clinical research glossary - jane...

24 APPLIED CLINICAL TRIALS actmagazine.com December 2005

See also approval letter, approvableletter, not-approvable letter.

admission criteria. Basis for selectingtarget population for a clinical trial.Subjects must be screened to ensure thattheir characteristics match a list ofadmission criteria and that none of theircharacteristics match any single one ofthe exclusion criteria set up for the study.See also inclusion criteria, exclusioncriteria.

Glossary Terms

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

action letter. An officialcommunication from FDA to an NDAsponsor announcing an agency decision.

adverse drug experience.See adverse drug reaction.

adverse drug reaction (ADR).Any noxious 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 modificationof physiological function. 2. Pre-approval: an adverse event that occurs at

Clinical Research GlossaryVersion 4.0

SPECIAL RESOURCE ISSUE

CDISC Glossary Group

Stephen A. Raymond, Chairperson

Core Committee: Helle-MaiGawrylewski, Johnson and JohnsonArthur Gertel, Beardsworth ConsultingStephen Raymond, PHT CorporationCara Willoughby, Lilly

Glossary Group Members:Cathy Barrows, GSK Lori J. Brozena,Merck Renee Creciun, Merck BrendaDuggan, NCI Julia Forjanic-Klapproth,Trilogy Writing Helle Mai Gawrylewski,Johnson & Johnson Arthur Gertel,Beardsworth Consulting Kathy Hollinger,FDA Rebecca Kush, CDISC Elinor Lebner-

Olesen, Novo Nordisk Jennifer Maginn,Novo Nordisk Stephen Raymond, PHTCorporation Anne Tompkins, NCI Marcella Tordosinsky, Merck KarenUnderkofler, SAIC Cara Willoughby, Lilly

Orientation: The following Glossary and list ofAcronyms, Abbreviations, and Initials is the fourthproduced by the Glossary Group of CDISC, which seeksto harmonize definitions (including acronyms,abbreviations and initials) used in the variousstandards initiatives undertaken by CDISC in clinicalresearch. The purpose of the Glossary is also to servethe community of clinical researchers by selecting anddefining terms pertaining to the conduct of federal-and pharmaceutical industry-sponsored clinicalresearch, particularly eClinical Trials. The Glossary ispublicly accessible on the CDISC Web site (CDISC.org),where comments on the Glossary are welcomed.

Note that this CDISC glossary is NOT comprehensivefor all words bearing on human health, medicine,laboratory methods. The Glossary includes referencesand links to other glossaries such as regulatorydictionaries or to health-related controlledterminologies that are known to be useful inconducting clinical research.

Glossary terms are organized alphabetically by firstword according to the opinion of the Glossary Groupconcerning most common usage in clinical research.Thus “source document verification” would appearunder “source,” not “verification.” The Glossaryfollows the practice of preceding certain terms with

the letter “e” to denote that they pertain toelectronic or Web implementation. Each term in theGlossary has the following conventions concerningcontent and order of presentation:

Term. The term or word is presented first, followedby a period. Terms are defined entities consisting ofmore than one word. Only proper nouns arecapitalized.

Definition. Multiple meanings of the same term arenumbered 1., 2., 3., etc.

NOTE: (optional) Comments including usage domainknowledge related to a term may follow the definition.

Source(s). The sources for definitions are cited (see“references”) in square brackets. Where the definitionhas been altered by CDISC, the citation states“modified from.” Where the definition has beendrawn by CDISC from text that is not itself adefinitions, the citation states “after” or “from.”Where no source is listed, the definition is from CDISC.

Related words. (optional) These include synonyms(“see”) as well as other words (“see also” or “compareto”) and comments to sharpen or expand upon thedefinition.

any dose and where a causal relationshipis at least a reasonable possibility. NOTE:FDA 21CFR 310.305 defines an adversedrug experience to include any adverseevent, “whether on not considered to bedrug-related.” CDISC recognizes thatcurrent usage incorporates the conceptof causality. [WHO technical Report498(1972); ICH E2A]

adverse event (AE). Any untowardmedical occurrence in a patient orclinical investigation subject administereda pharmaceutical product and whichdoes not necessarily have a causalrelationship with this treatment. Anadverse event (AE) can therefore be anyunintended sign (including an abnormallaboratory finding), symptom, or diseasetemporally associated with the use of a medicinal (investigational) product,whether or not related to the medicinalinvestigational) product. NOTE: Forfurther information, see the ICHGuideline for Clinical Safety DataManagement: Definitions and Standardsfor Expedited Reporting. “[Modifiedfrom ICH E2A]” Synonyms: side effect,adverse experience. See also seriousadverse event, serious adverseexperience.

adverse experience. See adverseevent.

adverse reaction. See adverse drugreaction.

algorithm. Step-by-step procedure for solving a mathematical problem; also used to describe step-by-stepprocedures for making a series ofchoices among alternative decisions toreach a calculated result or decision.

alpha error. The likelihood that arelationship observed between 2variables is due to chance. The prob-abaility of a Type 1 error. [Modified from AMA Manual of Style]

amendment. A written description of 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 the

coordinator for U.S. voluntary standardsefforts, acting as the approval body torecognize documents developed byother national organizations as AmericanNational Standards, acting as the U.S.representative in international andregional standards efforts, and serving as a clearinghouse for national andinternational standards developmentinformation. [HL7]

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 used totest the statistical hypotheses identifiedin the protocol and analysis plan;variables to be analyzed. [PR Group] Seealso variable.

applet. A small application, typicallydownloaded from a server.

application software.See application.

application. 1. Computer application:software designed to fill specific needsof a user; for example, software fornavigation, project management, orprocess control. 2. Regulatoryapplication: Application made to ahealth authority to investigate, market,or license a new product or indication.Synonyms: 1. computer application,application software.

approvable letter. An officialcommunication from FDA to anNDA/BLA sponsor that lists issues to be resolved 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).The affirmative decision of the IRB thatthe clinical trial has been reviewed andmay be conducted at the institution sitewithin the constraints set forth by theIRB, the institution, good clinical practice(GCP), and the applicable regulatoryrequirements. [ICH E6]

approval letter. An officialcommunication from FDA to inform an applicant of a decision to allowcommercial marketing consistent withconditions of approval. [Modified from21 CFR 314.3; Guidance to Industry and 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 term assessmentis intended to invoke some degree ofevaluation or judgment concerningsubject 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 (atan investigative site, CRO, or clinicalresearch department of a pharmaceuticalcompany). [ICH E6 Glossary]

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

audit trail. 1. Documentation thatallows reconstruction of the course ofevents. 2. A secure, time-stamped recordthat allows reconstruction of the courseof events relating to the creation,modification, and deletion of anelectronic study record. [1. ICH E6Glossary; 2. CSUCT]

December 2005 actmagazine.com APPLIED CLINICAL TRIALS 25

SPECIAL RESOURCE ISSUE Clinical Research Glossary


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 Group]

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. Assessment ofsubjects as they enter a trial and beforethey 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 tocompare groups of participants thatdiffer only with respect to theintervention (treatment). Althoughproper random assignment preventsselection bias, it does not guarantee that the groups are equivalent atbaseline. Any differences in baselinecharacteristics are, however, the result of 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 its featuresgiving a subjective interpretation toprobability, accepting the idea that it ispossible to talk about the probability ofhypotheses being true and of parametershaving particular values.

beta error. Probability of showing no significant difference when a truedifference exists; a false acceptance ofthe null hypothesis. See also Type 2error. [AMA Manual of Style]

bias. Situation or condition that causesa result to depart from the true value ina consistent direction. Bias refers todefects in study design or measurement.[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 is otherwiseavailable to the treatment site in thebody.

bioequivalence. Scientific basis onwhich drugs with the same activeingredient(s) are compared. NOTE: To beconsidered bioequivalent, thebioavailability of two products must notdiffer significantly when the twoproducts are given in studies at the samedosage under similar conditions.

biological marker. See biomarker.

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 and assessingdata prior to breaking the blind, for thepurpose of finalizing the plannedanalysis. [Modified ICH E9]

blinded (masked) medications.Products that appear identical in size,shape, color, flavor, and other attributesto make it very difficult for subjects and investigators (or anyone assessingthe outcome) to determine whichmedication is being administered.

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

blinding. Prevent identification oftreatments/procedures/test to testsubjects or study personnel results inorder to limit bias (e.g., open-label;single-blind; double-blind). NOTE:Blinding is a procedure in which one or more parties to the trial are keptunaware of the treatment assignment(s).Includes further distinction betweensingle- and double-blind. Masking, whileoften used synonymously with blinding,is usually associated with concealing thespecific study intervention used. [ICH E9]The term “masking” is often preferred inthe field of ophthalmology. [AMAManual of Style]

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

browser. Computer program that runson the user’s desktop computer and isused to navigate the World Wide Web.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 treatmenthas 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 to the investigation on each individualadministered the investigational drug(device or other therapy) or employed as a control in the investigation. NOTE:Case histories include the case reportforms and supporting data including, for example, signed and dated consentforms and medical records including, for example, progress notes of thephysician, the individual’s hospitalchart(s), and the nurses’ notes. The case history for each individual shalldocument that informed consent wasobtained prior to participation in thestudy. [21 CFR 312.62b]

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 observations andother information that a study protocoldesignates must be completed for eachsubject. NOTE: In common usage, CRFcan refer to either a CRF page, whichdenotes a group of one or more dataitems linked together for collection anddisplay, or a casebook, which includesthe entire group of CRF pages on whicha set of clinical study observations andother information can be or have beencollected, or the information actuallycollected by completion of such CRFpages for a subject in a clinical study[ICH E6 Glossary]. See also CRF (paper).

case report tabulations (CRT).In a 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. An evaluationperformed by a medical professionalconcerning the likelihood that a therapyor product under study caused orcontributed to an adverse event.

certified copy. A copy of originalinformation that has been verified by a certifying signature to preserveaccurately the content, information andintegrity of the original. The signaturecan be applied to the copy or be areference on the copy to a signature onthe validation documentation pertainingto an electronic means of accuratelycopying information.

