EMERGING ISSUES FOR SAFETY SURVEILLANCE: AN FDA PERSPECTIVE

1
EMERGING ISSUES FOR SAFETY SURVEILLANCE AN FDA
PERSPECTIVE

• Susan S. Ellenberg, Ph.D.
• Division of Biostatistics and Epidemiology
• Center for Biologics Evaluation and Research, FDA

Bio 99 Seattle, Washington May 19, 1999
2
THE TIMES THEY ARE ACHANGING

• International Harmonization
• Rapid technological advances
• New classes of products
• Increased consumer use of medical products
• Increasing public interest and awareness

3
MORE PRODUCTS, MORE USE

• New product classes for treatment of serious but
  common conditions
• myocardial infarction
• cancer
• diabetes
• arthritis
• New treatments aimed primarily at quality of
  life outcomes
• hair loss
• ED
• mood disorders/mild depression
• The aging baby boomers

4
INCREASED INTEREST IN PRODUCT SAFETY

• Medical community
• recent articles on number of deaths attributable
  to drug reactions need for new approaches to
  safety assessments
• Consumers
• books and articles in lay press on risks of
  medical treatments
• WWW
• activist groups (vaccines)

5
INTERNATIONAL HARMONIZATION

• Globalization of pharmaceutical industry
• Need for standardization of regulatory
  requirements
• reduce duplicative efforts
• ensure consistently high quality of worldwide
  drug development programs
• International Conference on Harmonization (ICH)
• Initiated in 1990
• Representatives of industry associations and
  regulatory authorities in U.S., Europe, Japan
• ICH Documents generate guidance documents and/or
  changes in regulations in each region

6
ICH AND PRODUCT SAFETY TWO AREAS

• Pre-clinical (in vitro, in vivo)
• toxicology
• carcinogenicity
• pharmacology
• Clinical (pre-market, post-market)
• size of clinical safety database (pre)
• standards for expedited reporting of adverse
  effects (pre, post)
• data elements for safety reporting (pre, post)
• periodic reports (post)

7
IMPACT OF ICH ON SAFETY REPORTING

• Expanded Reporting Definitions and Standards
• revision of regulations FR 10/6/97
• Data Elements for Transmission of Individual Case
  Safety Reports
• guidance document FR 1/15/98
• Periodic Safety Update Reports
• guidance document FR 5/19/97
• Electronic Submissions
• advance notice of proposed rulemaking FR
  11/5/98

8
ADVANCES IN TECHNOLOGY IMPLICATIONS FOR SAFETY
REPORTING

• Direct reporting by health professionals and
  consumers to MedWatch via the web
• Enhanced medical terminology (MedDRA) to replace
  COSTART
• Electronic submissions of periodic reports
  (non-serious and/or labeled events)
• Improving data base structure at FDA to
  facilitate report screening and review

9
FOR MORE INFORMATION ON ICH AND LINKS TO
GUIDELINES

• www.ifpma.org/ich1.html

10
POST-MARKETING REPORTING SYSTEMS FOR ADVERSE
EVENTS AT FDA

• Drugs and therapeutic biologics
• Adverse Event Reporting System (AERS) replaced
  old Spontaneous Reporting System in late 1997
• AERS contains more than 2 million reports, going
  back to 1960s
• AERS currently receives over 250,000 reports per
  year

11
POST-MARKETING REPORTING SYSTEMS FOR ADVERSE
EVENTS AT FDA (2)

• Vaccines
• Vaccine Adverse Event Reporting System (VAERS)
• Initiated in 1990
• Co-managed by FDA and CDC replaced separate
  agency systems
• 11,000-12,000 reports per year

12
POST-MARKETING REPORTING SYSTEMS FOR ADVERSE
EVENTS AT FDA (3)

• Medical Devices
• manufacturer and User Device Experience (MAUDE)
• mandatory reporting by user facilities in
  addition to manufacturers
• 80,000-85,000 reports per year

13
LIMITATIONS OF CURRENT REPORTING SYSTEMS

• Passive surveillance subject to substantial
  (and unquantified) underreporting
• Frequent inaccuracies and incompleteness
• Little incentive for reporting
• Causality assessment difficult/impossible with no
  comparator group
• Underreporting, plus lack of exposure data,
  preclude estimation of incidence rates
• Events with long latency period unlikely to be
  reported

14

• MANAGING THE RISKS FROM MEDICAL PRODUCT USE
• CREATING A RISK MANAGEMENT FRAMEWORK
• Report to FDA Commissioner issued May 10, 1999

15
FDA AND RISK MANAGEMENT

• FDA has an important role to play in managing
  medical product risk
• Many others play important roles
• product developers
• prescribers/caregivers
• pharmacists
• consumers
• Current systems of risk management should be
  re- examined and respective roles clarified

16
POSSIBLE NEW APPROACHES

• Pre-Market
• Large, community-based studies
• Staged roll-out of new products
• Post-Market
• Expanded access to large healthcare databases
• Sentinel reporting systems
• Expanded use of product registries
• Development of improved analytic methods

17
CONCLUSIONS OF FDA RISK MANAGEMENT ASSESSMENT

• Need for discussion with stakeholders
• Consider ways to improve
• risk interventions
• risk communication
• risk management

18
FULL COPY OF RISKMANAGEMENT REPORT AVAILABLE
ATwww.fda.gov/oc/tfrm/riskmanagement.pdf
19
SUMMARY

• FDA giving increased attention to safety
  assessment and safety surveillance problems
• Efforts are underway to modernize and expand
  current programs and activities
• New regulations and guidance documents should
  improve efficiency of international drug
  development programs and improve quality and
  utility of information provided to agency
• Risk management is everyones issue roles and
  optimal approaches need to be defined