CLINICALRESEARCHPROTOCOLCHECKLIST
[takenfrom ICHGCP E6: GuidanceforIndustry,E6GoodClinical Practice: ConsolidatedGuidance,Revision 1 (R1)June1996]
ICHGCPE6,Section6.CLINICALTRIALPROTOCOLANDPROTOCOL
A protocolis a document that describesthebackground,rationale,objectives, design,methodology,statistical considerations,andorganizationof a clinicalresearch study.TheICH Good ClinicalPracticeGuidelinesspecifysometopicsthat shouldgenerallybeincluded inaprotocol. Thetoolbelowincludes boththe ICHGCP recommendations forprotocolcontent.Additionalinformationmaybeprovided onseparateprotocolpage(s), oraddressed inaseparateagreement, andsomeoftheinformationlistedbelowmaybecontainedin otherprotocolreferenceddocuments,such asan Investigator’s Brochure.
6.1GeneralInformation
E6 / Description/Text / Included?Yes / No
6.1.1* / Protocoltitle,protocolidentifying number,anddate.Anyamendment(s)should alsobearthe amendment number(s)anddate(s).
6.1.2 * / Nameand addressof thesponsorand monitor(ifother than thesponsor).
6.1.3 / Nameandtitleoftheperson(s)authorizedto sign theprotocolandthe protocolamendment(s)forthesponsor.
6.1.4 / Name,title,address,andtelephonenumber(s)of the sponsor'smedicalexpert(ordentistwhen appropriate)forthetrial.
6.1.5* / Nameandtitleoftheinvestigator(s)whois(are)responsibleforconductingthetrial, andthe addressandtelephonenumber(s)ofthetrialsite(s).
*Listanycollaborating siteswhere the studywill beperformed.
6.1.6 / Name,title,address,andtelephonenumber(s)of thequalified physician (ordentist, ifapplicable)whois responsible forall trial-siterelatedmedical(ordental) decisions (ifotherthaninvestigator).
6.1.7 / Name(s)and address(es)oftheclinicallaboratory(ies)and othermedicaland/ortechnicaldepartment(s)and/orinstitutionsinvolved inthetrial.
6.2BackgroundInformation
E6 / Description/Text / Included?Yes / No
6.2.1* / Nameand description oftheinvestigationalproduct(s).
6.2.2* / A summaryoffindingsfromnonclinical studiesthatpotentiallyhaveclinical significanceand fromclinicaltrialsthatare relevanttothetrial.
6.2.3* / Summaryof theknownand potentialrisksandbenefits,if any,tohuman subjects.
6.2.4* / Descriptionof andjustification fortherouteof administration,dosage,dosageregimen,and treatmentperiod(s).
6.2.5 / A statement that thetrialwill beconductedin compliancewith the protocol,GCP, and theapplicableregulatoryrequirement(s).
6.2.6* / Descriptionof thepopulation tobestudied.
6.2.7* / Referencesto literatureand datathatare relevantto the trial,andthatprovidebackground forthetrial.
6.3TrialObjectivesandPurpose
E6 / Description/Text / Included?Yes / No
6.3* / A detaileddescription oftheobjectivesand thepurposeofthetrial.
6.4TrialDesign
Thescientificintegrity ofthe trialandthe credibilityofthedatafrom the trialdependsubstantiallyonthe trial design. Adescriptionofthe trialdesignshouldinclude:
E6 / Description/Text / Included?Yes / No
6.4.1* / A specific statementof the primaryendpointsandthesecondaryendpoints,ifany, tobemeasuredduring thetrial.
6.4.2 / A description ofthetype/design oftrial tobeconducted(e.g.,double-blind,placebo-controlled, paralleldesign)and a schematicdiagramoftrial design,procedures,andstages.
- Definitionofwhen the subject is considered‘enrolled’(on study).
*Identify any substudies.
*Include adetaileddescriptionofnumberofvisits,procedures ateach visit,visit windows,andlengthofstudy visitsfor subjects.
6.4.3 / A description ofthemeasurestaken to minimize/avoid bias,including (forexample):
(a) Randomization,(b) Blinding
6.4.4* / Drugs,supplements,orbiologics: A descriptionofthe trialtreatment(s)andthedosageand dosageregimen oftheinvestigationalproduct(s).Alsoinclude adescriptionofthedosageform,packaging,andlabeling ofthe investigationalproduct(s).
