cdisc clinical research glossary

12 APPLIED CLINICAL TRIALS appliedclinicaltrialsonline.com December 2008

match any single one of the exclusioncriteria set up for the study. See also inclusion criteria, exclusioncriteria.

clinical trial. Subjects must be screenedto ensure that their characteristicsmatch a list of admission criteria and that none of their characteristics

SPECIAL RESOURCE ISSUE

CDISC Clinical Research GlossaryVersion 7.0

Glossary Terms

510(k). Premarket Notification (PMN)required for certain medical devices. Seehttp://www.fda.gov/cdrh/510khome.html

abbreviation. A set of letters thatare drawn from a word or from asequence of words and that are usedfor brevity in place of the full word orphrase. NOTE: An abbreviation isNOT pronounced as a word, but eachletter is read in sequence (e.g., NIH).Compare to acronym.

absorption. The process by whichmedications reach the blood streamwhen administered other thanintravenously, for example, throughnasal membranes. See also ADME(pharmacokinetics).

acronym. 1. A word formed fromthe beginning letters (e.g., ANSI) ora combination of syllables andletters (e.g., MedDRA) of a name orphrase. 2. The short set of lettersthat identify a clinical study protocol.NOTE: An acronym is usuallypronounced as a word, not byspeaking each letter individually.Compare to abbreviation.

action letter. An officialcommunication from FDA to anNDA sponsor announcing anagency decision. See also approvalletter, approvable letter, not-approvable letter.

activation. Enabling an eClinicaltrial system to capture data; usuallyused for EDC systems.

admission criteria. Basis forselecting target population for a

Orientation: The following Glossary isthe seventh produced by the GlossaryProject of CDISC, which seeks toharmonize definitions (includingacronyms, abbreviations, and initials)used in the various standards initiativesundertaken by CDISC in clinicalresearch. The purpose of the CDISCGlossary is also to serve the communityof clinical researchers by selecting anddefining terms pertaining to clinicalresearch, particularly eClinicalinvestigations, sponsored by thepharmaceutical industry or a federalagency. The Glossary is publiclyaccessible on the CDISC Web site(CDISC.org), where comments on theGlossary are welcomed.

Note that this CDISC Glossary is NOTcomprehensive for all words bearingon human health, medicine, orlaboratory methods. The Glossaryincludes references and links to otherglossaries such as regulatorydictionaries and to health-relatedcontrolled terminologies that areknown to be useful in conductingclinical research, including the CDISCTerminology Project.

Glossary terms are organizedalphabetically by first word accordingto the opinion of the Glossary ProjectTeam concerning most common usagein clinical research. Thus “sourcedocument verification” would appearunder “source,” not “verification.” The

Glossary follows the practice ofpreceding certain terms with the letter“e” to denote that they pertain toelectronic or Web implementation.Each term in the Glossary has thefollowing conventions concerningcontent and order of presentation:

Term. The word or phrase beingdefined is followed by a period. Onlyproper nouns are capitalized.

Definition. Multiple meanings of thesame term are numbered 1., 2., 3., etc.

NOTE: Comments including usage ordomain knowledge related to a termmay follow the definition.

Source(s). The sources for definitionsare cited (see “Reference Citations”) insquare brackets. Where the definitionhas been altered by CDISC, the citationstates “modified from.” Where thedefinition has been drawn by CDISCfrom text that is not itself a definition,the citation states “after” or “from.”Where no source is listed, thedefinition is from CDISC.

Related terms. Some definitions offersynonyms (See), comments, or relatedterms (See also or Compare to) tosharpen or expand upon the definition.

*See Reference Citations, p. 52, forGlossary Project Team Members

Stephen A. Raymond, Project Leader

Glossary Project Core Team*:Patricia Beers Block, Liaison from theOffice of Science and Health, FDA;

Helle-Mai Gawrylewski, Johnson andJohnson PRD; Arthur Gertel, BeardsworthConsulting; Stephen A. Raymond, PHTCorporation

CDISC Glossary Project

adverse drug experience.See adverse drug reaction.

adverse drug reaction (ADR). Anynoxious and unintended responseassociated with the use of a drug inhumans. 1. Post-approval: an adverseevent that occurs at doses normally usedin man for prophylaxis, diagnosis, ortherapy of diseases or for modification ofphysiological function. 2. Pre-approval:an adverse event that occurs at any doseand where a causal relationship is atleast a reasonable possibility. NOTE: FDA21 CFR 310.305 defines an adverse drugexperience to include any adverse event,“whether or not considered to be drug-related.” CDISC recognizes that currentusage incorporates the concept ofcausality. [WHO Technical Report498(1972); ICH E2A]

adverse event (AE). Any untowardmedical occurrence in a patient or clinicalinvestigation subject administered apharmaceutical product and which doesnot necessarily have a causal relationshipwith this treatment. An adverse event(AE) can therefore be any unintended sign(including an abnormal laboratoryfinding), symptom, or disease temporallyassociated with the use of a medicinal(investigational) product, whether or notrelated to the medicinal (investigational)product. NOTE: For further information,see the ICH Guideline for Clinical SafetyData Management: Definitions andStandards for Expedited Reporting.“[Modified from ICH E2A]” Synonyms:side effect, adverse experience. See alsoserious adverse event, serious adverseexperience.

adverse experience. See adverseevent.

adverse reaction. See adverse drugreaction.

algorithm. Step-by-step procedurefor solving a mathematical problem;also used to describe step-by-stepprocedures for making a series of

choices among alternative decisions toreach a calculated result or decision.

alpha error. The likelihood that arelationship observed between 2variables is due to chance. Theprobability of a Type 1 error. [Modifiedfrom AMA Manual of Style]

amendment. A written descriptionof a change(s) to, or formal clarificationof, a protocol.

American National StandardsInstitute (ANSI). Founded in 1918,ANSI itself does not develop standards.ANSI’s roles include serving as thecoordinator for U.S. voluntary standardsefforts, acting as the approval body torecognize documents developed byother national organizations asAmerican National Standards, acting asthe U.S. representative in internationaland regional standards efforts, andserving as a clearinghouse for nationaland international standardsdevelopment information. [HL7]

analysis dataset. An organizedcollection of data or information with acommon theme arranged in rows andcolumns and represented as a single file;comparable to a database table. NOTE:Standardizing analysis datasets isintended to make review and assessmentof analysis more consistent [ADaM].

analysis set. A set of subjects whosedata are to be included in the mainanalyses. This should be defined in thestatistical section of the protocol.NOTE: There are a number of potentialanalysis sets, including, for example,

the set based upon the intent-to-treatprinciple. [ICH E9]

analysis variables. Variables usedto test the statistical hypothesesidentified in the protocol and analysisplan; variables to be analyzed. [PRProject] See also variable.

anchor. Designation for a plannedactivity, often marking the transitionbetween epochs or elements of aclinical study plan (e.g., “FPFV—firstpatient first visit”).

applet. A small application, typicallydownloaded from a server.

application software. Seeapplication.

application. 1. Computerapplication: software designed to fillspecific needs of a user; for example,software for navigation, projectmanagement, or process control. 2.Regulatory application: applicationmade to a health authority to invest-igate, market, or license a new productor indication. Synonyms: 1. computerapplication, application software.

approvable letter. An officialcommunication from FDA to anNDA/BLA sponsor that lists issues to beresolved before an approval can beissued. [Modified from 21 CFR 314.3;Guidance to Industry and FDA Staff(10/08/2003)]

approval (in relation toinstitutional review boards). Theaffirmative decision of the IRB that theclinical trial has been reviewed and may

December 2008 appliedclinicaltrialsonline.com APPLIED CLINICAL TRIALS 13

be conducted at the institution sitewithin the constraints set forth by theIRB, the institution, good clinicalpractice (GCP), and the applicableregulatory requirements. [ICH E6]

approval letter. An officialcommunication from FDA to inform anapplicant of a decision to allowcommercial marketing consistent withconditions of approval. [Modified from21 CFR 314.3; Guidance to Industryand FDA Staff (10/08/2003)]

arm. A planned sequence of elements,typically equivalent to a treatmentgroup. [SDTM] See element.

assessment. A measurement,evaluation, or judgment for a studyvariable pertaining to the status of asubject. NOTE: Assessments are usuallymeasured at a certain time, and usuallyare not compounded significantly bycombining several simultaneousmeasurements to form a derivedassessment (e.g., BMI) or a result ofstatistical analysis. See variable;outcome, endpoint; the termassessment is intended to invoke somedegree of evaluation or judgmentconcerning subject status.

audit. A systematic and independentexamination of trial-related activities anddocuments to determine whether theevaluated trial-related activities wereconducted and the data were recorded,analyzed, and accurately reportedaccording to the protocol, sponsor’sstandard operating procedures (SOPs),good clinical practice (GCP), and theapplicable regulatory requirement(s).[ICH E6 Glossary]

audit certificate. Document thatcertifies that an audit has taken place(at an investigative site, CRO, or clinicalresearch department of a pharm-aceutical company). [ICH E6 Glossary]

audit report. A written evaluation bythe auditor of the results of the audit.[Modified from ICH E6 Glossary]

audit trail. A process that capturesdetails such as additions, deletions, oralterations of information in anelectronic record without obliteratingthe original record. An audit trailfacilitates the reconstruction of thehistory of such actions relating to theelectronic record. [after ICH E6, CSUICI]

back translation (naturallanguage). The process of translatinga document that was translated fromone language to another back to theoriginal language. Used to ensure thatconsent forms, surveys, and otherclinical trial documents will be clearand accurate in the translated form.

background material. Informationpertinent to the understanding of aprotocol. NOTE: Examples includeinvestigator brochure, literature review,history, rationale, or otherdocumentation that places a study incontext or presents critical features.[PR Project]

balanced study. Trial in which aparticular type of subject is equallyrepresented in each study group.

bandwidth. An indicator of thethroughput (speed) of data flow on atransmission path; the width of therange of frequencies on which atransmission medium carries electronicsignals. All digital and analog signalchannels have a bandwidth.

baseline assessment. Assessmentof subjects as they enter a trial andbefore they receive any treatment.

baseline characteristics.Demographic, clinical, and other datacollected for each participant at thebeginning of the trial before theintervention is administered. NOTE:Randomized, controlled trials aim to

compare groups of participants thatdiffer only with respect to theintervention (treatment). Althoughproper random assignment preventsselection bias, it does not guaranteethat the groups are equivalent atbaseline. Any differences in baselinecharacteristics are, however, the resultof chance rather than bias. The studygroups should be compared at baselinefor important demographic and clinicalcharacteristics. Baseline data may beespecially valuable when the outcomemeasure can also be measured at thestart of the trial. [CONSORT Statement]

baseline imbalance. Systematic errorin creating intervention groups, suchthat they differ with respect toprognosis. That is, the groups differ inmeasured or unmeasured baselinecharacteristics because of the wayparticipants were selected or assigned.NOTE: Also used to mean that theparticipants are not representative of thepopulation of all possible participants.[ICH E9]

Bayesian approaches. Approachesto data analysis that provide a posteriorprobability distribution for someparameter (e.g., treatment effect),derived from the observed data and aprior probability distribution for theparameter. The posterior distribution isthen used as the basis for statisticalinference. [ICH E9 Glossary]

Bayesian statistics. Statisticalapproach named for Thomas Bayes(1701–1761) that has among itsfeatures giving a subjectiveinterpretation to probability, acceptingthe idea that it is possible to talk aboutthe probability of hypotheses beingtrue and of parameters havingparticular values.

beta error. Probability of showing nosignificant difference when a truedifference exists; a false acceptance ofthe null hypothesis. See also Type 2error. [AMA Manual of Style]

SPECIAL RESOURCE ISSUE CDISC CLINICAL RESEARCH GLOSSARY


bias. Situation or condition thatcauses a result to depart from the truevalue in a consistent direction. Biasrefers to defects in study design ormeasurement. [AMA Manual of Style.See also ICH E9, CONSORT Statement]

bioanalytical assays. Methods forquantitative measurement of a drug,drug metabolites, or chemicals inbiological fluids.

bioavailability. Rate and extent towhich a drug is absorbed or isotherwise available to the treatmentsite in the body.

bioequivalence. Scientific basis onwhich drugs with the same activeingredient(s) are compared. NOTE: Tobe considered bioequivalent, thebioavailability of two products mustnot differ significantly when the twoproducts are given in studies at thesame dosage under similar conditions.

biological marker. See biomarker.

Biologics Licensing Application(BLA). An application to FDA for alicense to market a new biologicproduct in the United States.

biomarker. A characteristic that isobjectively measured and evaluated asan indicator of normal biologicalprocesses, pathogenic processes, orpharmacologic responses to atherapeutic intervention. [Biomarkerdefinitions working group]

biostatistics. Branch of statisticsapplied to the analysis of biologicalphenomena.

blind review. Checking andassessing data prior to breaking theblind, for the purpose of finalizing theplanned analysis. [Modified ICH E9]

blinded (masked) medications.Products that appear identical in size,shape, color, flavor, and other attributesto make it very difficult for subjects andinvestigators (or anyone assessing the

outcome) to determine whichmedication is being administered.

blinded study. A study in which thesubject, the investigator, or anyoneassessing the outcome is unaware ofthe treatment assignment(s). NOTE:Blinding is used to reduce the potentialfor bias. [Modified ICH E6 Glossary] Seealso blinding/masking, double-blindstudy, single-blind study, triple-blindstudy; contrast with open-label orunblinded study.

blinding. A procedure to limit biasby preventing subjects and/or studypersonnel from identifying whichtreatments or procedures areadministered, or from learning theresults of tests and measuresundertaken as part of a clinicalinvestigation. NOTE: Masking, whileoften used synonymously withblinding, usually denotes concealingthe specific study intervention used.[from ICH E9] The term masking isoften preferred to blinding in the fieldof ophthalmology. [from AMA Manualof Style]. See also blinding, double-blind study, masking, single-blindstudy, triple-blind study. Contrast withopen-label and/or unblinded study.

branch. Point within a study designwhere there is an allocation of subjectsubsets to particular procedures ortreatment groups.

brand name. See proprietary name.Synonyms: trade name; proprietaryname. [SPL]

browser. Computer program thatruns on the user’s desktop computerand is used to navigate the World WideWeb. See also Web browser.

cache. Storage area on a computer’shard drive where the browser stores(for a limited time) Web pages and/orgraphic elements.

carry-over effect. Effects oftreatment that persist after treatment

has been stopped, sometimes beyondthe time of a medication’s knownbiological activity.

case history. An adequate andaccurate record prepared and maintainedby an investigator that records allobservations and other data pertinent tothe investigation on each individualadministered the investigational drug(device or other therapy) or employed asa control in the investigation. NOTE: Casehistories include the case report formsand supporting data including, forexample, signed and dated consentforms and medical records including, forexample, progress notes of the physician,the individual’s hospital chart(s), and thenurses’ notes. The case history for eachindividual shall document that informedconsent was obtained prior toparticipation in the study. [21 CFR312.62b]

case record form. See case reportform.

case report form (CRF). 1. Aprinted, optical, or electronic documentdesigned to record all of the protocol-required information to be reported tothe sponsor for each trial subject. 2. Arecord of clinical study observationsand other information that a studyprotocol designates must be completedfor each subject. NOTE: In commonusage, CRF can refer to either a CRFpage, which denotes a group of one ormore data items linked together forcollection and display, or a casebook,which includes the entire group of CRFpages on which a set of clinical studyobservations and other information canbe or have been collected, or theinformation actually collected bycompletion of such CRF pages for asubject in a clinical study [ICH E6Glossary]. See also CRF (paper).

case report tabulations (CRT). Ina paper submission, listings of datathat may be organized by domain (typeof data) or by subject. See also eCRT.



categorical data. Data evaluated bysorting values (for example, severe,moderate, and mild) into variouscategories.

causality assessment. Anevaluation performed by a medicalprofessional concerning the likelihoodthat a therapy or product under studycaused or contributed to an adverseevent.

