# Presentation: 410968

## New Drug Safety Initiatives & theDrug Safety Oversight Board

- Drug Safety and Risk Management Advisory Committee,
- Gaithersburg, MD
- February 10th, 2006

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

## Today’s Talk	

- Drug Safety landscape
- New Drug Safety initiatives
- Dr. Crawford’s November 2004 announcement
- Secretary Leavitt’s February 2005 announcement
- Drug Safety Oversight Board & New drug risk communication outlets

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety Landscape

- Drug Safety is a top priority for all of CDER at every stage of the product life cycle
- Pre-NDA phase
- New drugs
- Manufacturing/regulation of drug quality
- Generic drugs
- Regulation of clinical trials and promotional activities

- FDA SCIENCE BOARD

- April 15, 2005

## Half of all CDER Work Effort is Devoted to Drug Safety

**Half of all CDER Work Effort is Devoted to Drug Safety**

- TM Mullin, PhD, Office of Planning, Office of Commissioner
- FDA Science Board Presentation April 15, 2005

- 2004 CDER Work Time Analysis

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety Landscape

**Laws**:  FD& C Act requires safety evaluation before approval  ***“All tests reasonably applicable”*** to safety
**FDA Drug Regulations**:  Information that ***“the product is safe...for recommended use.”***
**Guidances**: FDA & International guidance documents spell out ***level of evidence needed for safety evaluation***.
**Bottom Line**:*  *_***Science***_*** plus ***_***judgment***_*** plus ***_***policy***_

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety Landscape

- Despite the rules, there is lots of room for honest disagreement
- How safe is “safe”?
- There is no single, simple risk/benefit equation
- Tension between:
- Drive for innovation and new products VS.
- Greater assurance of safety through larger and longer studies

- FDA SCIENCE BOARD

- April 15, 2005

## “The Drug Approval Pendulum” 	by Anne Applebaum  	Washington Post       	Wednesday, April 13, 2005; Page A17

***“******The Drug Approval Pendulum”***** **	**by Anne Applebaum****  ****	*****Washington Post***** ****      ****	****Wednesday, April 13, 2005; Page A17**

*"It just breaks my heart when I think of American citizens having to go to Switzerland or Mexico to get the drugs and devices they need to stay alive because the Washington bureaucracy won't approve them."*
- Rep. Thomas Bliley (R-Virginia), 1995
*"When the FDA approves a drug, it should be a Good Housekeeping seal of approval. . . . Consumers shouldn't have to second-guess the safety of what's in their medicine cabinet." *
- Sen. Chuck Grassley (R-Iowa), 2005

- FDA SCIENCE BOARD

- April 15, 2005

## November 2004:  FDA Drug Safety Announcement

*    **FDA Acting Commissioner Crawford announced a 5-Point Plan to improve management of drug safety concerns: *
- Sponsor an Institute of Medicine Study of the Drug Safety System 		     UNDERWAY—Report due out July 2006
- Implement a program for adjudicating differences of professional opinion
- Individual level–-Resolution through Ombudsman
- Organizational level—Drug Safety Oversight Board
- Appoint a permanent Director, Office of Drug Safety
*Gerald Dal Pan, MD, MHS *appointed, October 2005
- Conduct Drug Safety/Risk Management Consultations--UNDERWAY
- Publish Risk Management Guidances—DONE

- FDA SCIENCE BOARD

- April 15, 2005

## 2005 Published Risk Management Guidance for Industry

*Pre-marketing Risk Assessment*
*Development and Use of Risk Minimization Action Plans*
*Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment*

- FDA SCIENCE BOARD

- April 15, 2005

## 2005 Published FDA Reviewer Guidance

*Conducting a Clinical Safety Review of a New Product Application and Preparing a Report on the Review*
- Component of good review practice guidance for NDAs and BLAs
- Provides for standardization and consistency in format and content of safety reviews

- FDA SCIENCE BOARD

- April 15, 2005

## February 15th 2005HHS Secretary Mike LeavittAnnounces Drug Safety  Reforms

- "The public has spoken and they want more oversight and openness...We will address their concerns by cultivating openness and enhanced independence.“
- "We will keep the promise of the FDA brand by putting in place more rigorous oversight and collecting and sharing important and emerging information about drug safety and effectiveness.“
- HHS Secretary Mike Leavitt

- FDA SCIENCE BOARD

- April 15, 2005

## February 2005: HHS Secretary LeavittDrug Safety Announcement

*Overall vision:*
- Promote a culture of openness &
- Enhance oversight within the FDA
*Specific areas of change:*
- More outside expert consultations
- Improve drug safety management practices
- Communicate emerging drug safety concerns early
- Continue to improve scientific methods of adverse event signal detection

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety Initiative

*The initiative will:*
- Give patients, healthcare professionals & consumers quick & easy access to the most up-to-date and accurate information on medicines.

