Monitoring Plan Template - Molecular Medicine Ireland

Page 1 of 18Protocol No.:Protocol Title:Appendix A: Monitoring PlanIntroductionThe Monitoring Plan is based on the design of the trial (e.g. objective, complexity, size ...) and RiskAssessment performed. It states the level of monitoring required for above noted study.Study MilestonesEnrolment Start Enrolment End Last PatientLast VisitPlanneddatesActual datesTarget Enrolment:Target Number of Sites:DatabaseLockOtherEnrolment PlanAttached is a spreadsheet of projected monthly enrolment by site. Each Monitor should validatethis enrolment plan with their site during the site initiation and training process. This validationprocess should be documented in the initiation report. If the site is unable to achieve thisenrolment plan, this should be discussed with the Trial Manager. A plan of action will be drawnup.(Attach relevant file)The Monitor will provide the site(s) with a subject enrolment log to be completed on a(define frequency, e.g. weekly or monthly) basis.(Attach relevant file)The Monitor will review the progress of enrolment with the study site(s) and provide the updatedenrolment log(s) to the Trial Manager for discussion.If enrolment is slower than anticipated, the Monitor must establish the reasons and attempt to findways to correct the deficiencies. The INSERT INSTITUTION reserves the right to close a centreif no subjects have been screened within (define time period) of the site initiation. If enrolment isfaster than anticipated, the Monitor must establish the reasons, ensuring that subjects are trulyeligible and that supplies are still adequate.In centres where workload due to subject accrual rate is especially high or where there are issues(i.e.: site compliance, protocol violation) a for cause visit and/or audit may be required. Should theMonitor feel that a for cause visit and/or audit would be appropriate for a particular site, he/sheshould discuss this with the Trial Manager and prepare an action plan.If monitoring identifies serious and/or persistent non-compliance on the part of aninvestigator/institution, Trial Manager and Quality Assurance Committee must be notified and theCREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 2 of 18appropraite corrective action plan will be documented. When this occurs, INSERT INSTITUTIONwill promptly notify the regulatory authorities, if required by applicable regulations.Data Completion and Monitoring PlanThe Monitor and Trial Manager will use the enrolment log provided by the sites to project subjectvisits, CRF completion and CRF collection/shipment to the INSERT INSTITUTION. The Monitorwill review the plan with the site(s) and obtain their commitment to adhere to the agreed,projected schedule.(Attach relevant file)Based on the CRF collection schedule, the Monitor, Data Manager and Trial Manager will projectdata entry, data querying and data monitoring activities.(Attach relevant file)Source Document Verification (SDV)Based on trial design and risk assessment, the Trial Manager, Data Manager and Monitor willdefine which source documents will be reviewed (see Appendix B):for all subjects to confirm the information is present and consistently recorded on theCRFs (e.g. medical record exists for each subject, subject sex, and date of birth, statement that the subjectentered the clinical trial, the date of entry, signed Informed Consent Form, verification that the subject meetsthe inclusion exclusion criteria, adverse events…….).the % of SDV that must be performed on all data collected at each site.This may be accomplished by performing SDV on ___% (e.g. 20%) of the total number of visits by eachsubject or by reviewing the data on ___% (e.g. 20%) of enrolled subjects at each trial site.the % of additional SDV that must be performed if significant errors or problems areidentified during monitoring.SDV methods which are not performed as a site visit e.g. faxed documentation, will beexplained in this sectionCentral Data Monitoring CriteriaAdd central data monitoring criteria currently used by the INSERT INSTITUTION, e.g.: Definition of target number of queries for key efficacy and safety variables, % increase queries which would require escalation to TM % increase in queries which would trigger a “for cause” on site visit, criteria for missing data, non completion of CRF data (acceptable window and nonacceptable window resulting in a) escalation or b) for cause site visit, describe safety data reviews – within patient and cross patient, primary efficacy datareviews within patient and cross patient, acceptable negative screen and drop out ratios and triggers for non –acceptable plusresulting action, ……..etcConsistency & Missing Data ReportsBased on the CRF collection schedule, the Monitor, Data Manager and Trial Manager will projectdata entry, data querying and data monitoring activities.CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 3 of 18Target Monitoring Visit IntervalComplete the table below corresponding to the Risk assessed for this trial and delete the twotables that do not apply:Low Risk TrialTarget Schedule for each siteFirst monitoring visitDefine timing of first visit:(e.g. within 6 months)Within ............. months of the first subject visit.Interim monitoring visits Define frequency of interim visits (if any): (e.g. within 6 to 8months)Every ............. months