Certified IRB Professional (CIP).Certification awarded to persons whosatisfy the educational and employmentrequirements and pass an examinationconducted by the Applied ResearchEthics National Association (ARENA), the membership division of PublicResponsibility in Medicine and Research(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 a servicerequest of another program (the server)that fulfills the request. Web browsers(such as Netscape Navigator andMicrosoft Explorer) are clients thatrequest HTML files from Web servers.

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

clinical development plan.A document that describes the collectionof clinical studies that are to beperformed in sequence, or in parallel,with a particular active substance,device, procedure, or treatment strategy,typically with the intention of submittingthem as part of an application for amarketing authorization. NOTE: the planshould have appropriate decision pointsand allow 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 to produce a desired effect (i.e.,appropriate pharmacological activity in aspecified indication) in humans. [SQA]

clinical investigation. See clinicaltrial.

clinical pharmacology. Science thatdeals with the characteristics, effects,properties, reactions, and uses of drugs, particularly their therapeutic valuein humans, including their toxicology,safety, pharmacodynamics, andpharmacokinetics (ADME).

clinical protocol. See protocol.

clinical research anddevelopment. The testing of a drugcompound in humans primarily done todetermine its safety and pharmacologicaleffectiveness. Clinical development isdone in phases, which progress fromvery tightly controlled dosing of smallnumber of subjects to less tightlycontrolled studies involving largenumbers of patients. [SQA]

clinical research associate (CRA).Person employed by a sponsor, or by acontract research organization acting on



a sponsor’s behalf, who monitors theprogress of investigator sitesparticipating in a clinical study. At somesites (primarily in academic settings),clinical research coordinators are calledCRAs.

clinical research coordinator(CRC). Person who handles most of theadministrative responsibilities of a clinicaltrial, acts as liaison between investigativesite and sponsor, and reviews all dataand records before a monitor’s visit.Synonyms: trial coordinator, studycoordinator, research coordinator, clinicalcoordinator, research nurse, protocolnurse.

clinical significance. Change in asubject’s clinical condition regarded asimportant whether or not due to the testintervention. NOTE: Some statisticallysignificant changes (in blood tests, forexample) have no clinical significance.The criterion or criteria for clinicalsignificance should be stated in theprotocol . The term “clinicalsignificance” is not advisable unlessoperationally defined.

clinical study (trial) report.A written description of a study of anytherapeutic, prophylactic, or diagnosticagent conducted in human subjects, in which 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. [ICH E6 Glossary]

clinical study. See clinical trial.

Clinical trial. Any investigation inhuman subjects intended to discover orverify the clinical, pharmacologicaland/or other pharmacodynamic effectsof one of more investigational medicinalproduct(s), and /or to identify anyadverse reactions to one or moreinvestigational medicinal product(s),and/or to study absorption, distribution,metabolism and excretion of one ofmore investigational medicinal product(s)with the object of ascertaining its (their)safety and/or efficacy. [Directive2001/20/EC; Modified from ICH E6Glossary]

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

clinical trial exemption (CTX).A scheme that allows sponsors to applyfor approval for each clinical study inturn, submitting supporting data to the Medicines Control Agency (MCA),which approves or rejects the application (generally within 35 workingdays). NOTE: Approval means that the company is exempt from therequirement to hold a clinical trialcertificate (CTC). (UK).

clinical trial information.Data collected in the course of a clinicaltrial or documentation related to theintegrity or administration of that data.A superset of clinical trial data.

clinical trial materials. Complete setof supplies provided to an investigator bythe trial sponsor.

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

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, maybe coded using MedDRA.

cohort study. Study of a group ofindividuals, some of whom are exposedto a variable of interest, in whichsubjects are followed over time. Cohortstudies can be prospective orretrospective. [AMA Manual of Style] See also prospective study.

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]

combination product. 1. A productcomprising two or more individual

products. 2. Two or more separateproducts packaged together in a singlepackage or as a unit. 3. A product that is packaged separately but is used onlywith another product. [Modified fromSPL Glossary]

Common Technical Document.A format agreed upon by ICH toorganize applications to regulatoryauthorities for registration ofpharmaceuticals for human use. [ICH]See also eCTD.

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

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

Competent Authority (CA).The regulatory body charged withmonitoring compliance with the nationalstatutes and regulations of EuropeanMember 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 activeparticipation in a trial because thesubject has, or is presumed to have,followed all appropriate conditions of aprotocol. 2. Study completion: accordingto the study protocol, the point at whichall protocol-required activities have beenexecuted. [Modified EU CTD]

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

computer application.See application.

confidence interval. A measure ofthe precision of an estimated value. Theinterval represents the range of values,consistent with the data, that is believed



to encompass the “true” value with high probability (usually 95%). Theconfidence interval is expressed in thesame units as the estimate. Widerintervals indicate lower precision; narrowintervals, greater precision. [CONSORTStatement]

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

confirmatory trial. Phase III trialduring which the previously revealedactions of a therapeutic intervention are confirmed. NOTE: procedures inconfirmatory trials should be set firmly inadvance. Compare to exploratory trial.

conformity assessment. The processby which compliance with the EMEA’sEssential Requirements is assessed. See also Notified Body.

consent form. Document used duringthe informed consent process that is thebasis for explaining to potential subjectsthe risks and potential benefits of astudy and the rights and responsibilitiesof the parties involved. NOTE: Theinformed consent document provides asummary of a clinical trial (including itspurpose, the treatment procedures andschedule, potential risks and benefits,alternatives to participation, etc.) and explains an individual’s rights as a subject. It is designed to begin theinformed consent process, whichconsists of conversations between thesubject and the research team. If theindividual then decides to enter the trial, s/he gives her/his official consent by signing the document. Synonym:informed consent form; see alsoinformed consent.

consumer safety officer (CSO).FDA official who coordinates the reviewprocess of various applications.

content validity. The extent to whicha variable (for example, a rating scale)measures what it is supposed tomeasure. [ICH E9 Glossary]

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, and signed agreement between two or more involved parties that sets out any arrangements on delegation anddistribution of tasks and obligations and, if appropriate, on financial matters.The protocol may serve as the basis of a contract. [ICH E6 Glossary]

control group. The group of subjectsin a controlled study that receives notreatment, a standard treatment, or aplacebo. [21 CFR 314.126] See alsocontrols.

control(s). 1. Comparator againstwhich the study treatment is evaluated(e.g., concurrent (placebo, no treatment,dose-response, active), external(historical, published literature) 2. Computer: processes or operationsintended to ensure authenticity, integrity,and confidentiality 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 which atest article is compared with a treatmentthat has known effects. The controlgroup may receive no treatment, activetreatment, placebo, or dose comparisonconcurrent control. NOTE: For furtherinformation on “adequate and well-controlled study” see 21CFR 314.126.

controlled vocabulary. A finite setof values that represent the only allowedvalues for a data item. These values maybe codes, text or numeric. See alsocodelist.

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

coordinating investigator.An investigator assigned theresponsibility for the coordination ofinvestigators at different centersparticipating in a multicenter trial. [ICH E6]

correlation. The degree to which twoor more variables are related. Typicallythe linear relationship is measured witheither Pearson’s correlation orSpearman’s rho. NOTE: correlation doesnot necessarily mean causation. [AfterHyperStat Online Glossary; ADaM]

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

CRF (paper). Case report form inwhich the data items are linked by thephysical properties of paper to particularpages. NOTE: data are capturedmanually and any comments, notes, andsignatures are also linked to those dataitems by writing or typescript on thepaper pages. See also eCRF, case reportform.

crossover trial. A trial design forwhich subjects function as their owncontrol and are assigned to receiveinvestigational product and controls inan order determined by randomizations,typically with a washout period betweenthe two products. [Center for theAdvancement of Clinical Research;ADaM]

curriculum vitae (cv). Documentthat outlines a person’s educational andprofessional history.

data acquisition. Capture of datainto a structured computerized formatwithout a human-computer interface(from another automated orcomputerized source). Contrast withdata entry, electronic data capture.

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

data clarification. Answer suppliedby the investigator in response to aquery. NOTE: The investigator maysupply a new data point value to replacethe initial value or a confirmation of thequeried data point.

data clarification form. A formused to query an investigator and collectfeedback to resolve questions regardingdata.