CDISC Standard (The). CDISC termfor a proposed uniform CDISC standardintended to address the full life-cycle of aclinical trial including protocolrepresentation, capture of source data,submission, and archiving using a set offully integrated and consistent models,terms, and controlled vocabularies derivedfrom the current set of CDISC standards.

certified copy. A copy of originalinformation that has been verified asindicated by a dated signature, as anexact copy having all of the sameattributes and information as theoriginal. NOTE: The copy may beverified by dated signature or by avalidated electronic process. A certifiedcopy of a source document may serveas a source for a clinical investigation.See also source data, source. [AfterCSUICI]

Certified IRB Professional (CIP).Certification awarded to persons whosatisfy the educational andemployment requirements and pass anexamination conducted by the AppliedResearch Ethics National Association(ARENA), the membership division ofPublic Responsibility in Medicine andResearch (PRIM&R).

clean database. A set of revieweddata in which errors have been resolvedto meet QA requirements for error rateand in which measurements and othervalues are provided in acceptable units;database that is ready to be locked.See also database lock, clean file.

clean file. When all data cleaning iscompleted and database is ready forquality review and unblinding.

client. A program that makes aservice request of another program,usually running on a server, that fulfillsthe request. Web browsers (such asNetscape Navigator and MicrosoftExplorer) are clients that request HTMLfiles from Web servers.

clinical benefit. A therapeuticintervention may be said to conferclinical benefit if it prolongs life,improves function, and/or improves theway a subject feels.

clinical clarification. A queryresolution received from the sponsorstaff (medical monitors, DSMBmonitoring board, etc.). See also self-evident change.

clinical data. Data pertaining to themedical well-being or status of apatient or subject.

clinical development plan. Adocument that describes the collectionof clinical studies that are to beperformed in sequence, or in parallel,with a particular active substance,device, procedure, or treatmentstrategy, typically with the intention ofsubmitting them as part of anapplication for a marketingauthorization. NOTE: The plan shouldhave appropriate decision points andallow modification as knowledgeaccumulates. [from ICH E9] See alsodevelopment plan.

clinical document architecture.Specification for the structure andsemantics of “clinical documents” forthe purpose of exchange. [HL7; SPL]

clinical document. A documentationof clinical observations and services.NOTE: An electronic document shouldincorporate the following characteristics:

persistence, stewardship, potential forauthentication, wholeness, and humanreadability. [SPL]

clinical efficacy. Power or capacity toproduce a desired effect (i.e.,appropriate pharmacological activity in aspecified indication) in humans. [SQA]

clinical investigation. See clinicaltrial, clinical study. NOTE: Increasedusage of investigation or study in theU.S. rather than “trial,” may reflect theappearance of the term in FDAregulations concerning clinical researchactivities.

clinical pharmacology. Sciencethat deals with the characteristics,effects, properties, reactions, and usesof drugs, particularly their therapeuticvalue in humans, including theirtoxicology, safety, pharmacodynamics,and pharmacokinetics (ADME).

clinical protocol. See protocol.

clinical research anddevelopment. The testing of a drugcompound in humans primarily done todetermine its safety andpharmacological effectiveness. Clinicaldevelopment is done in phases, whichprogress from very tightly controlleddosing of a small number of subjects toless tightly controlled studies involvinglarge numbers of patients. [SQA]

clinical research associate (CRA).Person employed by a sponsor or by acontract research organization acting ona sponsor’s behalf, who monitors theprogress of investigator sites participatingin a clinical study. At some sites (primarilyin academic settings), clinical researchcoordinators are called CRAs.

clinical research coordinator(CRC). Person who handles most of theadministrative responsibilities of aclinical trial on behalf of a siteinvestigator, acts as liaison betweeninvestigative site and sponsor, andreviews all data and records before a



monitor’s visit. Synonyms: trialcoordinator, study coordinator, researchcoordinator, clinical coordinator,research nurse, protocol nurse.

clinical significance. Change in asubject’s clinical condition regarded asimportant whether or not due to thetest intervention. NOTE: Somestatistically significant changes (inblood tests, for example) have noclinical significance. The criterion orcriteria for clinical significance shouldbe stated in the protocol. The term“clinical significance” is not advisableunless operationally defined.

clinical study (trial) report. Awritten description of a study of anytherapeutic, prophylactic, or diagnosticagent conducted in human subjects, inwhich the clinical and statisticaldescription, presentations, and analysisare fully integrated into a single report.NOTE: For further information, see thethe ICH Guideline for Structure andContent of Clinical Study Reports. [ICHE6 Glossary]

clinical study. See clinical trial.

clinical trial. A research investigationinvolving human subjects that isdesigned to answer specific questionsabout the safety and efficacy of abiomedical intervention (drug,treatment, device) or new ways of usinga known drug, treatment, or device).[modified from ICH E6 Glossary,Directive 2001/20/EC] Synonym: clinicalinvestigation or study.

clinical trial data. Data collected inthe course of a clinical trial. See alsoclinical trial information.

clinical trial exemption (CTX). Ascheme that allows sponsors to applyfor approval for each clinical study inturn, submitting supporting data to theMedicines Control Agency (MCA),which approves or rejects theapplication (generally within 35

working days). NOTE: Approval meansthat the company is exempt from therequirement to hold a clinical trialcertificate (CTC). [UK]

clinical trial information. Datacollected in the course of a clinical trialor documentation related to theintegrity or administration of that data.A superset of clinical trial data.

clinical trial materials. Completeset of supplies provided to aninvestigator by the trial sponsor.

clinician reported outcome.Clinician assessment of patientoutcomes, based on objective orsubjective data evaluated by the clinician.

codelist. Finite list of codes and theirmeanings that represent the onlyallowed values for a data item. See alsocontrolled vocabulary. A codelist is onetype of controlled vocabulary.

coding. In clinical trials, the process ofassigning data to categories for analysisNOTE: Adverse events, for example,may be coded using MedDRA.

cognitive debriefing. A qualitativeresearch tool used to determinewhether concepts and items areunderstood by patients in the sameway that PRO instrument developersintend. NOTE: Cognitive debriefinginterviews involve incorporating follow-up questions in a field test interview togain better understanding of howpatients interpret questions asked ofthem and to collect and consider allconcepts elicited by an item. [from PRODraft Guidance Glossary]

cohort. 1. A group of individuals whoshare a common exposure, experience orcharacteristic. 2. A group of individualsfollowed-up or traced over time in acohort study. [AMA Manual of Style]

cohort study. Study of a group ofindividuals, some of whom are exposedto a variable of interest, in whichsubjects are followed over time. Cohort

studies can be prospective orretrospective. [AMA Manual of Style] Seealso prospective study.

combination product. 1. A productcomprising two or more individualproducts. 2. Two or more separateproducts packaged together in a singlepackage or as a unit. 3. A product thatis packaged separately but is used onlywith another product. [Modified fromSPL Glossary]

common data element. Astructured item characterized by a stemand response options together with ahistory of usage that can bestandardized for research purposesacross studies conducted by and forNIH. NOTE: The mark up or taggingfacilitates document indexing, searchand retrieval, and provides standardconventions for insertion of codes.[NCI, CaBIG]. See also item.

Common Technical Document. Aformat agreed upon by ICH to organizeapplications to regulatory authoritiesfor registration of pharmaceuticals forhuman use. [ICH] See also eCTD.

comparative study. One in whichthe investigative drug is comparedagainst another product, either activedrug or placebo.

comparator (product). Aninvestigational or marketed product(i.e., active control), or placebo, usedas a reference in a clinical trial. [ICH E6Glossary] See also control.

Competent Authority (CA). Theregulatory body charged withmonitoring compliance with thenational statutes and regulations ofEuropean Member States.

complete file. File for which all datacleaning is complete and database isready for quality review and unblinding.

completion. 1. Subject completion:the case where a subject ceases active


participation in a trial because thesubject has, or is presumed to have,followed all appropriate conditions of aprotocol. 2. Study completion:according to the study protocol, thepoint at which all protocol-requiredactivities have been executed.[Modified EU CTD]

compliance (in relation totrials). Adherence to trial-relatedrequirements, good clinical practice(GCP) requirements, and the applicableregulatory requirements. [Modified ICHE6 Glossary]

computer application. Seeapplication.

concept. Discrete notion having a singlemeaning. In a controlled vocabulary aconcept is mapped to one or more of thewords that convey its meaning.

confidence interval. A measure ofthe precision of an estimated value.The interval represents the range ofvalues, consistent with the data, that isbelieved to encompass the “true”value with high probability (usually95%). The confidence interval isexpressed in the same units as theestimate. Wider intervals indicate lowerprecision; narrow intervals, greaterprecision. [CONSORT Statement]

confidentiality. Prevention ofdisclosure to other than authorizedindividuals of a sponsor’s proprietaryinformation or of a subject’s identity.[ICH E6 Glossary]

confirmatory trial. Phase 3 trialduring which the previously revealedactions of a therapeutic intervention areconfirmed. NOTE: Procedures inconfirmatory trials should be set firmly inadvance. Compare to exploratory trial.

conformity assessment. Theprocess by which compliance with the

EMEA’s Essential Requirements isassessed. See also Notified Body.

consent form. Document usedduring the informed consent processthat is the basis for explaining topotential subjects the risks andpotential benefits of a study and therights and responsibilities of the partiesinvolved. NOTE: The informed consentdocument provides a summary of aclinical trial (including its purpose, thetreatment procedures and schedule,potential risks and benefits, alternativesto participation, etc.) and explains anindividual’s rights as a subject. It isdesigned to begin the informed consentprocess, which consists of conversationsbetween the subject and the researchteam. If the individual then decides toenter the trial, s/he gives her/his officialconsent by signing the document.Synonym: informed consent form; seealso informed consent.

consumer safety officer (CSO).FDA official who coordinates thereview process of various applications.

content validity. The extent towhich a variable (for example, a ratingscale) measures what it is supposed tomeasure. [ICH E9 Glossary]

contingent subject trial contact.Planned response to an anticipated butconditional event in a clinical trial.[CDISC Trial Design Project]

contract research organization(CRO). A person or an organization(commercial, academic, or other)contracted by the sponsor to performone or more of a sponsor’s trial-relatedduties and functions. [ICH E6 Glossary]

contract. A written, dated, andsigned agreement between two ormore involved parties that sets out anyarrangements on delegation anddistribution of tasks and obligationsand, if appropriate, on financialmatters. The protocol may serve as thebasis of a contract. [ICH E6 Glossary]

control (of electronic records). Toprepare and maintain case histories andother records for regulated clinicalinvestigations. NOTE: Control is oftenused as a casual synonym for the terms in21 CFR 312.62 requiring investigativesites to prepare, maintain, and retainadequate and accurate case histories.

control group. The group ofsubjects in a controlled study thatreceives no treatment, a standardtreatment, or a placebo. [21 CFR314.126] See also controls.

control(s). 1. Comparator againstwhich the study treatment is evaluated[e.g., concurrent (placebo, notreatment, dose-response, active), andexternal (historical, publishedliterature)] 2. Computer: processes oroperations intended to ensureauthenticity, integrity, andconfidentiality of electronic records.NOTE: The protocol incorporatesscientific rationale for selection ofcomparator and describes how thecomparator serves as a reference pointfor the evaluation. [1. After ICH E10. 2.After 21 CFR Part 11; CSUCT]

controlled study. A study in whicha test article is compared with atreatment that has known effects. Thecontrol group may receive notreatment, active treatment, placebo,or dose comparison concurrent control.NOTE: For further information on“adequate and well-controlled study”see 21 CFR 314.126.

controlled terminology. Synonymfor controlled vocabulary.

controlled vocabulary. A finite setof values that represent the onlyallowed values for a data item. Thesevalues may be codes, text, or numeric.See also codelist.

coordinating committee. Acommittee that a sponsor mayorganize to coordinate the conduct ofa multicenter trial. [ICH E6]



coordinating investigator. Aninvestigator assigned the responsibilityfor the coordination of investigators atdifferent centers participating in amulticenter trial. [ICH E6]

correlation. The degree to whichtwo or more variables are related.Typically the linear relationship ismeasured with either Pearson’scorrelation or Spearman’s rho. NOTE:Correlation does not necessarily meancausation. [After HyperStat OnlineGlossary; ADaM]

covariate (prognostic). Factor orcondition that influences outcome of atrial. [ADaM]

CRF data. Subset of clinical trial datathat are entered into fields on a CRF.

CRF (paper). Case report form inwhich the data items are linked by the

physical properties of paper toparticular pages. NOTE: Data arecaptured manually and any comments,notes, and signatures are also linked tothose data items by writing ortypescript on the paper pages. See alsoeCRF, case report form.

crossover trial. A trial design forwhich subjects function as their owncontrol and are assigned to receiveinvestigational product and controls inan order determined byrandomizations, typically with awashout period between the twoproducts. [Center for the Advancementof Clinical Research; ADaM]

curriculum vitae (cv). Documentthat outlines a person’s educationaland professional history.

data. Representations of facts,concepts, or instructions in a manner

suitable for communication,interpretation, or processing byhumans or by automated means. [FDA]

data acquisition. Capture of datainto a structured, computerized formatwithout a human-to-computerinterface (i.e., from another measuringinstrument or computerized source).Contrast with data entry, electronicdata capture.

data and safety monitoringboard (DSMB). See data monitoringcommittee.

data capture. See data entry.

data clarification. Answer suppliedby the investigator in response to aquery. NOTE: The investigator maysupply a new data point value toreplace the initial value or aconfirmation of the queried data point.


data clarification form. A formused to query an investigator andcollect feedback to resolve questionsregarding data.

data collection instrument. Asubstrate or tool (either electronic orpaper) used to record, transcribe, orcollect clinical data. [PR Project]

data element. 1. For XML, an itemof data provided in a mark up modeto allow machine processing. 2.Smallest unit of information in atransaction. 3. A structured itemcharacterized by a stem and responseoptions together with a history ofusage that can be standardized forresearch purposes across studiesconducted by and for NIH. NOTE: Themark up or tagging facilitatesdocument indexing, search andretrieval, and provides standardconventions for insertion of codes. [1.FDA - GL/IEEE. 2. Center forAdvancement of Clinical Research. 3.NCI, caBIG]

data encryption standard (DES).A FIPS approved cryptographicalgorithm for encrypting (enciphering)and decrypting (deciphering) binarycoded information. Encrypting dataconverts it to an unintelligible formcalled cipher. Decrypting cipherconverts the data back to its originalform called plaintext. The standardspecifies both enciphering anddeciphering operations, which arebased on a 64 bit binary number calleda key. Unauthorized recipients of thecipher who know the algorithm but donot have the correct key cannot derivethe original data algorithmically. NOTE:Data that is considered sensitive by theresponsible authority or data thatrepresents a high value should becryptographically protected if it isvulnerable to unauthorized disclosureor undetected modification duringtransmission or while in storage. [from

Federal Information ProcessingStandards (FIPS) Publication 46-2]

data entry. Human input of data intoa structured, computerized formatusing an interface such as a keyboard,pen-based tablet, or voice recognition.NOTE: Although data capture is oftenused synonymously, capture impliesdirect entry of original source data intoan electronic record rather thantranscription (entry) from paper source.Contrast with data acquisition,electronic data capture; direct entry.

data integrity. A dimension of datacontributing to trustworthiness andpertaining to the systems andprocesses for data capture, correction,maintenance, transmission, andretention. Key elements of dataintegrity include security, privacy, accesscontrols, a continuous pedigree fromcapture to archive, stability (of values,of attribution), protection against lossor destruction, ease of review by usersresponsible for data quality, properoperation and validation of systems,training of users. NOTE: In clinicalresearch the FDA requires that datarelied on to determine safety andefficacy of therapeutic interventions betrustworthy and establishes guidanceand regulations concerning practicesand system requirements needed topromote an acceptable level of dataintegrity. [FDA, CSUICI, IEEE]. Comparewith data quality.

data integrity verification. Processof manually supervised verification ofdata for internal consistency.

data interchange. Transfer ofinformation between two or moreparties, which maintains the integrityof the contents of the data for thepurpose intended. See alsointeroperability.

data item. A named component of adata element. Usually the smallest

component [ANSI]. See also datamodel, data element.

data management conventions.Procedures and policies for datamanagement (e.g., documentedprocedure(s) for resolving self-evidentchanges). [ICH E6] See self-evidentchange.

data management. Tasksassociated with the entry, transfer,and/or preparation of source data andderived items for entry into a clinicaltrial database. NOTE: Datamanagement could include databasecreation, data entry, review, coding,data editing, data QC, locking, orarchiving; it typically does not includesource data capture.

data model. Unambiguous, formallystated, expression of items, therelationship among items, and thestructure of the data in a certainproblem area or context of use. Adata model uses symbolic conventionsagreed to represent content so thatcontent does not lose its intendedmeaning when communicated.

data monitoring. Process by whichclinical data are examined forcompleteness, consistency, and accuracy.

data monitoring committee(DMC). Group of individuals withpertinent expertise that reviews on aregular basis accumulating data froman ongoing clinical trial. The DMCadvises the sponsor regarding thecontinuing safety of currentparticipants and those yet to berecruited, as well as the continuingvalidity and scientific merit of the trial.NOTE: A DMC can stop a trial if it findstoxicities or if treatment is provedbeneficial. [After FDA guidance onestablishment and operation of clinicaltrial data monitoring committees]

data quality. A dimension of datacontributing its trustworthiness andpertaining to accuracy, sensitivity,



validity, and suitability to purpose. Keyelements of data quality includeattributability, legibility (decipherable,unambiguous), contemporaneousness,originality (i.e., not duplicated),accuracy, precision, completeness,consistency (logical, not out of range).NOTE: Scientists may reasonably trustdata that are accurate (high quality) thathave also been reviewed by investigatorsand protected from unauthorizedalteration (high integrity). See alsoALCOA, data integrity.

data security. Degree to which dataare protected from the risk ofaccidental or malicious alteration ordestruction and from unauthorizedaccess or disclosure. [FDA]

data selection criteria. The rulesby which particular data are selectedand/or transferred between the pointof care and the patient record;subsequently, from the patient recordto the database; and from database toinclusion in sub-population analyses.

data transformations. Algorithmicoperations on data or data sets toachieve a meaningful set of deriveddata for analysis. [ADaM] See alsoderived variable.

