*NIH Clinical Trial Definition

DefinitionofClinicalTrial

NIHdefines a clinical trial* as aresearch studyin whichoneor morehuman subjectsareprospectivelyassigned tooneor more interventions(whichmayinclude placebo orothercontrol) to evaluatethe effects of thoseinterventions on health-relatedbiomedical or behavioraloutcomes. (Seedefinition below).

All NIHclinicaltrials are required to haveappropriate Data SafetyMonitoringPlans(DSMPs),approvedbythe PO. Pleaseviewthe NIHPoliciesandICGuidanceforData and Safety Monitoringof Clinical Trialsand theNIA-specific data safetyand monitoringpolicy.

*NIH Clinical Trial Definition:

NIHClinicalTrialDefinition

Aresearchstudy1inwhichoneormorehumansubjects2areprospectivelyassigned3tooneormoreinterventions4(whichmayincludeplaceboorothercontrol)toevaluatetheeffectsofthoseinterventionsonhealth-relatedbiomedicalorbehavioraloutcomes.5

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1.SeeCommonRuledefinitionofresearchat45CFR46.102(d).

2.SeeCommonRuledefinitionofhumansubjectat45CFR46.102(f).

3.Theterm“prospectivelyassigned”referstoapre-definedprocess(e.g.,randomization)specifiedinanapprovedprotocolthatstipulatestheassignmentofresearchsubjects(individuallyorinclusters)tooneormorearms(e.g.,intervention,placebo,orothercontrol)ofaclinicaltrial.

4.Aninterventionisdefinedasa manipulationofthesubjectorsubject’senvironmentforthepurposeofmodifyingoneormorehealth-relatedbiomedicalorbehavioralprocessesand/orendpoints.Examplesinclude:drugs/smallmolecules/compounds;biologics;devices;procedures(e.g.,surgicaltechniques);deliverysystems(e.g.,telemedicine,face-to-faceinterviews);strategiestochangehealth-relatedbehavior(e.g.,diet,cognitivetherapy,exercise,developmentofnewhabits);treatmentstrategies;preventionstrategies;and,diagnosticstrategies.

5.Health-relatedbiomedicalorbehavioraloutcomeisdefinedasthepre-specifiedgoal(s)orcondition(s)thatreflecttheeffectofoneormoreinterventionsonhumansubjects’biomedicalorbehavioralstatusorqualityoflife.Examplesinclude:positiveornegativechangestophysiologicalorbiologicalparameters(e.g.,improvementoflungcapacity,geneexpression);positiveornegativechangestopsychologicalorneurodevelopmentalparameters(e.g.,moodmanagementinterventionforsmokers;readingcomprehensionand/orinformationretention);positiveornegativechangestodiseaseprocesses;positiveornegativechangestohealth-relatedbehaviors;and,positiveornegativechangestoqualityoflife.

DATAAND SAFETYMONITORINGPLAN

TemplateandGuidelines

PREFACE

Investigators should consider usingthistemplatewhendevelopingtheDataand SafetyMonitoringPlan(DSMP) forclinicalstudiessponsored by theNationalInstituteonAging(NIA).

Note that all instructions andexplanatorytextareshownin italicsandshouldbereplacedwiththestudyspecifictext.There isno needtoincludesectionsthatare notrelevanttotheparticular study.

TABLEOFCONTENTS

Page

1.0PARTICIPANT SAFETY...... 1

1.1PotentialRisksandBenefitsfor Participants...... 1

1.2AdverseEventandSeriousAdverseEvent Collection andReporting...... 1

1.3ProtectionagainstStudyRisks...... 1

2.0INTERIMANALYSIS...... 2

3.0DATA AND SAFETYMONITORING...... 2

3.1FrequencyofDataandSafetyMonitoring...... 2

3.2ContentofDataandSafetyMonitoringReport...... 3

3.3DSMBMembershipandAffiliation...... 3

3.4Conflictof Interestfor DSMB’s...... 3

3.5ProtectionofConfidentiality...... 3

3.6DSMBResponsibilities...... 3

1.1PARTICIPANTSAFETY

1.2PotentialRisksandBenefits for Participants

This sectionoutlines thepotentialrisksandbenefitsoftheresearchfor thestudyparticipantsandforsociety.