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety Initiative

- New drug safety *information* outlets
- Patient Information Sheets
- Healthcare Professional Sheets
- Proposed Drug Watch Program
- Drug Safety Oversight Board

- FDA SCIENCE BOARD

- April 15, 2005

## 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

- FDA SCIENCE BOARD

- April 15, 2005

## 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

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety Oversight BoardCharge

- “Ensure that CDER decisions about a drug’s safety benefit from the input and perspective of experts within and outside FDA who have not conducted the primary review or served as a deciding official in the ongoing pre-market evaluation or post-market surveillance activities with respect to that drug.”

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety Oversight Board Organizational Principles

- Voting members independent of primary decision-making for a drug with an important safety issue
- Federal employees
- Equal number of representatives from Offices of Drug Safety & New Drugs
- 25% of membership external to CDER
- Other FDA Centers with related activities
- NIH & Veterans Administration
- Expert, Consumer or Patient Consultants  as needed

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety Oversight BoardOrganizational 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

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety Oversight Board Membership

- CDER Offices:
- Drug Safety (3)
- New Drugs (3)
- Counter-terrorism & Pediatrics
- Compliance
- Pharmaceutical Science
- Clinical Pharmacology & Biopharmaceutics
- Biostatistics
- Medical Policy (non-voting)

- External to CDER:
- Center for Biologic Evaluation & Research
- Center for Radiological Health
- Department of Veterans Affairs
- National Institute of Health (National Cancer Institute)

-   Chair—Deputy Director, CDER (non-voting)
-   Executive Secretary—Director, DSB (non-voting)

- FDA SCIENCE BOARD

- April 15, 2005

## Proposed Drug Watch: Definition, Goal and Status

*Definition:*  Web page on CDER Internet site about emerging important safety issues undergoing investigation
*Goal:*  Communicate emerging risk information to the public so that it can inform treatment decisions
*Status:*  Draft Guidance undergoing review and revision in response to public comment submitted during 2005 comment period

- FDA SCIENCE BOARD

- April 15, 2005

## When does FDA communicate about emerging risk?

- Factors that favor early communication:
- Risk is a “*important drug safety concern*”
- Affect prescribing or monitoring
- Whether measures can be taken in response to the information 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)

- FDA SCIENCE BOARD

- April 15, 2005

## Slide 23

- FDA SCIENCE BOARD

- April 15, 2005

## Slide 24

- FDA SCIENCE BOARD

- April 15, 2005

## Slide 25

## Slide 26

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety HC Professional & Patient Information Sheets 

- At least 44 drugs with safety postings through December 31, 2005
- 6 Product class issues
- 3 Market suspensions
- Palladone (hydromorphone hydrochloride extended release)
- Tysabri (natalizumab)
- Neutrospec [Technetium (99m Tc) fanolesomab]
- 2 Product withdrawals
- Bextra (valdecoxib)
- Cylert (pemoline)
- 37 with added warnings to product label

- FDA SCIENCE BOARD

- April 15, 2005

## 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

- FDA SCIENCE BOARD

- April 15, 2005

## Drug Safety HC Professional & Patient Information Sheets 

- At least 44 drugs with safety postings through December 31, 2005
- Examples:
- Accutane (isotretinoin)—new restricted access program to prevent pregnancy in treated women
*Paxil (paroxetine)—*Pregnancy Category changed from 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

- FDA SCIENCE BOARD

- April 15, 2005

## Summary

- Drug Safety Oversight Board established to:
- Improve public knowledge of emerging important drug safety concerns
- Strengthen internal drug safety management
- Foster practical policy development to improve consistency and timely resolution of important drug safety concerns
- Provide a standing venue for resolution of CDER organizational disputes
- Central component of CDER’s initiative to improve  management of drug safety & inform the public about emerging medication risks

- FDA SCIENCE BOARD

- April 15, 2005