dsur
DESCRIPTION
Presentation of how to write DSURTRANSCRIPT
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Developmental Safety
Update Report
(DSUR)Dr.S.Gunasakaran, MD
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OBJECTIVE
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Dr.S.Gunasakaran,MBBS,MD 3
Objective of DSUROngoing assessment of risk to trial subjectsNotification of Ethics Committees and
Regulators at regular intervalsActions proposed to address safety concerns
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US IND
Annual
Report
EU Annua
l Safety Report
DSUR
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Dr.S.Gunasakaran,MBBS,MD 5
Describe new safety issues
New information is in accord with previous knowledge
Update on the Clinical Development Programme
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SCOPE of DSUR
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Dr.S.Gunasakaran,MBBS,MD 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
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When should a DSUR be prepared?
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Dr.S.Gunasakaran,MBBS,MD 9
Sponsor overseeing more than one clinical trial of a single investigational product should prepare one DSUR
With single Data Lock Point (DLP)
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Periodicity and DSUR Data Lock
Point
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Dr.S.Gunasakaran,MBBS,MD 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 committeeIRBsInvestigators
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Dr.S.Gunasakaran,MBBS,MD 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 DIBD
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Dr.S.Gunasakaran,MBBS,MD 13
Change of DSUR Data Lock Point
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Dr.S.Gunasakaran,MBBS,MD 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 year
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Interruption or Discontinuation
Of Clinical Trials
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Dr.S.Gunasakaran,MBBS,MD 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 letter
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FINAL DSUR
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Dr.S.Gunasakaran,MBBS,MD 18
Final DSURWhen 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 elsewhere
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Dr.S.Gunasakaran,MBBS,MD 19
Responsibilities for Preparing & Submitting DSURSponsor’s ResponsibilitiesShared ResponsibilitiesNon-Commercial Sponsor ResponsibilitiesMultiple sponsors in formal agreements
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Reference Safety Info
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Dr.S.Gunasakaran,MBBS,MD 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 products
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FORMAT AND PRESENTATION
OF DSUR
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Dr.S.Gunasakaran,MBBS,MD 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 setting
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Dr.S.Gunasakaran,MBBS,MD 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 Trials
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Dr.S.Gunasakaran,MBBS,MD 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-up
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Dr.S.Gunasakaran,MBBS,MD 26
Table of Contents (Contd..)LiteratureOther DSURsSignificant manufacturing changesLack of efficacyPhase I protocol modificationsLate Breaking informationOverall safety assessment
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Dr.S.Gunasakaran,MBBS,MD 27
Table of Contents (Contd..)Evaluation of risksBenefit risks considerationsConclusionsSummary of important risksAppendices to DSUR
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TITLE PAGE
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Dr.S.Gunasakaran,MBBS,MD 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 DSUR
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Dr.S.Gunasakaran,MBBS,MD 30
EXECUTIVE SUMMARY
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Dr.S.Gunasakaran,MBBS,MD 31
Executive summaryConcise summary of the important
information contained in the reportTogether with title page, serves as Stand
alone document for EC submission
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Dr.S.Gunasakaran,MBBS,MD 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 IBConclusion
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INTRODUCTION
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Dr.S.Gunasakaran,MBBS,MD 34
IntroductionReporting period and sequential number of
reportBrief description of the drug, eg., therapeutic
class, mode of action, route of administration, formulation
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Dr.S.Gunasakaran,MBBS,MD 35
Worldwide Marketing Authorization statusMarketing application submitted in one or
more countriesTable format
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Dr.S.Gunasakaran,MBBS,MD 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
indications
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Dr.S.Gunasakaran,MBBS,MD 37
Changes to Reference Safety InfoSignificant safety related changes to IBChanges to ContraindicationsWarningsPrecautionsAdverse reactions of special interestInteractionCarcinogenicity, mutagenicity from non-
clinical studies
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Dr.S.Gunasakaran,MBBS,MD 38
Status of Clinical trials ongoing and completed during Re. PeriodSeparate tables can be provided by
IndicationFormulationStudy population
Table should contain the following informationProtocol no.Clinical trial phase (I-IV)Status
Ongoing completed
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Dr.S.Gunasakaran,MBBS,MD 39
Table should includeAbbreviated study titleStudy design
Uncontrolled, controlled, open, single blind, double blind, parallel, cross over etc
Dose and regimen of study drug and comparators
Subject populationAge, sex, indication, special population groups,
impaired renal or hepatic functionDate of first visit for first patientPlanned enrollment of study as a whole
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Estimated Exposure
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Dr.S.Gunasakaran,MBBS,MD 41
Cumulative subject exposreData on subject exposure to the
Investigational productActive comparatorsPlacebo
No of trial subjects by age group, gender and ethnic origin
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Dr.S.Gunasakaran,MBBS,MD 42
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Dr.S.Gunasakaran,MBBS,MD 43
Estimated Exposure
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Dr.S.Gunasakaran,MBBS,MD 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 included
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Dr.S.Gunasakaran,MBBS,MD 45
General Considerations
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Dr.S.Gunasakaran,MBBS,MD 46
General ConsiderationsVersion of Coding dictionary usedVersion of documentVersion used as Reference Safety Information
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Dr.S.Gunasakaran,MBBS,MD 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 variables
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Dr.S.Gunasakaran,MBBS,MD 48
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Dr.S.Gunasakaran,MBBS,MD 49
Cumulative Summary tabulationsContent of tabulationsCriteria for inclusionsSummary tabulations should present
cumulative safety data from the DBID to the data lock point
Summary tabulations include no. of SARs organised by SOC forInvestigational productPlacebocomparator
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Dr.S.Gunasakaran,MBBS,MD 50
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Dr.S.Gunasakaran,MBBS,MD 51
Deaths in theReporting Period
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Dr.S.Gunasakaran,MBBS,MD 52
Deaths in the Reporting PeriodA list of subjects who died during
participation in the investigationShould be provided as appendixFollowing information at a minimum
Case numberAssigned treatmentCause of death
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Dr.S.Gunasakaran,MBBS,MD 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 described
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Dr.S.Gunasakaran,MBBS,MD 54
Significant findings from clinical trials during reporting periodCompleted clinical trials and interim analysisOngoing clinical trials
Concise summary of any preliminary safety findings
Other therapeutic use of investigational drugNew safety data related to combination
therapies
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Relevant Findings
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Dr.S.Gunasakaran,MBBS,MD 56
Relevant findings from non-interventional studies
Relevant findings from meta-analysed or pooled data of RCT
Safety findings from marketing experience
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Dr.S.Gunasakaran,MBBS,MD 57
Other Information
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Dr.S.Gunasakaran,MBBS,MD 58
Other informationNon clinical data
Invivo or invitro studiesCarcinogenicity, reproduction, immunotoxicity
studiesLong term follow up
Gene herapy, cell therapy products, tissue engineered products
LiteratureOther DSURsSignificant manufacturing changesLack of efficacy
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Overall Safety Assessment
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Dr.S.Gunasakaran,MBBS,MD 60
Overall Safety AssessmentConcise, integrated assessment of all new
Clinical informationNon-clinical informationEpidemiological information
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Dr.S.Gunasakaran,MBBS,MD 61
Evaluation of RisksBenefit Risk ConsiderationsConclusionSummary of important risks
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Appendices
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Dr.S.Gunasakaran,MBBS,MD 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)
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Regional Appendices
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Dr.S.Gunasakaran,MBBS,MD 65
Regional AppendicesDrop outs in association with Adverse eventsDeathsSummary Tabulations of SARs
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Questions….?
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Thank You