New Drug Safety Initiatives & theDrug Safety Oversight Board
Drug Safety and Risk Management Advisory Committee,
Gaithersburg, MD
February 10th, 2006
Susan K. Cummins, MD, MPHExecutive Director, Drug Safety Oversight BoardCenter for Drug Evaluation and ResearchFood and Drug Administration
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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
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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
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32% Pre-Market Safety Work Effort
18% Post-Market Safety Work Effort
50% Non-SafetyWork Effort
Half of all CDER Work Effort is Devoted to Drug Safety
TM Mullin, PhD, Office of Planning, Office of CommissionerFDA Science Board Presentation April 15, 2005
2004 CDER Work Time Analysis
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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
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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
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“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
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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
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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
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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
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February 15th 2005HHS Secretary Mike LeavittAnnounces 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
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February 2005: HHS Secretary LeavittDrug 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
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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.
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Drug Safety Initiative
New drug safety information outlets
Patient Information Sheets Healthcare Professional Sheets Proposed Drug Watch Program
Drug Safety Oversight Board
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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
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Drug Safety Oversight BoardCharge
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
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Drug Safety Oversight BoardCharge
“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.”
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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
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Drug Safety Oversight BoardOrganizational 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
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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)
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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
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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)
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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
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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
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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
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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