Data Management in Pharmacovigilance

1. Data Management in Pharmacovigilance Sanjeev Miglani MD COO and Scientific Director CIDP Biotech India International Conference and CME workshop on Pharmacovigilance Systems and Rational Use of Drugs: An integrated approach ; 27 Nov 2010

2. Overview Importance of Pharmacovigilance Source of ADRs Triage Case Processing Different PharmacovigilanceSoft Wares

3. Pharmacovigilance Collection of the information Processing in a Database Medical Evaluation, Analysis and Signal Detection Reporting

4. Importance of Safety Monitoring Capture of Complete safety data Regulatory agencies becoming proactive Ethical requirements Serious consequences due to Non compliance

5. SOURCE OF REPORT • Spontaneous Reports Unsolicited communication by a healthcare professional or consumer to a company, regulatory authority or other organization that describes one or more ADRs in a patient who was given one or more medicinal products and that does not derive from a study or any organized data collection scheme.

6. Literature • Each MAH is expected to regularly screen the worldwide scientific literature by accessing widely used systematic literature reviews or reference databases. • The frequency of the literature searches should be according to local requirements • A copy of the article might be requested by the local regulatory authority to accompany the report.

7. Solicited Sources Solicited reports are those derived from organized data collection systems, which include clinical trials, registries, post-approval named patient use programs, other patient support and disease management programs, surveys of patients or healthcare providers, or information gathering on efficacy or patient compliance.

8. Contractual Agreements • The marketing of many medicines increasingly takes place through contractual agreements between two or more companies, which may market same product in the same or different countries/region. • Arrangements vary considerably with respect to inter-company communication and regulatory responsibilities.

9. Regulatory Authority Sources • Individual serious unexpected ADRs originating from foreign RAs are subject to expedited reporting to other authorities by each MAH. • Re-submission of serious ADR cases without new information to the originating RA is not usually necessary, unless otherwise specified by local regulation.

10. Call Centers • A centralized office used for the purpose of receiving and transmitting a large volume of requests by telephone. • They provide service to pharmaceutical companies with a complete post-marketing surveillance solution including adverse event monitoring and reporting; drug information services; and product complaint management.

12. TRIAGE OF CASES • Once the complaint is received at PV department of a company, it must be properly classified for processing. • The initial triage should be to determine whether the report needs urgent processing in order to be transmitted to the RAs, or business partners. • Experienced and qualified personnel should always supervise triage

13. Triage should cover, at the least, the following: • ADRs • PQCs associated with ADRs • PQCs • Medical Inquiries • legal • ADRs can further be triaged using the following criteria: • Serious or non serious • Expected or unexpected • Causality (Specially for SAEs from Clinical Trials)

14. The minimum information required for reporting purposes is: • An identifiable patient • the name of a suspect medicinal product • an identifiable reporting source, and, • an event or outcome that can be identified as serious and unexpected and for which, in clinical investigation cases, there is a reasonable suspected causal relationship.

15. Case Processing • Data entry into safety database • Medical coding • QC review • Medical review

16. Data Entry: • For user friendliness, the front end of these software are made in such a way that end user can enter data very easily and more accurately. • These systems generally require additional mandatory fields like date of receipt of ADR, Source Country, type of source. • Once the case with minimum information for reporting is entered, the case is saved

17. Information can be divided into following fields, • Subject (data related to subject like name or initials, height, weight, gender, age ,pregnancy etc) • Suspect Drug (data relate to suspected medicinal product like name, start date, end date, duration of exposure, formulation, dose and dosage form, indication etc), • Event (which includes fields like, reporter’s verbatim, company’s verbatim, MedDRA terms, event onset date, event end date, etc).

18. Reporter’s information may include (reporter’s name, contact address, phone number, e-mail id, whether reporter is a Health care professional or not, secondary or tertiary reporter, etc), • Reportability or submission fields may include country where the case is reportable, schedule of reports, including due date of submission, etc)

21. Narratives • The objective of the narrative is to summarize all relevant clinical and related information • The narrative should serve as a comprehensive, stand-alone “medical story”. • The information should be presented in a logical time sequence; ideally this should be presented in the chronology of the patient’s experience, rather than in the chronology in which the information was received.

22. MedDRA • Coding of: – Adverse events – Medical history – Signs and symptoms – Diagnoses – Physical examination data – Laboratory tests

23. WHO-DD • The WHO Drug Dictionaries consist of medicinal product names - both proprietary and nonproprietary - from more than 90 countries. • All drugs in the WHO Drug Dictionary and the WHO Drug Dictionary Enhanced are classified according to the Anatomical Therapeutic Chemical classification – ATC.

24. FOLLOW-UP INFORMATION • All efforts should be made to seek additional information for good assessment of case • The priority of cases for follow-up should be as follows: • Serious and unexpected, • Serious and expected, and • Non-serious and unexpected • In addition to seriousness and expectedness as criteria, cases “of special interest” also deserve extra attention as a high priority

25. QC Review • After Data entry, a drug safety specialist reviews the data entry against the source documents and reviews the case narrative. • A clear methodology on the quality check should be developed • Follow-up information should be requested when the initial case is incomplete or unclear.

26. Medical Review • The medical review should generally cover the medical content of the case with particular attention paid to the narrative, the suspect and concomitant drugs (including dosages), the past medical history, and coding. • The review should also include, but is not limited to, the following considerations: •Is a diagnosis possible? •Have the relevant diagnostic procedures been performed? •Were alternative causes of the reaction(s) considered? •What additional information is needed? • .

27. Tracking and Metrics • It is critical that all cases reports be tracked • The tracking of cases should base on the workflow step • Each drug safety specialist and manager should be aware of status of all the cases • The manager can reallocate cases or other work to ensure that the time-critical cases are handled appropriately. • Similarly, non expedited cases that need to be completed for aggregate reports should be tracked so that they are completed by the time of data lock.

28. Line Listings: Example

29. Vigiflow • Safety data Base is hosted by the Uppsala Monitoring Center • Internationally recognised standards –E2B report format –WHO-ART and ICD or MedDRA –WHO Drug Dictionary • One server installation –maintained in UMC

30. Oracle's Argus Safety suite • Oracle Argus Affiliate: local affiliates and among partners, lowering risk from unanticipated reporting delays. • Oracle Argus Interchange: Electronic exchange • Oracle Argus Reconciliation: SAE reconciliation • Oracle Argus Dossier: Periodic safety update report • Oracle Argus Insight: Multidimensional analysis of drug safety data. It can generate preformatted filterable safety reports • Oracle Argus Perceptive: an integrated solution for signal management.

31. Aris G Safety Soft ware Suite • ARISg™: Used for the Collection, coding, Assessment and Reporting of Adverse events data • ARISj™: Japanese pharmacovigilance system • agXchange ESM™: Electronic exchange • agXchange IRT™: Inbound receipt and triage of ADRs • agConnect™: Clinical safety reconciliation system • agComposer™:Comprehensive periodic and aggregate reporting system • agSignals™:Advanced signal detection and data mining system