data type. Data types define thestructural format of the data carried inthe attribute and influence the set ofallowable values an attribute mayassume. [HL7]

data validation. 1. Checking datafor correctness and/or compliance withapplicable standards, rules, andconventions. 2. Process used todetermine if data are inaccurate,incomplete, or unreasonable. Theprocess may include format checks,completeness checks, check key tests,reasonableness checks, and limitchecks. [1. FDA. 2. ISO]

data listing. Set of observationsorganized by domain.

database. A collection of data orinformation, typically organized forease and speed of search and retrieval.

database lock. Action taken toprevent further changes to a clinicaltrial database. NOTE: Locking of adatabase is done after review, queryresolution, and a determination hasbeen made that the database is readyfor analysis.

dataset. A collection of structureddata in a single file. [CDISC, ODM, andSDS] Compare with analysis dataset,tabulation dataset.

decision rule. Succinct statement ofhow a decision will be reached basedupon the expected foreseen clinicalbenefits in terms of outcomes of theprimary endpoint. [FDA documentation]

Declaration of Helsinki. A set ofrecommendations or basic principlesthat guide medical doctors in theconduct of biomedical researchinvolving human subjects. It wasoriginally adopted by the 18th WorldMedical Assembly (Helsinki, Finland,1964) and recently revised (52nd WMAGeneral Assembly, Edinburgh,Scotland, October 2000).

define.XML. Table used by XMLreview tools to configure a reviewengine to deal with CDISC standarddata for a trial.

demographic data. Characteristicsof subjects or study populations, whichinclude such information as age, sex,family history of the disease or conditionfor which they are being treated, andother characteristics relevant to thestudy in which they are participating.

dependent variable. Outcomesthat are measured in an experimentand that are expected to change as aresult of an experimental manipulationof the independent variable(s). [Centerfor Advancement of Clinical Research]

deployment. Readying an electronicclinical trial system for field use byproviding or disseminating capturedevices, tokens, or passwords for usersof an activated system. See activation.

derived variable. New variablecreated as a function of existingvariables and/or application ofmathematical functions. See alsovariable, raw data.

design. 1. In the context of clinicaltrials, see design configuration. 2. Inthe context of eClinical trials systems, adesign for an application to supportactions on electronic records.

design configuration. Clinical trialdesign developed to comparetreatment groups in a clinical trial.NOTE: The configuration usuallyrequires randomization to one or moretreatment arms, each arm beingallocated a different (or no) treatment.Examples include: Parallel GroupDesign, Crossover Design, FactorialDesigns. [from ICH E9]

development plan. An orderedprogram of clinical trials, each withspecific objectives. [Adapted from ICHE9, see ICH E8]. See also clinicaldevelopment plan.

development process. See drugdevelopment process.

direct access. Permission to examine,analyze, verify, and reproduce anyrecords and reports that are importantto evaluation of a clinical trial. NOTE:The party (e.g., domestic and foreignregulatory authorities, sponsor’smonitors and auditors) with directaccess should take all reasonableprecautions within the constraints ofthe applicable regulatoryrequirement(s) to maintain theconfidentiality of subjects’ identitiesand sponsor’s proprietary information.[ICH E6 Glossary]



direct entry. Recording of data byhuman or automated action where anelectronic record is the original meansof capturing the data into an electronicrecords system without a paper sourcedocument. Examples are an individualkeying original observations into asystem or the automatic recording intothe system of the output frommeasuring devices such as a balancethat measures subject’s body weight oran ECG machine. Compare with dataentry, data acquisition.

discontinuation. The act ofconcluding participation, prior tocompletion of all protocol-requiredelements, in a clinical study by anenrolled subject. NOTE: Four categoriesof discontinuation are distinguished: 1)dropout: active discontinuation by asubject [also a noun referring to such adiscontinued subject]; 2) investigator-initiated discontinuation [e.g., subjectexperiences an unexpected adverseevent]; 3) loss to follow-up: cessation ofparticipation without notice by thesubject and without ability tosubsequently contact the subject toobtain further data; 4) sponsor-initiateddiscontinuation [e.g., change inprotocol]. Note that subjectdiscontinuation does not necessarilyimply exclusion of subject data fromanalysis. “Termination” has a history ofsynonymous use, but is now considerednon-standard. See also withdrawal andICH E3, Section 10.1 and FDA Guidancefor Industry: Submission of AbbreviatedReports & Synopses in Support ofMarketing Applications, IV A.

discrepancy. The failure of a datapoint to pass a validation check. NOTE:Discrepancies may be detected bycomputerized edit checks orobserved/identified by the datareviewer as a result of manual datareview. See also query.

disease. Any deviation from orinterruption of the normal structure or

function of a part, organ, or system ofthe body as manifested bycharacteristic symptoms and signs.[Dorland’s Medical Dictionary]

distribution. 1. In statistics, a groupof ordered values; the frequencies orrelative frequencies of all possible val-ues of a characteristic. 2. In pharma-cokinetics, the processes that controltransfer of a drug from the site ofmeasurement to its target and othertissues. [1. AMA Manual of Style]. Seealso ADME.

document (HL7). An orderedpresentation of XML elements, possiblyincluding text and tabular analyses,description, and figures. Descriptors forHL7 documents include type, class, andelement. NOTE: In HL7, a document canbe either physical (referring to the paper)or logical (referring to the content) withthe following characteristics: 1) Steward-ship; 2) Potential for authentication; 3)Wholeness; 4) Human readability; 5)Persistence; 6) Global vs. local context.

document root. The element in anXML document that contains all other


Ethics CommitteesBodies convened to protect human clinical research subjectswork under a variety of other names. For convenience andconsistency, Applied Clinical Trials generally uses the termsinstitutional review board and ethics committee. Other namesand abbreviations for such bodies are shown below.

CCI committee on clinical investigations

CCPPRB Comité Consultative pour la Protection des Personnes dans lesRecherches Biomédicales (France)

CHR committee on human research

CPPHS committee for the protection of human subjects

CRB central review board

EAB ethical advisory board

EC ethics committee

HEX human experimentation committee

HSRC human subjects review committee

IEC independent ethics committee

IRB independent review board; institutional review board

LREC local research ethics committees (UK)

MREC multicentre research ethics committees (UK)

NIRB noninstitutional review board

NRB noninstitutional review board, also known as an independentreview board

REB research ethics board (Canada)

elements; the first element in thedocument. [SPL Glossary]

document type definition (DTD).XML specification for content andpresentation of data and text in adocument including definitions for theelements considered to be legal in thedocument. NOTE: Agreeing on acommon DTD facilitates interoperabilityamong systems incorporating theagreed standards. [from XML files.com]

documentation. All records, in anyform (including but not limited towritten, electronic, magnetic, andoptical records, and scans, x-rays, andelectrocardiograms) that describe orrecord the methods, conduct, and/or results of a trial, the factorsaffecting a trial, and the actions taken.[ICH E6 Glossary]

domain. A collection of observationswith a topic-specific commonalityabout each subject in a clinicalinvestigation. NOTE: CDISC classifiesdomains. For example, theInterventions class is a domain thatcaptures investigational treatments,therapeutic treatments, and surgicalprocedures that are intentionallyadministered to the subject (usually fortherapeutic purposes) either asspecified by the study protocol (e.g.,exposure), coincident with the studyassessment period (e.g., concomitantmedications), or other substances self-administered by the subject (such asalcohol, tobacco, or caffeine). TheEvents class captures occurrences orincidents independent of planned studyevaluations occurring during the trial(e.g., “adverse events” or“disposition”) or prior to the trial (e.g.,“medical history”). The Findings classcaptures the observations resultingfrom planned evaluations such asobservations made during a physicalexamination, laboratory tests, ECGtesting, and sets of individual questionslisted on questionnaires.

domain name. The way a particularWeb server is identified on theInternet. For example, www.fda.govnames the World Wide Web (www)server for the Food and DrugAdministration, which is a government(.gov) entity. [Center for Advancementof Clinical Research]

dosage. The amount of drugadministered to a patient or test subjectover the course of the clinical study; aregulated administration of individualdoses. [AMA Manual of Style]

dosage form. Physical characteristicsof a drug product, (e.g., tablet,capsule, or solution) that contains adrug substance, generally—but notnecessarily—in association with one ormore other ingredients. [21 CFR§314.3]. See also drug product.

dosage regimen. The number ofdoses per given time period; theelapsed time between doses (forexample, every six hours) or the timethat the doses are to be given (forexample, at 8 a.m. and 4 p.m. daily);and/or the amount of a medicine (thenumber of capsules, for example) to begiven at each specific dosing time.[from Center for Advancement ofClinical Research]

dosage strength. 1. Proportion ofactive substance to excipient, measuredin units of volume or concentration. 2.The strength of a drug product tellshow much of the active ingredient ispresent in each dosage. [2. FDAGlossary of Terms]

dose. The amount of drugadministered to a patient or test subjectat one time or the total quantityadministered. [AMA Manual of Style]

double-blind study. A study inwhich neither the subject nor theinvestigator nor the research teaminteracting with the subject or dataduring the trial knows what treatmenta subject is receiving.

double-dummy. A technique forretaining the blind when administeringsupplies in a clinical trial, when the twotreatments cannot be made identical.Supplies are prepared for Treatment A(active and indistinguishable placebo)and for Treatment B (active andindistinguishable placebo). Subjectsthen take two sets of treatment; eitherA (active) and B (placebo), or A(placebo) and B (active). [ICH E9]

dropout. A subject in a clinical trialwho for any reason fails to continue inthe trial until the last visit orobservation required of him/her by thestudy protocol. [from ICH E9]

drug. 1. Article other than foodintended for use in the diagnosis, cure,mitigation, treatment, or prevention ofdisease; or intended to affect thestructure or any function of the body.Not a device or a component, part, oraccessory of a device. 2. Substancerecognized by an official pharmacopiaor formulary. [from FDA Glossary ofTerms, CDER]

drug development process. Theprogram for advancing aninvestigational product from preclinicalstudies through approval for marketingfollowing review by regulatory agencies.

drug product. 1. A dosage form thatcontains an active drug ingredient orplacebo. 2. A finished dosage form asdescribed in regulations. [SPL Glossary]

dynamic HTML. Collective term for acombination of tags and options, stylesheets, and programming that allowsusers to create Web pages in HypertextMark-up Language (HTML) that aremore responsive to user interactionthan previous versions of HTML.

eClinical trial. Clinical trial in whichprimarily electronic processes are usedto plan, collect (acquire), access,exchange, and archive data requiredfor conduct, management, analysis,



and reporting of the trial. Synonyms:eClinical study, eClinical investigation.

eCRF. 1. Auditable electronic recorddesigned to capture informationrequired by the clinical trial protocol tobe reported to the sponsor on eachtrial subject. 2. A CRF in which relateddata items and their associatedcomments, notes, and signatures arelinked electronically. NOTE: eCRFs mayinclude special display elements,electronic edit checks, and otherspecial properties or functions and areused for both capture and display ofthe linked data. [FDA CSUCT]

eCRT. CRTs provided in electronicformat for eSubmissions (electronicregulatory submissions). NOTE:According to FDA guidance, eCRTs aredatasets provided as SAS Transport fileswith accompanying documentation inelectronic submissions. They enablereviewers to analyze each dataset foreach study. Each CRF domain should beprovided as a single dataset; however,additional datasets suitable forreproducing and confirming analysesmay also be needed. Becomingobsolete, being replaced by SDTM.

edit check. An auditable process,usually automated, of assessing thecontent of a data field against itsexpected logical, format, range, orother properties that is intended toreduce error. NOTE: Time-of-entry editchecks are a type of edit check that isrun (executed) at the time data arefirst captured or transcribed to anelectronic device at the time entry iscompleted of each field or group offields on a form. Back-end edit checksare a type that is run against data thathas been entered or capturedelectronically and has also beenreceived by a centralized data store.

effect. An effect attributed to atreatment in a clinical trial. In mostclinical trials, the treatment effect ofinterest is a comparison (or contrast) of

two or more treatments. [ICH E9] Seealso treatment effect.

effectiveness. The desired measureof a drug’s influence on a disease orcondition as demonstrated bysubstantial evidence from adequateand well-controlled investigations.

efficacy. The capacity of a drug ortreatment to produce beneficial effectson the course or duration of a diseaseat the dose tested and against theillness (and patient population) forwhich it is designed.

electronic data capture (EDC).The process of collecting clinical trialdata into a permanent electronic form.NOTE: Permanent in the context ofthese definitions implies that anychanges made to the electronic dataare recorded with an audit trail. EDCusually denotes manual entry of CRFdata by transcription from sourcedocuments. The transcription istypically done by personnel atinvestigative sites. See also data entry,direct data entry, data acquisition.

electronic health record (EHR).An electronic record for health careproviders to create, import, store, anduse clinical information for patientcare, according to nationallyrecognized interoperability standards.NOTE: The EHR has the followingdistinguishing features: able to beobtained from multiple sources;shareable; interoperable; accessible toauthorized parties. [After NationalOffice of Health InformationTechnology—HIT, USHHS]

electronic medical record (EMR).An electronic record for health careproviders within one healthcareorganization to create, store, and useclinical information for patient care. Anelectronic record derived from acomputerized system used primarily fordelivering patient care in a clinicalsetting. NOTE: EMRs may serve assource documents, and such data could

serve also as source data for clinicaltrials provided that the controls on theEMR system and the transfer of suchdata to the eClinical trial system wereto fulfill regulatory requirements (e.g.,21 CFR Part 11).

electronic personal healthrecord (ePHR). An electronic recordfor individuals to create, import, store,and use clinical information to supporttheir own health.

electronic record. Any combinationof text, graphics, data, audio, pictorial,or any other information representationin digital form that is created, modified,maintained, archived, retrieved, ordistributed by a computer system. [FDACSUCT; 21 CFR Part 11.3 (7)]

electronic signature. A computerdata compilation of any symbol orseries of symbols, executed, adopted,or authorized by an individual to be thelegally binding equivalent of theindividual’s handwritten signature.[CSUCT Glossary; 21 CFR Part 11.3(7)]

element. 1. In trial design, a basicbuilding block for time within a clinicaltrial comprising the followingcharacteristics: a description of whathappens to the subject during theelement; a definition of the start of theelement; a rule for ending the element.2. A section of text in an XMLdocument delimited by start and endtags; or, in the case of empty elements(elements with no content, onlyattributes) indicated by an empty tag.[1. PR Project. 2. HL7]

endpoint. Variable that pertains tothe efficacy or safety evaluations of atrial. NOTE: Not all endpoints arethemselves assessments since certainendpoints might apply to populationsor emerge from analysis of results. Thatis, endpoints might be facts aboutassessments (e.g., prolongation ofsurvival). See also variable.


enroll. To register or enter a subjectinto a clinical trial. NOTE: Once asubject has been enrolled, the clinicaltrial protocol applies to that subject.

enrollment. 1. The act of enrollingone or more subjects. 2. The class ofenrolled subjects in a clinical trial.

enrollment (cumulative). Currentenrollment as well as any ever-enrolledsubjects who have ended participation.

enrollment (current). Subjectsactively continuing to participate in aclinical trial as of the current date.

enrollment (target). The numberof subjects in a class or group(including the total for the entire trial)intended to be enrolled in a trial.NOTE: Target enrollments are set sothat statistical and scientific objectivesof a trial will have a likelihood of beingmet as determined by agreement,algorithm, or other specified process.

Enterprise Vocabulary Services(EVS). A U.S. national resource to houseand maintain a number of health-relatedglossaries and controlled vocabulariesunder strict versioning. NOTE: Includesthe CDISC Glossary. [NCI]

epoch. Interval of time in the plannedconduct of a study. An epoch isassociated with a purpose (e.g.,screening, randomization, treatment,follow-up), which applies across all armsof a study. NOTE: Epoch is intended as astandardized term to replace: period,cycle, phase, stage. See also arm, visit.

ePRO. PRO data initially capturedelectronically. NOTE: Usually ePRO datais captured as eSource. [DIA ePROWorking Group]. See also patientreported outcome, PRO, eSource.

equipoise. A state in which aninvestigator is uncertain about whicharm of a clinical trial would betherapeutically superior for a patient.

NOTE: An investigator who has atreatment preference or finds out thatone arm of a comparative trial offers aclinically therapeutic advantage shoulddisclose this information to subjectsparticipating in the trial.

equivalence trial. A trial with theprimary objective of showing that theresponse to two or more treatmentsdiffers by an amount that is clinicallyunimportant. NOTE: This is usuallydemonstrated by showing that the truetreatment difference is likely to liebetween a lower and an upperequivalence margin of clinicallyacceptable differences.

eSource. Source record that iselectronic. See also source, electronicrecord.

eSource data (electronic sourcedata). Source data captured initiallyinto a permanent electronic recordused for the reconstruction andevaluation of a clinical study. NOTE:“Permanent” in the context of thesedefinitions implies that any changesmade to the electronic data arerecorded via an audit trail. [ICH,CDISC]. See also source data,permanent data.

eSource document. The electronicrecord used to aggregate a particularinstance of eSource data items forcapture, transmission, storage, and/ordisplay, and serving as a sourcedocument for a clinical investigation.NOTE: Electronic source documents arerecorded in electronic systemsaccording to conventions (such asthose for PDF documents) that ensurethat all the fields of eSource data andassociated contextual information(e.g., time of capture, time zone,authorship, signatures, revisions) arelinked to each other in a particularstructure for presentation. Theencoded specifications in theelectronic record thus serve the samerole as have the physical properties of

paper (binding items together).eSource documents are subject toregulations and guidance that apply tosource documents. See also sourcedocuments. [after eSDI, CDISC]

essential documents. Documentsthat individually and collectively permitevaluation of the conduct of a studyand the quality of the data produced.[ICH E6 Glossary]

established name. The officialname of a drug substance. [Food,Drug, and Cosmetic Act]

ethics committee. See institutionalreview board, independent ethicscommittee.

ethnicity. Denotes social groups witha shared history, sense of identity,geography, and cultural roots.

