DSUR

Developmental Safety

Update Report

(DSUR)Dr.S.Gunasakaran, MD

OBJECTIVE

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

US IND

Annual

Report

EU Annua

l Safety Report

DSUR


Describe new safety issues

New information is in accord with previous knowledge

Update on the Clinical Development Programme

SCOPE of DSUR


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

When should a DSUR be prepared?


Sponsor overseeing more than one clinical trial of a single investigational product should prepare one DSUR

With single Data Lock Point (DLP)

Periodicity and DSUR Data Lock

Point


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


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


Change of DSUR Data Lock Point


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

Interruption or Discontinuation

Of Clinical Trials


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

FINAL DSUR


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


Responsibilities for Preparing & Submitting DSURSponsor’s ResponsibilitiesShared ResponsibilitiesNon-Commercial Sponsor ResponsibilitiesMultiple sponsors in formal agreements

Reference Safety Info


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

FORMAT AND PRESENTATION

OF DSUR


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


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


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


Table of Contents (Contd..)LiteratureOther DSURsSignificant manufacturing changesLack of efficacyPhase I protocol modificationsLate Breaking informationOverall safety assessment


Table of Contents (Contd..)Evaluation of risksBenefit risks considerationsConclusionsSummary of important risksAppendices to DSUR

TITLE PAGE


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


EXECUTIVE SUMMARY


Executive summaryConcise summary of the important

information contained in the reportTogether with title page, serves as Stand

alone document for EC submission


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

INTRODUCTION


IntroductionReporting period and sequential number of

reportBrief description of the drug, eg., therapeutic

class, mode of action, route of administration, formulation


Worldwide Marketing Authorization statusMarketing application submitted in one or

more countriesTable format


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


Changes to Reference Safety InfoSignificant safety related changes to IBChanges to ContraindicationsWarningsPrecautionsAdverse reactions of special interestInteractionCarcinogenicity, mutagenicity from non-

clinical studies


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


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

Estimated Exposure


Cumulative subject exposreData on subject exposure to the

Investigational productActive comparatorsPlacebo

No of trial subjects by age group, gender and ethnic origin


Estimated Exposure


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


General Considerations


General ConsiderationsVersion of Coding dictionary usedVersion of documentVersion used as Reference Safety Information


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


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


Deaths in theReporting Period


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


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


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

Relevant Findings


Relevant findings from non-interventional studies

Relevant findings from meta-analysed or pooled data of RCT

Safety findings from marketing experience


Other Information


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

Overall Safety Assessment


Overall Safety AssessmentConcise, integrated assessment of all new

Clinical informationNon-clinical informationEpidemiological information


Evaluation of RisksBenefit Risk ConsiderationsConclusionSummary of important risks

Appendices


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)

Regional Appendices


Regional AppendicesDrop outs in association with Adverse eventsDeathsSummary Tabulations of SARs

Questions….?

Thank You

DSUR

Health & Medicine

Transcript of DSUR