to review the progress of a clinical
study and to ensure protocol adherence, objective. The reason for performing
accuracy of data, safety of subjects, nomenclature. Application of a trial in terms of the scientific questions
and compliance with regulatory naming conventions. Compare with to be answered by the analysis of data
requirements and good clinical practice vocabulary, terminology. collected during the trial. NOTE: The
guidelines. [from ICH E6, 5.18] primary objective is the main question
to be answered and drives any statistical
nonclinical study. Biomedical planning for the trial (e.g., calculation
multicenter study. See multicenter studies not performed on human of the sample size to provide the
trial. subjects. [ICH E6 Glossary] appropriate power for statistical testing).
Secondary objectives are goals of a trial
that will provide further information on
multicenter trial. Clinical trial not approvable letter. An official the use of the treatment.
conducted according to a single communication from FDA to inform
protocol but at more than one site a sponsor of a marketing application
and, therefore, carried out by more that the important deficiencies objective measurement. A
than one investigator. [ICH E9 Glossary] described in the letter preclude measurement of a physiological or
Synonym: multicenter study. See approval unless corrected. medical variable such as blood glucose
investigator/institution. level that is obtained by a measuring
device rather than a human judgment
Notified Body (NB). A private or assessment. See also outcome,
natural language. Language as institution charged by the Competent patient-reported outcome; objective
used in ordinary communications Authority with verifying compliance measures are observations (SDTM) and
among humans and distinguished of medical devices (not drugs) with could be endpoints. Patient-reported
from controlled terminologies and the applicable Essential Requirements outcomes are subjective measurements
structured languages used exclusively stated in the Medical Device Directive.
for communication and interoperability This process, called Conformity
among machines. Assessment, has EU-wide validity once observation. 1. An assessment of
completed by the NB. patient condition or analysis of data
original data. The first recorded packaging. The material, both a certain pre-set period. NOTE: FDA
study data values. NOTE: FDA is physical and informational, that requires that passwords that are part
allowing original documents and contains or accompanies a marketed of electronic signatures be “periodically
the original data recorded on those or investigational therapeutic agent checked, recalled or revised,” but does
documents to be replaced by copies once it is fully prepared for release to not mandate password aging. [After
provided that the copies have been patients and/or subjects in clinical trials NIST, 21 CFR Part 11]
verified as identical in content and
meaning. (See FDA Compliance Policy
Guide 7150.13). [Modified from pairing. A method by which subjects patient. Person under a physician’s
CSUICI] See also certified copy, source. are selected so that two subjects with care for a particular disease or condition.
similar characteristics (for example, NOTE: A subject in a clinical trial is not
weight, smoking habits) are assigned necessarily a patient, but a patient in a
outcome (of adverse event). to a set, but one receives Treatment clinical trial is a subject. See also subject,
Refers to the resolution of an adverse A and the other receives Treatment B. trial subject, healthy volunteer. Although
event. NOTE: Often denoted using a See also matched-pair design. often used interchangeably as a
pick list from a controlled terminology synonym for subject, a healthy volunteer
such as: Recovered/resolved, is not a patient.
recovering/resolving, not recovered/ parallel trial. Subjects are
not resolved, recovered/resolved with randomized to one of two or more
sequelae, fatal, or unknown. [SDTM differing treatment groups (usually patient file. One that contains
Events class of observation] investigational product and placebo) demographic, medical, and treatment
and usually receive the assigned information about a patient or subject.
treatment during the entire trial. It may be paper- or computer-based or a
outcome. 1. Events or experiences Synonyms: parallel group trial, parallel mixture of computer and paper records.
that clinicians or investigators examining design trial.
the impact of an intervention or
exposure measure because they patient-reported outcome (PRO).