European Medicines Agency(EMEA). The regulatory agency forthe EU.

evaluable (for efficacy andsafety). Pertains to data or subjectsthat meet Statistical Analysis Plan criteriafor inclusion in Efficacy/Safety datasets.

exclusion criteria. List ofcharacteristics in a protocol, any one ofwhich may exclude a potential subjectfrom participation in a study.

excretion. The act or process ofeliminating waste products from thebody. See also ADME.

exploratory IND study. A clinicalstudy that is conducted early in Phase1; involves very limited humanexposure and has no therapeutic ordiagnostic intent (e.g., screeningstudies, microdose studies) [FDAGuidance for Industry, Investigators,and Reviewers: Exploratory IND Studies,January 2006] See also Phase 0.

exploratory study. Phase 1 or 2study during which the actions of a



therapeutic intervention are assessedand measured. NOTE: Procedures inexploratory studies may appropriatelybe altered to expand the scope ormethod of investigation. Compare toconfirmatory study.

extraction transformation load(ETL). A class of software applicationsfor data extraction, transformation,and loading that are used toimplement data interfaces betweendisparate database systems, often topopulate data warehouses.

field. Locus on a data collection instru-ment (usually a CRF) for recording ordisplaying a data element. See data item.

File Transfer Protocol (FTP). Astandard protocol for exchanging filesbetween computers on the Internet.See also TCP/IP.

final report. A written description ofa trial/study of any therapeutic,prophylactic, or diagnostic agentconducted in human subjects, in whichthe clinical and statistical description,presentations, and analyses are fullyintegrated into a single report. [ICH E3]

finding. A meaningful interpretationof data or observations resulting fromplanned evaluations. Compare toconclusion, hypothesis.

first subject in (FSI, FPI). The dateand time the first subject is enrolledand randomized into a study. Thesubject will have met theinclusion/exclusion criteria toparticipate in the trial and will havesigned an informed consent form.Synonym: first patient in.

first subject screened. First subjectwho signs the informed consent form

and is screened for potentialenrollment and randomization into astudy but has not yet been determinedto meet the inclusion/exclusion criteriafor the trial.

first subject treated. First subjectwho receives the test article or placeboin a clinical investigation.

first-in-humans study. The firstPhase 1 study in which the test product is administered to human beings.

first-in-man study. See first-in-humans study.

Food and Drug Administration(FDA). The United States regulatoryauthority charged with, among otherresponsibilities, granting IND and NDA approvals.


Form. A collection of items and itemgroups for capturing and displayingclinical trial data.

frequentist methods. Statisticalmethods, such as significance tests andconfidence intervals, which can beinterpreted in terms of the frequency ofcertain outcomes occurring inhypothetical repeated realizations of thesame experimental situation. [ICH E9]

frozen. Status of a database, file, orelement that has been presumed to bein its final state pending “lock” andwhere further editing is preventedwithout “unfreezing.” NOTE: Freezingand unfreezing are usually formalizedin audit trails and differ from “locking”and “unlocking” only in the degree ofapproval required. See database lock.

functional roles (in a study).See role.

gender. Subject self-identification re:masculine/feminine. [IOM] See also sex.

generalizability. The extent to whichthe findings of a clinical trial can bereliably extrapolated from the subjectswho participated in the trial to a broaderpatient population and a broader rangeof clinical settings. [ICH E9]

generic name. The drug identifyingname to which all branded (proprietary)names for that indication are associated.

global assessment variable. Asingle variable, usually a scale of orderedcategorical ratings, which integratesobjective variables and the investigator’soverall impression about the state orchange in state of a subject. [ICH E9]

glossary. A collection of specializedwords or terms with their meanings.

good clinical practice (GCP). Astandard for the design, conduct,performance, monitoring, auditing,recording, analyses, and reporting of

clinical trials that provides assurancethat the data and reported results arecredible and accurate and that therights, integrity, and confidentiality oftrial subjects are protected. NOTE: ForGuidance on Good Clinical Practice seeCOMP/ICH/135/95; Declaration ofHelsinki; 21 CFR 50, 21 CFR 54, 21 CFR56, and 21 CFR 312. [ICH]

good clinical research practice(GCRP). Term sometimes used todescribe GCP. See good clinical practice.

granularity. Refers to the size of aninformation unit in relation to a whole.NOTE: Structuring “privileges” inelectronic systems is said to be highlygranular when each of many roles candiffer in their capacity to act onelectronic records.

group sequential design. A trialdesign that allows a look at the data atparticular time points or after a definednumber of patients have been enteredand followed up based on formulatinga stopping rule derived from repeatedsignificance tests. [Center forAdvancement of Clinical Research]

handwritten signature. Thescripted name or legal mark of anindividual handwritten by thatindividual and executed or adoptedwith the present intention toauthenticate a writing in a permanentform. NOTE: The act of signing with awriting or marking instrument such asa pen or stylus is preserved. [21CFR 11]

harmonized standard. A EuropeanNorm (EN) that has been accepted byall Member States and has beenpublished in the Official Journal of theEuropean Communities (OJEC).

health authority. Synonym forregulatory authority. NOTE: Used in theEuropean Union.

Health Level 7 (HL7). An ANSI-accredited Standards Developing

Organization (SDO) operating in thehealthcare arena. NOTE: Level 7 refersto the highest level of the InternationalStandards Organization’s (ISO)communications model for OpenSystems Interconnection (OSI), theapplication level. The application leveladdresses definition of the data to beexchanged, the timing of theinterchange, and the communication ofcertain errors to the application. Level 7supports such functions as securitychecks, participant identification,availability checks, exchangemechanism negotiations, and, mostimportantly, data exchange structuring.

healthcare provider. 1. One whodirectly or indirectly administersinterventions that are designed toimprove the physical or emotional statusof patients. 2. A person licensed,certified, or otherwise authorized orpermitted by law to administerhealthcare in the ordinary course ofbusiness or practice of a profession,including a healthcare facility. [1. PRProject. 2. HL7]

healthy volunteer. Subject (not apatient) in a clinical trial. NOTE: Usuallyhealthy volunteers serve as subjects inPhase 1 trials.

human subject. Individual who is orbecomes a participant in research,either as a recipient of the test articleor as a control. A subject may be eithera healthy human or a patient. [21 CFR50.3]. Synonym: subject/trial subject.

Huriet Law. France’s regulationscovering the initiation and conduct ofclinical trials.

HyperText Markup Language(HTML). A specification of the W3Cthat provides markup of documents fordisplay in a Web browser. [HL7]Contrast to XML.

hypertext. Links in a document thatpermit browsers to jump immediatelyto another document. NOTE: In most



browsers links are displayed as colored,underlined text.

hypothesis to test. In a trial, astatement relating to the possibledifferent effect of the interventions onan outcome. The null hypothesis of nosuch effect is amenable to explicitstatistical evaluation by a hypothesistest, which generates a P value.[CONSORT Statement]

impartial witness. A person who isindependent of the trial, who cannotbe unfairly influenced by peopleinvolved with the trial, who attends theinformed consent process if the subjector the subject’s legally acceptablerepresentative cannot read, and whoreads the informed consent form andany other written information suppliedto the subject. [ICH]

inclusion criteria. The criteria in aprotocol that prospective subjects mustmeet to be eligible for participation ina study. NOTE: Exclusion and inclusioncriteria define the study population.See also exclusion criteria.

independent data monitoringcommittee (IDMC). A committeeestablished by the sponsor to assess atintervals the progress of a clinical trial,safety data, and critical efficacyvariables and recommend to thesponsor whether to continue, modify,or terminate the trial. [ICH E9] See alsodata monitoring committee.

independent ethics committee(IEC). An independent body (a reviewboard or a committee, institutional,regional, national, or supranational)constituted of medical/scientificprofessionals and non-scientificmembers, whose responsibility it is toensure the protection of the rights,safety, and well-being of humansubjects involved in a trial and toprovide public assurance of thatprotection 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 materialto be used in obtaining anddocumenting informed consent of thetrial subjects. NOTE: The legal status,composition, function, operations, andregulatory requirements pertaining toindependent ethics committees maydiffer among countries but should allowthe independent ethics committee toact in agreement with GCP as describedin the ICH guideline. [ICH] See alsoinstitutional review board.

indication. A health problem ordisease that is identified as likely to bebenefited by a therapy being studied inclinical trials. NOTE: Where such abenefit has been established andapproved by regulatory authorities, thetherapy is said to be approved for suchan indication.

informed consent. An ongoingprocess that provides the subject withexplanations that will help in makingeducated decisions about whether tobegin or continue participating in atrial. Informed consent is an ongoing,interactive process rather than a one-time information session. NOTE: Under21 CFR 50.20, no informed consentform may include any “languagethrough which the subject or therepresentative is made to waive orappear to waive any of the subject’slegal rights, or releases or appears torelease the investigator, the sponsor,the institution, or its agents fromliability for negligence.” [ICH] See alsoconsent form.

inspection. The act by a regulatoryauthority(ies) of conducting an officialreview of documents, facilities, records,and any other resources that aredeemed by the authority(ies) to berelated to the clinical trial and that maybe located at the site of the trial, at thesponsor’s and/or contract researchorganization’s (CRO’s) facilities, or at

other establishments deemedappropriate by the regulatoryauthority(ies). [ICH] See also audit.

institution (medical). Any public orprivate entity or agency or medical ordental facility where clinical trials areconducted. [ICH]

institutional review board (IRB).An independent body constituted ofmedical, scientific, and non-scientificmembers, whose responsibility it is toensure the protection of the rights,safety, and well-being of humansubjects involved in a trial by, amongother things, reviewing, approving, andproviding continuing review of trialprotocol and of the methods andmaterial to be used in obtaining anddocumenting informed consent of thetrial subjects. [ICH E6 1.31] Synonyms:independent review board, independentethics committee, committee for theprotection of human subjects.

instrument. A means to capturedata (e.g., questionnaire, diary) plusall the information anddocumentation that supports its use.NOTE: Generally, instruments includeclearly defined methods andinstructions for administration orresponding, a standard format fordata collection, and well-documentedmethods for scoring, analysis, andinterpretation of results. [from PRODraft Guidance] Compare toquestionnaire, survey (see Commentson Draft PRO Guidance, April 4, 2006,by ISOQoL, p. 8).

intention-to-treat. The principlethat asserts that the effect of atreatment policy can be best assessedby evaluating the basis of the intentionto treat a subject (i.e., the plannedtreatment regimen) rather than theactual treatment given. NOTE: This hasthe consequence that subjectsallocated to a treatment group shouldbe followed up, assessed, and analyzedas members of that group irrespective



of their compliance with the plannedcourse of treatment. The principle isintended to prevent bias caused by lossof participants that may reflect non-adherence to the protocol and disruptbaseline equivalence established byrandom assignment. [ICH E9; afterCONSORT Statement]

interaction (qualitative andquantitative). The situation in whicha treatment contrast (e.g., differencebetween investigational product andcontrol) is dependent on another factor(for example, the center). Aquantitative interaction refers to thecase where the magnitude of thecontrast differs at the different levels ofthe factor; for a qualitative interaction,the direction of the contrast differs forat least one level of the factor.

interim analysis(es). Analysiscomparing intervention groups at anytime before the formal completion ofthe trial, usually before recruitment iscomplete. [CONSORT Statement]

interim analysis schedule. Thetime/information points at whichinterim analyses are planned.

interim clinical trial/studyreport. A report of intermediateresults and their evaluation based onplanned analyses performed during thecourse of a trial. [ICH]

internal consistency. Pertaining todata that do not include contradictions.

Internet. A global system ofcomputer networks that provides thecommon TCP IP infrastructure foremail, the World Wide Web, and otheronline activities.

Internet service provider (ISP). Acompany that provides access to theInternet for individuals and organizations.

interoperability. Ability of two ormore systems or components toexchange information and to use theinformation that has been exchanged.

[IEEE Standard Computer Dictionary].See also syntactic, semantic.

inter-rater reliability. The propertyof scales yielding equivalent resultswhen used by different raters ondifferent occasions. [ICH E9]

intervention. The drug, device,therapy, or process under investigationin a clinical study that is believed to havean effect on outcomes of interest in astudy (e.g., health-related quality of life,efficacy, safety, pharmacoeconomics).Synonyms: therapeutic intervention,medical product. See also: test articles;devices; drug product; medicinalproduct; combination product.

investigational product. Apharmaceutical form of an activeingredient or placebo being tested orused as a reference in a clinical trial,including a product with a marketingauthorization when used or assembled(formulated or packaged) in a waydifferent from the approved form, orwhen used for an unapprovedindication, or when used to gainfurther information about an approveduse. NOTE: CDISC includes test articlesin its definition of investigationalproducts. [ICH]

investigational treatment. Anintervention under investigation in aclinical study.

investigator. An individual whoactually conducts a clinicalinvestigation (i.e., under whoseimmediate direction the test article isadministered or dispensed to, or usedinvolving a subject, or, in the event ofan investigation conducted by a teamof individuals, is the responsible leaderof that team). [21 CFR 50.3] See alsosponsor-investigator, site investigator.

investigator/institution. Anexpression meaning “the investigatorand/or institution, where required bythe applicable regulatoryrequirements.” [ICH E6 1.35]

investigator’s brochure. Acompilation of the clinical and non-clinical data on the investigationalproduct(s) that is relevant to the studyof the investigational product(s) inhuman subjects.

item. 1. A representation of a clinicalvariable, fact, concept, or instruction in amanner suitable for communication,interpretation, or processing by humansor by automated means. NOTE: Items arecollected together to form item groups.2. An individual question, statement, ortask that is evaluated by the patient toaddress a particular concept to bemeasured by a PRO instrument. [1.CDISC. 2. from PRO Draft Guidance] Seealso response option.

item definition. 1. In aquestionnaire or form to be completedin a clinical trial, the specification of aquestion and the specification of theformat and semantics of the response.2. Formal specification of theproperties of an item or field of data inan eClinical trial. [2. ODM]

item generation. Establishing thecontent to be covered by the items ina PRO instrument, includinggenerating item wording, evaluatingthe completeness of item coverage ofthe concepts of interest, andperforming initial assessment of clarityand readability. NOTE: PRO instrumentitem generation is potentiallyincomplete without patientinvolvement. [from ISOQOL commentson PRO Draft Guidance]

item group definition. Thespecification in an eClinical trial of acollection of items often clinically relatedto each other and useful to consider asan ensemble. NOTE: Item groups arelikely to have greater granularity inanalysis datasets using SDTM which can,for example, distinguish betweendifferent therapy types: study therapy,prior therapy, concomitant therapy,protocol forbidden therapies, rescuetherapies. [ODM]



Janus. 1. A logical design conceivedby the FDA for a data warehouseintended to integrate submission data,protocol descriptions, and analysisplans from clinical and animal studiesinto as an FDA review environmentthat uses a set of validated, standards-based tools to allow reproduciblecross-study, data mining, andretrospective comparative analysis. 2.The name assigned to a component ofthe NCI’s caBIG Clinical ResearchInformation Exchange (CRIX) initiative,representing a joint NCI/FDA project todevelop a physical implementation ofthe Janus model. NOTE: Sometimeswritten as JANUS, the term is not anacronym, but harkens to the Romangod of gates and doors, beginningsand endings.

label. Description of a drugproduct/device that includes: theindication, who should use it, adverseevents, instructions for use, and safetyinformation. NOTE: Labels must beapproved by regulatory authorities.[FDA; SPL] Synonyms: package insert,patient package leaflet.

labeling (content of). All text,tables, and figures in labeling asdescribed in regulations for a specificproduct (e.g., 21 CFR 201.56 and201.57 for human prescription drugs;201.66 for human over-the-counterdrugs; 21 CFR 801 for medical devices;and 21 CFR 606.122 for bloodproducts). See also structured productlabel.

laboratory (clinical). A laboratoryproviding analyses of samples collectedin clinical care or research.

last subject out/complete(LSC/LPC or LSO/LPO). 1. The dateand time when the last subject hasreached a planned or achievedmilestone representing the completionof the trial. 2. The last subject tocomplete a trial. See also subject,patient, completion.

last subject/patient in (LSI/LPI).Date and time when the last subject toparticipate in a clinical trial is enrolled.See also enroll, study initiation.

legal authentication. A completionstatus in which a document has beensigned manually or electronically by theindividual who is legally responsible forthat document. [HL7]

legally acceptablerepresentative. An individual orjuridical or other body authorizedunder applicable law to consent, onbehalf of a prospective subject, to thesubject’s participation in the clinicaltrial. [ICH, E6 Glossary]

Leiter der klinischen Prüfung.Under the German Drug Law, thephysician who is head of the clinicalinvestigation.

life-threatening adverseevent/experience. Any adverse drugexperience that places the patient orsubject, in the view of the investigator,at immediate risk of death from thereaction as it occurred (i.e., it does notinclude a reaction that, had it occurredin a more severe form, might havecaused death). [FDA 21 CFR §312.32;ICH-E2A]

longitudinal study. Investigation inwhich data are collected from anumber of subjects over a long periodof time (a well-known example is theFramingham Study).

mapping. In the context ofrepresenting or exchanging data,connecting an item or symbol to acode or concept. Compare withtranslation.

marketing support trials. Clinicalstudies that are designed to clarifytherapeutic benefits of a marketedproduct or to show potential decision-makers the rationale for preferring onetherapy over another.

markup. Computer-processableannotations within a multimediadocument. NOTE: In the context of theHL7 specification, markup syntax isaccording to the XML Specification. [HL7]

masking. See blinding.

matched-pair design. A type ofparallel trial design in whichinvestigators identify pairs of subjectswho are “identical” with respect torelevant factors, then randomize themso that one receives Treatment A andthe other Treatment B. See also pairing.

matching. See pairing.

mean. The sum of the values of allobservations or data points divided bythe number of observations; anarithmetical average.

median. The middle value in a dataset; that is, just as many values aregreater than the median and lowerthan the median value. (With an evennumber of values, the conventionalmedian is halfway between the twomiddle values.)

medical monitor. A sponsorrepresentative who has medicalauthority for the evaluation of the safetyaspects of a clinical trial.

medical product. See intervention.

medicinal product. Synonym fortherapeutic intervention, but usually adrug.

