1. 1 Drug Safety Oversight Board Update DIA Annual Meeting Philadelphia, PA June 21 st, 2006 Susan K. Cummins, MD, MPH Executive Director Drug Safety Oversight Board Center for Drug Evaluation and Research Food and Drug Administration

2. 2 Today’s Talk  Review the first year’s activities for the Drug Safety Oversight Board  Provide update on other DSB Activities Draft Drug Watch Guidance Posting of information sheets about emerging important drug safety concerns

3. 3 Definition: Important Drug Safety Issue A Drug Safety issue with the potential to:  Significantly alter the risk-benefit analysis of a drug  Affect physician’s decision to prescribe  Affect patient’s decision to use  Includes and is broader than regulatory definition of “serious and/or life-threatening” adverse event

4. 4 Drug Safety Oversight Board

5. 5 Definition: Oversight Oversight 1 (n): 1. Watchful care or management; supervision. 2. An unintentional omission or mistake. 1 The American Heritage® Dictionary of the English Language, Fourth Edition, 2000 by Houghton Mifflin Company

6. 6 Drug Safety Oversight Board Charge  Provide independent oversight and advice to Center Director on: Management of Important Drug Safety Issues Adjudication of organizational disputes Policies about management of drug safety issues Risk communication about important emerging drug safety concerns Development of HCP & patient information sheets

7. 7 Drug Safety Oversight Board Operational Principles  Fosters effective CDER management of important emerging drug safety concerns  DOES NOT replace Public Advisory Committees  DOES NOT replace current internal responsibility for Regulatory Decision-making

8. 8 Drug Safety Oversight Board: the First Year  Held nine meetings June 17 th 2005 to June 15 th 2006 Public Summaries are at: http://www.fda.gov/cder/drug/DrugSafety/DS OBmeetings/default.htm http://www.fda.gov/cder/drug/DrugSafety/DS OBmeetings/default.htm

9. 9 Drug Safety Oversight Board: the First Year  Focus of meetings Didactic sessions about CDER processes Defining role within CDER Advising on when and what to communicate about emerging risk Consider how to track emerging important drug safety issues Pre-decisional discussions about many drugs

10. 10 When does FDA communicate about emerging risk? Factors that favor early communication:  If a new risk is a “important drug safety concern” Affects prescribing or monitoring  When there are measures to be taken to prevent harm  If unapproved (off-label) use poses a significant and/or yet undescribed risk  If a specific and/or vulnerable subpopulation may be affected (children or the elderly)

11. 11 DSB does Not Replace AC Meetings or Reduce Public Input  DSB Meetings : Many products discussed Process-oriented Surfaces & addresses internal conflicts Discusses confidential commercial information  AC Meetings : Reviews single drug or drug class Regulatory action oriented Venue for obtaining public input FDA information provided to public

12. 12 Drug Safety Oversight Board Staff Activities

13. 13 Proposed Drug Watch Draft Guidance  Many comments  Support for early communication; unfavorable comments about Watch concept  Comments have been collated, synthesized & evaluated by team  New draft under development

14. 14 Risk Communication Venues for Patients and the General Public  Plain Language health communication  Public Health Advisory Summarizes the specific public health concern with actions to take  Patient Information Sheet “FDA Alert” summarizing safety concern Highlights about product from the approved label

15. 15 Risk Communication Venue for Health Care Professionals  Health Care Professional Information Sheet “FDA Alert” summarizing the safety concern  Recommendations and Considerations— implications for practice  Information & data that are the basis for concern  Studies being done to better understand the concern

16. 16 Drug Safety Alert Challenges  Striking the right balance—don’t want to Over warn OR Under warn  Communicating complex information simply  Determining when to inform the public when the nature of the data is evolving and early  Anticipating & managing unintended consequences  Balancing the communication of emerging risk with communication of benefit

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18. 18 Drug Safety HC Professional and Patient Information Sheets  At least 49 drugs with safety postings through May 31 2006 6 Product class issues 3 Market suspensions  Palladone ( hydromorphone hydrochloride ext release)  Tysabri (natalizumab) (Return to Market 06/05/06)  Neutrospec [Technetium (99m Tc) fanolesomab] 3 Product withdrawals  Bextra (valdecoxib)  Cylert (pemoline)  Tequin (gatifloxin) 40 with added warnings to product label

19. 19 Drug Class Risks Described in HC Professional & Patient Information Sheets  Antidepressants—suicidality in adults & children  Atypical antipsychotics—increased risk of death in dementia (unapproved use)  Non-steroidal anti-inflammatory drugs—increased cardiovascular risk  Erectile dysfunction drugs—non-arteritic anterior ischemic optic neuropathy  Topical Immunosuppressant calcineurin inhibitors— potential cancer risk  Long-acting beta agonists—increased risk of severe asthma episodes that may lead to death

20. 20 Drug Safety HC Professional & Patient Information Sheets: Examples  Accutane (isotretinoin)—new restricted access program to prevent pregnancy in treated women  Paxil (paroxetine)—Pregnancy Category changed--C to D  Strattera (atomoxetine)—increased pediatric suicidality risk  Palladone (hydromorphone)— Withdrawn due to dose dumping with concomitant alcohol exposure  Campath (alemtuzumab)—idiopathic thrombocytopenic purpura in patients with multiple sclerosis (unlabeled use)  Neutrospec (99mTechnetium fanolesomab)—serious and life threatening cardiopulmonary events shortly after administration

21. 21 Summary  Drug Safety Oversight Board and its risk communication efforts are a major component of CDER’s effort to strengthen drug safety efforts Sharing emerging important issues early Improving management through internal oversight

22. 22 susan.cummins@fda.hhs.gov