Devices: A description ofthetrialtreatment(s)and thedeviceimplantation/application,removal.Also include a description ofthedevicespecifications,packaging,and labeling ofthe investigationalproduct(s).
6.4.5* / Theexpecteddurationofsubjectparticipation,and adescriptionofthe sequenceandduration ofall trialperiods,including follow-up, if any.
6.4.6* / A description ofthe"stopping rules"or"discontinuation criteria" forindividualsubjects,parts oftrial,andentiretrial.
6.4.7* / Accountabilityproceduresfortheinvestigationalproduct(s),including theplacebo(s)/shamproceduresand comparator(s), if any.
6.4.8 / Maintenanceoftrialtreatmentrandomization codesand proceduresforbreakingcodes.
6.4.9 / Theidentificationof anydatatoberecordeddirectly on theCRFs(i.e., nopriorwrittenorelectronicrecord ofdata),and tobeconsideredto besourcedata.
6.4.10 / If yourstudyisinvestigator-initiated andmulti-site,refertoSection7 foradditionalguidance.
6.5SelectionandWithdrawalofSubjects
E6 / Description/Text / Included?Yes / No
*Subject identificationandrecruitmentmethods.
6.5.1* / Subjectinclusioncriteria.
6.5.2* / Subjectexclusioncriteria.
Describehowthe eligibilitycriteriawillbedetermined
- Informationreportedbythesubject
- Medicalrecordreview
- Resultsofscreeningassessments(e.g.questionnaires,diaries,etc.)
6.5.3 / Subjectwithdrawal criteria(i.e.,terminating investigationalproducttreatment/trialtreatment)and proceduresspecifying:
(a)Whenandhowto withdrawsubjectsfromthetrial/investigationalproducttreatment.
- Whatifasubjectdevelopsanexclusionarycondition?
- Whatifasubjectbeginstakinganexclusionarymedication?
(c)Whetherandhowsubjectsaretobereplaced.
(d) Thefollow-up forsubjectswithdrawn frominvestigationalproducttreatment/trialtreatment.
6.6TreatmentofSubjects
E6 / Description/Text / Included?Yes / No
6.6.1* / Thetreatment(s)tobeadministered, including thename(s)of allthe product(s),thedose(s),thedosing schedule(s),the route/mode(s)ofadministration, and thetreatmentperiod(s), including thefollow-up period(s)forsubjectsforeachinvestigationalproducttreatment/trialtreatmentgroup/arm of thetrial.
6.6.2* / Medication(s)/treatment(s)permitted(including rescuemedication)and notpermittedbeforeand/orduring thetrial.
6.6.3 / Proceduresformonitoringsubjectcompliance.
6.7AssessmentofEfficacy
E6 / Description/Text / Included?Yes / No
6.7.1 / Specification oftheefficacyparameters.
6.7.2 / Methods andtiming forassessing,recording, andanalyzing efficacyparameters.
6.8AssessmentofSafety
E6 / Description/Text / Included?Yes / No
6.8.1 / Specification ofsafetyparameters.
6.8.2* / Themethods andtiming forassessing,recording, andanalyzing safetyparameters.
6.8.3* / Proceduresforeliciting reportsof andforrecording and reporting adverseeventandintercurrentillnesses.
6.8.4 / Thetypeand durationof thefollow-upof subjectsafteradverseevents.
6.9Statistics
E6 / Description/Text / Included?Yes / No
6.9.1* / A description ofthestatisticalmethodstobeemployed,including timing ofany plannedinterimanalysis(ses).
6.9.2* / Thenumber ofsubjectsplanned tobeenrolled.Inmulticentertrials,thenumberofenrolledsubjectsprojectedforeach trialsite should bespecified.
Reason forchoiceof samplesize,including reflectionson (orcalculationsof)thepowerofthe trialandclinical justification.
6.9.3 / Thelevelof significanceto beused.
6.9.4* / Criteria fortheterminationofthe trial.
6.9.5 / Procedureforaccounting formissing,unused, andspurious data.
6.9.6 / Proceduresforreporting anydeviation(s)fromtheoriginalstatisticalplan (anydeviation(s)fromtheoriginalstatisticalplanshould bedescribedand justified in theprotocoland/or inthe finalreport,as appropriate).
6.9.7 / Theselectionof subjectsto beincluded intheanalyses(e.g., all randomizedsubjects,alldosedsubjects,all eligiblesubjects,evaluate-ablesubjects).