Medicines and Healthcareproducts Regulatory Agency(MHRA). The UK government agencyresponsible for ensuring thatmedicines and medical devices work,and are acceptably safe. [MHRA]

mega-trials. Massive clinical trialsthat test the advantages oftherapeutic interventions by enrolling10,000 or more subjects. Synonym:large sample trials.


Memorandum of Understand-ing (MOU). A formal agreementbetween the Food and DrugAdministration (FDA) and federal,state, or local government agencies;academic institutions; and otherentities. NOTE: The MOU constitutesan understanding between the partiesbut is a non-binding agreement. It isFDA’s policy to enter into MOUs withother entities whenever there is aneed to define lines of authority orresponsibility, or to clarify cooperativeprocedures.

message (HL7). The atomic unit ofdata transferred between systems. Itcomprises a group of segments in adefined sequence. Each message has amessage type that defines its purpose.NOTE: For example, the Admission,Discharge and Transfer (ADT) Messagetype is used to transmit portions of apatient’s ADT data from one system toanother. In HL7, a three-charactercode contained within each messageidentifies its type. [HL7]

meta-analysis. The formalevaluation of the quantitativeevidence from two or more trialsbearing on the same question. NOTE:This most commonly involves thestatistical combination of summarystatistics from the various trials, butthe term is sometimes also used torefer to the combination of the rawdata. [from ICH E9 Glossary]

metabolism. The biochemicalalteration of substances introducedinto the body.

metadata. Data that describe otherdata, particularly XML tagscharacterizing attributes of values inclinical data fields.

migration. The act of moving asystem or software product (includingdata) from an old to new operationalenvironment in accordance with a

software quality system. [ISO/IEC/IEEE12207:1995 §5.5.5]

missing data. 1. Data not completedor corrupted in reports and case reportforms. 2. Particularly the data notcaptured when a subject withdrawsfrom a trial. NOTE: Reviewers areconcerned about missing data (meaning2) since patients who are not improvedor who believe they have experiencedside effects may be particularly prone toleave a trial, thus skewing the analysisof results if such analysis were to bedone only on the subjects who hadcontinued with the trial. Trial designstherefore specify plans for how suchmissing data will be treated in analysis.See also intention to treat.

mode. The most frequently occurringvalue in a data set.

model. A formal structure forrepresenting and analyzing a processsuch as a clinical trial or the informationpertaining to a restricted context (e.g.,clinical trial data). [CDISC]

modem. From modulator/demodulator; a device that convertsdigital data into analog data that canbe transmitted via telephone or cablelines used for communications.

monitor. Person employed by thesponsor or CRO who is responsible fordetermining that a trial is beingconducted in accordance with theprotocol and GCP guidance. NOTE: Amonitor’s duties may include but arenot limited to helping to plan andinitiate a trial, assessing the conduct oftrials, and assisting in data analysis,interpretation, and extrapolation.Monitors work with the clinicalresearch coordinator to check all dataand documentation from the trial.[from ICH E6, 5.18] See also clinicalresearch associate.

monitoring. The act of overseeing theprogress of a clinical trial and ofensuring that it is conducted, recorded,

and reported in accordance with theprotocol, standard operating procedures(SOPs), good clinical practice (GCP), andthe applicable regulatory requirement(s).[ICH E6 Glossary]

monitoring committee. Seeindependent data-monitoring committee.

monitoring report. A written reportfrom the monitor to the sponsor aftereach site visit and/or other trial-relatedcommunication according to thesponsor’s SOPs. [ICH]

monitoring visit. A visit to a studysite to review the progress of a clinicalstudy and to ensure protocol adherence,accuracy of data, safety of subjects, andcompliance with regulatoryrequirements and good clinical practiceguidelines. [from ICH E6, 5.18]

multicenter study. See multicentertrial.

multicenter trial. Clinical trialconducted according to a singleprotocol but at more than one site and,therefore, carried out by more thanone investigator. [ICH E9 Glossary]Synonym: multicenter study. Seeinvestigator/institution.

natural language. Language asused in ordinary communicationsamong humans and distinguished fromcontrolled terminologies and structuredlanguages used exclusively forcommunication and interoperabilityamong machines.

New Drug Application (NDA). Anapplication to FDA for a license tomarket a new drug in the United States.

n-of-1 study. A trial in which anindividual subject is administered atreatment repeatedly over a number ofepisodes to establish the treatment’seffect in that person, often with theorder of experimental and controltreatments randomized.



nomenclature. Application ofnaming conventions. Compare withvocabulary, terminology.

nonclinical study. Biomedicalstudies not performed on humansubjects. [ICH E6 Glossary]

not approvable letter. An officialcommunication from FDA to inform asponsor of a marketing applicationthat the important deficienciesdescribed in the letter precludeapproval unless corrected.

Notified Body (NB). A privateinstitution charged by the CompetentAuthority with verifying compliance ofmedical devices (not drugs) with theapplicable Essential Requirementsstated in the Medical Device Directive.This process, called ConformityAssessment, has EU-wide validity oncecompleted by the NB.

null hypothesis. The assertion thatno true association or difference in thestudy outcome or comparison ofinterest between comparison groupsexists in the larger population fromwhich the study samples are obtained.NOTE: A null hypothesis (forexample,“subjects will experience nochange in blood pressure as a result ofadministration of the test product”) isused to rule out every possibilityexcept the one the researcher is tryingto prove, and is used because moststatistical methods are less able toprove something true than to providestrong evidence that it is false. Theassertion that no true association ordifference in the study outcome orcomparison of interest betweencomparison groups exists in the largerpopulation from which the studysamples are obtained. See alsoresearch hypothesis. [from AMAManual of Style]

Nuremberg Code. Code of ethics,set forth in 1947, for conductinghuman medical research.

objective. The reason for performinga trial in terms of the scientific questionsto be answered by the analysis of datacollected during the trial. NOTE: Theprimary objective is the main question tobe answered and drives any statisticalplanning for the trial (e.g., calculation ofthe sample size to provide theappropriate power for statistical testing).Secondary objectives are goals of a trialthat will provide further information onthe use of the treatment.

objective measurement. Ameasurement of a physiological ormedical variable such as blood glucoselevel that is obtained by a measuringdevice rather than a human judgmentor assessment. See also outcome,patient-reported outcome; objectivemeasures are observations (SDTM) andcould be endpoints. Patient-reportedoutcomes are subjectivemeasurements.

observation. 1. An assessment ofpatient condition or analysis of datacollected on an individual patient orgroup of patients. 2. (SDTM) A discretepiece of information collected during astudy. NOTE: Observations (meaning 1)are required by protocol (e.g., requireevaluation of patient or data byinvestigator/staff). Such plannedobservations are typically distinguishedfrom anecdotal comments noted duringa clinical trial (which qualify asobservations under meaning 2). See alsovariable. Referring to an ad hoccomment as an observation is colloquial.[1. CONSORT Statement. 2. SDTM]

observer assessment. Anassessment of patient condition madeby an observer (investigator, nurse,clinician, family member, etc.). NOTE:Distinguished from self-assessment.The observer relies on his or herjudgment to assess the subject. Aninterviewer simply capturing subjectself assessments is not making anobserver assessment. Compare to PRO,proxy assessment.

ontology. An explicit formalspecification of how to representrelationships among objects, concepts,and other entities that belong to aparticular domain of experience orknowledge. See also terminology.

open-label study. A trial in whichsubjects and investigators know whichproduct each subject is receiving;opposite of a blinded or double-blindstudy. See blinding.

open to enrollment. The status ofa study such that a subject can beenrolled into that study. NOTE: Registryterminology in common use is “opento recruitment”; however, recruitmentcan begin upon IRB approval of thesite; whereas enrollment requiresavailability of study supplies, subjectinformed consent, etc., to allowparticipation of eligible subjects.

operational model. The set ofCDISC data standards (including ODMand LAB) used to capture and archivedata from clinical trials.

opinion (in relation toindependent ethics committee).The judgment and/or the adviceprovided by an independent ethicscommittee. [ICH E6 Glossary]

origin. 1. Source of informationcollected in the course of a clinical trial.Specifically used to differentiate betweendata collected at point of patient contactand data that are derived or calculated.2. (SDTM) A metadata attribute definedfor each dataset variable in the “Define”document of an SDTM submission thatrefers to the source of a variable (e.g.,CRF, derived, sponsor defined, PRO, etc.).[1. CONSORT Statement. 2. from SDTMfor descriptions of the Define document]

original data. The first recordedstudy data values. NOTE: FDA isallowing original documents and theoriginal data recorded on those


documents to be replaced by copiesprovided that the copies have beenverified as identical in content andmeaning. (See FDA Compliance PolicyGuide 7150.13). [Modified fromCSUICI] See also certified copy, source.

outcome (of adverse event).Refers to the resolution of an adverseevent. NOTE: Often denoted using apick list from a controlled terminologysuch as: Recovered/resolved,recovering/resolving, not recovered/notresolved, recovered/resolved withsequelae, fatal, or unknown. [SDTMEvents class of observation]

outcome. 1. Events or experiences thatclinicians or investigators examining theimpact of an intervention or exposuremeasure because they believe suchevents or experiences may be influencedby the intervention or exposure. 2.(SDTM) The result of carrying out amathematical or statistical procedure.NOTE: 1. Such events and experiencesare called clinical outcomesindependently of whether they are partof the original question/protocol of theinvestigation. [1. Guyatt, G.,Schunemann H., Dept. Epidemiology &Statistics, McMaster University—personalcommunication] See also variable;outcome can be a result of analysis;outcome is more general than endpointin that it does not necessarily relate to aplanned objective of the study.

outcomes research. Researchconcerned with benefits, financialcosts, healthcare system usage, risks,and quality of life as well as theirrelation to therapeutic interventions.NOTE: Usually distinguished fromresearch conducted solely to determineefficacy and safety. [Guyatt et al.,1993] See also pharmacoeconomics,quality of life.

outliers. Values outside of anexpected range.

packaging. The material, bothphysical and informational, that

contains or accompanies a marketed orinvestigational therapeutic agent onceit is fully prepared for release topatients and/or subjects in clinical trials.

pairing. A method by which subjectsare selected so that two subjects withsimilar characteristics (for example,weight, smoking habits) are assignedto a set, but one receives Treatment Aand the other receives Treatment B. Seealso matched-pair design.

parallel trial. Subjects arerandomized to one of two or morediffering treatment groups (usuallyinvestigational product and placebo)and usually receive the assignedtreatment during the entire trial.Synonyms: parallel group trial, paralleldesign trial.

parameter. A variable in a model, ora variable that wholly or partiallycharacterizes a probability distribution(mathematics and statistics). NOTE: Inclinical trials the term is often usedsynonymously with “variable” forfactual information (age, date ofrecovery), measurements, and clinicalassessments. It is most appropriatelylinked to statistical conventions and asa numeric characteristic of apopulation. Parameters are rarelyknown and are usually estimated bystatistical computation from samples.Thus the term is narrower than variable.[Parexel Barnett; ADaM; HyperStatOnline] See also variable, outcome.

participant. A person or entity witha role in healthcare or a clinical study.NOTE: Participants in a clinical trial mayinclude subjects and study personnel. Asubject participates as part of thegroup of people who are administeredthe therapeutic intervention or control.See also subject, patient.

password aging. A practiceapplying to multi-user computersystems where the validity of apassword expires after a certain pre-set

period. NOTE: FDA requires thatpasswords that are part of electronicsignatures be “periodically checked,recalled or revised,” but does notmandate password aging. [After NIST,21 CFR Part 11]

patient. Person under a physician’s carefor a particular disease or condition.NOTE: A subject in a clinical trial is notnecessarily a patient, but a patient in aclinical trial is a subject. See also subject,trial subject, healthy volunteer. Althoughoften used interchangeably as asynonym for subject, a healthy volunteeris not a patient.

patient file. One that containsdemographic, medical, and treatmentinformation about a patient or subject.It may be paper- or computer-based or amixture of computer and paper records.

patient-reported outcome (PRO).Information coming directly frompatients or subjects through interviewsor self-completed questionnaires orother data capture tools such as diariesabout their life, health condition(s), andtreatment. NOTE: PROs are used toassess outcomes involving thepatients’/subjects’ perceptions,symptoms, satisfaction with treatment,adherence to prescribed regimens. PROsinclude outcomes recorded byinterviewers transcribing the viewsexpressed by the patient, but the termdoes not apply to outcomes recordedby observers who rely on their ownjudgment. A PRO is usually a subjectiveassessment of feeling or functiondistinguished from a self-reportedobjective measurement such as bodyweight. [from PRO Draft Guidance,Gordon Guyatt and Holger Schuneman-personal communication; Patrick, D.L.,2003. After Acquardo C., Berzon C., etal., 2001] Synonym: subject-reportedoutcome (SRO). See also outcome,subject, patient, instrument.

performed activity. Clinical trialevents as they actually occurred



(as compared with events planned inthe protocol).

permissible values. Limiteduniverse of options for data items.(e.g., drop-down menus, codelists,pick lists).

per-protocol analysis set. The setof data generated by the subset ofsubjects who complied with theprotocol sufficiently to ensure thatthese data would be likely to exhibit theeffects of treatment according to theunderlying scientific model. [ICH E9]

period effect. An effect occurringduring a period of a trial in whichsubjects are observed and no treatmentis administered.

permanent data. Data that becomeor are intended to become part of anelectronic record in relation to aregulatory submission. NOTE: Anychanges made to such permanent dataare recorded via an audit trail so thatprior values are not obscured.

pharmacodynamics. Branch ofpharmacology that studies reactionsbetween drugs and living structures,including the physiological responses topharmacological, biochemical,physiological, and therapeutic agents.

pharmacoeconomics. Branch ofeconomics that applies cost-benefit,cost-utility, cost-minimization, andcost-effectiveness analyses to assessthe utility of different pharmaceuticalproducts or to compare drug therapyto other treatments.

pharmacogenetic test. An assayintended to study interindividualvariations in DNA sequence related todrug absorption and disposition ordrug action. Compare topharmacogenomic test.

pharmacogenetics. Study of theway drugs interact with genetic

makeup or the study of geneticresponse to a drug.

pharmacogenomic test. An assayintended to study interindividualvariations in wholegenome orcandidate gene maps, biomarkers, andalterations in gene expression orinactivation that may be correlatedwith pharmacological function andtherapeutic response. Compare topharmacogenetic test.

pharmacogenomics. Science thatexamines inherited variations in genesthat dictate drug response and exploresthe ways such variations can be used topredict whether a person will respondfavorably, adversely, or not at all to aninvestigational product.

pharmacokinetics. Study of theprocesses of bodily absorption,distribution, metabolism, and excretion(ADME) of medicinal products.

pharmacology. Science that dealswith the characteristics, effects, anduses of drugs and their interactionswith living organisms.

pharmacovigilance. Term used foradverse event monitoring and reporting.

phase. One in a set of successivestages in a progression or sequencesuch as 1. a step in the progression ofa therapy from initial experimental usein humans to postmarket evaluation. 2.a stage in the conduct of a clinical trial.NOTE: Clinical trials are generallycategorized into four (sometimes five)phases. A therapeutic intervention maybe evaluated in two or more phasessimultaneously in different trials, andsome trials may overlap two differentphases. For meaning 1, see Phase 0–5.For meaning 2, see epoch.