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

data element. 1. For XML, an item ofdata provided in a mark up mode toallow machine processing. 2. Smallestunit of information in a transaction.NOTE: The mark up or tagging facilitatesdocument indexing, search and retrieval,and provides standard conventions forinsertion of codes. [1. FDA - GL/IEEE. 2.Center for Advancement of ClinicalResearch]

Data Encryption Standard (DES).A FIPS approved cryptographic algorithmfor encrypting (enciphering) anddecrypting (deciphering) binary codedinformation. Encrypting data converts itto an unintelligible form called cipher.Decrypting cipher converts the data backto its original form called plaintext. Thestandard specifies both enciphering anddeciphering operations, which are basedon a 64 bit binary number called a key.Unauthorized recipients of the cipherwho know the algorithm but do nothave the correct key cannot derive theoriginal data algorithmically. NOTE: Datathat is considered sensitive by theresponsible authority, or data thatrepresents a high value should becryptographically protected if it isvulnerable to unauthorized disclosure orundetected modification duringtransmission or while in storage. [fromFederal Information Processing Standards(FIPS) Publication 46-2]

data entry. Human input of data intoa structured, computerized format usingan interface such as a keyboard, pen-based tablet, or voice recognition.Contrast with data acquisition, electronicdata capture.

data integrity. An attribute of datapertaining to clinical trials depending onthe quality of processes for data capture,correction, maintenance, transmission,and retention. Key dimensions of dataintegrity include that data beattributable, legible, contemporaneous,original and accurate. NOTE: in clinicalresearch the FDA requires that datarelied on to determine safety andefficacy of therapies be trustworthy and

establishes guidance and regulationsconcerning practices and systemrequirements needed to promote anacceptable level of data integrity. [FDA, CSUCT; IEEE]

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

data interchange. Transfer ofinformation between two or moreparties, which maintains the integrity ofthe contents of the data for the purposeintended. See also interoperability.

data item. A named component of a data element. Usually the smallestcomponent [ANSI]. See also data model,data element.

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

data management. Tasks associatedwith the entry, transfer and/orpreparation of source data and deriveditems for entry into a clinical trialdatabase. NOTE: data managementcould include database creation, dataentry, review, coding, data editing, dataQC, locking, or archiving; it typicallydoes not include source 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. A datamodel uses symbolic conventions agreedto represent content so that contentdoes not lose its intended meaningwhen communicated.

data monitoring committee(DMC). Group of individuals withpertinent expertise that reviews on aregular basis accumulating data from anongoing clinical trial. The DMC advisesthe sponsor regarding the continuingsafety of current participants and thoseyet to be recruited, as well as thecontinuing validity and scientific merit ofthe trial. NOTE: A DMC can stop a trial ifit finds toxicities or if treatment is proved

beneficial. [After FDA guidance onestablishment and operation of clinicaltrial data monitoring committees]

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

data quality. Describes thecharacteristics that confirm “fitness for use”-that is ability to supportmeaningful and trustworthy conclusionsand interpretations. Quality isestablished through formal assessment,quality control and auditing. NOTE:Because assessments of data quality arelinked to the needs of the study andexpectations of the user, the qualitycriteria may vary from one project toanother. See also ALCOA, data integrity.

data security. Degree to which dataare protected from the risk of accidentalor malicious alteration or destructionand from unauthorized access ordisclosure. [FDA]

data selection criteria. The rules bywhich particular data are selected and/ortransferred between the point of careand the patient record; subsequently,from the patient record to the database;and from database to inclusion in sub-population analyses.

data transformations. Algorithmicoperations on data or data sets toachieve a meaningful set of derived datafor analysis. [ADaM] See also derivedvariable.

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

data validation. 1. Checking data for correctness and/or compliance with applicable standards, rules, and conventions. 2. Process used to determine if data are inaccurate,incomplete, or unreasonable. Theprocess may include format checks,completeness checks, check key tests,reasonableness checks, and limit checks.[1. FDA 2. ISO]




data. Representations of facts,concepts, or instructions in a mannersuitable for communication,interpretation, or processing by humansor by automated means. [FDA]

database lock. Action taken toprevent further changes to a clinical trialdatabase. NOTE: locking of a database isdone after review, query resolution and a determination has been made that thedatabase is ready for analysis.

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

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 principles thatguide medical doctors in the conduct of biomedical research involving humansubjects. It was originally adopted by the 18th World Medical Assembly(Helsinki, Finland, 1964) and recentlyrevised (52nd WMA General Assembly,Edinburgh, Scotland, October 2000).

demographic data. Characteristics of 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 the studyin which they are participating.

dependent variable. Outcomes thatare measured in an experiment and that are expected to change as a resultof an experimental manipulation of theindependent variable(s). [Center forAdvancement of Clinical Research]

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

design configuration. Clinical trialdesign developed to compare treatmentgroups in a clinical trial. NOTE: The configuration usually requiresrandomization to one or more treatment

arms, each arm being allocated adifferent (or no) treatment. Examplesinclude: Parallel Group Design, CrossoverDesign, Factorial Designs. [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 important to evaluation of a clinical trial. NOTE:Any party (e.g., domestic and foreignregulatory authorities, sponsor’smonitors and auditors) with direct accessshould take all reasonable precautionswithin the constraints of the applicableregulatory requirement(s) to maintain the confidentiality of subject’s identitiesand sponsor’s proprietary information.[ICH E6 Glossary]

discontinuation. The act ofconcluding participation, prior tocompletion of all protocol-requiredelements, in a trial by an enrolled subjectNOTE: Four categories of discontinuationare distinguished: a) dropout: Activediscontinuation by a subject (also a nounreferring to such a discontinued subject);b) investigator-initiated discontinuation(e.g., for cause); c) loss to follow-up:cessation of participation without notice or action by the subject; d)sponsor-initiated discontinuation. Notethat subject discontinuation does notnecessarily imply exclusion of subjectdata from analysis. “Termination” has ahistory of synonymous use, but is nowconsidered non-standard. See alsowithdrawal.

discrepancy. The failure of a datapoint to pass a validation check. NOTE: Discrepancies may be detected by computerized edit checks orobserved/identified by the data revieweras a result of manual data review. Seealso query.

distribution. 1. In statistics, a group of ordered values; the frequencies orrelative frequencies of all possible valuesof a characteristic.

2. In pharmacokinetics, the processesthat control transfer of a drug from thesite of measurement to its target andother tissues. [1. AMA Manual of Style].See also 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) with the following characteristics: 1) Stewardship; 2) Potential forauthentication; 3) Wholeness; 4) Humanreadability; 5) Persistence; 6) Global vs.local context.

document root. The element in anXML document that contains all otherelements; 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 the document. NOTE: agreeing on acommon DTD facilitates interoperabilityamong systems incorporating the agreed standards. [from XML files.com]

documentation. All records, in anyform (including, but not limited to,written, electronic, magnetic, and opticalrecords, and scans, x-rays, andelectrocardiograms) that describe orrecord the methods, conduct and/orresults of a trial, the factors affecting atrial, and the actions taken. [ICH E6Glossary]

domain name. The way a particularWeb server is identified on the Internet.For example, www.fda.gov names theWorld Wide Web (www) server for theFood and Drug Administration, which isa government (.gov) entity. [Center forAdvancement of Clinical Research]

dosage form. Physical characteristicsof a drug product, (e.g., tablet, capsule,or solution) that contains a drugsubstance, generally, but not necessarily,in association with one or more otheringredients. [21 CFR §314.3]. See alsodrug product.

dosage regimen. The number ofdoses per given time period; the elapsedtime between doses (for example, everysix hours) or the time that the doses areto be given (for example, at 8 a.m. and 4 p.m. daily); and/or the amount of amedicine (the number of capsules, forexample) to be given at each specificdosing time. [From Center forAdvancement of Clinical 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. FDA Glossaryof Terms]

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]

dose. The amount of drug administeredto a patient or test subject at one timeor the total quantity administered.[AMA Manual of Style]

double-blind study. A study in whichneither the subject nor the investigatornor the research team interacting withthe subject or data during the trialknows what treatment a subject isreceiving.

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). Subjects then take two sets of treatment; either A (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 or observationrequired of him/her by the studyprotocol. [From ICH E9]

drug development process. Theprogram for advancing an investigationalproduct from preclinical studies throughapproval for marketing following reviewby regulatory agencies.

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

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 pharmacopia or formulary. [from FDA Glossary ofTerms, CDER]

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 are moreresponsive to user interaction thanprevious versions of HTML.

eClinical trial. Clinical trial in whichprimarily electronic processes are used toplan, collect (acquire), access, exchangeand archive data required for conduct,management, analysis and reporting ofthe trial. Synonyms: eClinical study;eClinical investigation.

eCRF. 1. Auditable electronic recorddesigned to capture information requiredby the clinical trial protocol to bereported to the sponsor on each trialsubject. 2. A CRF in which related dataitems and their associated comments,notes, and signatures are linkedelectronically. NOTE: eCRFs may includespecial display elements, electronic editchecks, and other special properties orfunctions and are used for both captureand display of the linked data. [FDA CSUCT]

eCRT. CRTs provided in electronic formatfor eSubmissions (electronic regulatorysubmissions). NOTE: According to FDAguidance, eCRTs are datasets provided asSAS Transport files with accompanyingdocumentation in electronic submissions.They enable reviewers to analyze eachdataset for each study. Each CRF domainshould be provided as a single dataset,however additional datasets suitable forreproducing and confirming analysesmay also be needed. Becoming obsolete,being replaced by SDTM.

edit check. An auditable process,usually automated, of assessing thecontent of a data field against itsexpected logical, format, range or otherproperties that is intended to reduceerror. NOTE: Time-of-Entry Edit Checksare a type of edit check that is run(executed) at the time data are firstcaptured or transcribed to an electronicdevice at the time entry is completed of each field or group of fields on aform. Back-end Edit Checks are a typethat is run against data that has beenentered or captured electronically andhas also been received by a centralizeddata 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] See also treatment effect.

effectiveness. The desired measure of a drug’s influence on a disease orcondition as demonstrated by substantialevidence from adequate and well-controlled investigations.

efficacy. The capacity of a drug ortreatment to produce beneficial effectson the course or duration of a disease at the dose tested and against the illness(and patient population) for which 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 data are recorded via an audit trail. See alsodata entry, data acquisition.

