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Presentation of how to write DSUR

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  1. 1. Developmental Safety <br />Update Report<br />(DSUR)<br />Dr.S.Gunasakaran, MD<br />Dr.S.Gunasakaran,MBBS,MD<br />1<br />
  2. 2. OBJECTIVE<br />Dr.S.Gunasakaran,MBBS,MD<br />2<br />
  3. 3. Objective of DSUR<br />Ongoing assessment of risk to trial subjects<br />Notification of Ethics Committees and Regulators at regular intervals<br />Actions proposed to address safety concerns<br />Dr.S.Gunasakaran,MBBS,MD<br />3<br />
  4. 4. Dr.S.Gunasakaran,MBBS,MD<br />4<br />
  5. 5. Dr.S.Gunasakaran,MBBS,MD<br />5<br />
  6. 6. SCOPE of DSUR<br />Dr.S.Gunasakaran,MBBS,MD<br />6<br />
  7. 7. Scope of DSUR<br />Data from Interventional Clinical Trials<br />Commercial and Non-Commercial Sponsors<br />Safety findings from non-clinical studies<br />Safety findings from clinical trials conducted by co-development partner<br />Non-interventional / Compassionate use <br />Dr.S.Gunasakaran,MBBS,MD<br />7<br />
  8. 8. When should a DSUR be prepared?<br />Dr.S.Gunasakaran,MBBS,MD<br />8<br />
  9. 9. Sponsor overseeing more than one clinical trial of a single investigational product should prepare one DSUR<br />With single Data Lock Point (DLP)<br />Dr.S.Gunasakaran,MBBS,MD<br />9<br />
  10. 10. Periodicity and DSUR Data Lock Point<br />Dr.S.Gunasakaran,MBBS,MD<br />10<br />
  11. 11. Periodicity and DSUR Data Lock Point<br />Intended to be annual report<br />As long as sponsor conducts clinical trials with ID<br />As long as appropriate to satisfy local regulatory requirements<br />DSUR Executive Summary supplemented with line listings of SAE for <br />Ethics committee<br />IRBs<br />Investigators<br />Dr.S.Gunasakaran,MBBS,MD<br />11<br />
  12. 12. Periodicity and DSUR Data Lock Point<br />DSUR should be submitted no later than 60 calendar days from DSUR data lock point<br />Development International Birth Date (DIBD):<br />Date of the sponsor’s first authorization to conduct a clinical trial in any country<br />For administrative convenience, DIBD is the last day of MOA<br />Clinical trials going in one country and are later initiated in any other countries, one DSUR on same DIBD<br />Dr.S.Gunasakaran,MBBS,MD<br />12<br />
  13. 13. Change of DSUR Data Lock Point<br />Dr.S.Gunasakaran,MBBS,MD<br />13<br />
  14. 14. Change of DSUR Data Lock Point<br />Once the drug has received a marketing approval in any country<br />Change the DSUR data lock point to Coincide with IBD<br />DSUR and PSUR should be synchronized<br />During synchronization, the period covered by next DSUR should not be longer than 1 year<br />Dr.S.Gunasakaran,MBBS,MD<br />14<br />
  15. 15. Interruption or Discontinuation<br />Of <br />Clinical Trials<br />Dr.S.Gunasakaran,MBBS,MD<br />15<br />
  16. 16. Interruption or Discontinuation of Clinical Trials<br />DSUR should be prepared and submitted <br />Sponsor not collected any further data pertinent to the clinical development programme in the period of DSUR, a covering letter<br />Dr.S.Gunasakaran,MBBS,MD<br />16<br />
  17. 17. FINAL dSUR<br />Dr.S.Gunasakaran,MBBS,MD<br />17<br />
  18. 18. Final DSUR <br />When annual reports of clinical trials no longer required in a country, DSUR should be accompanied by a Cover letter <br />Whether or not clinical trials are continuing elsewhere<br />Dr.S.Gunasakaran,MBBS,MD<br />18<br />