Phase 0. First-in-human trials, in asmall number of subjects, that areconducted before Phase 1 trials and

are intended to assess new candidatetherapeutic and imaging agents. Thestudy agent is administered at a lowdose for a limited time, and there isno therapeutic or diagnostic intent.NOTE: FDA Guidance for Industry,Investigators, and Reviewers:Exploratory IND Studies, January 2006classifies such studies as Phase 1.[Improving the Quality of CancerClinical Trials: Workshop Summary—Proceedings of the National CancerPolicy Forum Workshop, Improving theQuality of Cancer Clinical Trials(Washington, DC, Oct 2007)]

Phase 1. The initial introduction ofan investigational new drug intohumans. Phase 1 studies are typicallyclosely monitored and may beconducted in patients or normalvolunteer subjects. NOTE: Thesestudies are designed to determine themetabolism and pharmacologicactions of the drug in humans, theside effects associated with increasingdoses, and, if possible, to gain earlyevidence on effectiveness. DuringPhase 1, sufficient information aboutthe drug’s pharmacokinetics andpharmacological effects should beobtained to permit the design of well-controlled, scientifically valid Phase 2studies. The total number of subjectsand patients included in Phase 1studies varies with the drug, but isgenerally in the range of 20 to 80.Phase 1 studies also include studies ofdrug metabolism, structure–activityrelationships, and mechanism ofaction in humans, as well as studies inwhich investigational drugs are usedas research tools to explore biologicalphenomena or disease processes.[After FDA CDER Handbook, ICH E8]

Phase 2. Controlled clinical studiesconducted to evaluate the effectivenessof the drug for a particular indicationor indications in patients with thedisease or condition under study and todetermine the common short-term sideeffects and risks associated with the



drug. NOTE: Phase 2 studies aretypically well controlled, closelymonitored, and conducted in arelatively small number of patients,usually involving no more than severalhundred subjects. [After FDA CDERHandbook, ICH E8]

Phase 2A. Controlled clinical studiesthat occur after the completion ofPhase 1 studies and the first set ofexposure-response studies in patients,and before beginning Phase 2B (i.e.,patient dose-ranging trial) and Phase 3clinical efficacy-safety studies. [FDAdraft Guidance for Industry End ofPhase 2A meetings, 9/08].

Phase 3. Studies are expandedcontrolled and uncontrolled trials. Theyare performed after preliminaryevidence suggesting effectiveness ofthe drug has been obtained and areintended to gather the additionalinformation about effectiveness andsafety that is needed to confirmefficacy and evaluate the overallbenefit–risk relationship of the drugand to provide an adequate basis forphysician labeling. NOTE: Phase 3studies usually include from severalhundred to several thousand subjects.[After FDA CDER Handbook, ICH E8]

Phase 3B. A subcategory of Phase 3trials done near the time of approval toelicit additional findings. NOTE: Dossierreview may continue while associatedPhase 3B trials are conducted. Thesetrials may be required as a condition ofregulatory authority approval.

Phase 4. Postmarketing (Phase 4)studies to delineate additionalinformation about the drug’s risks,benefits, and optimal use that may berequested by regulatory authorities inconjunction with marketing approval.NOTE: These studies could include, butwould not be limited to, studyingdifferent doses or schedules ofadministration than were used in

Phase 2 studies, use of the drug inother patient populations or otherstages of the disease, or use of thedrug over a longer period of time.[After FDA CDER Handbook, ICH E8]

Phase 5. Postmarketing surveillance issometimes referred to as Phase 5. Seealso outcomes research.

placebo. A pharmaceuticalpreparation that does not contain theinvestigational agent. In blindedstudies, it is generally prepared to bephysically indistinguishable from thepreparation containing theinvestigational product.

population. Any finite or infinitecollection of subjects from which asample is drawn for a study to obtainestimates for values that would beobtained if the entire population weresampled. [AMA Style Manual]

postmarketing surveillance.Ongoing safety monitoring ofmarketed drugs. See also Phase 4studies, Phase 5 studies.

pragmatic trial. Term used todescribe a clinical study designed toexamine the benefits of a productunder real world conditions.

preamble. A section preceding thetext of a final FDA regulation publishedin the Federal Register. NOTE: “Thepreamble is to contain a thorough andcomprehensible explanation of thereasons for the Commissioner’s decisionon each issue” raised in commentssubmitted in response to the proposedregulation. [from 21CFR10.40]

preclinical studies. Animal studiesthat support Phase 1 safety andtolerance studies and must complywith good laboratory practice (GLP).NOTE: Data about a drug’s activities

and effects in animals help establishboundaries for safe use of the drug insubsequent human testing (clinicalstudies or trials).

Pre-Market ApprovalApplication (PMA). An applicationto FDA for a license to market a newdevice in the United States.

primary objective. The primaryobjective(s) is the main question to beanswered and drives any statisticalplanning for the trial (e.g., calculationof the sample size to provide the appro-priate power for statistical testing). [ICHE6 6.3] See also objective.

primary variable. An outcomevariable specified in the protocol to beof greatest importance to the primaryobjective of the trial, usually the oneused in the sample size calculation.NOTE: Differences between groups inthe primary and secondary variable(s)are believed to be the result of thegroup-specific interventions. [PRProject; CONSORT Statement]Synonyms: primary endpoint, outcome.See also primary objective.

product. 1. Drug product: A finisheddosage form that contains a drugsubstance. 2. A physical entity that isintended to diagnose, treat, or preventa disease or other abnormal conditionand subject to regulatory authority.[Modified from FDA Glossary of Terms]

PROMIS. NIH-sponsored project forthe development and evaluation ofPRO item banks and computer adaptivetesting for pain, fatigue, physicalfunction, social function, andemotional well-being. [NIH]

proprietary name. A commercialname granted by a naming authorityfor use in marketing a drug/deviceproduct. [SPL] Synonyms: trade name,brand name.


prospective study. Investigation inwhich a group of subjects is recruitedand monitored in accordance withcriteria described in a protocol.

protocol. A document that describesthe objective(s), design, methodology,statistical considerations, andorganization of a trial. The protocolusually also gives the background andrationale for the trial, but these couldbe provided in other protocolreferenced documents. Throughout theICH GCP Guideline the term protocolrefers to protocol and protocolamendments. NOTE: Present usage canrefer to any of three distinct entities: 1)the plan (i.e., content) of a protocol, 2)the protocol document, and 3) a seriesof tests or treatments (as in oncology).[ICH E6 Glossary]

protocol amendment(s). A writtendescription of a change(s) to or formalclarification of a protocol. [ICH E3]

protocol approval (Sponsor).Sponsor action at the completion ofprotocol development that is markedwhen the signature of the last revieweron the protocol approval form hasbeen obtained, signifying that allreviewer changes to the protocol havebeen incorporated. NOTE: Approval bythe sponsor usually initiates secondaryapprovals by IRBs, regulatoryauthorities, and sites. Protocolamendments usually also require acycle of approval by sponsor and studystaff prior to taking effect.

protocol deviation. A variationfrom processes or procedures definedin a protocol. Deviations usually do notpreclude the overall evaluability ofsubject data for either efficacy orsafety, and are often acknowledgedand accepted in advance by thesponsor. NOTE: Good clinical practicerecommends that deviations besummarized by site and by category aspart of the report of study results sothat the possible importance of the

deviations to the findings of the studycan be assessed. Compare to protocolviolation. [See ICH E3]

Protocol Identifying Number.Any of one or more unique codes thatrefers to a specific protocol. NOTE:There may be multiple numbers (Nat’lnumber, coop group number). [PRProject; eudraCT]

protocol referenced documents.Protocol referenced documents thatoptionally supplement the ICH GCPrecommended sections of a protocolgiving background information andrationale for the trial. [from ICH E61.44] See also protocol.

protocol title. Three categories ofprotocol title have evolved to addressdistinct standardized use cases. 1)Scientific Title: A comprehensivesummary of study design and objectives,aimed at scientific audience. 2) PublicTitle: A brief description intended forthe lay public in easily understoodlanguage. 3) Trial Acronym: Briefpopular identifier. NOTE: The scientifictitle should include the trial acronym, ifapplicable [WHO http://www.who.int/ictrp/data_set/en/index1.html]. Scientifictitle may also be referred to as ”officialtitle.” Public title may also be referred toas “brief title.”

protocol violation. A significantdeparture from processes or proceduresthat were required by the protocol.Violations often result in data that arenot deemed evaluable for a per-protocol analysis, and may require thatthe subject(s) who violate the protocolbe discontinued from the study.Compare to protocol deviation.

proxy (as an origin of outcomemeasures). A proposed standardizedqualifier variable to describe the originof observations of the Findings classresulting from outcomes measures.Proxy describes outcome data

furnished by someone other than thepatient and distinguishes the origin ofthe outcome from a self-report (PRO)directly from the patient. NOTE: Theterm proxy helps qualify outcomesmeasures that record feelings andsymptoms reported by the patient butnot recorded directly. [CDISC (extensionof SDTM based on Table 2 Patrick, D.L.,2003)] See also observer assessment.

proxy respondent. Someone otherthan the patient who is respondingabout the patient on behalf of thepatient, not as an observer. [Patrick,D.L., 2003; DIA ePRO Workgroup]Compare to observer assessment.

psychometric reliability. Seereliability, psychometric.

psychometric validation. Thespecialized process of validatingquestionnaires used in outcomesresearch to show that they measurewhat they purport to measure. NOTE:Several types of validity aredistinguished. For example, face validitymeans that an assessment instrumentappears by inspection andconsideration of the semantic contentof items in it to be measuring what it issupposed to measure. Constructvalidity means that a scale based onone or more items measures anunobservable psychological construct(e.g., “distress”) that it is proposed tomeasure. Construct validity is usuallytested by measuring the correlation inassessments obtained from severalscales purported to measure the sameconstruct. [Guyatt et al., 1993; DIAePRO Workgroup] See also validation;compare to psychometric reliability.

psychometrics. The science ofassessing the measurementcharacteristics of scales that assesshuman psychological characteristics.

p-value. Study findings can also beassessed in terms of their statistical



significance. The p-value represents theprobability that the observed data (or amore extreme result) could have arisenby chance when the interventions didnot differ. [CONSORT Statement]

qualitative variable. One thatcannot be measured on a continuumand represented in quantitative relationto a scale (race or sex, for example).Data that fit into discrete categoriesaccording to their attributes.

quality assurance (QA). All thoseplanned and systematic actions that areestablished to ensure that the trial isperformed and the data are generated,documented (recorded), and reportedin compliance with good clinicalpractice (GCP) and the applicableregulatory requirement(s). [ICH]

quality control (QC). Theoperational techniques and activitiesundertaken within the quality assurancesystem to verify that the requirementsfor quality of the trial related activitieshave been fulfilled. [ICH]

quality of life. A broad rangingconcept that incorporates anindividual’s physical health,psychological state, level ofindependence, social relationships,personal beliefs, and their relationshipsto salient features of the environment.NOTE: Quality of Life is one way tomeasure the benefits or negativeimpacts of an “improvement”measured in terms of a physiological orpsychological symptom. QOL researchseeks to quantify what an interventionmeans to a patient’s sense that theirlife has changed. [WHO Group, 1994]

quantitative variable. One thatcan be measured and reportednumerically to reflect a quantity oramount, ideally on a continuum.

query. A request for clarification on adata item collected for a clinical trial;specifically a request from a sponsor or

sponsor’s representative to an investigatorto resolve an error or inconsistencydiscovered during data review.

query management. Ongoingprocess of data review, discrepancygeneration, and resolving errors andinconsistencies that arise in the entryand transcription of clinical trial data.

query resolution. The closure of aquery usually based on informationcontained in a data clarification.

questionnaire. A set of questions oritems shown to a respondent in orderto get answers for research purposes.[PRO Draft Guidance] See alsoinstrument, survey.

random allocation. Assignment ofsubjects to treatment (or control)groups in an unpredictable way. NOTE:In a blinded study, assignmentsequences are concealed, but availablefor disclosure in the event a subject hasan adverse experience.

random number table. Table ofnumbers with no apparent patternused in the selection of randomsamples for clinical trials.

random sample. Members of apopulation selected by a methoddesigned to ensure that each person inthe target group has an equal chanceof selection.

randomization. The process ofassigning trial subjects to treatment orcontrol groups using an element ofchance to determine the assignments inorder to reduce bias. NOTE: Unequalrandomization is used to allocatesubjects into groups at a differentialrate; for example, three subjects may beassigned to a treatment group for everyone assigned to the control group. [ICHE6 1.48] See also balanced study.

raw data. Data as originally collected.Distinct from derived. Raw data includes

records of original observations,measurements, and activities (such aslaboratory notes, evaluations, datarecorded by automated instruments)without conclusions or interpretations.Researcher’s records of subjects/patients,such as patient medical charts, hospitalrecords, X-rays, and attending physician’snotes. NOTE: These records may or maynot accompany an application to aRegulatory Authority, but must be keptin the researcher’s file. See also eSource,source data, source documents.

RCRIM. Regulated Clinical Researchand Information Management, which isa Technical Committee within HL7 (anacronym pronounced “arcrim”).

reconstruction (of a study). ForeClinical trials FDA expects archival trialrecords to support review of the data aswell as the processes used for obtainingand managing the data so that thetrustworthiness of results obtained canbe evaluated. NOTE: Reconstructionfrom records should support evaluationof the operation and validity ofcomputerized systems and theconformance of the systems toapplicable regulations during design andexecution of the trial as well as duringthe period of record retention. [fromCSUCT VI D, 21 CFR Parts 11, 312]

recruitment (investigators).Process used by sponsors to identify,select, and arrange for investigators toserve in a clinical study.

recruitment (subjects). Processused by investigators to find and enrollappropriate subjects (those selected onthe basis of the protocol’s inclusion andexclusion criteria) into a clinical study.

recruitment period. Time periodduring which subjects are or areplanned to be enrolled in a clinical trial.

recruitment target. Number ofsubjects that must be recruited as


candidates for enrollment into a studyto meet the requirements of theprotocol. In multicenter studies, eachinvestigator has a recruitment target.

Reference Information Model(RIM). An information model used asthe ultimate defining reference for allHL7 standards. [HL7]

registry. A data bank of informationon clinical trials for drugs for serious orlife-threatening diseases andconditions. NOTE: The registry shouldcontain basic information about eachtrial sufficient to inform interestedsubjects (and their healthcarepractitioners) how to enroll in the trial.[FDAMA 113]

regulatory authorities. Bodieshaving the power to regulate. NOTE: Inthe ICH GCP guideline the term includesthe authorities that review submittedclinical data and those that conductinspections. These bodies are sometimesreferred to as competent authorities.[ICH] Synonym: regulatory agencies.

reliability, psychometric. Thedegree to which a psychometric“instrument” is free from random erroreither by testing the homogeneity ofcontent on multi-item tests withinternal consistency evaluation ortesting the degree to which theinstrument yields stable scores overtime. NOTE: Reliability pertains toquestions concerning whether aninstrument is accurate, repeatable,sensitive. Reliability is distinguishedfrom validation, which answerswhether the instrument (e.g.,questionnaire) actually measure theselected “construct” (latent variable).For example a balance (scale) is easilyunderstood as a possibly validinstrument to measure body weight. Itsreliability would be assessed bymeasuring the sensitivity, repeatabilityand accuracy of the balance. Thevalidity of using the balance for a

particular purpose could then beestablished by comparing the measuredreliability to the reliability required forthat purpose. [After Patrick, D.L., 2003]Compare to psychometric validation;see also validation; instrument.

repeat rule. Guide for repeatingactivities specified in protocol,including such features as the numberof cycles and the criteria for stopping.

replacement. The act of enrolling aclinical trial subject to compensate forthe withdrawal of another.

representative. See legallyacceptable representative.

research hypothesis. The propositionthat a study sets out to support (ordisprove); for example, “blood pressurewill be lowered by [specific endpoint] insubjects who receive the test product.”See also null hypothesis.

response option. One of severalchoices to be available for selection inresponse to a prompt, question orinstruction (i.e., a stem) in a PRO item.See also common data element, stem.

result synopsis. The brief reportprepared by biostatisticians summarizingprimary (and secondary) efficacy resultsand key demographic information.

retrospective. Capture of clinicaltrial data is retrospective when it isrecalled from memory rather thancaptured contemporaneously in real-time. NOTE: Retrospective capture isimportant in PROs because of “recallbias” and other errors documented inpsychological research comparingcontemporaneous self-reportedassessments and those that rely onrecall from memory.

risk. In clinical trials, the probability ofharm or discomfort for subjects. NOTE:Acceptable risk differs depending on

the condition for which a product isbeing tested. A product for sore throat,for example, will be expected to have alow incidence of troubling side effects.However, the possibility of unpleasantside effects may be an acceptable riskwhen testing a promising treatment fora life-threatening illness.

role. 1. The function or responsibilityassumed by a person in the context ofa clinical study. Examples include datamanager, investigator. 2. Classifier forvariables that describe “observations”in the SDTM. Role is a metadataattribute that determines the type ofinformation conveyed by anobservation-describing variable andstandardizes rules for using thedescribing variable. [1. HL7. 2. SDTM]See also functional role.

safety. Relative freedom from harm. Inclinical trials, this refers to an absence ofharmful side effects resulting from useof the product and may be assessed bylaboratory testing of biological samples,special tests and procedures, psychiatricevaluation, and/or physical examinationof subjects.