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. [FDA CSUCT; 21 CFR Part 11.3 (7)]

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




element. 1. In trial design, a basicbuilding block for time within a clinical trial 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 XML documentdelimited by start and end tags; or, inthe case of empty elements (elementswith no content, only attributes)indicated by an empty tag. [1. PR Group, 2. HL7]

eMedical record. An electronic record derived from a computerizedsystem used primarily for deliveringpatient care in a clinical setting. NOTE:eMedical records may serve as sourcedocuments, and such data could servealso as source data for clinical trialsprovided that the controls on theeMedical record system and the transferof such data to the eClinical trial systemwere to fulfill the requirements of 21CFR Part 11.

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

enroll. To register or enter into a clinicaltrial; transitive and intransitive. NOTE:Informed consent precedes enrollment,which precedes or is contemporaneouswith randomization.

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 number of subjects in a class or group (includingthe total for the entire trial) intended tobe enrolled in a trial. NOTE: Target

enrollments are set so that statistical andscientific objectives of a trial will have alikelihood of being met as determined byagreement, algorithm or other specifiedprocess.

epoch. An interval of time in theplanned conduct of a study during which the treatment is consistent. NOTE:Consistent treatment of subjects acrossarms during an epoch does not meanthat the treatment in all arms is thesame; rather that the treatment,whatever it is, is to be consistent duringthe epoch for each arm. Synonyms:period, cycle, phase, stage. See also arm, visit.

ePRO. PRO data initially capturedelectronically. NOTE: usually ePRO data iscaptured as eSource. [DIA ePRO WorkingGroup]. See also 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. This is usuallydemonstrated by showing that the true treatment difference is likely to lie between a lower and an upperequivalence margin of clinicallyacceptable differences.

eSource data (electronic sourcedata). Source data captured initiallyinto a permanent electronic record usedfor the reconstruction and evaluation of a trial. NOTE: “Permanent” in thecontext of these definitions implies thatany changes made to the electronic data are recorded via an audit trail. [ICH, CDISC]. See also source data.

essential documents. Documentsthat individually and collectively permitevaluation of the conduct of a study andthe quality of the data produced.

established name. The official nameof a drug substance. [Food, Drug &Cosmetic Act]

ethics committee. See institutionalreview board, independent ethicscommittee.

European Agency for theEvaluation of Medicinal Products(EMEA). The regulatory agency for the 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 trial. Phase I or II trialduring which the actions of atherapeutic intervention are assessedand measured. NOTE: Procedures inexploratory trials may appropriately bealtered to expand the scope or methodof investigation. Compare toconfirmatory trial.

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

final report. A written description of a 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 enrolled andrandomized into a study. The subject willhave met the inclusion/exclusion criteriato participate in the trial and will havesigned an informed consent form.Synonym: first patient in.

first subject screened. First subjectwho signs the informed consent formand is screened for potential enrollmentand randomization into a study, but hasnot yet been determined to meet theinclusion/ exclusion criteria for the trial.

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

first-in-humans study. The firstPhase I 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 NDAapprovals.

frequentist methods. Statisticalmethods, such as significance tests and confidence intervals, which can beinterpreted in terms of the frequency of certain 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 formalized inaudit trails and differ from “locking” and “unlocking” only in the degree ofapproval required. See lock.

functional roles (in a study).See role.

gender. Subject self-identification re: Male/ Female. [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.A single variable, usually a scale ofordered categorical ratings, whichintegrates objective variables and theinvestigator’s overall impression aboutthe state or change in state of a subject.[ICH E9]

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

good clinical practice (GCP).A standard for the design, conduct,performance, monitoring, auditing,recording, analyses, and reporting ofclinical trials that provides assurance that the data and reported results arecredible and accurate, and that therights, integrity, and confidentiality of trial subjects are protected. NOTE: For Guidance on Good Clinical Practicesee COMP/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 wholeNOTE: 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 formulating a stopping rule derived from repeatedsignificance tests. [Center forAdvancement of Clinical Research]

harmonized standard. A EuropeanNorm (EN) that has been accepted by allMember States and has been publishedin the Official Journal of the EuropeanCommunities (OJEC).

Health Level 7 (HL7). An ANSI-accredited Standards DevelopingOrganization (SDO) operating in thehealthcare arena. NOTE: Level 7 refers to the highest level of the InternationalStandards Organization’s (ISO)communications model for Open

Systems Interconnection (OSI) theapplication level. The application leveladdresses definition of the data to be exchanged, the timing of theinterchange, and the communication ofcertain errors to the application. Level 7supports such functions as securitychecks, participant identification,availability checks, exchange mechanismnegotiations and, most importantly, dataexchange 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 administer healthcare in the ordinary course of business or practice of a profession, including ahealth care facility. [1. PR Group; 2. HL7]

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

human subject. Individual who is orbecomes a participant in research, eitheras a recipient of the test article or as acontrol. A subject may be either ahealthy 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 immediately toanother document. NOTE: In mostbrowsers 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 hypothesis test,which generates a P value. [CONSORTStatement]




impartial witness. A person, who is independent of the trial, who cannotbe unfairly influenced by people involvedwith the trial, who attends the informedconsent process if the subject or thesubject’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 in a 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 efficacy variablesand recommend to the sponsor whetherto continue, modify, or terminate thetrial. [ICH E9] See also data monitoringcommittee.

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 human subjectsinvolved in a trial and to provide publicassurance of that protection by, amongother things, reviewing andapproving/providing favorable opinionon the trial protocol, the suitability ofthe investigator(s), facilities, and themethods and material to be used inobtaining and documenting informedconsent of the trial subjects. NOTE: The legal status, composition, function,operations, and regulatory requirementspertaining to independent ethicscommittees may differ among countries,but should allow the independent ethicscommittee to act in agreement with GCPas described in the ICH guideline. [ICH]See also institutional review board.

indication. A health problem ordisease that is identified as likely to bebenefited by a therapy being studied in clinical trials. NOTE: Where such a

benefit 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 a trial. Informed consent is an ongoing,interactive process, rather than a one-time information session. NOTE: Under 21 CFR 50.20, no informedconsent form may include any“language through which the subject or the representative is made to waive or appear to waive any of the subject’slegal rights, or releases or appears torelease the investigator, the sponsor, the institution, or its agents from liabilityfor negligence.” [ICH] See also consentform.

inspection. The act by a regulatoryauthority(ies) of conducting an officialreview of documents, facilities, records,and any other resources that are deemedby the authority(ies) to be related to the clinical trial and that may be locatedat the site of the trial, at the sponsor’sand/or contract research organization’s(CRO’s) facilities, or at otherestablishments deemed appropriate bythe regulatory authority(ies) [ICH] Seealso audit.

institution (medical). Any public or private 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 human subjects involved in a trial by, amongother things, reviewing, approving, and providing continuing review of trialprotocol and of the methods andmaterial to be used in obtaining anddocumenting informed consent of thetrial subjects. Synonyms: independentreview board, independent ethicscommittee, committee for the protectionof human subjects.

intention-to-treat. The principle thatasserts that the effect of a treatmentpolicy can be best assessed by evaluatingthe basis of the intention to treat asubject (i.e., the planned treatmentregimen) rather than the actualtreatment given. NOTE: This has theconsequence that subjects allocated to a treatment group should be followed up, assessed, and analyzed as membersof that group irrespective of theircompliance with the planned course oftreatment. The principle is intended to prevent bias caused by loss ofparticipants that may reflect nonadherence 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 centre). A quantitativeinteraction refers to the case where themagnitude of the contrast differs at the different levels of the factor; for aqualitative interaction, the direction ofthe contrast differs for at least one levelof the factor.

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

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

interim clinical trial/study report.A report of intermediate results and theirevaluation based on planned analysesperformed during the course of a trial.[ICH]

internal consistency. Pertaining todata that do not include contradictions.

Internet service provider (ISP).A company that provides access to theInternet for individuals andorganizations.

Internet. A global system of computernetworks that provides the common TCP

IP infrastructure for e-mail, the WorldWide Web, and other online activities.

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 results whenused by different raters on differentoccasions. [ICH E9]

intervention. The drug, device,therapy or process under investigation in a clinical trial which has an effect on outcome of interest in a study: e.g.,quality of life, efficacy, safety,pharmacoeconomics. Synonym:therapeutic intervention. See also: testarticles; devices; drug product; medicinalproduct; combination product.

investigational product.A pharmaceutical 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, or when used for an unapprovedindication, or when used to gain furtherinformation about an approved use.NOTE: CDISC includes test articles in its definition of investigational products.[ICH]

investigational treatment.An intervention under investigation in a clinical trial.