  19. 19. Responsibilities for Preparing & Submitting DSUR<br />Sponsor’s Responsibilities<br />Shared Responsibilities<br />Non-Commercial Sponsor Responsibilities<br />Multiple sponsors in formal agreements<br />Dr.S.Gunasakaran,MBBS,MD<br />19<br />
  20. 20. Reference Safety Info<br />Dr.S.Gunasakaran,MBBS,MD<br />20<br />
  21. 21. Reference Safety Information<br />Used to assess whether the safety information received during the reporting period remains consistent with previous knowledge of safety profile of ID.<br />IB is the RSI<br />SmPC is the RSI for non-commercial sponsors conducting clinical trial with marketed products<br />Dr.S.Gunasakaran,MBBS,MD<br />21<br />
  22. 22. Format and presentation<br />Of <br />DSUR<br />Dr.S.Gunasakaran,MBBS,MD<br />22<br />
  23. 23. Table of contents<br />Title page<br />Executive summary<br />Introduction<br />Worldwide Marketing Authorization Status<br />Update on actions taken in the Reporting Period for Safety Reasons<br />Changes to Reference Safety Information<br />Estimated Exposure<br />Cumulative subject exposure in Clinical Trials<br />Patient Exposure from Marketed setting<br />Dr.S.Gunasakaran,MBBS,MD<br />23<br />
  24. 24. Table of Contents (Contd..)<br />Presentation of Safety Data from Clinical Trials<br />General considerations<br />Interval line listing of SARs<br />Cumulative summary tabulations<br />Deaths in reporting period<br />Subjects who dropped out<br />Significant findings from Clinical trials<br />Completed CTs and Interim Analysis<br />Ongoing Clinical Trials<br />Dr.S.Gunasakaran,MBBS,MD<br />24<br />
  25. 25. Table of Contents (Contd..)<br />Other therapeutic use of investigational drug<br />New safety data related to combination therapies<br />Relevant findings from non-interventional clinical studies<br />Relevant findings from other studies<br />Safety findings from marketing experience<br />Other information<br />Non-clinical data<br />Long-term follow-up<br />Dr.S.Gunasakaran,MBBS,MD<br />25<br />
  26. 26. Table of Contents (Contd..)<br />Literature<br />Other DSURs<br />Significant manufacturing changes<br />Lack of efficacy<br />Phase I protocol modifications<br />Late Breaking information<br />Overall safety assessment<br />Dr.S.Gunasakaran,MBBS,MD<br />26<br />
  27. 27. Table of Contents (Contd..)<br />Evaluation of risks<br />Benefit risks considerations<br />Conclusions<br />Summary of important risks<br />Appendices to DSUR<br />Dr.S.Gunasakaran,MBBS,MD<br />27<br />
  28. 28. TITLE PAGE<br />Dr.S.Gunasakaran,MBBS,MD<br />28<br />
  29. 29. Title page<br />DSUR number (reports should be numbered sequentially)<br />Investigational drug(s)<br />Reporting Period<br />Date of Report<br />Sponsor name and address<br />Confidentiality statement<br />Note regarding the inclusion of unblinded information in the DSUR<br />Dr.S.Gunasakaran,MBBS,MD<br />29<br />
  30. 30. EXECUTIVE SUMMARY<br />Dr.S.Gunasakaran,MBBS,MD<br />30<br />
  31. 31. Executive summary<br />Concise summary of the important information contained in the report<br />Together with title page, serves as Stand alone document for EC submission<br />Dr.S.Gunasakaran,MBBS,MD<br />31<br />
  32. 32. Information in Executive summary<br />Introduction – Report version & Reporting period<br />ID: MOA, class, indications, dose , RoA<br />Estimated cumulative clinical trial exposure<br />Marketing Authorization? Yes / No – If yes, no. of countries<br />Summary of overall safety assessment<br />Summary of important risks<br />Actions taken for safety reasons including changes to IB<br />Conclusion<br />Dr.S.Gunasakaran,MBBS,MD<br />32<br />