depending on recruitment rate.Central MonitoringDefine frequency and nature of central monitoring reviewsand the criteria which will trigger an escalation to TrialManager or “for cause” site visit:Every ............. months depending on recruitment rate.Criteria triggering escalation or “for cause” site visit:............................................................................................................................................................Remote trainings (phone, webbased, meeting at aconference etc.)QA AuditsClose out visitDefine remote site training schedule:Within ............. weeks of recruitment start then everymonths.Specify the in-house and on-site Audit plan foreseen for thistrial: (e.g. % TMF review, database audit and number of onsiteaudit visit, also detail the criteria which will trigger a “forcause” audit)Audit of:.................... % of TMF.................... % of Trial DBnumber of sites.Criteria triggering “for cause” audit:................................................................................................................................................................................................................NoneCREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 4 of 18Medium Risk TrialFirst monitoring visitInterim monitoring visitsCentral MonitoringRemote trainings (phone, webbased, meeting at aconference etc.)QA AuditsClose out visitTarget Schedule for each siteDefine timing of first visit:(e.g. within 1 to 2 months)Within ............. months of the first subject visit.Define frequency of interim visits: (e.g. within 6 to 8 months)Every ............. months depending on recruitment rate.Define frequency of central monitoring reviews and the criteriawhich will trigger an escalation to Trial Manager or “forcause” site visit:Every ............. months depending on recruitment rate.Criteria triggering escalation or “for cause” site visit:............................................................................................................................................................Define remote site training schedule (if any):Within ............. weeks of recruitment start then everymonths.Specify the in-house and on-site Audit plan foreseen for thistrial: (e.g. % TMF review, database audit and number of onsiteaudit visit, also detail the criteria which will trigger a “forcause” audit)Audit of:.................... % of TMF.................... % of Trial DBnumber of sites.Criteria triggering “for cause” audit:............................................................................................................................................................Define timing of close out visit: (e.g. within 2 months)Within ............. months of database closure or as agreedwith the Trial Manager.CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 5 of 18High Risk TrialsFirst monitoring visitInterim monitoring visitsCentral MonitoringQA AuditsClose out visitTarget Schedule for each siteDefine timing of first visit:(e.g. within 2 weeks)Within ............. weeks of the first subject visit.Define frequency of interim visits: (e.g. within 2 to 8 weeks)Every ............. weeks depending on recruitment rate.Ongoing and will be solved at site visitsSpecify the in-house and on-site Audit plan foreseen for thistrial: (e.g. % TMF review, database audit and number of onsiteaudit visit, also detail the criteria which will trigger a “forcause” audit)Audit of: .................... % of TMF.................... % of Trial DBnumber of sites.Criteria triggering “for cause” audit:............................................................................................................................................................Define timing of close out visit: (e.g. within 2 months)Within ............. months of database closure or as agreedwith the Trial Manager.Updates to Monitoring PlanThe Monitoring Plan will be reviewed periodically and updated as needed. Updated versions willbe noted in the footer and will take precedence over previous versions.Monitoring Plan ApprovalThis Monitoring Plan has been approved by:Trial Manager Signature Date:Medic Responsible Signature Date:QA Auditor Signature Date:Revision History:Original (date):Revision Number:CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 6 of 18Appendix B: Source Data Verification ChecklistStudyDrug/Patient Initials :Indication:Protocol Number Patient ScreeningNo.:Subset of data variables requiring 100% SDV for % Study Subjects enrolled (see Monitoring Plan)Form (define based on trial design,Commentse.g.:)(space for the Monitor)ITEM for 100% SDVONLY (define parametersbased on risk assessment,e.g.:)Informed consent Written ICF date (100)% ofSubjects(define %based on riskassessment,e.g.:)DemographicsDOBInclusion/Exclusion criteria All items (100)Extra criteria 1……….. All items (100)History of disease area Date of first onset (20)History of Other significantmedical historyDate of first onset (20)History of disease related Medication name, start and (20)conc. Medsend dateStudy specific assessments All items (20)(e.g. physical exam, Globalassessment scores,Depression rating scales etc)Central Lab. Sample (blood Collection date (20)/Urine)Serum/Urine Pregnancy Test All items (20)Concomitant Medications forOther indicationsName of medication (20)Concomitant