Post-Approval Safety Data Management:Definitions and Standards for Expedited               Reporting               ICH-E2D...
Definition and Terminology                      Basic TermsAdverse Event (AE) (or Adverse Experience)  Any untoward medi...
Definition and Terminology                   Basic TermsAdverse Drug Reaction (ADR)  All noxious and unintended response...
Definition and Terminology                    Basic TermsAdverse Drug Reaction (ADR)  A reaction in contrast to an event...
Definition and Terminology    Serious Adverse Event or Adverse Drug ReactionSerious adverse event / ADR (experience)  Re...
Definition and Terminology                     Basic TermsUnexpected Adverse Drug Reaction  If AE is not consistent with...
Definition and Terminology                    Basic TermsUnexpected Adverse Drug Reaction  Drug Class ADRs considers exp...
Definition and Terminology                   Basic TermsUnexpected Adverse Drug Reaction  “Listed or unlisted” terms des...
Definition and Terminology                    Basic TermsUnexpected Adverse Drug Reaction  Labeled or unlabeled (Expecte...
Definition and Terminology                      Basic TermsHealthcare Professional (HP)   A medically – qualified person...
Sources of individual Case Safety Reports               Unsolicited SourcesSpontaneous ReportsLiteratureInternetOther ...
Sources of individual Case Safety Reports                 Unsolicited SourcesSpontaneous Reports  A communication by HP ...
Sources of individual Case Safety Reports                   Unsolicited SourcesSpontaneous Reports     e.g.     healthca...
Sources of individual Case Safety Reports                Unsolicited SourcesLiterature Reports  MAH regularly should rev...
Sources of individual Case Safety Reports                      Unsolicited SourcesLiterature ADR Reports  Identifiable p...
Sources of individual Case Safety Reports                 Unsolicited SourcesLiterature Reports  If multiple products ar...
Sources of individual Case Safety Reports               Unsolicited SourcesInternet report  If MAH become aware of an AD...
Sources of individual Case Safety Reports                 Unsolicited SourcesInternet report   Unsolicited cases should ...
Sources of individual Case Safety Reports                 Unsolicited SourcesOther Sources  A non medical sources e.g. t...
Sources of individual Case Safety Reports                 Solicited Sources Reports Derived from Organized Data Collectio...
Sources of individual Case Safety Reports                  Solicited SourcesReports Derived from Organized Data Collectio...
Sources of individual Case Safety Reports              Contractual AgreementsMarketing of medicines takes place between t...
Sources of individual Case Safety Reports        Contractual Agreements (cont.d)Safety personnel to be involved in develo...
Sources of individual Case Safety Reports           Regulatory Authority SourcesIndividual serious unexpected adverse dru...
Standards for Expedited Reporting            What Should be ReportedSerious and unexpected ADRs (15 days)Serious, Expect...
Standards for Expedited Reporting           What Should Not be ReportedNon-Serious and Unexpected ADRsNon-Serious and Ex...
Standards for Expedited Reporting            What Should Not be ReportedOther observations  Any observation that could c...
Standards for Expedited Reporting            What Should Not be ReportedLack of Efficacy  Evidence of lack of efficacy s...
Standards for Expedited Reporting           What Should Not be ReportedOverdose  Collect any information on overdose  R...
Standards for Expedited Reporting          Minimum Criteria for ReportingMinimum Criteria for Reporting  An identifiable...
Standards for Expedited Reporting               Reporting Time FramesAll Serious, Unexpected ADRs  No later than 15 cale...
Standards for Expedited Reporting              Reporting Time FramesAll Serious ADRs  Time frames varies among countries...
Standards for Expedited Reporting        Good Case Management PracticesReports to be  Authentic  Accurate  Complete as...
Standards for Expedited Reporting     Assessing Patient and Reporter IdentifiabilityIdentifiability   Verify the existen...
Standards for Expedited Reporting     Assessing Patient and Reporter IdentifiabilityIdentifiable Reporter  All parties p...
Standards for Expedited Reporting                 The Role of Narratives Objective of Narratives   Summarize all relevan...
Standards for Expedited Reporting               The Role of NarrativesObjective of Narratives Avoid abbreviations and ac...
Standards for Expedited Reporting                Clinical Case Evaluation Medical Review  Ensure correct interpretations...
Standards for Expedited Reporting              Follow-up informationPrioritization of case reports1.Serious and unexpecte...
Standards for Expedited Reporting                Follow-up informationObtain the follow up information via1.Telephone cal...
Standards for Expedited Reporting                          How to Report CIOMS-I It’s important that certain basic data ...