  33. 33. INTRODUCTION<br />Dr.S.Gunasakaran,MBBS,MD<br />33<br />
  34. 34. Introduction<br />Reporting period and sequential number of report<br />Brief description of the drug, eg., therapeutic class, mode of action, route of administration, formulation<br />Dr.S.Gunasakaran,MBBS,MD<br />34<br />
  35. 35. Worldwide Marketing Authorization status<br />Marketing application submitted in one or more countries<br />Table format<br />Dr.S.Gunasakaran,MBBS,MD<br />35<br />
  36. 36. Update on Actions Taken in the Reporting Period for Safety Reasons<br />Refusal of authorization of clinical trial<br />Partial or complete trial suspension for ethical or safety reasons<br />Failure to obtain marketing approval for tested indication<br />Protocol modifications due to safety reasons<br />Formulation changes due to safety reasons<br />Restrictions in study populations or indications<br />Dr.S.Gunasakaran,MBBS,MD<br />36<br />
  37. 37. Changes to Reference Safety Info<br />Significant safety related changes to IB<br />Changes to Contraindications<br />Warnings<br />Precautions<br />Adverse reactions of special interest<br />Interaction<br />Carcinogenicity, mutagenicity from non-clinical studies<br />Dr.S.Gunasakaran,MBBS,MD<br />37<br />
  38. 38. Status of Clinical trials ongoing and completed during Re. Period<br />Separate tables can be provided by<br />Indication<br />Formulation<br />Study population<br />Table should contain the following information<br />Protocol no.<br />Clinical trial phase (I-IV)<br />Status<br />Ongoing<br />completed<br />Dr.S.Gunasakaran,MBBS,MD<br />38<br />
  39. 39. Table should include<br />Abbreviated study title<br />Study design<br />Uncontrolled, controlled, open, single blind, double blind, parallel, cross over etc<br />Dose and regimen of study drug and comparators<br />Subject population<br />Age, sex, indication, special population groups, impaired renal or hepatic function<br />Date of first visit for first patient<br />Planned enrollment of study as a whole<br />Dr.S.Gunasakaran,MBBS,MD<br />39<br />
  40. 40. Estimated Exposure<br />Dr.S.Gunasakaran,MBBS,MD<br />40<br />
  41. 41. Cumulative subject exposre<br />Data on subject exposure to the <br />Investigational product<br />Active comparators<br />Placebo<br />No of trial subjects by age group, gender and ethnic origin<br />Dr.S.Gunasakaran,MBBS,MD<br />41<br />
  42. 42. Dr.S.Gunasakaran,MBBS,MD<br />42<br />
  43. 43. Estimated Exposure<br />Dr.S.Gunasakaran,MBBS,MD<br />43<br />
  44. 44. Presentation of Safety data from Clinical trials<br />Should contain both cumulative and interval safety information related to IP<br />Interval line listings of SAR<br />Cumulative tabulations of SARs since DBID<br />If MedDRA used, PT should be used<br />Tabulations of only Serious<br />Non-Serious and Incidental findings should not be included<br />Dr.S.Gunasakaran,MBBS,MD<br />44<br />
  45. 45. General Considerations<br />Dr.S.Gunasakaran,MBBS,MD<br />45<br />
  46. 46. General Considerations<br />Version of Coding dictionary used<br />Version of document<br />Version used as Reference Safety Information<br />Dr.S.Gunasakaran,MBBS,MD<br />46<br />
  47. 47. Interval line listings of SARs<br />Key information on all blinded and unblinded SARs reported during reporting period<br />SARs should be listed by protocol, indication or other variables<br />Dr.S.Gunasakaran,MBBS,MD<br />47<br />