PotentialRisks:(Outlinepotentialrisks for study participants.)

Example:Thepotential risks tostudyparticipantsinclude(e.g.,theremay betemporaryslightdiscolorationof theskin afterblood draws.)

PotentialBenefits:(Outlinepotentialbenefitsfor studyparticipants.)

Example:Thepotentialbenefitstostudyparticipantsinclude(e.g., ongoing nutritionalcounselingwill beprovidedto all participants).

1.3AdverseEvent and SeriousAdverseEvent Collection and Reporting

This sectiondescribestheproceduresandtimelinesforadverseevents (AE) andseriousadverseevents (SAE)collectionand reporting. It shouldalsoincludethedefinition,grading scaleand“studyrelatedness”criteriafor adverseeventsandspecify therecipientsofadverseeventandseriousadverseeventreports(e.g.,theIRB, the NIA,theSafety Officer or DataandSafetyMonitoringBoard).

Refer totheNIAAdverseEventandSeriousAdverseEventGuidelines for details.

1.4ProtectionAgainstStudyRisks

This sectionprovidesinformation onhow adverseeventsand otherrisks toparticipants in thestudy will bemediatedandshouldspecifyanyeventsthatwouldprecludea participantfromcontinuingwiththeintervention. This sectionshouldalsoincludethe informedconsentproceduresandmeasures toprotectparticipantsagainstriskduringthestudy.Ingeneral,theformatandcontentof thissection aresimilar tothe HumanSubjectssectionof theapplication.

InformedConsentProcess. Explaintheinformed consentprocessandhowitwill beusedtoprotectparticipants.

Example:The consentprocess informsavolunteeraboutthestudy,indicatestheparticipation is voluntaryandhe/shehasthe righttostopatanytime.Risksareenumeratedintheinformedconsentformanddescribedorallyduringthe consentprocess.

Refer totheInformedConsentTemplateand InformedConsentChecklistfor details.

ProtectionAgainstRisks. Describe measures to protectparticipantsagainststudyspecific risks.

Example:Theprocedures to protectagainstrisks (describe knownrisks)include(e.g.,a safe,hygienicenvironment for all medicalproceduresandanexperienced,certifiedstaff)

2.0INTERIMANALYSIS

This sectionprovidesinformation onplannedinterimanalysis, if any,for safety orefficacy monitoring.

Example:Interim analysis ofthestudyis plannedaccording to thealphaspendingrule[LanandDeMets].The proportionofexpectedevents is considered astheinformationstatistic.The p-valuesare constructedtomaintaintheoverall studypowerof0.05,two-sided.Ifthe teststatisticexceedstheboundary, thenthestudycould beconsideredfor earlyterminationduetoemerging differences.Theinterimlookisrecommendedattheendofyearone as weexpectapproximately50% of thepatientsfollowedfor atleastsix months.

Rules for stoppingthestudy,basedon interimanalysis, shouldalso bedescribed.

3.1DATA AND SAFETY MONITORING

This sectiondescribeswho is responsiblefordata and safety monitoring,includingnames, typeof informationthatwill bereviewedandfrequencyof such reviews.

Single-site,minimal riskclinicaltrialsandnon-interventionalstudiescan bemonitoredby anindependentSafetyOfficer(SO) or thestudy staffifNIA deemsappropriate,whilemorethana minimalrisk single-site andall multi-site clinical trialsand all PhaseIII clinicaltrialsrequiretheoversightofa DataSafetyMonitoringBoard (DSMB).

Example:ThePrincipalInvestigator(PI)willbe responsibleforensuringparticipants’safetyona dailybasis. TheDataandSafetyMonitoringBoard (DSMB)will act in anadvisorycapacityto the NIA Directorto monitorparticipantsafety,evaluatetheprogressofthestudy,toreviewproceduresfor maintainingtheconfidentialityof data,the qualityof data collection,management,and analyses.

Refer toDSMBCharter for details.