Medications Start and/or End date (20)Concomitant Procedure Name of procedure (20)detailsRandomisation/enrolment No Assigned nos. (100)Drug x administration All items (20)Drug y administration All items (20)Visit Dates All visits (20)Visit Date (unscheduled visit) Date of visit (20)Reason for unscheduled visit Reason for visit (20)Adverse Events All items (100)Serious Adverse Events All items (100)CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 7 of 18Form (define based on trial design,e.g.:)ITEM for 100% SDVONLY (define parametersbased on risk assessment,e.g.:)DrugAll items (20)Accountability/ComplianceQuality of Life Questionnaires Date completed (20)% ofSubjects(define %based on riskassessment,e.g.:)Comments(space for the Monitor)Diary cards All items (20)Post treatment Follow up All items (20)Significant Issues raised with PISigned:Date:Monitor:CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 8 of 18Appendix B: Source Data Location ChecklistSource Data Location ChecklistProtocol No.:Site/Centre Number:Short Title:Principal Investigator:CRFData(define based on CRF and trialdesign, e.g.:)Informed consentDemographicsInclusion/Exclusion criteriaExtra criteria 1………..History of disease areaHistory of Other significantmedical historyHistory of disease relatedconc. MedsTrial specific assessments(e.g. physical exam, Globalassessment scores,Depression rating scales etc)Central Lab. Sample (blood/Urine)Serum/Urine Pregnancy TestConcomitant Medications forOther indicationsConcomitant MedicationsConcomitant ProceduredetailsRandomisation/enrolment NoDrug x administrationDrug y administrationVisit DatesVisit Date (unscheduled visit)Reason for unscheduled visitAdverse EventsSerious Adverse EventsDrugAccountability/ComplianceSite SDV location(e.g: medical notes, lab report, radiology report, CRF….)CommentsCREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 9 of 18Quality of Life QuestionnairesDiary cardsPost treatment Follow upSigned:Date:Trial Manager:Signed:PrincipalInvestigator:Date:CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 10 of 18Appendix C: On-Site Data Monitoring Visit Checklist/ReportChecklist and record of monitoring activities conducted at each site visit by the assigned Monitor:Monitoring Visit ReportIndication: Inv. Product: Protocol No.Investigator: Centre: Centre No:Monitor: Date of last visit: Visit date:Site personnel present:INSERT INSTITUTION personnelpresent:Action itemsFrom visit/contact(date)Responsible personResolved?Study ConductTick if performed and comment, asappropriate:o Verify compliance withprotocol and protocolamendment(s).o Document any protocoldeviations, violations andcorrective actions.o Review with investigator/staffany systematic problems thathave been discovered.o Check actual recruitmentversus planned recruitment.o If below planned recruitment,evaluate the probablecause(s) and propose possiblesolution(s) to investigator(s) orTrial Manager as applicable.o Document any subjectwithdrawalsInformed Consent:Tick if performed and comment, asappropriate:o Check informed consent forevery new subject enrolled.Comments:Comments:CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 11 of 18CRFs:Tick if performed and comment, asappropriate:o Review CRFs forcompleteness and accuracy.o With investigator/staff makecorrections / additions asappropriate before collectingCRF.o Review edits and ensurecorrections are made, asappropriate.o Verify completed CRFs arebeing submitted within 5working days.CRFs reviewed and source data verified forSubjects No.: ..................................................................CRF Visit No. or Pages: ........................................................Comments:Adverse Events:Tick if performed and comment, asappropriate:o Repeat importance ofreporting all AEs.o Check for any unreportedAEs, SAEs and assist theinvestigator in properreporting.Source Data Verification:Tick if performed and comment, asappropriate:o Perform SDV to assureaccuracy of the data asrequired defined for the study.o Document informationregarding SDV.Body fluids/tissue Samples:(if applicable)Tick if performed and comment, asappropriate:o Check if written informedconsent has been obtainedprior to taking any samples.o Verify samples are collected atrequired time points andstored according to protocoland GCP.o Ensure that site is maintaininga Sample Tracking Log.Comments:Comments:Comments:CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 12 of 18Investigational Product (IMP):(if applicable)Tick if performed and comment, asappropriate:o Check and document thatclinical supplies are storedaccording to protocol andGCP.o Check and document productaccountability form foraccuracy and protocolcompliance.o Check IMP supply is adequateand has not expired.o Confirm that IMPreturns/destruction exists andare appropriately filed.o Check and document integrityof subject emergencytreatment unblindinginformation.Investigator File:Tick if performed and comment, asappropriate:o Add the current visit to theVisitors Log and signo Check Investigator File forcompleteness.o Retrieve copies ofnew/updated documents.o Ensure appropriatedocuments for the Trial MasterFile are sent to the TrialManager or delegateSite Management:Tick if performed and comment, asappropriate:o Document staff availability.o Document changes in staffassigned to conduct studyo Ensure “Signature andDelegation of Responsibilitieslog” is updated when neededand signed by the PIo Ensure adequate anddocumented training of newstudy staffo Document availability ofmedical records/completedCRFs for reviewComments:Comments:Comments:CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 13 of 18Monitoring Visit Reports:Tick if performed and comment, asappropriate:o Check and document if allitems outstanding from lastvisit were solved.o Document all activitiesperformed and relevantfindings observed at the visit.o Submit the Monitoring VisitReport to the Trial Managerwithin ___ business dayso Send a follow-up letter to thesiteComments:Report prepared by: Date of report: Date of next visit:Report reviewed by Trial Manager:Date of review:Trial Manager to ensure the original signed report is filed in the TMFCREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 14 of 18Appendix D: Central Data Monitoring Checklist/ReportChecklist and record of monitoring activities conducted at the INSERT INSTITUTION by the assigned Monitor:Central Monitoring ReportIndication: Inv. Product: Protocol No.Investigator: Centre: Centre No:Monitor:Action itemsFrom visit/contactResponsible personResolved?(date)Study ConductTick if performed and comment, asappropriate:o Verify compliance withprotocol and protocolamendment(s).o Document any protocoldeviations, violations andcorrective actions.o Review with investigator/staffany systematic problems thathave been discovered.o Check actual recruitmentversus planned recruitment.o If below planned recruitment,evaluate the probablecause(s) and propose possiblesolution(s) to investigator(s) orTrial Manager as applicable.o Document any subjectwithdrawalsInformed Consent:Tick if performed and comment, asappropriate:o Check informed consent forevery new subject enrolled(comparing CRF entry withInformed Consent log completedand faxed by the site).Comments:Comments:CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 15 of 18CRFs:Tick if performed and comment, asappropriate:o Verify completed CRFs aresent for data entry as per CRFcollection plan agreed with thesite.o Review the Consistency &Missing Data Report for CRFcompleteness and accuracy.o Send CRF queries to the sitefor resolution.o Review CRF queries withinvestigator/site staff ifassistance and/or additionalsite training is needed.o Review edits and ensurecorrections are made, asappropriate.Adverse Events:Tick if performed and comment, asappropriate:o Repeat importance ofreporting all AEs.o Check for any unreportedAEs, SAEs and assist theinvestigator in properreporting.Body fluids/tissue Samples:(if applicable)Tick if performed and comment, asappropriate:o Check if written informedconsent has been obtainedprior to taking any samples.o Verify samples are collected atrequired time pointso Obtain confirmation thatsamples are stored accordingto protocol and GCP.o Ask site to send copy ofSample Tracking LogCRFs entered, queried and reviewed forSubjects No.: ..................................................................CRF Visit No. or Pages: ........................................................Number of Queries issued: ....................................................Comments:Comments:Comments:CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 16 of 18Investigational Product (IMP):(if applicable)Tick if performed and comment, asappropriate:o Obtain confirmation thatclinical supplies are storedaccording to protocol andGCP.o Obtain copy of IMP receiptsand completed productaccountability forms foraccuracy and protocolcomplianceo Obtain confirmation that IMPsupply is adequate and hasnot expiredo Collect copy of IMPreturns/destruction.Comments:Investigator File:Tick if performed and comment, asappropriate:o Send list of documents thatshould be on file and obtainconfirmation that theInvestigator File is complete.o Ensure appropriatedocuments for the Trial MasterFile are sent to the TrialManager.Site Management:Tick if performed and comment, asappropriate:o Document staff availability forthe study.o Document changes in staffassigned to conduct studyo Ensure “Signature andDelegation of Responsibilitieslog” is updated when neededand signed by the PIo Ensure adequate anddocumented training of newstudy staffComments:Comments:CREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 17 of 18Central Monitoring Reports:Tick if performed and comment, asappropriate:o Check and document if allitems outstanding from lastcontact were solved.o Document all activitiesperformed and relevantfindings observedo Submit the Central MonitoringReport to the Trial Managerwithin ___ business dayso Send a follow-up letter to thesiteComments:Report prepared by: Date of report: Date of next visit:Report reviewed by TrialManager:Date of review:Trial Manager to ensure the original signed report is filed in the TMFCREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX

Page 18 of 18Appendix E: Site Contact ReportSite Contact ReportIndication: Inv. Product: Protocol No.Investigator: Centre: Centre No:Contact at site: Contact made by: Date:Action itemsFrom contact Responsible person(date)Resolved?Summary of conversation:Report prepared by:Copy of report sent for information to:Date of report:Editor to submit the original signed report for inclusion in the TMFCREATED BY THE ICRIN QUALITY MANAGEMENT SUBGROUP VERSION XX DATE XX/XXX/XXXX