Investigator. 1. A person responsiblefor the conduct of the clinical trial at atrial site. If a trial is conducted by a teamof individuals at a trial site, theinvestigator is the responsible leader ofthe team and may be called the principalinvestigator. 2. The individual “underwhose immediate direction the testarticle is administered or dispensed to, or used involving, a subject, or, in theevent of an investigation conducted by a team of individuals, is the responsibleleader of that team.” [1. ICH E6 1.35. 2. From 21CFR 50.3] See also sponsor-investigator.

investigator/institution.An expression meaning “the investigatorand/or institution, where required by theapplicable regulatory requirements.”[ICH E6 1.35]

investigator’s brochure.A compilation of the clinical andnonclinical data on the investigationalproduct(s) which is relevant to the studyof the investigational product(s) inhuman subjects.

item. A representation of a clinicalvariable, fact, concept or instruction in a manner suitable for communication,interpretation or processing by humansor by automated means. NOTE: Items arecollected together to form item groups.

item definition. 1. In a questionnaireor form to be completed in a clinicaltrial, the specification of a question andthe specification of the format andsemantics of the response. 2. Formalspecification of the properties of an itemor field of data in a clinical trial. [2. ODM]

item group definition.The specification 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]

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, patientpackage leaflet.

labeling (content of). All text, tablesand figures in labeling as described inregulations for a specific product (e.g.,21CFR 201.56 and 201.57 for humanprescription drugs, 201.66 for humanover-the-counter drugs). See alsostructured product label.

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

last subject out/complete(LSC/LPC or LSO/LPO). The lastpatient to complete a trial (all datacollected), a planned or achievedmilestone marked by a date and time.See also subject, patient, completion.

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

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

legally acceptable representative.An individual or juridical or other bodyauthorized under applicable law toconsent, on behalf of a prospectivesubject, to the subject’s participation inthe clinical trial. [ICH]

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

life-threatening adverseevent/experience. Any adverseevent/experience that, in the view of the investigator, places a subject atimmediate risk of death. [SQA]

longitudinal study. Investigation inwhich data are collected from a numberof subjects over a long period of time (awell-known example is the FraminghamStudy).

marketing support trials. Clinicalstudies that are designed to improve thesales of a product or to show potentialbuyers the rationale for preferring onetherapy over another.

markup. Computer-processableannotations within a multimedia docu-ment. NOTE: in the context of the HL7specification, markup syntax is accordingto the XML Specification. [HL7]

masking. See blinding.




matched-pair design. A type ofparallel trial design in which investigatorsidentify pairs of subjects who are“identical” with respect to relevantfactors, then randomize them so thatone receives Treatment A and the otherTreatment 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 data set;that is, just as many values are greaterthan the median and lower than themedian value. (With an even number of values, the conventional median ishalfway between the two middle values.)

medical monitor. A sponsorrepresentative who has medical authorityfor the evaluation of the safety aspectsof a clinical trial.

Medicines Control Agency (MCA).The United Kingdom regulatory authoritythat approves or rejects CTX/CTC and PLapplications.

mega-trials. Massive randomizedclinical trials that test the advantages oftherapeutic interventions by enrolling10,000 or more subjects. Synonym: largesample trials.

Memorandum of Understanding(MOU). An MOU between FDA and aregulatory agency in another countryallows mutual recognition of inspections.

message (HL7). The atomic unit ofdata transferred between systems. It iscomprised of a group of segments in adefined sequence. Each message has amessage type that defines its purposeNOTE: 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 character codecontained within each message identifiesits type. [HL7]

meta-analysis. A statistical process forpooling data from multiple clinical trialand summarizing results through formalstatistical means.

metabolism. The sum of the processesby which a substance is handled in theliving body. See also ADME.

metadata. Data that describe otherdata

migration. The act of moving a systemor software product (including data)from an old to new operationalenvironment in accordance with asoftware quality system [ISO/IEC/IEEE12207:1995 §5.5.5]

mode. The most frequently occurringvalue in a data set.

modem. From modulator/demodulator;a device that converts digital data intoanalog data that can be transmitted viatelephone or cable lines used forcommunications.

monitor. Person employed by thesponsor or CRO who is responsible for determining that a trial is beingconducted in accordance with theprotocol. NOTE: A monitor’s duties mayinclude, but are not limited to, helping

to plan and initiate a trial, assessing the conduct of trials, and assisting indata analysis, interpretation, andextrapolation. Monitors work with theclinical research coordinator to check alldata and documentation from the trial.See also clinical research associate.

monitoring committee.See independent data-monitoringcommittee.

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 regulatory requirementsand good clinical practice guidelines.[SQA]

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

Ethics CommitteesBodies convened to protect human clinical research subjects workunder a variety of other names. For convenience and consistency,Applied Clinical Trials generally uses the terms institutional reviewboard and ethics committee. Other names and abbreviations forsuch bodies are shown below.

CCI committee on clinical investigations

CCPPRB Comité Consultative pour la Protection des Personnes dansles Recherches 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)

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

multicenter study. See multicentertrial.

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

New Drug Application (NDA).An application 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 of episodes to establish the treatment’seffect in that person, often with theorder of experimental and controltreatments randomized.

nonclinical study. Biomedical studiesnot performed on human subjects.[ICH]

not approvable letter. An officialcommunication from FDA to inform an NDA sponsor that the importantdeficiencies described therein precludeapproval unless corrected.

Notified Body (NB). A privateinstitution charged by the CompetentAuthority with verifying compliance ofmedical devices (not drugs) with theapplicable Essential Requirements statedin the Medical Device Directive. Thisprocess, called Conformity Assessment,has EU-wide validity once completed bythe NB.

null hypothesis. A null hypothesis(for example,“subjects will experience no change in blood pressure as a resultof administration of the test product”) isused to rule out every possibility exceptthe one the researcher is trying to prove, an assumption about a researchpopulation that may or may not berejected as a result of testing. Usedbecause most statistical methods are less

able to prove something true than toprovide strong evidence that it is false.The assertion that no true association or difference in the study outcome orcomparison of interest betweencomparison groups exists in the largerpopulation from which the studysamples are obtained. See also researchhypothesis.

Nuremberg Code. Code of ethics forconducting human medical research setforth in 1947.

objective. The reason for performing a trial in terms of the scientific questionsto be answered by the data collectedduring the trial. NOTE: The primaryobjective is the main question to beanswered and drives any statisticalplanning for the trial (e.g., calculation of the 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 judgment or assessment. See also outcome, patientreported outcome; objective measuresare observations (SDTM), and could beendpoints. Patient reported outcomesare subjective measurements.

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 during a 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 made byan observer (investigator, nurse, clinician,family member, etc.). Compare to PRO.

NOTE: Distinguished from self-assessment. The observer relies on his orher judgment to assess the subject. Aninterviewer simply capturing subject selfassessments is not making an observerassessment. Compare to proxyrespondent.

open study. A trial in which subjectsand investigators know which producteach subject is receiving; opposite of ablinded or double-blind study. Seeblinding.

open-label study. See open study.

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

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.). [Consolidated Glossary, SDTM fordescriptions of the Define document]NOTE: See SDTM “Model concepts andterms.” [1.CONSORT Statement. 2. From SDTM for descriptions of theDefine document]

original data. Those values thatrepresent the first recording of studydata [CSUCT Definitions]

outcome (of adverse event).Refers to the resolution of an adverseevent. NOTE: often denoted using a picklist from a controlled terminology suchas: Recovered/resolved, recovering/resolving, not recovered/not resolved,recovered /resolved with sequelae, fatal,or unknown. [SDTM Events class ofobservation]

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] See alsovariable; can be a result of analysis;outcome is more general than endpointin that it does not necessarily relate to aplanned objective of the study variableor endpoint.

outcomes research. Researchconcerned with benefits, financial costs,healthcare system usage, risks, andquality of life as well as their relation totherapeutic interventions. NOTE: Usuallydistinguished from research conductedsolely to determine efficacy and safety.[Guyatt et. al, 1993]. See alsopharmacoeconomics, quality of life.

outliers. Data anomalies which areextreme from a univariate or multivariateperspective.

packaging. The material, both physicaland informational, that surrounds anactive therapeutic agent once it is fullyprepared for release to pharmacies andto patients

pairing. A method by which subjectsare selected so that two subjects withsimilar characteristics (for example,weight, smoking habits) are assigned toa set, but one receives Treatment A andthe other receives Treatment B. See alsomatched-pair design.

parallel trial. Subjects are randomizedto one of two differing treatment groups(usually investigational product andplacebo) and usually receive the assignedtreatment during the entire trial.Synonyms: parallel group trial, paralleldesign trial.

parameter. A variable in a model, or a variable that wholly or partiallycharacterizes a probability distribution(mathematics and statistics). NOTE: Inclinical trials the term is often usedsynonymously with “variable” for factualinformation (age, date of recovery),measurements, and clinical assessments.

It is most appropriately linked tostatistical conventions and as a numericcharacteristic of a population.Parameters are rarely known and are usually estimated by statisticalcomputation from samples. Thus theterm is narrower than variable [ParexelBarnett; ADaM; HyperStat Online] See also variable, outcome.

participant. A person or entity with a role in healthcare or a clinical study.NOTE: Participants in a clinical trial may include subjects, study personnel,patients, and others. A subjectparticipates as part of the group ofpeople who are administered thetherapeutic intervention or control.Patients in a clinical trial are subjectswho are also under medical care for theindication under study. See also subject,patient.

