# Presentation: 374587

## Susan K. Cummins, MD, MPH
Executive Director Drug Safety Oversight Board
Center for Drug Evaluation and Research
Food and Drug Administration

- Susan K. Cummins, MD, MPH
- Executive Director Drug Safety Oversight Board
- Center for Drug Evaluation and Research
- Food and Drug Administration

## 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

## 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

## Drug Safety Oversight Board

## Definition:  Oversight

- Oversight1 *(n)*:
- Watchful care or management; supervision.
- An unintentional omission or mistake.

*1**The American Heritage® Dictionary of the English Language, Fourth Edition, 2000 by Houghton Mifflin Company*

## 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

## 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

## Drug Safety Oversight Board: the First Year

- Held nine meetings
- June 17th 2005 to June 15th 2006
- Public Summaries are at: _[http://](http://www.fda.gov/cder/drug/DrugSafety/DSOBmeetings/default.htm)__[www.fda.gov/cder/drug/DrugSafety/DSOBmeetings/default.htm](http://www.fda.gov/cder/drug/DrugSafety/DSOBmeetings/default.htm)_

## 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

## 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)

## 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

## Drug Safety Oversight Board Staff Activities

## 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

## Risk Communication Venuesfor Patients and the General Public

- Plain Language health communication
*Public Health Advisory *
- Summarizes the specific public health concernwith actions to take
*Patient Information Sheet*
- “**FDA Alert**” summarizing safety concern
- Highlights about product from the approved label

## 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

## 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

## Slide 17

## 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

## 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

## 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

## 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

## susan.cummins@fda.hhs.gov