DSUR
Download as PPTX, PDF19 likes8,661 views
The document provides guidance on preparing Developmental Safety Update Reports (DSURs). It outlines the objectives, scope, periodicity and format of DSURs. Key information to include in a DSUR are estimated clinical trial exposure, safety data from trials, actions taken for safety reasons, changes to the reference safety information, and an overall safety assessment. The DSUR is intended to provide regulators with the latest safety information on investigational products.
DSUR
- 1. Developmental Safety Update Report(DSUR)Dr.S.Gunasakaran, MDDr.S.Gunasakaran,MBBS,MD1
- 3. Objective of DSUROngoing assessment of risk to trial subjectsNotification of Ethics Committees and Regulators at regular intervalsActions proposed to address safety concernsDr.S.Gunasakaran,MBBS,MD3
- 7. Scope of DSURData from Interventional Clinical TrialsCommercial and Non-Commercial SponsorsSafety findings from non-clinical studiesSafety findings from clinical trials conducted by co-development partnerNon-interventional / Compassionate use Dr.S.Gunasakaran,MBBS,MD7
- 8. When should a DSUR be prepared?Dr.S.Gunasakaran,MBBS,MD8
- 9. Sponsor overseeing more than one clinical trial of a single investigational product should prepare one DSURWith single Data Lock Point (DLP)Dr.S.Gunasakaran,MBBS,MD9
- 10. Periodicity and DSUR Data Lock PointDr.S.Gunasakaran,MBBS,MD10
- 11. Periodicity and DSUR Data Lock PointIntended to be annual reportAs long as sponsor conducts clinical trials with IDAs long as appropriate to satisfy local regulatory requirementsDSUR Executive Summary supplemented with line listings of SAE for Ethics committeeIRBsInvestigatorsDr.S.Gunasakaran,MBBS,MD11
- 12. Periodicity and DSUR Data Lock PointDSUR should be submitted no later than 60 calendar days from DSUR data lock pointDevelopment International Birth Date (DIBD):Date of the sponsor’s first authorization to conduct a clinical trial in any countryFor administrative convenience, DIBD is the last day of MOAClinical trials going in one country and are later initiated in any other countries, one DSUR on same DIBDDr.S.Gunasakaran,MBBS,MD12
- 13. Change of DSUR Data Lock PointDr.S.Gunasakaran,MBBS,MD13
- 14. Change of DSUR Data Lock PointOnce the drug has received a marketing approval in any countryChange the DSUR data lock point to Coincide with IBDDSUR and PSUR should be synchronizedDuring synchronization, the period covered by next DSUR should not be longer than 1 yearDr.S.Gunasakaran,MBBS,MD14
- 15. Interruption or DiscontinuationOf Clinical TrialsDr.S.Gunasakaran,MBBS,MD15
- 16. Interruption or Discontinuation of Clinical TrialsDSUR should be prepared and submitted Sponsor not collected any further data pertinent to the clinical development programme in the period of DSUR, a covering letterDr.S.Gunasakaran,MBBS,MD16
- 18. Final DSUR When annual reports of clinical trials no longer required in a country, DSUR should be accompanied by a Cover letter Whether or not clinical trials are continuing elsewhereDr.S.Gunasakaran,MBBS,MD18
- 19. Responsibilities for Preparing & Submitting DSURSponsor’s ResponsibilitiesShared ResponsibilitiesNon-Commercial Sponsor ResponsibilitiesMultiple sponsors in formal agreementsDr.S.Gunasakaran,MBBS,MD19
- 21. Reference Safety InformationUsed to assess whether the safety information received during the reporting period remains consistent with previous knowledge of safety profile of ID.IB is the RSISmPC is the RSI for non-commercial sponsors conducting clinical trial with marketed productsDr.S.Gunasakaran,MBBS,MD21
- 22. Format and presentationOf DSURDr.S.Gunasakaran,MBBS,MD22
- 23. Table of contentsTitle pageExecutive summaryIntroductionWorldwide Marketing Authorization StatusUpdate on actions taken in the Reporting Period for Safety ReasonsChanges to Reference Safety InformationEstimated ExposureCumulative subject exposure in Clinical TrialsPatient Exposure from Marketed settingDr.S.Gunasakaran,MBBS,MD23
- 24. Table of Contents (Contd..)Presentation of Safety Data from Clinical TrialsGeneral considerationsInterval line listing of SARsCumulative summary tabulationsDeaths in reporting periodSubjects who dropped outSignificant findings from Clinical trialsCompleted CTs and Interim AnalysisOngoing Clinical TrialsDr.S.Gunasakaran,MBBS,MD24
- 25. Table of Contents (Contd..)Other therapeutic use of investigational drugNew safety data related to combination therapiesRelevant findings from non-interventional clinical studiesRelevant findings from other studiesSafety findings from marketing experienceOther informationNon-clinical dataLong-term follow-upDr.S.Gunasakaran,MBBS,MD25
- 26. Table of Contents (Contd..)LiteratureOther DSURsSignificant manufacturing changesLack of efficacyPhase I protocol modificationsLate Breaking informationOverall safety assessmentDr.S.Gunasakaran,MBBS,MD26
- 27. Table of Contents (Contd..)Evaluation of risksBenefit risks considerationsConclusionsSummary of important risksAppendices to DSURDr.S.Gunasakaran,MBBS,MD27
- 29. Title pageDSUR number (reports should be numbered sequentially)Investigational drug(s)Reporting PeriodDate of ReportSponsor name and addressConfidentiality statementNote regarding the inclusion of unblinded information in the DSURDr.S.Gunasakaran,MBBS,MD29