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. Oftenused interchangeably as a synonym forsubject but healthy volunteers are not,strictly speaking, patients.

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

patient reported outcome (PRO).Report coming directly from patients or subjects through interviews or self-completed questionnaires or other datacapture tools such as diaries about theirlife, health condition(s) and treatment.NOTE: PROs are used to assess outcomesinvolving the patients’/subjects’perceptions, symptoms, satisfaction with treatment, adherence to prescribedregimens. Historically observations onpatients have been made by observers,which has produced scientific recordslacking high quality data on subjectivesymptom intensity, perceived benefit,etc. PROs include outcomes recorded by interviewers transcribing the viewsexpressed by the patient, but the termdoes not apply to outcomes recorded by observers who rely on their own

judgment. [DIA ePRO Workgroup,modified by Gordon Guyatt and HolgerSchuneman; Patrick, 2003. AfterAcquardo C., Berzon C., et. al., 2001.]Synonym: subject reported outcomes(SRO). See also outcome; subject,patient.

per protocol analysis set. The set ofdata generated by the subset of subjectswho complied with the protocolsufficiently to ensure that these datawould be likely to exhibit the effects oftreatment according to the underlyingscientific model. [ICH E9]

period effect. An apparent or realeffect of passing through a period oftime designated during the course of atrial in which subjects are observed andno treatment is administered.

permanent data. Data that becomeor are intended to become part of anelectronic record in relation to aregulatory submission. Any changesmade to such permanent data arerecorded via an audit trail so that priorvalues are not obscured.

pharmacodynamics. Branch ofpharmacology that studies reactionsbetween drugs and living structures,including the processes of bodilyresponses to pharmacological,biochemical, physiological, andtherapeutic effects.

pharmacoeconomics. Branch ofeconomics that applies cost-benefit,cost-utility, cost-minimization, and cost-effectiveness analyses to compare theeconomics of different pharmaceuticalproducts or to compare drug therapy toother treatments.

pharmacogenetic test. An assayintended to study interindividualvariations in DNA sequence related todrug absorption and disposition or drugaction. Compare to pharmacogenomictest.

pharmacogenetics. Study of the waydrugs interact with genetic makeup orthe genetic response to a drug.

pharmacogenomic test. An assayintended to study interindividual

variations in wholegenome or candidategene maps, biomarkers, and alterationsin gene expression or inactivation thatmay be correlated with pharmacologicalfunction and therapeutic response.Compare to pharmacogenetic test.

pharmacogenomics. Science thatexamines inherited variations in genesthat dictate drug response and exploresthe ways such variations can be used topredict whether a person will have agood response to a drug, a bad responseto a drug, or no response at all.

pharmacokinetics. Study of theprocesses of bodily absorption,distribution, metabolism, and excretion(ADME) of compounds and medicines.

pharmacology. Science that dealswith the characteristics, effects, and usesof drugs and their interactions withliving organisms.

pharmacovigilance. Term used foradverse event monitoring and reportingin some countries.

phase. Clinical trials are generallycategorized into four (sometimes five)phases described below. A therapeuticintervention may be evaluated in two ormore phases simultaneously in differenttrials, and some trials may overlap twodifferent phases.

Phase I. The initial introduction of aninvestigational new drug into humans.Phase I studies are typically closelymonitored and may be conducted inpatients or normal volunteer subjects.NOTE: These studies are designed todetermine the metabolism andpharmacologic actions of the drug inhumans, the side effects associated withincreasing doses, and, if possible, to gainearly evidence on effectiveness. DuringPhase I, sufficient information about the drug’s pharmacokinetics andpharmacological effects should beobtained to permit the design of well-controlled, scientifically valid, Phase IIstudies. The total number of subjectsand patients included in Phase I studiesvaries with the drug, but is generally inthe range of 20 to 80. Phase I studiesalso include studies of drug metabolism,structure-activity relationships, andmechanism of action in humans, as well

as studies in which investigational drugsare used as research tools to explorebiological phenomena or diseaseprocesses. [FDA]

Phase II. Controlled clinical studiesconducted to evaluate the effectivenessof the drug for a particular indication orindications in patients with the diseaseor condition under study and todetermine the common short-term sideeffects and risks associated with thedrug. NOTE: Phase II studies are typicallywell controlled, closely monitored, andconducted in a relatively small number ofpatients, usually involving no more thanseveral hundred subjects. [FDA]

Phase III. Studies are expandedcontrolled and uncontrolled trials. Theyare performed after preliminary evidencesuggesting effectiveness of the drug hasbeen obtained, and are intended togather the additional information abouteffectiveness and safety that is neededto confirm efficacy and evaluate theoverall benefit–risk relationship of thedrug and to provide an adequate basisfor physician labeling. NOTE: Phase IIIstudies usually include from severalhundred to several thousand subjects.[FDA]

Phase IIIb. A subcategory of Phase IIItrials done near the time of approval toelicit additional findings. [FDA]

Phase IV. Postmarketing (Phase IV)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, but would not be limited to, studyingdifferent doses or schedules ofadministration than were used in Phase II studies, use of the drug in otherpatient populations or other stages ofthe disease, or use of the drug over alonger period of time. [FDA]

Phase V. Postmarketing surveillance is sometimes referred to as Phase V. See also outcomes research.

placebo. A pharmaceutical preparationthat contains no active agent. In blindedstudies, it is generally made to look justlike the active 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 of marketeddrugs. See also Phase IV studies, Phase Vstudies.

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

preclinical studies. Animal studiesthat support Phase I safety and tolerancestudies and must comply with goodlaboratory practice (GLP). Data about adrug’s activities and effects in animalshelp establish boundaries for safe use ofthe drug in subsequent human testing(clinical studies or trials).

primary objective. The primaryobjective(s) is the main question to beanswered and drives any statisticalplanning for the trial (e.g., calculation of the sample size to provide theappropriate power for statistical testing).[ICH E6 6.3] See also objective.

primary variable. An outcomevariable specified in the protocol to be of 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. [PR Group;CONSORT Statement] Synonyms:primary endpoint; outcome. See alsoprimary objective.

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

proprietary name. A commercialname granted by a naming authority foruse in marketing a drug/device product.[SPL] Synonym: trade name; brandname.




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 could be provided in other protocol referenceddocuments. Throughout the ICH GCPGuideline the term protocol refers toprotocol and protocol amendments. [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 has beenobtained, signifying that all reviewerchanges to the protocol have beenincorporated. NOTE: Approval by thesponsor usually initiates secondaryapprovals by IRBs, regulatory authorities,and sites. Protocol amendments usuallyalso require a cycle of approval bysponsor and study staff prior to takingeffect.

Protocol Identifying Number. Anyof one or more unique codes that refersto a specific protocol. NOTE: There maybe multiple numbers (Nat’l number, coopgroup number) [PR Group; EUDRACT]

protocol referenced documents.Protocol referenced documents thatoptionally supplement the ICH GCPrecommended sections of a protocolgiving background information andrationale for the trial. [From ICH E6 1.44]See also protocol.

proxy (as an origin of outcomemeasures). A proposed standardizedqualifier variable to describe the origin of observations of the Findings classresulting from outcomes measures. Proxy describes outcome data furnishedby someone other than the patient anddistinguishes the origin of the outcomefrom a self-report (PRO) directly from

the patient. NOTE: The term proxy helpsqualify outcomes measures that recordfeelings and symptoms reported by thepatient but not recorded directly. Proxyoutcomes seem to be part of theoutcomes literature with a consistentmeaning. [CDISC (extension of SDTMbased on Table 2 Patrick, DL, 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 DL,2003; DIA ePRO Workgroup] Compareto observer assessment.

psychometric reliability.See reliability, psychometric.

psychometric validation.The specialized 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 and considerationof the semantic content of items in it to be measuring what it is supposed tomeasure. Construct validity means that a scale based on one or more itemsmeasures an unobservable psychologicalconstruct (e.g., “distress”) that it isproposed to measure. Construct validityis usually tested by measuring thecorrelation in assessments obtained fromseveral scales purported to measure thesame construct. [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 statisticalsignificance. 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 relation

to 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 reported in compliance with good clinical practice(GCP) and the applicable regulatoryrequirement(s). [ICH]

quality control (QC). The operationaltechniques and activities undertakenwithin the quality assurance system toverify that the requirements for qualityof the trial related activities have beenfulfilled. [ICH]

quality of life. A broad rangingconcept that incorporates an individual’sphysical health, psychological state, levelof independence, social relationships,personal beliefs and their relationships to salient features of the environment.NOTE: Quality of Life is one way tomeasure the benefits or negative impactsof an ‘improvement’ measured in termsof a physiological or psychologicalsymptom. QOL research seeks toquantify what an intervention means to a patient’s sense that their life haschanged. [WHO Group, 1994]

quantitative variable. One that canbe measured and reported numerically to reflect a quantity or amount, ideallyon 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 aninvestigator to resolve an error orinconsistency discovered during datareview.

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.

random allocation. Assignment ofsubjects to treatment (or control) groupsin an unpredictable way. NOTE: in ablinded study, assignment sequences areconcealed, but available for disclosure in the event a subject has an adverseexperience.

random number table. Table ofnumbers with no apparent pattern usedin the selection of random samples forclinical trials.