3.2Frequencyof Data and SafetyMonitoring

This section describesthefrequencyof data and safety monitoringreviews.

Example:ThePI will be informedofseriousadverseevents assoon as theyoccurand willnotifythe NIAand(e.g.DSMB) within 24hoursofnotification.The(e.g.

DSMB) will meet twiceannually, either in-person orbyteleconference calltoreviewstudyprogress,dataquality, andparticipantssafety.

Safetyreports are sentto theSO twice a year andwill include adetailedanalysis ofstudyprogress,dataand safetyissues.

3.3Content of Data and SafetyMonitoring Report

This section describesthe contentof thedataand safetymonitoringreports.

Example: The contentofthedataandsafetymonitoringreport will include: (e.g.,study status,participantdescriptiveinformation,safetyinformation,studyquality)

Refer totheDSMB ReportsTemplatesfor guidance.

3.4DSMBMembership andAffiliation

This sectionincludes aroster oftheDSMB ortheSafetyOfficer’s(SO) nameandtheiraffiliations.

Example:Thefollowing individual(s)has/haveaccepted position(s)as partof the(e.g., DSMB).DSMBmembership(safetyofficer) will be reviewed and approvedbythe NIA.Shouldtherebe anyquestionsregarding the independenceoftheDSMB,itwill be addressedandcorrectedifnecessaryat thattime.

Name

Title,Organization

Name

Title,OrganizationEtc.

3.5Conflict ofInterestforDSMB’s

This sectiondescribesthe conflictof interestprocedure for DSMBmembers.

Example:DSMB membersshouldhave nodirectinvolvementwiththestudyinvestigators or intervention.EachDSMBmemberwillsign aConflictofInterestStatementwhich includes currentaffiliations,if any,withpharmaceuticalandbiotechnologycompanies(e.g.,stockholder,consultant),andanyotherrelationshipthat couldbeperceived asa conflictofinterestrelated tothestudyand/ or associatedwithcommercialinterestspertinenttostudyobjectives.

3.6Protection ofConfidentiality

This sectiondescribesprotectionofdata presentedtotheDSMBorSO.

Example:Datawill be presentedin a blindedmannerduringtheopensessionsoftheDSMB or in SOreportsAt DSMBmeetingsorin SO reports,dataanddiscussion areconfidential. Participantidentitieswill not be knowntotheDSMBmembers or totheSO.

3.7DSMBResponsibilities

TheDSMBCharterprovidesa detailedlist ofthe DSMB/ SO responsibilities. Theyinclude:

• Reviewthe researchprotocol, informedconsentdocumentsandplansfordatasafetyandmonitoring;

• Recommendsubjectrecruitmentbe initiatedafter receiptofasatisfactoryprotocol;
• Evaluatetheprogressofthetrial,including periodicassessmentsofdataqualityand timeliness,recruitment,accrual andretention,participantriskversusbenefit,performanceofthetrial sites,andotherfactors thatcanaffectstudyoutcome;
• Considerfactors external to thestudywhenrelevant informationbecomesavailable, suchas scientific or therapeuticdevelopmentsthatmayhave animpactonthe safetyof theparticipantsor theethics ofthetrial;
• Reviewstudyperformance,makerecommendationsandassist intheresolution ofproblemsreported bythePrincipalInvestigator;
• Protectthesafetyofthestudyparticipants;
• Report to NIAonthesafetyand progressofthetrial;
• Makerecommendations to the NIAandthePrincipalInvestigatorconcerningcontinuation,termination orothermodificationsofthetrialbasedontheobservedbeneficialoradverseeffectsofthetreatmentunderstudy;
• If appropriate,reviewinterim analyses in accordancewithstopping rules,which are clearlydefined inadvanceofdataanalysis andhavetheapprovaloftheDSMB;
• Ensuretheconfidentialityofthestudydataandthe resultsofmonitoring;and,
• Assist theNIAbycommentingonanyproblems with studyconduct,enrollment,sample size, and/ordatacollection.

Detailed DataandSafetyMonitoringPlan (DSMP)Checklist

12/19/2016 DSM PlanChecklist- Version1.01