6.10DirectAccesstoSourceData/Documents
E6 / Description/Text / Included?Yes / No
6.10 / Thesponsorshould ensure that it isspecified in theprotocolorotherwrittenagreementthat theinvestigator(s)/institution(s) willpermittrial-relatedmonitoring,audits, IRB/IEC
review,and regulatoryinspection(s)byproviding directaccesstosourcedata/documents.
6.11QualityControlandQualityAssurance
E6 / Description/Text / Included?Yes / No
6.11 / A description oftheQuality Controland QualityAssuranceprocessesandmeasurestobetaken
6.12Ethics
E6 / Description/Text / Included?Yes / No
6.12 / Descriptionofethical considerationsrelating to thetrial.
6.13DataHandlingandRecordkeeping
E6 / Description/Text / Included?Yes / No
6.13* / Descriptionof the Data Handling andRecordKeepingprocessesandmeasuresto betaken
*Provideinformation aboutconfidentialityprotections,sharing ofdata,and disposition ofdata
*Identifyinformation thatwill beextractedfrommedicalrecords
6.14FinancingandInsurance
E6 / Description/Text / Included?Yes / No
6.14 / Financing andinsuranceifnot addressed inaseparateagreement.
6.15PublicationPolicy
E6 / Description/Text / Included?Yes / No
6.15 / Publicationpolicy, if notaddressed in aseparateagreement.
6.16Supplements
E6 / Description/Text / Included?Yes / No
6.16 / (NOTE:Sincetheprotocol and theclinicaltrial/studyreportarecloselyrelated, furtherrelevantinformationcan befound in the ICHGuidancefor Structureand ContentofClinicalStudyReports.)
7.Investigator-InitiatedMultisiteResearchStudies
Description/Text / Included?Yes / No
7.1Identificationofa singlesitetoserveasthe leadsite/coordinatingcenterforthestudy. Alead site orcoordinating center istypicallyresponsibleforcoordinating activitiesat allothersites,receiving and analyzing data, anddeveloping andupdating thestudyprotocolas needed.
7.2Descriptionof howthe lead site/coordinating centerwill communicatewithanddisseminateinformationtoothersites/personnel(e.g.,regularlyscheduled conferencecalls ormeetings,notificationstoallsitesregarding protocolupdatesorotherchangestothe study,etc.)
Description/Text / Included?
Yes / No
7.3A description ofhowthelead site/coordinating centerwillensure thatall participatingsitesuse thesameversionof theprotocol,including a description oftheprocedures thatmustbefollowed inordertoamend theprotocol.
7.4Descriptionof howunanticipated problems,adverseevents,noncompliance,and/ornewinformation aboutthe studywillbe managed, including:
- What eventsneedtobereported
- When reportsmustbemade
- Howthe reportsaremade
- To whom the reportsaremade
- Howrelevantinformationaboutsuch reportswillbedisseminatedtostudysites/personnel,including anychangesof protocol
7.5Descriptionof howeach site’scompliancewith theprotocoland applicablehumansubjectsregulationswillbemonitored and whowill providethemonitoring
7.6Identificationofall sitesthat will beinvolved in theconductofthe research,including:
- Theroleof each site(e.g.,subjectrecruitment, laboratoryanalyses,dataanalyses)
- Identificationofallpersonnelengaged in human subjectsresearch ateach site
- Descriptionof anydifferencesamong sitesin studyprocedures orsubjectpopulations
7.7Descriptionof howpotentialsubjects will beidentrecruitssubjects / ified and recruitedat each sitethat
7.8Descriptionof howinformed consentisobtainedateachsiteandwhoconductstheconsentprocess,including any specialprocessesforsubjectswhomaybenon-Englishspeaking,illiterate,orhave impaireddecision-making capacity.
7.9Descriptionof datastorage,including:
- Allsitesatwhichdatawillbestored
- What datawillbestored at whatsite(s)
- Data securitymeasures
- Whowill haveaccessto identifiabledata
- When datawill beanonymized or destroy
7.10If the studyinvolvestissuebanking,theprotocolshould describe:
- Allsitesatwhichsampleswill bestored
- What sampleswillbestored at whatsite
- Howsampleconfidentialitywillbeprotected
- Whowill haveaccessto identifiablesamples
- When sampleswill beanonymizedor destroyed