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

randomization. The process ofassigning trial subjects to treatment orcontrol groups using an element ofchance to determine the assignments in order to reduce bias. NOTE: Unequalrandomization is used to allocatesubjects into groups at a differential rate; for example, three subjects may beassigned to a treatment group for everyone assigned to the control group. [ICH E6 1.48] See also balanced study.

raw data. Data as originally collected.Distinct from derived. Raw data includesrecords 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 Research and Information Management, which isa Technical Committee within HL7 (anacronym pronounced “arcrim”).

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

recruitment (subjects). Process used by investigators to find and enroll

appropriate subjects (those selected onthe basis of the protocol’s inclusion andexclusion criteria) into a clinical study.

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

recruitment target. Number ofsubjects that must be recruited ascandidates for enrollment into a study to 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]

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.The degree to which a psychometric‘instrument’ is free from random erroreither by testing the homogeneity ofcontent on multi-item tests with internalconsistency evaluation or testing thedegree to which the instrument yieldsstable scores over time. NOTE: Reliability pertains to questionsconcerning whether an instrument isaccurate, repeatable, sensitive. Reliabilityis distinguished from validation, whichanswers whether the instrument (e.g.,questionnaire) actually measure theselected “construct” (latent variable). For example a balance (scale) is easilyunderstood as a possibly valid instrumentto measure body weight. Its reliabilitywould be assessed by measuring thesensitivity, repeatability and accuracy ofthe balance. The validity of using thebalance for a particular purpose couldthen be established by comparing themeasured reliability to the reliabilityrequired for that purpose. [After Patrick,2003] Compare to psychometricvalidation; see also validation.

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

representative. See legally acceptablerepresentative.

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.

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

retrospective. Capture of clinical trialdata is retrospective when it is recalledfrom memory rather than capturedcontemporaneously in real-time. NOTE:Retrospective capture is important inPROs because of “recall bias” and othererrors documented in psychologicalresearch comparing contemporaneousself reported assessments and those thatrely on recall from memory.

risk. In clinical trials, the probability ofharm or discomfort for subjects. NOTE:Acceptable risk differs depending on thecondition for which a product is beingtested. A product for sore throat, forexample, will be expected to have a lowincidence 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 of a clinical study . Examples include DataManager, Investigator. 2. Classifier forvariables that describe “observations” inthe SDTM. Role is a metadata attributethat determines the type of informationconveyed by an observation-describingvariable and standardizes rules for usingthe describing variable. [1. HL7. 2.SDTM] See also functional role.

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, clinical adverseevents (diseases, signs and symptoms),and other special safety tests (e.g.,ECGs, ophthalmology). The tolerability




of the medical product represents thedegree to which overt adverse effectscan be tolerated by the subject. [ICH E9]

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

sample size adjustment. An interimcheck conducted on blinded data tovalidate the sample size calculations orre-evaluate the sample size.

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

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

screen/screening (of substances).Screening is the process by whichsubstances are evaluated in a battery oftests or assays (screens) designed todetect a specific biological property or activity. It can be conducted on arandom basis in which substances aretested without any PREselection criteriaor on a targeted basis in whichinformation on a substance with knownactivity and structure is used as a basisfor selecting other similar substances onwhich to run the battery of tests. [SQA]

screening (of sites). Determining thesuitability of an investigative site andpersonnel to participate in a clinical trial.

screening of subjects. A process ofactive consideration of potential subjectsfor enrollment in a trial. See also screenfailure.

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

script. A program or a sequence ofinstructions that are interpreted orcarried out by another program.

secondary objective. See objective.

secondary variable. The primaryoutcome is the outcome of greatestimportance. Data on secondaryoutcomes are used to evaluate additionaleffects of the intervention. [CONSORTStatement] See also outcome, 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 ismale and a date of last pregnancy isprovided. See also discrepancy.

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 untoward medicaloccurrence that at any dose: results in death, is life threatening, requiresinpatient hospitalization or prolongationof existing hospitalization, results inpersistent or significant disability/incapacity, or is a congenital anomaly/birth defect. [ICH] See also adverseexperience.

serious adverse experience. Anyexperience that suggests a significanthazard, contra-indication, side effect orprecaution. See also serious adverseevent.

server. A computer program orcomputer running such a program thatprovides services to other computerprograms in the same or othercomputers. See also Web server.

sex. Maleness or Femaleness, as definedby chromosomal makeup. See alsogender.

side effects. Any actions or effects of a drug or treatment other than theintended effect. Negative or adverseeffects may include headache, nausea,

hair loss, skin irritation, or other physicalproblems. Experimental drugs must beevaluated for both immediate and long-term side effects. See also adversereaction.

single-blind study. A study in whichone party, either the investigator or the subject, does not know whichmedication or placebo is administered tothe subject; also called single-maskedstudy. See also blind study, double-blindstudy, triple-blind study.

single-masked study. See single-blind study.

software validation. Confirmationby examination and provision ofobjective evidence that softwarespecifications conform to user needs andintended uses, and that the particularrequirements implemented throughsoftware can be consistently fulfilled.NOTE: Validating software thus shouldinclude evaluation of the suitability ofthe specifications to “ensure user needsand intended uses can be fulfilled on aconsistent basis” (21 CFR 820.20).General Principles of SoftwareValidation; Final Guidance for Industryand FDA Staff, Jan 11, 2002.ISO/IEC/IEEE 12207:1995 §3.35; 21 CFR820.20; 21CFR11.10(a); ISO 9000-3;Huber, L. (1999) See also validation,verification. Verification also concernsconfirmation that specified requirementshave been met, but typically refers to thetracing of requirements and evidence ofconformance in the individual phases ormodules rather than suitability of thecomplete product. Validation is, “theevaluation of software at the end of thesoftware development process to ensurecompliance with the user requirements”(ANSI/ASQC A3-1978) and should not bethought of as an “end-to-end”.verification.

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

source data verification.The process of ensuring that data thathave been derived from source dataaccurately represent the source data.

source data. All information in originalrecords and certified copies of originalrecords of clinical findings, observations,or other activities in a clinical trialnecessary for the reconstruction andevaluation of the trial. Source data arecontained in source documents (originalrecords or certified copies). [ICH E6;CSUCT]

source document verification.The process by which the informationreported by an investigator is comparedwith the original records to ensure that itis complete, accurate and valid. [Schuyland Engel, 1999; Khosla et. al. Indian J.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 evaluation checklists,pharmacy dispensing records, recordeddata from automated instruments,copies or transcriptions certified afterverification as being accurate copies,microfiches, photographic negatives,microfilm or magnetic media, x-rays,subject files, and records kept at thepharmacy, at the laboratories and atmedico-technical departments involvedin the clinical trial). [ICH; CSUCT]

special populations. Subsets ofstudy populations of particular interestincluded 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,management, and/or financing of aclinical trial. 2. A corporation or agencywhose employees conduct theinvestigation is considered a sponsor andthe employees are consideredinvestigators. [1. ICH. 2. 21 CFR 50.3]

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 any

person 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 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 performance ofa specific function. [ICH]

standard treatment. A treatmentcurrently in wide use and approved bythe FDA or other health authority,considered to be effective in thetreatment of a specific disease orcondition .

statistical analysis plan. Adocument that contains a more technicaland detailed elaboration of the principalfeatures of the analysis described in theprotocol, and includes detailedprocedures for executing the statisticalanalysis of the primary and secondaryvariables 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 may say“significant at the 5% level”. Thisimplies that when the null hypothesis istrue there is only a 1 in 20 chance ofrejecting it.

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 avoid puttingparticipants at risk unnecessarily or

because the intervention effect is sogreat that further data collection isunnecessary.

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

study. See clinical trial. NOTE:Occasionally refers to a project of severalrelated clinical trials.

study coordinator. See clinicalresearch coordinator.

study description. Representation ofkey 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 actual timingof events, choice of control group,method of allocating treatments,blinding methods; assigns a subject topass through one or more epochs in the course of a trial. Specific designelements, e.g., crossover, parallel; dose-escalation [Modified from Pocock,Clinical Trials: A Practical Approach] See Trial Design Model. See also, arm,epoch, and visit.

study design rationale. Reason forchoosing the particular study design.

study design schematic.Diagrammatic representation of keyactivities within the study.

study population. Defined byprotocol inclusion/exclusion criteria.

study protocol. See protocol.

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

sub-investigator. Any member of theclinical 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] See alsoinvestigator.




subject data event. A subject visit orother encounter where subject data arecollected, generated or reviewed. [SDTM]

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

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

subject-reported outcome (SRO).An outcome reported directly by a subjectin a clinical trial. [Patrick, 2003] See alsopatient reported outcome (PRO).

superiority trial. A trial with theprimary objective of showing that theresponse to the investigational product issuperior to a comparative agent (activeor placebo control). [ICH E9]

supplier. An organization that entersinto a contract with the acquirer for thesupply of a system, software product, orsoftware service under the terms of acontract. [ISO/IEC/IEEE 12207:1995§3.30]

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

surrogate marker. A measurement of a drug’s biological activity thatsubstitutes for a clinical endpoint such as 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]

syntactic. The order, format, contentof clinical trial data and/or documents as distinct 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 specific functionsor objectives. [ANSI]

target enrollment. The number ofsubjects in a class or group (includingthe total for the entire trial) intended to be enrolled in a trial to reach theplanned sample size. Target enrollmentsare set so that statistical and scientificobjectives of a trial will have a likelihoodof being met as determined byagreement, algorithm or other specifiedprocess.

technology provider. A person,company or other entity who develops,produces and sells software applicationsand/or hardware for use in conductingclinical trials and/or in analyzing clinicaltrial data and or submitting clinical trialinformation for regulatory approval.Synonym: vendor.

term. Single glossary entry composedof more than one word.

termination (of subject).Now considered nonstandard. See discontinuation.