  48. 48. Dr.S.Gunasakaran,MBBS,MD<br />48<br />
  49. 49. Cumulative Summary tabulations<br />Content of tabulations<br />Criteria for inclusions<br />Summary tabulations should present cumulative safety data from the DBID to the data lock point<br />Summary tabulations include no. of SARs organised by SOC for<br />Investigational product<br />Placebo<br />comparator<br />Dr.S.Gunasakaran,MBBS,MD<br />49<br />
  50. 50. Dr.S.Gunasakaran,MBBS,MD<br />50<br />
  51. 51. Deaths in the<br />Reporting Period<br />Dr.S.Gunasakaran,MBBS,MD<br />51<br />
  52. 52. Deaths in the Reporting Period<br />A list of subjects who died during participation in the investigation<br />Should be provided as appendix<br />Following information at a minimum<br />Case number<br />Assigned treatment<br />Cause of death<br />Dr.S.Gunasakaran,MBBS,MD<br />52<br />
  53. 53. Subjects who dropped out<br />Tabulations and listing on drop outs should be provided<br />Should be provided as an appendix<br />Safety issued identified from a review of these withdrawals should be described<br />Dr.S.Gunasakaran,MBBS,MD<br />53<br />
  54. 54. Significant findings from clinical trials during reporting period<br />Completed clinical trials and interim analysis<br />Ongoing clinical trials<br />Concise summary of any preliminary safety findings<br />Other therapeutic use of investigational drug<br />New safety data related to combination therapies<br />Dr.S.Gunasakaran,MBBS,MD<br />54<br />
  55. 55. Relevant Findings<br />Dr.S.Gunasakaran,MBBS,MD<br />55<br />
  56. 56. Relevant findings from non-interventional studies<br />Relevant findings from meta-analysed or pooled data of RCT<br />Safety findings from marketing experience<br />Dr.S.Gunasakaran,MBBS,MD<br />56<br />
  57. 57. Other Information<br />Dr.S.Gunasakaran,MBBS,MD<br />57<br />
  58. 58. Other information <br />Non clinical data<br />Invivo or invitro studies<br />Carcinogenicity, reproduction, immunotoxicity studies<br />Long term follow up<br />Gene herapy, cell therapy products, tissue engineered products<br />Literature<br />Other DSURs<br />Significant manufacturing changes<br />Lack of efficacy<br />Dr.S.Gunasakaran,MBBS,MD<br />58<br />
  59. 59. Overall Safety Assessment<br />Dr.S.Gunasakaran,MBBS,MD<br />59<br />
  60. 60. Overall Safety Assessment<br />Concise, integrated assessment of all new<br />Clinical information<br />Non-clinical information<br />Epidemiological information<br />Dr.S.Gunasakaran,MBBS,MD<br />60<br />
  61. 61. Evaluation of Risks<br />Benefit Risk Considerations<br />Conclusion<br />Summary of important risks<br />Dr.S.Gunasakaran,MBBS,MD<br />61<br />
  62. 62. Appendices<br />Dr.S.Gunasakaran,MBBS,MD<br />62<br />
  63. 63. Appendices to the DSUR<br />Investigator’s Brochure<br />Cumulative table of important regulatory advice<br />Status of ongoing and completed clinical trials<br />Cumulative summary tabulations of Demographic Data<br />Line listings of SARs<br />Cumulative summary tabulation of SAEs<br />Scientific abstracts (if relevant)<br />Dr.S.Gunasakaran,MBBS,MD<br />63<br />
  64. 64. Regional Appendices<br />Dr.S.Gunasakaran,MBBS,MD<br />64<br />
  65. 65. Regional Appendices<br />Drop outs in association with Adverse events<br />Deaths<br />Summary Tabulations of SARs<br />Dr.S.Gunasakaran,MBBS,MD<br />65<br />
  66. 66. Questions….?<br />Dr.S.Gunasakaran,MBBS,MD<br />66<br />
  67. 67. Thank You<br />Dr.S.Gunasakaran,MBBS,MD<br />67<br />