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

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

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

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 approach—the FDA's adverse event reporting system and the European EudraVigilance programme—relies 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 An analysis of 21 drugs withdrawn in France between 1998 and 2004 showed that 19 withdrawals were linked to spontaneous case reports[2].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

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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

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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)

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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.

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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

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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

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

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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

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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

Current Work

HIMSS Meeting New Orleans February 2007 Brigham & Women’s Hospital – Dr. David Bates CRIX

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Brigham & Women’s 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

Improving Spontaneous Reporting at the Point of Care

Capture Pt Data in EMR Physician Interaction with EMR (RFD) to report ADR CRIX Processes / Stores ICSR F

DA

FD

AR

FD

RF

DC

RIX

CR

IXM

AH

MA

HE

MR

EM

R Physician d/c’s drug due to ADR

Pt’s info. recorded in EMR

RFD invoked

Appropriate AE Form

Retrieved

Complete prepopulated AE

Form

Digitally sign form / release form

Convert to HL7 ICSR

(E2B) / send form to CRIX

ICSR rec’d / Triaged

ICSR stored in database

Drug(s) matched

against MAHs

Terms

EMR: Electronic Medical RecordADR: Adverse Drug ReactionAE: Adverse EventICSR: Individual Case Safety ReportMAH: Manufacturing Authorization Holder

Improving Spontaneous Reporting at the Point of Care

CRIX Reports ICSRs to MAHs / FDA

FD

AF

DA

MA

HM

AH

CR

IXC

RIX

RF

DR

FD

EM

RE

MR

E2B ICSRs sent via EDC Gateway to

MAHs

Receive ICSR vis

EDC Gateway

E2B ICSRs sent via EDC Gateway to

FDA

Receive ICSR vis

EDC Gateway

Transmission Problems?

Transmission Problems?

CRIX troubleshoots transmission

Issues

YES

YES

NO

NO

Transmission Problems?

Transmission Problems?

Site handles case questions

YES

YES

End

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Vision: The foundations of a Sentinel Network

Computer-assisted Surveillance

RFD

RFD+

E2B

EMR

Manufacturers

RegulatorsCRIX

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

Demonstration

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A Continuing Effort…

1-Jul-07 22-Dec-08

10/1/2007 1/1/2008 4/1/2008 7/1/2008 10/1/2008

12/19/2007Complete training

11/9/2007Complete build

31-Jul-07

7/2/2007 - 12/31/2007Study PHASE I

12/7/2007Complete testing

31-Dec-07Roll out PHASE I

Today

9/1/2007Final design of RFD form

7/31/2007Mtg with FDA

8/18/2007Complete primary requirements

30-Mar-08Interim Report /

possible expansion of study to other sources

14-Apr-0812/10/2007 1-Oct-081-Jul-08

6/23/2008Interim Report

31-Dec-08Study COMPLETION (final reports to follow)

RFD and CRIX Development Continue Throughout

Go / No-go decision points

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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)

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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

Thank you