safety and tolerability. The safetyof a medical product concerns themedical risk to the subject, usuallyassessed in a clinical trial by laboratorytests (including clinical chemistry andhematology), vital signs, clinicaladverse events (diseases, signs, andsymptoms), and other special safetytests (e.g., ECGs, ophthalmology). Thetolerability of the medical productrepresents the degree to which overtadverse effects can be tolerated by thesubject. [ICH E9]

sample size. 1. A subset of a largerpopulation, selected for investigationto draw conclusions or make estimatesabout the larger population. 2. Thenumber of subjects in a clinical trial. 3.Number of subjects required forprimary analysis.



sample size adjustment. An interimcheck conducted on blinded data tovalidate the sample size calculations orreevaluate the sample size.

schedule of activities. Astandardized representation of plannedclinical trial activities includinginterventions (e.g., administering drug,surgery) and study administrativeactivities (e.g., obtaining informedconsent, distributing clinical trialmaterial and diaries, randomization) aswell as assessments. See also scheduleof assessments.

schedule of assessments. Atabular representation of plannedprotocol events and activities, insequence. [after E3 Annexes IIIa andIIIb] Synonym: flow chart. Compare tostudy design schematic.

screen failure. Potential subject whodid not meet one or more criteriarequired for participation in a trial. Seealso screening of subjects.

screen/screening (ofsubstances). Screening is the processby which substances are evaluated in abattery of tests or assays (screens)designed to detect a specific biologicalproperty or activity. It can be conductedon a random basis in which substancesare tested without any preselectioncriteria or on a targeted basis in whichinformation on a substance withknown activity and structure is used asa basis for selecting other similarsubstances on which to run the batteryof tests. [SQA]

screening (of sites). Determiningthe suitability of an investigative siteand personnel to participate in aclinical trial.

screening (of subjects). A processof active consideration of potentialsubjects for enrollment in a trial. Seealso screen failure.

screening trials. Trials conducted todetect persons with early, mild, andasymptomatic disease.

script. A program or a sequence ofinstructions that are interpreted or carriedout by another program or by a person.

secondary objective. See objective.

secondary sponsor. Additionalindividuals, organizations or other legalpersons, if any, that have agreed withthe primary sponsor to take onresponsibilities of sponsorship. [WHO,CTR Item 6]

secondary variable. The primaryoutcome is the outcome of greatestimportance. Data on secondaryoutcomes are used to evaluateadditional effects of the intervention.[CONSORT Statement] See alsooutcome, endpoint.

self-evident change. A datadiscrepancy that can be easily andobviously resolved on the basis ofexisting information on the CRF (e.g.,obvious spelling errors or the patient isknown to be a male and a date of lastpregnancy is provided). See alsodiscrepancy.

semantic. In the context of a technicalspecification, semantic refers to themeaning of an element as distinct fromits syntax. Syntax can change withoutaffecting semantics. [HL7]

serious adverse event (SAE) orserious adverse drug reaction(serious ADR). Any untowardmedical occurrence that at any dose:results in death, is life threatening,requires inpatient hospitalization orprolongation of existing hospitalization,results in persistent or significantdisability/incapacity, or is a congenitalanomaly/birth defect. [ICH] See alsoadverse experience.

serious adverse experience.Any experience that suggests asignificant hazard, contra-indication,side effect or precaution. See alsoserious adverse event.

server. A computer that controls acentral repository of data, files, and/orapplications that can be accessed and/ormanipulated in some manner by clientcomputers. A file server hosts files foruse by client machines. An applicationserver runs programs that may processand display data exchanged with clientmachines. After the arrival of the Web,server often refers to software andcomputers that perform databasequeries and collect and present timelydata to users running browsers or otherclient applications.

sex. Phenotypic expression ofchromosomal makeup that defines astudy subject as male, female, or other.Compare to gender.

side effects. Any actions or effectsof a drug or treatment other than theintended effect. Negative or adverseeffects may include headache, nausea,hair loss, skin irritation, or otherphysical problems. Experimental drugsmust be evaluated for both immediateand long-term side effects. See alsoadverse reaction.

single-blind study. A study inwhich one party, either the investigatoror the subject, does not know whichmedication or placebo is administeredto the subject; also called single-masked study. See also blind study,double-blind study, triple-blind study.

single-masked study. See single-blind study.

site. See trial site.

site investigator. A personresponsible for the conduct of theclinical trial at a trial site. If a trial is


conducted by a team of individuals at atrial site, the investigator is theresponsible leader of the team and maybe called the principal investigator. [ICHE6 1.35. 2.] See also investigator.

software. Computer programs,procedures, rules, and any associateddocumentation pertaining to theoperation of a system.

software validation. Confirmationby examination and provision ofobjective evidence that softwarespecifications conform to user needsand intended uses, and that theparticular requirements implementedthrough software can be consistentlyfulfilled. NOTE: Validating softwarethus should include evaluation of thesuitability of the specifications to“ensure user needs and intended usescan be fulfilled on a consistent basis”(21 CFR 820.20). General Principles ofSoftware Validation; Final Guidance forIndustry and FDA Staff, Jan 11, 2002.ISO/IEC/IEEE 12207:1995 §3.35; 21CFR 820.20; 21 CFR 11.10(a); ISO9000-3; Huber, L. (1999) See alsovalidation, verification. Verificationusually concerns confirmation thatspecified requirements have been met,but typically refers to the tracing ofrequirements and evidence ofconformance in the individual phasesor modules rather than suitability ofthe complete product. Validation is,“the evaluation of software at the endof the software development processto ensure compliance with the userrequirements” (ANSI/ASQC A3-1978)and should not be thought of as an“end-to-end” verification.

source. 1. The specific permanentrecord(s) upon which a user will rely forthe reconstruction and evaluation of aclinical investigation. 2. Sometimes usedas shorthand for source documentsand/or source data. NOTE: Accuracy,suitability, and trustworthiness are notdefining attributes of “source.” Theterm identifies records planned

(designated by the protocol) orreferenced as the ones that provide theinformation underlying the analyses andfindings of a clinical investigation.[After ICH E6, CSUICI] See also originaldata, certified copy

source data. All information inoriginal records and certified copies oforiginal records of clinical findings,observations, or other activities in aclinical trial necessary for thereconstruction and evaluation of the trial.Source data are contained in sourcedocuments (original records or certifiedcopies). [ICH E6; CSUCT]

source data verification. Theprocess of ensuring that data that havebeen derived from source dataaccurately represent the source data.

source document verification.The process by which the informationreported by an investigator iscompared with the source records ororiginal records to ensure that it iscomplete, accurate, and valid. [Schuyland Engel, 1999; Khosla et al., IndianJ. Pharm 32:180-186, 2000] Synonym:SDV. See also validation of data.

source documents. Originaldocuments, data, and records (e.g.,hospital records, clinical and officecharts, laboratory notes, memoranda,subjects’ diaries or evaluationchecklists, pharmacy dispensingrecords, recorded data from automatedinstruments, copies or transcriptionscertified after verification as beingaccurate copies, microfiches,photographic negatives, microfilm ormagnetic media, x-rays, subject files,and records kept at the pharmacy, atthe laboratories, and atmedicotechnical departments involvedin the clinical trial). See also eSourcedocument, source, original data,certified copy. [ICH; CSUICI]

special populations. Subsets ofstudy populations of particular interest

included in clinical trials to ensure thattheir specific characteristics areconsidered in interpretation of data(e.g., geriatric). [FDA]

sponsor. 1. An individual, company,institution, or organization that takesresponsibility for the initiation andmanagement of a clinical trial,although may or may not be the mainfunding organization. If there is also asecondary sponsor, this entity would beconsidered the primary sponsor. 2. Acorporation or agency whoseemployees conduct the investigation isconsidered a sponsor and theemployees are considered investigators.[1. After ICH E6 and WHO. 2. 21 CFR50.3 (e)] See also secondary sponsor.

sponsor-investigator. An individualwho both initiates and conducts, aloneor with others, a clinical trial and underwhose immediate direction theinvestigational product is administeredto, dispensed to, or used by a subject.NOTE: The term does not include anyperson other than an individual (i.e., itdoes not include a corporation or anagency). The obligations of a sponsor-investigator include both those of asponsor and those of an investigator.[21 CFR 50.3f] [ICH]

standard. Criterion or specificationestablished by authority or consensusfor 1. measuring performance orquality; 2. specifying conventions thatsupport interchange of commonmaterials and information. NOTE:CDISC standards exist to support theexchange of clinical data, for example,at both the syntactic and semanticlevels. See interoperability.

standard deviation. Indicator of therelative variability of a variable around itsmean; the square root of the variance.

standard of care. A guideline formedical management and treatment.



standard operating procedures(SOPs). Detailed, written instructions toachieve uniformity of the performanceof a specific function. [ICH]

standard treatment. A treatmentcurrently in wide use and approved byFDA or other health authority, consideredto be effective in the treatment of aspecific disease or condition.

statistical analysis plan. Adocument that contains a moretechnical and detailed elaboration ofthe principal features of the analysisdescribed in the protocol, and includesdetailed procedures for executing thestatistical analysis of the primary andsecondary variables and other data.[ICH E9]

statistical method. The particularmathematical tests and techniques thatare to be used to evaluate the clinicaldata in a trial. [ICH E9; from the Centerfor Advancement of Clinical Research]

statistical significance. State thatapplies when a hypothesis is rejected.Whether or not a given result issignificant depends on the significancelevel adopted. For example, one maysay “significant at the 5% level.” Thisimplies that when the null hypothesis istrue there is only a 1 in 20 chance ofrejecting it.

stem. The prompt, question, orinstruction in a PRO item. See alsoresponse option, item.

stochastic. Involving a randomvariable; involving chance or probability.

stopping rules. A statistical criterionthat, when met by the accumulatingdata, indicates that the trial can orshould be stopped early to avoidputting participants at riskunnecessarily or because theintervention effect is so great thatfurther data collection is unnecessary.

stratification. Grouping defined byimportant prognostic factors measuredat baseline. [ICH E9]

structured product label (SPL).The Structured Product Labeling (SPL)specification is an HL7 ANSI-approveddocument markup standard thatspecifies the structure and semanticsfor the exchange of productinformation. [HL7]

study. See clinical trial. NOTE:Occasionally refers to a project ofseveral related clinical trials.

study coordinator. See clinicalresearch coordinator.

study description. Representationof key elements of study (e.g., control,blinding, gender, dose, indication,configuration).

study design. Plan for the preciseprocedure to be followed in a clinicaltrial, including planned and actualtiming of events, choice of controlgroup, method of allocatingtreatments, blinding methods; assignsa subject to pass through one or moreepochs in the course of a trial. Specificdesign elements (e.g., crossover,parallel, dose-escalation) [Modifiedfrom Pocock, Clinical Trials: A PracticalApproach] See Trial Design Model. Seealso, arm, epoch, and visit.

study design rationale. Reason forchoosing the particular study design.

study design schematic.Schematic diagram (not tabular) ofstudy design, procedures, and stages.[example: ICH E3 Annexes IIIa and IIIb]Compare to schedule of assessments.

study initiation date. Date andtime of first subject enrollment into astudy, as verifiable by a convention thatis consistent with authoritative

regulatory criteria. [modified from ICHE3] Compare with study start.Synonym: date of first enrollment.

study population. Defined byprotocol inclusion/exclusion criteria.

study protocol. See protocol.

study start. The formal recognition ofthe beginning of a clinical trial that isreferred to in the clinical study report.

study treatment. See investigationalintervention.

study variable. A term used in trialdesign to denote a variable to becaptured on the CRF. See also variable.

sub-investigator. Any member ofthe clinical trial team designated andsupervised by the investigator at a trialsite to perform critical trial-relatedprocedures and/or to make importanttrial-related decisions (e.g., associates,residents, research fellows). [ICH] Seealso investigator.

subject data event. A subject visitor other encounter where subject dataare collected, generated, or reviewed.[SDTM]

subject identification code. Aunique identifier assigned by theinvestigator to each trial subject toprotect the subject’s identity and usedin lieu of the subject’s name when theinvestigator reports adverse eventsand/or other trial-related data. [ICH]

subject trial contact. Any activity,anticipated in the study protocol,involving a subject and pertaining tocollection of data. See visit.

subject/trial subject. An individualwho participates in a clinical trial,either as recipient of the investigationalproduct(s) or as a control. [ICH] Seealso healthy volunteer, human subject.


subject-reported outcome (SRO).An outcome reported directly by asubject in a clinical trial. [Patrick, D.L.,2003] See also patient-reportedoutcome (PRO).

submission model. A set of datastandards (including SDTM, ADaM, anddefine.xml) for representing data thatare submitted to regulatory authoritiesto support product marketingapplications. NOTE: CDISC submissiondata consist of: tabulations thatrepresent the essential data collectedabout patients; analysis data structuredto support analysis and interpretation;and metadata descriptions.

superiority trial. A trial with theprimary objective of showing that theresponse to the investigational productis superior to a comparative agent(active or placebo control). [ICH E9]

supplier. An organization that entersinto a contract with the acquirer forthe supply of a system, softwareproduct, or software service under theterms of a contract. [ISO/IEC/IEEE12207:1995 §3.30]

supporting variables. See variable.[FDA Drug Review Glossary]

surrogate marker. A measurementof a drug’s biological activity thatsubstitutes for a clinical endpoint suchas death or pain relief.

surrogate variable. A variable thatprovides an indirect measurement ofeffect in situations where directmeasurement of clinical effect is notfeasible or practical. [ICH E9]

survey. Any means (e.g.,questionnaire, diary, interview script,group of items) that is used to collectPRO data. NOTE: Survey refers to thecontent of the group of items and doesnot necessarily include the training andscoring documents generally not seenby respondents. [from ISOQOL

comments on PRO Guidance] Compareto instrument.

synopsis. Brief overview prepared atthe conclusion of a study as a routinepart of a regulatory submission,summarizing the study plan andresults; includes numerical summary ofefficacy and safety results, studyobjective, criteria for inclusion,methodology, etc. [after ICH E3]

syntactic. The order, format, contentof clinical trial data and/or documents asdistinct from their meaning. NOTE:Syntactic interoperability is achievedwhen information is correctly exchangedbetween two systems according tostructured rules whether or not sensiblemeaning is preserved. See also semantic,semantic interoperability.

system. People, machines, software,applications, and/or methods organizedto accomplish a set of specificfunctions or objectives. [ANSI]

table of roles and responsibilities.A cumulative record documentingoperational access and authorizationsof study personnel to electronicsystems used in eClinical trials.

tabulation dataset. A datasetstructured in a tabular format. NOTE:The CDISC Study Data TabulationModel (SDTM) defines standards fortabulation datasets that fulfill FDArequirements for submitting clinicaltrial data.

target enrollment. The number ofsubjects in a class or group (includingthe total for the entire trial) intendedto be enrolled in a trial to reach theplanned sample size. Targetenrollments are set so that statisticaland scientific objectives of a trial willhave a likelihood of being met asdetermined by agreement, algorithm,or other specified process.

target study population.Demographic and health condition ofthe population to be included in aclinical study.

technology provider. A person,company, or other entity who develops,produces, and sells softwareapplications and/or hardware for use inconducting clinical trials and/or inanalyzing clinical trial data and orsubmitting clinical trial information forregulatory approval. Synonym: vendor.

term. One or more words designatingsomething. NOTE: In a controlledvocabulary, terms are considered torefer to an underlying concept having asingle meaning. Concepts may belinked to several synonymous terms.

termination (of subject). Nowconsidered nonstandard. Seediscontinuation.

termination (of trial). Prematurediscontinuation of a trial prior to plan.[EU Clinical Trial Directive]

terminology. 1. Set of concepts,designations, and relationships for aspecialized subject area. See Glossary.2. In the context of clinical research inhuman subjects, a standardized, finiteset of terms (e.g., picklists, MedDRAcodes) that denote patient findings,circumstances, events, andinterventions. Compare with glossary,which is a list of words and theirdefinitions pertaining to usage in aparticular field or context. Often usedsynonymously with vocabulary.Contrast with nomenclature.

therapeutic intervention. Seeintervention.

token. Physical key that provides accessto a secure electronic system or location.

transcription. Process of transformingdictated or otherwise documented



information from one storage mediumto another. NOTE: often refers explicitlyto data that is manually transcribed fromsource docs or measuring devices toCRFs or to eCRFs.

transition rule. A guide thatgoverns the allocation of subjects tooperational options at a discretedecision point or branch (e.g.,assignment to a particular arm,discontinuation) within a clinical trialplan. See branch.

translation. Converting informationfrom one natural language to anotherwhile preserving meaning. Comparewith mapping.

transmit. To transfer data, usuallyelectronically. NOTE: In eClinicalinvestigations data are commonlytransmitted from subjects to clinicalstudy sites, within or among clinicalstudy sites, contract researchorganizations, data managementcenters, and sponsors, or to regulatoryauthorities. [modified from CSUICI].

treatment effect. An effectattributed to a treatment in a clinicaltrial. In most clinical trials thetreatment effect of interest is acomparison (or contrast) of two ormore treatments. [ICH E9]

treatment-emergent adverseevent. An event that emerges duringtreatment, having been absentpretreatment, or worsens relative tothe pretreatment state. [ICH E9]

trial coordinator. See clinicalresearch coordinator.