believe such events or experiences parameter. A variable in a model, Information coming directly from
may be influenced by the intervention or a variable that wholly or partially patients or subjects through interviews
or exposure. 2. (SDTM) The result of characterizes a probability distribution or self-completed questionnaires or
carrying out a mathematical or statistical (mathematics and statistics). NOTE: other data capture tools such as diaries
procedure. NOTE: 1. Such events and In clinical trials the term is often about their life, health condition(s),
experiences are called clinical outcomes used synonymously with “variable” and treatment. NOTE: PROs are used to
independently of whether they are for factual information (age, date of assess outcomes involving the patients’/
part of the original question/protocol recovery), measurements, and clinical subjects’ perceptions, symptoms,
of the investigation. [1. Guyatt, G., assessments. It is most appropriately satisfaction with treatment, adherence
Schunemann H., Dept. Epidemiology & linked to statistical conventions and as a to prescribed regimens. PROs include
Statistics, McMaster University—personal numeric characteristic of a population. outcomes recorded by interviewers
communication] See also variable; Parameters are rarely known and transcribing the views expressed by the
outcome can be a result of analysis; are usually estimated by statistical patient, but the term does not apply to
outcome is more general than endpoint computation from samples. Thus the outcomes recorded by observers who
in that it does not necessarily relate to a term is narrower than variable. [Parexel rely on their own judgment. A PRO
planned objective of the study. Barnett; ADaM; HyperStat Online] See is usually a subjective assessment of
also variable, outcome. feeling or function distinguished from
a self-reported objective measurement
outcomes research. Research such as body weight. [from PRO Draft
concerned with benefits, financial participant. A person or entity with Guidance, Gordon Guyatt and Holger
costs, healthcare system usage, risks, a role in healthcare or a clinical study. Schuneman-personal communication;
and quality of life as well as their NOTE: Participants in a clinical trial may Patrick, D.L., 2003. After Acquardo
relation to therapeutic interventions. include subjects and study personnel. C., Berzon C., et al., 2001] Synonym:
NOTE: Usually distinguished from A subject participates as part of the subject-reported outcome (SRO).
research conducted solely to determine group of people who are administered See also outcome, subject, patient,
efficacy and safety. [Guyatt et al., the therapeutic intervention or control. instrument.
1993] See also pharmacoeconomics, See also subject, patient.
quality of life.
performed activity. Clinical trial
password aging. A practice applying events as they actually occurred
outliers. Values outside of an to multi-user computer systems where (as compared with events planned in
expected range. the validity of a password expires after the protocol).
hundred subjects. [After FDA CDER drug over a longer period of time. comprehensible explanation of the
Handbook, ICH E8] [After FDA CDER Handbook, ICH E8] reasons for the Commissioner’s decision
on each issue” raised in comments
submitted in response to the proposed
Phase 2A. Controlled clinical studies Phase 5. Postmarketing surveillance is regulation. [from 21CFR10.40]
that occur after the completion of sometimes referred to as Phase 5. See
Phase 1 studies and the first set of also outcomes research.
exposure-response studies in patients, preclinical studies. Animal studies
that support Phase 1 safety and
and before beginning Phase 2B (i.e.,
placebo. A pharmaceutical tolerance studies and must comply
patient dose-ranging trial) and Phase
with good laboratory practice (GLP).
3 clinical efficacy-safety studies. [FDA preparation that does not contain
NOTE: Data about a drug’s activities
draft Guidance for Industry End of the investigational agent. In blinded
and effects in animals help establish
Phase 2A meetings, 9/08]. studies, it is generally prepared to boundaries for safe use of the drug
be physically indistinguishable from in subsequent human testing (clinical
the preparation containing the studies or trials).
Phase 3. Studies are expanded investigational product.
controlled and uncontrolled trials.
They are performed after preliminary Pre-Market Approval
evidence suggesting effectiveness of population. Any finite or infinite Application (PMA). An application
the drug has been obtained and are collection of subjects from which a to FDA for a license to market a new
sample is drawn for a study to obtain device in the United States.
intended to gather the additional
estimates for values that would be
information about effectiveness and obtained if the entire population were
safety that is needed to confirm sampled. [AMA Style Manual] primary objective. The primary
efficacy and evaluate the overall objective(s) is the main question to
benefit–risk relationship of the drug be answered and drives any statistical
and to provide an adequate basis for postmarketing commitment planning for the trial (e.g., calculation
physician labeling. NOTE: Phase 3 (PMC). Studies and clinical trials that of the sample size to provide the appro
studies usually include from several applicants have agreed to conduct, but priate power for statistical testing). [ICH
hundred to several thousand subjects. that will generally not be considered E6 6.3] See also objective.
