1. Improving Spontaneous Reporting: A new business model Incorporating postmarket medical product safety data collection into the clinical practice workflow at the point-of-care Demonstration for FDA 31 July 2007

2. 2 Pfizer / CDISC Participants Pfizer Tom Swanekamp (Exec. Director, Safety & Risk Management) Bill Rosen (Exec. Director, Policy and Intelligence) Michael Celeste (Project Manager, RFD/Bates Study) Michael A. Ibara (Head of Pharmacovigilance Information Management) CDISC Landen Bain (CDISC Liaison to Healthcare) David Iberson-Hurst (Assero Limited / CDISC Technical Contact)

3. 3 Goals for this meeting Describe rationale for using the RFD and a public/private consortium to change the business model for pharmacovigilance Describe ongoing work Discuss FDA involvement with ongoing work

4. 4 Spontaneous Reporting Problems… …The broader question is how this reflects on regulatory processes used to monitor drug safety. Postmarketing surveillance, or pharmacovigilance, remains the weakest link in the regulatory process on both sides of the Atlantic. The current approachthe FDA's adverse event reporting system and the European EudraVigilance programmerelies heavily on passive surveillance… …it is important to note that the spontaneous reporting of suspected adverse drug reactions to regulatory authorities (in the UK to the Yellow Card scheme) continues to be of major importance in detecting potential safety signals. An analysis of 21 drugs withdrawn in France between 1998 and 2004 showed that 19 withdrawals were linked to spontaneous case reports[2]. A similar analysis of 11 product withdrawals between 1999 and 2001 in the UK and US showed evidence from spontaneous reports supported the withdrawal of 8 products[3]. BMJ 2007;334:1233-1234 (16 June), doi:10.1136/ bmj.39245.502546.BE

5. 5 Improving Spontaneous Reporting Many activities to improve signal generation and hypothesis testing Data mining Molecular techniques Electronic medical records / Observational data To date the spontaneous reporting system (SRS) is the primary source regarding potential adverse events SRS Advantage –Large number of heterogeneity of individuals potentially exposed –Easy to implement SRS Limitations –Sparse/inaccurate data –Underreporting / Limited recognition –Significant burden of reporting

6. 6 Improving safety at the point of care To improve SRS we must: 1.Improve physician reporting Improve recognition Decrease burden Improve data quality 2.Augment physician reporting Use other medical personnel Use automated methods that avoid physician time/attention A [system] design...suitable to a world in which the scarce factor is information may be exactly the wrong one for a world in which the scarce factor is attention (H.Simon)

7. 7 Hypothesis 1.Improving SRS - by increasing the number of number of high- data-quality reports of adverse events - can have a direct and beneficial effect on public safety 2.We can produce this result by lowering the burden of reporting on physicians and other health care professionals, and obtaining source data directly in the report 3.The proper application of health information technology (HIT) can produce the result in #2.

8. 8 Parts of the safety system Patients Providers Payers Health care provider organizations Hospitals Point-of-care applications (vendors) Other data collection and storage technologies (vendors) Communication technologies (vendors) Pharmaceutical companies FDA EMEA Regulators in each country in the world

9. 9 Improving the Spontaneous Reporting System To be successful we must address the system as whole If we increase the number of number of high-data-quality reports of adverse events, we must increase our capabilities to handle these events A complete solution involves: Addressing the burden of reporting events; Technologies that will enable a new solution; A new model for receiving and processing these events – e.g., a public/private organization to offload the burden of processing from industry and regulators

10. 10 Inconvenience Constrains Reporting Reporting adverse events interrupts the normal routine of providing care and imposes a burden on providers – greatly decreasing the probability that these events and conditions will be reported Not part of normal routine Not available at point of recognition Duplicate data entry High nuisance factor

11. 11 Enabling Technologies Must… Address major limitations Have persistent impact (vs., e.g., one-time training) Work with current systems and technologies (including reporting systems) Be adaptable to future systems and technologies RFD bridges point of care with SRS

12. 12 Public / Private Consortium If we increase the number of number of high-data-quality reports of adverse events, we must increase our capabilities to handle them A new model replaces the vertical industry organizations currently receiving and processing events with a public/private consortium This will allow us to Streamline the initial collection and reporting Offload the burden of processing from industry and regulators CRIX, International is now developing this service offering

13. Current Work HIMSS Meeting New Orleans February 2007 Brigham & Womens Hospital – Dr. David Bates CRIX

14. 14 Brigham & Womens Study Dr. David Bates, Partners Healthcare / Brigham and Women's Hospital Study use of RFD in Partners EMR (to begin 4Q) Participants Partners Healthcare CDISC CRIX Pfizer Would like to discuss FDA involvement Goal is to test hypotheses regarding use of RFD and CRIX to improve SRS

17. 17 Vision: The foundations of a Sentinel Network Computer-assisted Surveillance RFD + E2B EMR Manufacturers Regulators CRIX Provider / Patient E2B Data collection incorporated at point of care Leverage the EMR, both current and future Global solution – uses E2B standard Addresses issues common to Pharmacovigilance and Biosurveillance

18. Demonstration

19. 19 A Continuing Effort…

20. 20 Considerations for future work Expanding automatic triggering of forms Adding automated recognition of event class – customized form for that event class Adding bidirectional communication to the reporting process Adding additional reporting sources to supplement physicians (e.g., pharmacists)

21. 21 Discussion Would like to review with FDA the current study at Partners and receive input, opinions Would like to discuss specific involvement: To have FDA assessment of quality of triggered spontaneous reports from the study To use study as test organization for HL7 ICSR To explore enlargement (e.g. year 2) to augment MedSun work

22. Thank you