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ICH - E2D Pharmacovigilance and Drug Safety - Professor Peivand Pirouzi

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ICH - E2D Pharmacovigilance and Drug Safety - Pharmaceuticals

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ICH - E2D Pharmacovigilance and Drug Safety - Professor Peivand Pirouzi

  1. 1. Post-Approval Safety Data Management:Definitions and Standards for Expedited Reporting ICH-E2D Professor Peivand Pirouzi 2010
  2. 2. Definition and Terminology Basic TermsAdverse Event (AE) (or Adverse Experience) Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
  3. 3. Definition and Terminology Basic TermsAdverse Drug Reaction (ADR) All noxious and unintended responses to a medicinal product. “responses to a medicinal product” means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility.
  4. 4. Definition and Terminology Basic TermsAdverse Drug Reaction (ADR) A reaction in contrast to an event is characterized by the fact that a causal relationship between the drug and the occurrence is suspected. “if an event is spontaneously reported, even if the relationship is unknown or unstated, it meets the definition of an adverse drug reaction.
  5. 5. Definition and Terminology Serious Adverse Event or Adverse Drug ReactionSerious adverse event / ADR (experience) Results in death. Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent or significant disability/incapacity, Is a congenital anomaly/birth defect.
  6. 6. Definition and Terminology Basic TermsUnexpected Adverse Drug Reaction If AE is not consistent with the term or description used in the product labeling (Package Insert or summary of Product Characteristics) If uncertain whether an ADR is expected or unexpected, the ADR should be treated as unexpected. ADR with fatal outcome should be unexpected unless the local /regional product labeling states that the ADR might be associated with a fatal outcome.
  7. 7. Definition and Terminology Basic TermsUnexpected Adverse Drug Reaction Drug Class ADRs considers expected if the event is in the local /regional product labeling of the specific drug.
  8. 8. Definition and Terminology Basic TermsUnexpected Adverse Drug Reaction “Listed or unlisted” terms describe the expectedness of ADRs in association with the Development Core Safety Information (DSCI) in an Investigator’s Brochure.
  9. 9. Definition and Terminology Basic TermsUnexpected Adverse Drug Reaction Labeled or unlabeled (Expected or unexpected) are terms should be used in connection with official product information for marketed medicines such as US Package insert, an EU SPC or other country data sheets.
  10. 10. Definition and Terminology Basic TermsHealthcare Professional (HP) A medically – qualified person such as physician, dentist, pharmacist, nurse, coroner or as otherwise specified by local regulations.Consumer A person who is not a healthcare professional such as a patient, lawyer, friend, or relative of a patient.
  11. 11. Sources of individual Case Safety Reports Unsolicited SourcesSpontaneous ReportsLiteratureInternetOther Sources
  12. 12. Sources of individual Case Safety Reports Unsolicited SourcesSpontaneous Reports A communication by HP or consumer to a company, Regulatory Authority or other organization. Describes one or more adverse drug reactions A patient was given one or more medicinal products Not reported from a study or any organized data collection scheme
  13. 13. Sources of individual Case Safety Reports Unsolicited SourcesSpontaneous Reports e.g. healthcare professional letter publication in the press Questioning of HP by company representatives Consumer adverse reaction reports Note: If reports received from consumers which do not qualify for regulatory reporting, the cases should be retained.
  14. 14. Sources of individual Case Safety Reports Unsolicited SourcesLiterature Reports MAH regularly should review the reference databases or literatures. Frequency of the literature searches depends to local requirements or at least every two weeks.
  15. 15. Sources of individual Case Safety Reports Unsolicited SourcesLiterature ADR Reports Identifiable patient Report source (a copy of article to sent if requested) Expedited reporting time clock starts as soon as minimum criteria is available If product source not specified, the MAH should assume that the product is its product. (the report should indicate that the specific brand was not identified).
  16. 16. Sources of individual Case Safety Reports Unsolicited SourcesLiterature Reports If multiple products are in the literature, a report should be submitted only by the applicant whose product is suspected. Suspected product which is identified by the article’s author
  17. 17. Sources of individual Case Safety Reports Unsolicited SourcesInternet report If MAH become aware of an ADR on a website and is not managed by MAH, the MAH should review and determine the reportability of the ADR.
  18. 18. Sources of individual Case Safety Reports Unsolicited SourcesInternet report  Unsolicited cases should be handled as spontaneous reports Verify the reporter refer to existence of a real person (verify the patient and reporter exist) e.g. report from email
  19. 19. Sources of individual Case Safety Reports Unsolicited SourcesOther Sources A non medical sources e.g. the lay press or other media Should be handled as a spontaneous report For reportability, the same criteria should be applied as for other reports
  20. 20. Sources of individual Case Safety Reports Solicited Sources Reports Derived from Organized Data Collection Systems Clinical Trials Registries Post approval named patient use programs SAP) Other patient support and disease management programs Surveys of patients or healthcare providers
  21. 21. Sources of individual Case Safety Reports Solicited SourcesReports Derived from Organized Data Collection Systems Should not be considered as spontaneous reports. Should be classified as study reports. Should have causality assessment by HP or MAH.