Trial Design Model. Defines astandard structure for representing theplanned sequence of events and thetreatment plan of a trial. NOTE: Acomponent of the SDTM that buildsupon elements, arms epochs, visits;suitable also for syntactic interpretationby machines. [CDISC] See study design.

trial monitoring. Oversight ofquality of study conduct and statisticalinterim analysis. [ICH E9]

trial site. Synonym for investigativesite, investigator site, site, site of thetrial, study site. [ICH E6]

trial statistician. A statistician whohas a combination of education/training and experience sufficient toimplement the principles in the ICH E9guidance and who is responsible for thestatistical aspects of the trial. [ICH E9]

trial subject. Subject in a clinical trial.See also participant, patient, subject.

triple-blind study. A study in whichknowledge of the treatmentassignment(s) is concealed from thepeople who organize and analyze thedata of a study as well as from subjectsand investigators.

t-test. A statistical test used tocompare the means of two groups oftest data.

trustworthy (electronic records).An attribute of records (data anddocuments) and signatures submittedto regulatory agencies referring to theirsuitability for making scientific findingsof safety and efficacy that underliepublic policy decisions pertaining tomarket authorization. Two keydimensions that determine thetrustworthiness of eClinical trial dataare data quality and data integrity.[after 21CFR Part 11]

type 1 (or type I) error. Error madewhen a null hypothesis is rejected butis actually true. Synonym: false positive.

type 2 (or type II) error. Errormade when an alternative hypothesis isrejected when it is actually true.Synonym: false negative.

type 3 (or type III) error. Somestatisticians use this designation for an

error made when calling the less effectivetreatment the more effective one.

type of comparison. Howtreatment arms will be compared (e.g.,Safety, Efficacy, PK/PD). May alsoinclude comparison to data from otherstudies or sources (e.g., historicalcontrol). [ICH E9, EUDRACT (p.18)]

unblinding. Identification of thetreatment code of a subject or groupedresults in studies where the treatmentassignment is unknown to the subjectand investigators.

unequal randomization. Seerandomization.

unexpected adverse drugreaction. An adverse reaction, whosenature, severity, specificity, or outcomeis not consistent with the term ordescription used in the applicableproduct information. [ICH E2] See alsoadverse drug reaction.

uniform resource locator (URL).Address of a Web page, for example,appliedclinicaltrialsonline.com.

use case. An explicit scenario designedto help in determining whether asystem/process is capable of performingthe functions required for a particularuse. A use case might describe, forexample, how a study coordinatorwould use a tablet computer to capturemedical history data.

user site testing (UST). Any testingthat takes place outside of thedeveloper’s controlled environment.NOTE: Terms such as beta test, sitevalidation, user acceptance test,installation verification, and installationtesting have all been used to describeuser site testing. User site testingencompasses all of these and any othertesting that takes place outside of thedeveloper’s controlled environment. [fromGeneral Principles of Software Validation;Final Guidance, section 5.2.6]


valid. 1. Sound. 2. Well grounded onprinciples of evidence. 3. Able towithstand criticism or objection. [FDAGlossary of Computerized System andSoftware Development Terminology]

validation. 1. Process ofestablishing suitability to purpose. 2.For software and systems, establishingdocumented evidence which providesa high degree of assurance that aspecific process will consistentlyproduce a product meeting itspredetermined specifications andquality attributes. NOTE: Validation isaccomplished by planning how tomeasure and/or evaluate suitability topurpose; then executing the plan anddocumenting the results. [FDAGlossary of Computerized System andSoftware Development Terminology]

validation of data. 1. A processused to determine if data areinaccurate, incomplete, orunreasonable. The process may includeformat checks, completeness checks,check key tests, reasonableness checksand limit checks. 2. The checking ofdata for correctness or compliance withapplicable standards, rules, andconventions. NOTE: Meaning 1 is not“data verification” but meaning 2could be [1. ISO. 2. FDA Glossary ofComputerized System and SoftwareDevelopment Terminology] See sourcedocument verification.

validity. See validation.

validity, psychometric. Seepsychometric validation.

variable. 1. Any entity that varies; anyattribute, phenomenon, or event thatcan have different qualitative orquantitative values. 2. In SDTM“variables” are used to describeobservations. Such describing variableshave roles that determine the type ofinformation conveyed by the variableabout each observation and how it canbe used. NOTE: 1. There is usually aform of metadata that goes with the

variable, there is a variable definitionthat describes what is varying, andthere is a value for the variable. In thecontext of a protocol, variables pertainto the study. 2. In SDTM a “studyvariable” would be an observation.Variable is an enveloping term thatincludes specific subtypes used inclinical research. “Study variable” is aterm used in trial design to denote avariable to be captured on the CRF. An“assessment” is a study variablepertaining to the status of a subject.Assessments are usually measured at acertain time, and usually are notcompounded significantly by combiningseveral simultaneous measurements toform a derived assessment (e.g., BMI) ora result of statistical analysis. An“endpoint” is a variable that pertains tothe trial objectives. Not all endpointsare themselves assessments sincecertain endpoints might apply topopulations or emerge from analysis ofresults. That is, endpoints might befacts about assessments (e.g.,prolongation of survival). When a“variable” is captured or measured,there is no necessary sense that anyevaluation or judgment is involved.However, when a variable is to bemeasured that obviously or activelypertains to subject status, which isalways the concern of the physician,that variable becomes or will always bean assessment. The term assessment isintended to invoke some degree ofevaluation or judgment concerningsubject status. A parameter is mostproperly a variable pertaining tostatistical distributions though the wordis often used synonymously withvariable by engineers.

variance. A measure of thevariability in a sample or population. Itis calculated as the mean squareddeviation (MSD) of the individualvalues from their common mean. Incalculating the MSD, the divisor n iscommonly used for a populationvariance and the divisor n-1 for asample variance.

verification. 1. The act of reviewing,inspecting, testing, checking, auditing,or otherwise establishing anddocumenting whether items, processes,services, or documents conform tospecified requirements. 2. (of software).Provides objective evidence that thedesign outputs of a particular phase ofthe software development life cyclemeet all of the specified requirementsfor that phase. NOTE: 2. Softwareverification looks for consistency,completeness, and correctness of thesoftware and its supportingdocumentation, as it is being developed,and provides support for a subsequentconclusion that software is validated[FDA General Principles of SoftwareValidation; ANSI/ASQC A3-1978;ISO/IEC Guide 25]. Verification is used inthe sense of matching elements of areport or results of system testing toindividual requirements. Compare tovalidation where suitability to purpose isalso established.

verification of data. See sourcedocument verification (SDV).

visit. A clinical encounter thatencompasses planned and unplannedtrial interventions, procedures, andassessments that may be performedon a subject. A visit has a start and anend, each described with a rule.[CDISC Trial Design Project]

vocabulary. Terms that function ingeneral reference to concepts thatapply over a variety of languages arewords, and their totality is avocabulary. Synonym: terminology.See controlled vocabulary.

volunteer. A person volunteering toparticipate as a subject in a clinicaltrial, often a healthy person agreeingto participate in a Phase 1 trial. Seealso Phase 1.

vulnerable subjects. Individualswhose willingness to volunteer in aclinical trial may be unduly influencedby the expectation, whether justified



or not, of benefits associated withparticipation, or of a retaliatoryresponse from senior members of ahierarchy in case of refusal toparticipate. Examples are members ofa group with a hierarchical structure,such as medical, pharmacy, dental, andnursing students, subordinate hospitaland laboratory personnel, employeesof the pharmaceutical industry,members of the armed forces, andpersons kept in detention. Othervulnerable subjects include patientswith incurable diseases, persons innursing homes, unemployed orimpoverished persons, patients inemergency situations, ethnic minoritygroups, homeless persons, nomads,refugees, minors, and those incapableof giving consent. [ICH]

Warning Letter. A writtencommunication from FDA notifying anindividual or firm that the agencyconsiders one or more products,practices, processes, or other activitiesto be in violation of the Federal FD&CAct, or other acts, and that failure ofthe responsible party to takeappropriate and prompt action tocorrect and prevent any future repeatof the violation may result inadministrative and/or regulatoryenforcement action without furthernotice. [FDA]

washout period. A period in aclinical study during which subjectsreceive no treatment for the indicationunder study and the effects of aprevious treatment are eliminated (orassumed to be eliminated).

Web browser. A computer programthat interprets HTML and other Internetlanguages and protocols and displaysWeb pages on a computer monitor.

Web page. A single page on a Website, such as a home page.

Web server. A computer server thatdelivers HTML pages or files over theWorld Wide Web. See also server.

Web site. A collection of Web pagesand other files. A site can consist of asingle Web page, thousands of pages,or custom created pages that draw ona database associated with the site.

weighting. An adjustment in a valuebased on scientific observations withinthe data.

well-being (of the trialsubjects). The physical and mentalintegrity of the subjects participatingin a clinical trial. [ICH]

withdrawal. The subject-initiatedact of discontinuing participation in aclinical study. NOTE: Withdrawal can

range from the subject’s completewithdrawal from study procedures andfollow-up activities, to the subject’swithdrawal from study-relatedinterventions while the subject permitscontinued access to his/her medicalrecords or identifiable information.Note that according to FDAregulations, when a subject withdrawsfrom a study, the data collected onthe subject to the point of withdrawalremain part of the study database andmay not be removed. See alsodiscontinuation.

within-subject differences. In acrossover trial, variability in each subjectis used to assess treatment differences.

World Wide Web. All the resourcesand users on the Internet that areusing HTTP protocols. Also called theWeb and www.




Note: The references below are cited in both the CDISC Glossary and Abbreviations & Acronyms.n 21 CFR 820.20. Available at http://www.fda.gov (http://www.accessdata.fda.

gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=820.20 )n 21 CFR Part 11. Electronic Records; Electronic Signatures Final Rule, 62 Fed-

eral Register 13430 (March 20, 1997). Available at http://www.fda.gov(Code of Federal Regulations)

n A Drug Review Glossary. Available at: http://www.fda.gov/fdac/special/newdrug/bengloss.html

n C.Acquardo, C. Berzon et al. Incorporating the Patient's Perspective into DrugDevelopment and Communication:An Ad Hoc Task force Report of the Patient-Reported Outcomes (PRO) Harmonization Group Meeting at the Food andDrug Administration, Feb. 16, 2001, Value in Health, 6 (5) 522–531 (2001).

n D.G. Altman, K.F. Schultz, D. Moher et al., “The Revised CONSORT Statementfor Reporting Randomized Trials: Explanation and Elaboration,” Ann InternMed., 134, 663–694 (2001).Available at: http://www.consort-statement.org/

n American Medical Association Manual of Style, a guide for authors andeditors. 9th Ed. (Baltimore, MD: Williams & Wilkins, 1998).

n Analysis Dataset Model (CDISC). Available at http://www.cdisc.org/standards/index.html

n Biomarkers Definitions Working Group: Biomarkers and Surrogate Endpoints:Preferred Definitions and Conceptual Framework. Clin Pharmacol Ther,69, 89–95 (2001).

n CDER acronym list.Available at: http://www.fda.gov/cder/handbook/acronym.htm#W Drug Development and Review Definitions (CDER). Available at:http://www.fda.gov/cder/about/smallbiz/definitions.htm

n CDISC Glossary Project Team Members: Cathy Barrows, GSK; Patricia BeersBlock, Liaison from Office of Science and Health, FDA; Lori J. Brozena, Merck;Renee Creciun, Merck; Brenda Duggan, NCI; Julia Forjanic-Klapproth, TrilogyWriting; Jane Ganter, Editor Emeritus, Applied Clinical Trials;Helle-Mai Gawrylewski, Johnson & Johnson PRD; Art Gertel, Beardsworth Consulting; J. J. Hantsch, Takeda; Kathy Hollinger, FDA; Rebecca Kush, CDISC;Elinor Lebner-Olesen, Novo Nordisk; Beverly Meadows, NCI; Stephen A.Raymond, PHT Corporation; Anne Tompkins, NCI; Marcella Tordosinsky,Merck; Cara Willoughby, Lilly.

n Center for the Advancement of Clinical Research—Clinical Research Dic-tionary. Available at: http://www.med.umich.edu/cacr/dictionary/A-B.htm

n Comments on Draft PRO Guidance, Docket 2006D-0044 by ISOQOL, 4 April2006. Available at: http://www.fda.gov/ohrms/dockets/dockets/06d0044/06D-0044-EC17-Attach-1.pdf

n CONSORT Statement (see D.G. Altman et al., above).n CRIX and FIREBIRD projects, Available at: http://crix.nci.nih.gov/ and

http://crix.nci.nih.gov/projects/Firebird/n CSUCT; see Guidance.n Declaration of Helsinki available at: http://www.nihtraining.com/ohsrsite/

guidelines/helsinki.htmln Document type definition available at: http://www.XMLfiles.comn European Agency for the Evaluation of Medicinal Products (EMEA) Web site

http://www.emea.eu.int/n Federal Information Processing Standards (FIPS) Publication 46-2. 30 Decem-

ber 1993. Available at: http://www.itl.nist.gov/fipspubs/fip46-2.htmn General Principles of Software Validation; Final Guidance for Industry and FDA

Staff, Jan 11, 2002. Available at: http://www.fda.gov/cdrh/comp/guidance/938.pdf

n Glossary for Healthcare Standards, W.E. Hammond, 1995. Available at:http://72.14.209.104/search?q=cache:Adz5tXfOdqEJ:dmi=www.mc.duke.edu/dukemi/acronyms.htm+W.+Ed+Hammond,+Glossary+for+Healthcare+Standards.+1995&hl=en&gl=us&ct=clnk&cd=1

n Glossary of Computerized System and Software Development Terminology,Division of Field Investigations, Office of Regional Operations, Office of Regu-latory Affairs, Food and Drug Administration, August 1995. Available at:http://www.fda.gov/ora/inspect_ref/igs/gloss.html

n Guidance For Industry: Computerized Systems Used in Clinical Trials (CSUCT),April 1999. Available at: http://www.fda.gov/ora/compliance_ref/bimo/ffinalcct.htm

n Guidance for Industry: Computerized Systems Used in Clinical Investigations(CSUICI), U.S. Department of Health and Human Services, Food and DrugAdministration (FDA), Office of the Commissioner (OC), May 2007. Availableat: http://www.fda.gov/cder/guidance/7359fnl.htm

n G.H. Guyatt, D.H. Feeney, D.L. Patrick, “Measuring Health-Related Quality ofLife,” Ann Intern Med., 118, 622–629 (1993).

n HL7 Glossary of Terms. January 2002. Available at: https://www.hl7.org/library/bookstore/

n L. Huber, “In Search of Standard Definitions for Validation, Qualification, Veri-fication and Calibration,” BioPharm, 12 (4) 56–58 (1999).

n HyperStat Online Glossary. Available at: http://davidmlane.com/hyperstat/glossary.html

n ICH Efficacy Guideline page (E2a, E3, E6, E7, E8, E9, E10, E11). Available at:http://www.ich.org/ or http://www.ich.org/cache/compo/276-254-1.html

n IEEE Standard Computer Dictionary; a compilation of IEEE standard com-puter glossaries, 1990.

n ISO 9000-3:1997, Quality management and quality assurance standards—Part 3: Guidelines for the application of ISO 9001:1994 to the development,supply, installation and maintenance of computer software. InternationalOrganization for Standardization, 1997.

n ISO/IEC/IEEE 12207:1995 §3.35; from ISO/IEC 12207:1995, Informationtechnology—Software life cycle processes, Joint Technical Committee ISO/IECJTC 1, Subcommittee SC 7, International Organization for Standardization andInternational Electrotechnical Commission, 1995.

n R. Khosla, D.D. Verma, A. Kapur et al.,“Efficient Source Data Verification,”Indian J. Pharm, 32, 180–186 (2000).

n Medicinces and Healthcare products Regulatory Agency in the UK, Web site:http://www.mhra.gov.uk

n NIST: Minimum Security Requirements for Multi-user Operating Systems NISTIR 5153, March 1993, available at http://csrc.nist.gov/publications/nistir/ir5153.txt section 3.2.1.1

n D.L. Patrick, “Patient-Reported Outcomes (PROs): An Organizing Tool for Con-cepts, Measures, and Applications,” MAPI Quality of Life News Letter, 31,1–5 (2003).

n PRO Draft Guidance, FDA, “Patient-Reported Outcome Measures: Use in Med-ical Product Development to Support Labeling Claims,” Feb. 2006. Availableat: http://www.fda.gov/cder/guidance/5460dft.htm

n Protocol Representation Group (PR Project), CDISC, Protocol Elements Spread-sheet, 2005. Available at: http://www.cdisc.org/standards/index.html

n M.L. Schuyl and T. Engel, “A Review of the Source Document VerificationProcess in Clinical Trials,” DIA Journal, 33, 789–797 (1999).

n Structured Product Labeling (SPL). Available at: https://www.hl7.org.library/bookstore/

n Study Data Tabulation Model (SDTM). Available at: http://www.cdisc.org/standards/index.html

n The WHO Group, “The Development of the World Health Organization Qualityof Life Assessment Instrument (WHOQOL),” in J. Orley and W. Kuyken (Eds.),Quality of Life Assessment: International Perspectives (Berlin, Heidelberg:Springer-Verlag, p. 41, 1994).

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