as meeting statutory purposes (see
[After FDA CDER Handbook, ICH E8]
postmarketing requirement) and so will
not be required. primary variable. An outcome
variable specified in the protocol to
Phase 3B. A subcategory of Phase 3
be of greatest importance to the
trials done near the time of approval to postmarketing requirement primary objective of the trial, usually
elicit additional findings. NOTE: Dossier (PMR). FDA-required postmarketing the one used in the sample size
review may continue while associated studies or clinical trials. [FDAAA; 21 calculation. NOTE: Differences between
Phase 3B trials are conducted. These CFR Part 314, Subpart H; 21 CFR Part groups in the primary and secondary
trials may be required as a condition of 601, Subpart E] variable(s) are believed to be the result
regulatory authority approval. of the group-specific interventions.
[PR Project; CONSORT Statement]
postmarketing surveillance. Synonyms: primary endpoint, outcome.
Ongoing safety monitoring of marketed See also primary objective.
Phase 4. Postmarketing (Phase
drugs. See also Phase 4 studies, Phase
4) studies to delineate additional
5 studies.
information about the drug’s risks,
product. 1. Drug product: A finished
benefits, and optimal use that may be
dosage form that contains a drug
requested by regulatory authorities in pragmatic trial. Term used to
substance. 2. A physical entity that is
conjunction with marketing approval. describe a clinical study designed to
examine the benefits of a product intended to diagnose, treat, or prevent
NOTE: These studies could include,
under real world conditions. a disease or other abnormal condition
but would not be limited to, studying
and subject to regulatory authority.
different doses or schedules of
[Modified from FDA Glossary of Terms]
administration than were used in
preamble. A section preceding the
Phase 2 studies, use of the drug in text of a final FDA regulation published
other patient populations or other in the Federal Register. NOTE: “The PROMIS. NIH-sponsored project
stages of the disease, or use of the preamble is to contain a thorough and for the development and evaluation
sample size. 1. A subset of a larger screening (of sites). Determining serious adverse event (SAE) or
population, selected for investigation the suitability of an investigative site serious adverse drug reaction
to draw conclusions or make estimates and personnel to participate in a clinical (serious ADR). Any untoward
about the larger population. 2. The trial. medical occurrence that at any dose:
number of subjects in a clinical trial. results in death, is life threatening,
3. Number of subjects required for requires inpatient hospitalization or
primary analysis. screening (of subjects). A process prolongation of existing hospitalization,
of active consideration of potential results in persistent or significant
subjects for enrollment in a trial. See disability/incapacity, or is a congenital
sample size adjustment. An interim also screen failure. anomaly/birth defect. [ICH] See also
check conducted on blinded data to adverse experience.
validate the sample size calculations or
reevaluate the sample size. screening trials. Trials conducted
to detect persons with early, mild, and serious adverse experience.
asymptomatic disease. Any experience that suggests a
schedule of activities. A significant hazard, contra-indication,
standardized representation of side effect or precaution. See also
planned clinical trial activities including script. A program or a sequence of serious adverse event.
interventions (e.g., administering drug, instructions that are interpreted or
surgery) and study administrative carried out by another program or by a
activities (e.g., obtaining informed person. serious risk. Risk of a serious adverse
consent, distributing clinical trial drug experience. [505-1(b) of FD&C Act
material and diaries, randomization) as (21 U.S.C. 355-1(b)]
well as assessments. See also schedule secondary objective. See objective.
of assessments.
server. A computer that controls a
secondary sponsor. Additional central repository of data, files, and/or
schedule of assessments. A individuals, organizations or other applications that can be accessed and/or
tabular representation of planned legal persons, if any, that have agreed manipulated in some manner by client
protocol events and activities, in with the primary sponsor to take on computers. A file server hosts files for
sequence. [after E3 Annexes IIIa and responsibilities of sponsorship. [WHO, use by client machines. An application
IIIb] Synonym: flow chart. Compare to CTR Item 6] server runs programs that may process
study design schematic. and display data exchanged with client
machines. After the arrival of the
secondary variable. The primary Web, server often refers to software
screen failure. Potential subject outcome is the outcome of greatest and computers that perform database
who did not meet one or more criteria importance. Data on secondary queries and collect and present timely
required for participation in a trial. See outcomes are used to evaluate data to users running browsers or other
also screening of subjects. additional effects of the intervention. client applications.