- 31. Executive summaryConcise summary of the important information contained in the reportTogether with title page, serves as Stand alone document for EC submissionDr.S.Gunasakaran,MBBS,MD31
- 32. Information in Executive summaryIntroduction – Report version & Reporting periodID: MOA, class, indications, dose , RoAEstimated cumulative clinical trial exposureMarketing Authorization? Yes / No – If yes, no. of countriesSummary of overall safety assessmentSummary of important risksActions taken for safety reasons including changes to IBConclusionDr.S.Gunasakaran,MBBS,MD32
- 34. IntroductionReporting period and sequential number of reportBrief description of the drug, eg., therapeutic class, mode of action, route of administration, formulationDr.S.Gunasakaran,MBBS,MD34
- 35. Worldwide Marketing Authorization statusMarketing application submitted in one or more countriesTable formatDr.S.Gunasakaran,MBBS,MD35
- 36. Update on Actions Taken in the Reporting Period for Safety ReasonsRefusal of authorization of clinical trialPartial or complete trial suspension for ethical or safety reasonsFailure to obtain marketing approval for tested indicationProtocol modifications due to safety reasonsFormulation changes due to safety reasonsRestrictions in study populations or indicationsDr.S.Gunasakaran,MBBS,MD36
- 37. Changes to Reference Safety InfoSignificant safety related changes to IBChanges to ContraindicationsWarningsPrecautionsAdverse reactions of special interestInteractionCarcinogenicity, mutagenicity from non-clinical studiesDr.S.Gunasakaran,MBBS,MD37
- 38. Status of Clinical trials ongoing and completed during Re. PeriodSeparate tables can be provided byIndicationFormulationStudy populationTable should contain the following informationProtocol no.Clinical trial phase (I-IV)StatusOngoingcompletedDr.S.Gunasakaran,MBBS,MD38
- 39. Table should includeAbbreviated study titleStudy designUncontrolled, controlled, open, single blind, double blind, parallel, cross over etcDose and regimen of study drug and comparatorsSubject populationAge, sex, indication, special population groups, impaired renal or hepatic functionDate of first visit for first patientPlanned enrollment of study as a wholeDr.S.Gunasakaran,MBBS,MD39
- 41. Cumulative subject exposreData on subject exposure to the Investigational productActive comparatorsPlaceboNo of trial subjects by age group, gender and ethnic originDr.S.Gunasakaran,MBBS,MD41
- 44. Presentation of Safety data from Clinical trialsShould contain both cumulative and interval safety information related to IPInterval line listings of SARCumulative tabulations of SARs since DBIDIf MedDRA used, PT should be usedTabulations of only SeriousNon-Serious and Incidental findings should not be includedDr.S.Gunasakaran,MBBS,MD44
- 46. General ConsiderationsVersion of Coding dictionary usedVersion of documentVersion used as Reference Safety InformationDr.S.Gunasakaran,MBBS,MD46
- 47. Interval line listings of SARsKey information on all blinded and unblinded SARs reported during reporting periodSARs should be listed by protocol, indication or other variablesDr.S.Gunasakaran,MBBS,MD47
- 49. Cumulative Summary tabulationsContent of tabulationsCriteria for inclusionsSummary tabulations should present cumulative safety data from the DBID to the data lock pointSummary tabulations include no. of SARs organised by SOC forInvestigational productPlacebocomparatorDr.S.Gunasakaran,MBBS,MD49
- 51. Deaths in theReporting PeriodDr.S.Gunasakaran,MBBS,MD51
- 52. Deaths in the Reporting PeriodA list of subjects who died during participation in the investigationShould be provided as appendixFollowing information at a minimumCase numberAssigned treatmentCause of deathDr.S.Gunasakaran,MBBS,MD52
- 53. Subjects who dropped outTabulations and listing on drop outs should be providedShould be provided as an appendixSafety issued identified from a review of these withdrawals should be describedDr.S.Gunasakaran,MBBS,MD53
- 54. Significant findings from clinical trials during reporting periodCompleted clinical trials and interim analysisOngoing clinical trialsConcise summary of any preliminary safety findingsOther therapeutic use of investigational drugNew safety data related to combination therapiesDr.S.Gunasakaran,MBBS,MD54
- 56. Relevant findings from non-interventional studiesRelevant findings from meta-analysed or pooled data of RCTSafety findings from marketing experienceDr.S.Gunasakaran,MBBS,MD56
- 58. Other information Non clinical dataInvivo or invitro studiesCarcinogenicity, reproduction, immunotoxicity studiesLong term follow upGene herapy, cell therapy products, tissue engineered productsLiteratureOther DSURsSignificant manufacturing changesLack of efficacyDr.S.Gunasakaran,MBBS,MD58
- 60. Overall Safety AssessmentConcise, integrated assessment of all newClinical informationNon-clinical informationEpidemiological informationDr.S.Gunasakaran,MBBS,MD60
- 61. Evaluation of RisksBenefit Risk ConsiderationsConclusionSummary of important risksDr.S.Gunasakaran,MBBS,MD61
- 63. Appendices to the DSURInvestigator’s BrochureCumulative table of important regulatory adviceStatus of ongoing and completed clinical trialsCumulative summary tabulations of Demographic DataLine listings of SARsCumulative summary tabulation of SAEsScientific abstracts (if relevant)Dr.S.Gunasakaran,MBBS,MD63
- 65. Regional AppendicesDrop outs in association with Adverse eventsDeathsSummary Tabulations of SARsDr.S.Gunasakaran,MBBS,MD65