  22. 22. Sources of individual Case Safety Reports Contractual AgreementsMarketing of medicines takes place between two or more companyMay market same product in the same or different counties/regionThis can be a complex issue Define in the agreements, the processes for exchange of safety information, including timelines and regulatory reporting Process to be in place to avoid duplicate of the reporting
  23. 23. Sources of individual Case Safety Reports Contractual Agreements (cont.d)Safety personnel to be involved in development of any agreementsOne company to be responsible for literature screeningMAH is ultimately responsible for regulatory reportingMinimize the data exchange period between contracting partners and MAH
  24. 24. Sources of individual Case Safety Reports Regulatory Authority SourcesIndividual serious unexpected adverse drug reaction reports (ISUADR) originating from foreign regulatory authority to be expedited reporting to other authorities by MAHDo not report SADR without new information to the originating regulatory authority unless specified by local regulations
  25. 25. Standards for Expedited Reporting What Should be ReportedSerious and unexpected ADRs (15 days)Serious, Expected ADRs (varies among countries) (PSUR)
  26. 26. Standards for Expedited Reporting What Should Not be ReportedNon-Serious and Unexpected ADRsNon-Serious and Expected ADRs Note: These to be reported in the PSUR Note: FDA requires everything
  27. 27. Standards for Expedited Reporting What Should Not be ReportedOther observations Any observation that could change the risk benefit evaluation of the product to be communicated to RA in accordance with local regulation as soon as possible E.g. lack of efficacy with a drug used in a serious disease.
  28. 28. Standards for Expedited Reporting What Should Not be ReportedLack of Efficacy Evidence of lack of efficacy should be discussed in the PSUR Medicinal Products used for the treatment of life- threatening/serious diseases, vaccines and contraceptives, the lack of efficacy report should be considered for expedited reporting.
  29. 29. Standards for Expedited Reporting What Should Not be ReportedOverdose Collect any information on overdose Reports with no associated adverse outcome not to be reported as Adverse Reactions. SADR are consider subject to expedited reporting, unless specified by local regulation. Follow up to ensure the information is as complete as possible with regard to symptoms, treatment and outcome.
  30. 30. Standards for Expedited Reporting Minimum Criteria for ReportingMinimum Criteria for Reporting An identifiable reporter An identifiable patient An adverse reaction Suspect product
  31. 31. Standards for Expedited Reporting Reporting Time FramesAll Serious, Unexpected ADRs No later than 15 calendar days. The date report fulfills minimum criteria considered day 0
  32. 32. Standards for Expedited Reporting Reporting Time FramesAll Serious ADRs Time frames varies among countries depending on source, expectedness and outcome.
  33. 33. Standards for Expedited Reporting Good Case Management PracticesReports to be Authentic Accurate Complete as possible Non duplicative
  34. 34. Standards for Expedited Reporting Assessing Patient and Reporter IdentifiabilityIdentifiability Verify the existence of a patient and a reporter Apply local data privacy laws Prevent duplication of the report Identifiable Patient Age or age category (adolescent, adult, elderly) Gender Initials Date of Birth Name Patient identification number
  35. 35. Standards for Expedited Reporting Assessing Patient and Reporter IdentifiabilityIdentifiable Reporter All parties providing the information should be identifiable
  36. 36. Standards for Expedited Reporting The Role of Narratives Objective of Narratives Summarize all relevant clinical information Patient characteristics Therapy details Medical history Clinical course of the events Diagnosis Outcome Laboratory evidence Any other information supports or refutes an ADR
  37. 37. Standards for Expedited Reporting The Role of NarrativesObjective of Narratives Avoid abbreviations and acronyms (except of laboratory parameters and units) Summarize the autopsy or post-mortem finding Reflect the Terms e.g. adverse event, ADRs, indication and medical conditions in appropriate data field
  38. 38. Standards for Expedited Reporting Clinical Case Evaluation Medical Review Ensure correct interpretations of medical information Review for the quality and completeness Is a diagnosis possible? Have the relevant diagnostic procedures been performed? Were alternative causes of the reactions (s) considered? What additional information is needed? Use the verbatim term is used by the reporter
  39. 39. Standards for Expedited Reporting Follow-up informationPrioritization of case reports1.Serious and unexpected2.Serious and expected3.Non-serious and unexpected4.Cases might lead to labeling change
  40. 40. Standards for Expedited Reporting Follow-up informationObtain the follow up information via1.Telephone call2.Site visit3.Written request (make specific questions by questioners or specific form) Note: if information refused by the reporter, a regulatory authority might be able to help in obtaining follow up data
  41. 41. Standards for Expedited Reporting How to Report CIOMS-I It’s important that certain basic data elements be included with any expedited report, whether in a tabular or narrative presentation. MedDRA to be used for coding medical information Links: Canada Guide book:  http://www.hc-sc.gc.ca/dhp-mps/medeff/report-declaration/ar- ei_form-eng.php CIOMS Form:  http://www.hc-sc.gc.ca/dhp-mps/medeff/report-declaration/ar- ei_form-eng.php
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