[CONSORT Statement] See also
outcome, endpoint.
screen/screening (of sex. Phenotypic expression of
substances). Screening is the chromosomal makeup that defines a
process by which substances are self-evident change. A data study subject as male, female, or other.
evaluated in a battery of tests or assays discrepancy that can be easily and Compare to gender.
(screens) designed to detect a specific obviously resolved on the basis of
biological property or activity. It can existing information on the CRF (e.g.,
be conducted on a random basis in obvious spelling errors or the patient side effects. Any actions or effects
which substances are tested without is known to be a male and a date of of a drug or treatment other than the
any preselection criteria or on a last pregnancy is provided). See also intended effect. Negative or adverse
targeted basis in which information on discrepancy. effects may include headache, nausea,
a substance with known activity and hair loss, skin irritation, or other
structure is used as a basis for selecting physical problems. Experimental drugs
other similar substances on which to semantic. In the context of a technical must be evaluated for both immediate
run the battery of tests. [SQA] specification, semantic refers to the and long-term side effects. See also
meaning of an element as distinct from adverse reaction.
its syntax. Syntax can change without
affecting semantics. [HL7]
investigational product is administered data in a trial. [ICH E9; from the Center blinding, gender, dose, indication,
to, dispensed to, or used by a subject. for Advancement of Clinical Research] configuration).
NOTE: The term does not include any
person other than an individual (i.e., it
does not include a corporation or an statistical significance. State that study design. Plan for the precise
agency). The obligations of a sponsor- applies when a hypothesis is rejected. procedure to be followed in a
investigator include both those of a Whether or not a given result is clinical trial, including planned and
sponsor and those of an investigator. significant depends on the significance actual timing of events, choice of
[21 CFR 50.3f] [ICH] level adopted. For example, one may control group, method of allocating
say “significant at the 5% level.” This treatments, blinding methods; assigns
implies that when the null hypothesis a subject to pass through one or more
standard. Criterion or specification is true there is only a 1 in 20 chance of epochs in the course of a trial. Specific
established by authority or consensus rejecting it. design elements (e.g., crossover,
for 1. measuring performance or parallel, dose-escalation) [Modified
quality; 2. specifying conventions from Pocock, Clinical Trials: A Practical
that support interchange of common stem. The prompt, question, or Approach] See Trial Design Model. See
materials and information. NOTE: instruction in a PRO item. See also also, arm, epoch, and visit.
CDISC standards exist to support the response option, item.
exchange of clinical data, for example,
at both the syntactic and semantic study design rationale. Reason for
levels. See interoperability. stochastic. Involving a random choosing the particular study design.
variable; involving chance or probability.
vocabulary, terms are considered to translation. Converting information implement the principles in the ICH E9
refer to an underlying concept having from one natural language to another guidance and who is responsible for the
a single meaning. Concepts may be while preserving meaning. Compare statistical aspects of the trial. [ICH E9]
linked to several synonymous terms. with mapping.
token. Physical key that provides access Trial Design Model. Defines a type 1 (or type I) error. Error made
to a secure electronic system or location. standard structure for representing when a null hypothesis is rejected but is
the planned sequence of events and actually true. Synonym: false positive.
the treatment plan of a trial. NOTE: A
transcription. Process of transforming component of the SDTM that builds
dictated or otherwise documented upon elements, arms epochs, visits; type 2 (or type II) error. Error
information from one storage medium suitable also for syntactic interpretation made when an alternative hypothesis
to another. NOTE: often refers explicitly by machines. [CDISC] See study design. is rejected when it is actually true.
to data that is manually transcribed from Synonym: false negative.
source docs or measuring devices to
CRFs or to eCRFs. trial monitoring. Oversight of
quality of study conduct and statistical type 3 (or type III) error. Some
interim analysis. [ICH E9] statisticians use this designation for an
transition rule. A guide that governs error made when calling the less effective
the allocation of subjects to operational treatment the more effective one.