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

terminology. A standardized, finiteset of terms (e.g., picklists, ICD9 codes)that denote patient findings,circumstances, events, and interventions.NOTE: The terms should have sufficientdetail to support clinical research,healthcare decisions, outcomes researchand quality improvement.Standardization should be sufficient thatthe same set of terms may be extendedto administrative, regulatory, and fiscalapplications. [JJ Cimino] Compare toglossary, which is a list of words andtheir definitions pertaining to usage in aparticular field or context.

therapeutic intervention.See intervention.

transcription. Process of transformingdictated or otherwise documentedinformation from one storage mediumto another. NOTE: often refers explicitly

to data that is manually transcribed fromsource docs or measuring devices toCRFs or to eCRFs.

treatment effect. An effectattributed to a treatment in a clinicaltrial. In most clinical trials the treatmenteffect of interest is a comparison (orcontrast) of two or more treatments.[ICH E9]

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

trial coordinator. See clinical researchcoordinator.

Trial Design Model. Defines astandard structure for representing the planned sequence of events and the treatment 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 of qualityof study conduct and statistical interimanalysis. [ICH E9]

trial site. The location(s) where trial-related activities are actually conducted.[ICH]

trial statistician. A statistician whohas a combination of education/trainingand experience sufficient to implementthe principles in the ICH E9 guidanceand who is responsible for the statisticalaspects of the trial. [ICH E9]

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

triple-blind study. A study in which knowledge 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 to comparethe means of two groups of test data.

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

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

type 3 (or type III) error.Some statisticians use this designationfor an error made when calling the lesseffective treatment the more effectiveone

type of comparison. How treatmentarms will be compared, e.g., Safety,Efficacy, PK/PD. [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.See randomization.

unexpected adverse drugreaction. An adverse reaction, whosenature, severity, specificity, or outcome isnot 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.actmagazine.com, for example.

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

validation. 1. Process of establishingsuitability to purpose. 2. For softwareand systems, establishing documentedevidence which provides a high degreeof assurance that a specific process willconsistently produce a product meetingits predetermined specifications andquality attributes. NOTE: Validation isaccomplished by planning how tomeasure and/or evaluate suitability topurpose; then executing the plan anddocumenting the results. [FDA Glossaryof Computerized System and SoftwareDevelopment Terminology]

validation of data. 1. A process used to determine if data are inaccurate,incomplete, or unreasonable. Theprocess may include format checks,completeness checks, check key tests,reasonableness checks and limit checks.2. The checking of data for correctnessor compliance with applicable standards,rules, and conventions. NOTE: Meaning1. is not “data verification” but meaning2. could be [1. ISO; 2. FDA Glossary ofComputerized System and SoftwareDevelopment Terminology] See sourcedocument verification.

validity, psychometric.See psychometric validation.

validity. See validation.

variable. 1. Any quantity that varies;any attribute, phenomenon or event that can 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 a formof metadata that goes with the variable,there is a variable definition thatdescribes what is varying, and there is avalue for the variable. In the context of aprotocol, variables pertain to the study.2. In SDTM a “study variable” would bean observation Variable is an envelopingterm that includes specific subtypes usedin clinical research. “Study variable” is a term 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)or a result of statistical analysis. An

“endpoint” is a variable that pertains to the trial objectives. Not all endpointsare themselves assessments since certainendpoints might apply to populations oremerge from analysis of results. That is,endpoints might be facts aboutassessments (e.g., prolongation ofsurvival). When a “variable” is capturedor measured, there is no necessary sensethat any evaluation or judgment is

involved. However, when a variable is to be measured 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 synonomously with variableby engineers.

variance. A measure of the variabilityin a sample or population. It is calculatedas the mean squared deviation (MSD) ofthe individual values from their commonmean. In calculating the MSD, the divisorn is commonly used for a populationvariance and the divisor n-1 for a samplevariance.

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 cycle meetall of the specified requirements for thatphase. NOTE: 2. Software verificationlooks for consistency, completeness,and correctness of the software and its

supporting documentation, as it is beingdeveloped, and provides support for asubsequent conclusion that software isvalidated [FDA General Principles ofSoftware Validation; ANSI/ASQC A3-1978; ISO/IEC Guide 25] Verification isused in the sense of matching elementsof a report 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 unplanned trialinterventions, procedures and assessmentsthat may be performed on a subject. A visit has a start and an end, eachdescribed with a rule. NOTE: For manydomains each visit results in one recordper visit. [SDTM, Trial Design Model]




volunteer. A person volunteering toparticipate as a subject in a clinical trial,often a healthy person agreeing to par-ticipate in a Phase I trial. See also Phase 1.

vulnerable subjects. Individualswhose willingness to volunteer in aclinical trial may be unduly influenced bythe expectation, whether justified or not,of benefits associated with participation,or of a retaliatory response from senior

members of a hierarchy in case of refusalto participate. Examples are members of a group with a hierarchical structure,such as medical, pharmacy, dental andnursing students, subordinate hospitaland laboratory personnel, employees ofthe pharmaceutical industry, members ofthe armed forces, and persons kept indetention. Other vulnerable subjectsinclude patients with incurable diseases,persons in nursing homes, unemployed

or impoverished 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 activities

Reference Citationsn 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 Federal Register 13430 (March 20, 1997).Available at http://www.fda.gov (Code of Fed-eral 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 Drug Development and Communication: An Ad Hoc Task force Report of the Patient-Reported Outcomes (PRO) Harmonization Group Meeting at the Food and Drug 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 Statement for Reporting Randomized Trials: Explanation and Elaboration,” Ann Intern Med.,134, 663–694 (2001). Available at: http://www.consort-statement.org/

n American Medical Association Manual of Style, a guide for authors and editors. 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 Center for the Advancement of Clinical Research – Clinical Research Dictionary. Available at: http://www.med.umich.edu/cacr/dictionary/A-B/htm

n Document type definition from: http://www.XMLfiles.com

n Federal Information Processing Standards (FIPS) Publication 46-2. 1993 December 30. Available at: http://www.itl.nist.gov/fipspubs/fip46-2.htm

n 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.pdfor www.fda.gov/cber/guidelines.htm

n W. Ed Hammond, Glossary for Healthcare Standards, 1995. Available at http://dmi-www.mc.duke.edu/dukemi/acronyms.htm

n Glossary of Computerized System and Software Development Terminology, Division of Field Investigations, Office of Regional Operations, Office of RegulatoryAffairs, 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 definitions, 1999. http://www.fda.gov/ora/compliance_ref/bimo/ffinalcct.htm NewDraft available at: http://www.fda.gov/cder/guidance/6032dft.htm

n G.H. Guyatt, D.H. Feeney, D.L. Patrick, “Measuring Health-Related Quality of Life,” Ann Internal Medicine, 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, Verification 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/cache/compo/276-254-1.html

n IEEE Standard Computer Dictionary; a compilation of IEEE standard computer 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. International Organization for Standardization, 1997.

n ISO/IEC/IEEE 12207:1995 §3.35; from ISO/IEC 12207:1995, Information technology – Software life cycle processes, Joint Technical Committee ISO/IEC JTC 1, Sub-committee SC 7, International Organization for Standardization and International 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 D.L. Patrick, “Patient-Reported Outcomes (PROs): An Organizing Tool for Concepts, Measures, and Applications,” MAPI Quality of Life News Letter, 31, 1–5(2003).

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

n M.L. Schuyl and T. Engel, “A Review of the Source Document Verification Process 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 Quality of Life Assessment Instrument (WHOQOL),” in J. Orley and W. Kuyken (Eds.), Qual-ity of Life Assessment: International Perspectives (Berlin, Heidelberg: Springer-Verlag, p. 41, 1994).

to be in violation of the Federal FD&CAct, or other acts, and that failure of the responsible party to take appropriateand prompt action to correct andprevent any future repeat of theviolation may result in administrativeand/or regulatory enforcement actionwithout further notice. [FDA]

washout period. A period in a clinicalstudy during which subjects receive notreatment for the indication under studyand the effects of a previous treatmentare eliminated (or assumed to beeliminated).

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 program thatdelivers HTML pages or files. Sometimesthe computer on which a server programruns is also referred to as a 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 on a database associated with the site.

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

well-being (of the trial subjects).The physical and mental integrity of thesubjects participating in a clinical trial. [ICH]

withdrawal. The act of reducing thedegree of participation by a subject ina clinical trial. Subjects may withdraw

permission for Sponsor use of dataderived from study participation, privacywaivers, informed consent, or they maywithdraw from the active treatmentcomponent of a clinical trial butcontinue to be observed. Withdrawalfrom participation in a study is calleddiscontinuation. 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 are usingHTTP protocols. Also called the Web andwww.