options at a discrete decision point or trial site. Synonym for investigative
branch (e.g., assignment to a particular site, investigator site, site, site of the
arm, discontinuation) within a clinical trial, study site. [ICH E6] type of comparison. How
trial plan. See branch. treatment arms will be compared
(e.g., Safety, Efficacy, PK/PD). May
trial statistician. A statistician who also include comparison to data from
has a combination of education/ other studies or sources (e.g., historical
training and experience sufficient to control). [ICH E9, EUDRACT (p.18)]
verification. 1. The act of reviewing, vulnerable subjects. Individuals Web server. A computer server that
inspecting, testing, checking, whose willingness to volunteer in a delivers HTML pages or files over the
auditing, or otherwise establishing clinical trial may be unduly influenced World Wide Web. See also server.
and documenting whether items, by the expectation, whether justified
processes, services, or documents or not, of benefits associated with
conform to specified requirements. participation, or of a retaliatory Web site. A collection of Web pages
2. (of software). Provides objective response from senior members of and other files. A site can consist of a
evidence that the design outputs of a hierarchy in case of refusal to single Web page, thousands of pages,
a particular phase of the software participate. Examples are members of or custom created pages that draw on
development life cycle meet all of the a group with a hierarchical structure, a database associated with the site.
specified requirements for that phase. such as medical, pharmacy, dental,
NOTE: 2. Software verification looks and nursing students, subordinate
for consistency, completeness, and hospital and laboratory personnel, weighting. An adjustment in a value
correctness of the software and its employees of the pharmaceutical based on scientific observations within
supporting documentation, as it is being industry, members of the armed the data.
developed, and provides support for a forces, and persons kept in detention.
subsequent conclusion that software Other vulnerable subjects include
is validated [FDA General Principles of patients with incurable diseases, well-being (of the trial
Software Validation; ANSI/ASQC A3- persons in nursing homes, unemployed subjects). The physical and mental
1978; ISO/IEC Guide 25]. Verification is or impoverished persons, patients in integrity of the subjects participating
used in the sense of matching elements emergency situations, ethnic minority in a clinical trial. [ICH]
of a report or results of system testing groups, homeless persons, nomads,
to individual requirements. Compare to refugees, minors, and those incapable
withdrawal. The subject-initiated
validation where suitability to purpose is of giving consent. [ICH]
act of discontinuing participation in a
also established.
clinical study. NOTE: Withdrawal can
Warning Letter. A written range from the subject’s complete
verification of data. See source communication from FDA notifying withdrawal from study procedures and
document verification (SDV). an individual or firm that the agency follow-up activities, to the subject’s
considers one or more products, withdrawal from study-related
practices, processes, or other activities interventions while the subject permits
visit. A clinical encounter that to be in violation of the Federal continued access to his/her medical
encompasses planned and unplanned FD&C Act, or other acts, and that records or identifiable information.
trial interventions, procedures, and failure of the responsible party to Note that according to FDA
assessments that may be performed take appropriate and prompt action regulations, when a subject withdraws
on a subject. A visit has a start and to correct and prevent any future from a study, the data collected on
an end, each described with a rule. repeat of the violation may result the subject to the point of withdrawal
[CDISC Trial Design Project in administrative and/or regulatory remain part of the study database
enforcement action without further and may not be removed. See also
notice. [FDA] discontinuation.
vocabulary. Terms that function in
general reference to concepts that
apply over a variety of languages washout period. A period in a within-subject differences. In a
are words, and their totality is a clinical study during which subjects crossover trial, variability in each subject
vocabulary. Synonym: terminology. receive no treatment for the indication is used to assess treatment differences.
See controlled vocabulary. under study and the effects of a
previous treatment are eliminated (or
World Wide Web. All the resources
assumed to be eliminated).
volunteer. A person volunteering and users on the Internet that are
to participate as a subject in a clinical using HTTP protocols. Also called the
trial, often a healthy person agreeing Web browser. A computer program Web and www.
to participate in a Phase 1 trial. See that interprets HTML and other Internet
also Phase 1. languages and protocols and displays
Web pages on a computer monitor.