New Drug Safety Initiatives

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New Drug Safety Initiatives theDrug 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
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Todays Talk

• Drug Safety landscape
• New Drug Safety initiatives
• Dr. Crawfords November 2004 announcement
• Secretary Leavitts 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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Half of all CDER Work Effort is Devoted to Drug
Safety
2004 CDER Work Time Analysis
TM Mullin, PhD, Office of Planning, Office of
Commissioner FDA Science Board Presentation April
15, 2005
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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 safefor 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 UNDERWAYReport due out
  July 2006
• Implement a program for adjudicating differences
  of professional opinion
• Individual level-Resolution through Ombudsman
• Organizational levelDrug 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 GuidancesDONE

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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 opennessWe 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 physicians decision to prescribe
• Affect patients 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 drugs 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

• ChairDeputy Director, CDER (non-voting)
• Executive SecretaryDirector, DSB (non-voting)

• 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)

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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

• Antidepressantssuicidality in adults children
• Atypical antipsychoticsincreased risk of death
  in dementia (unapproved use)
• Non-steroidal anti-inflammatory drugsincreased
  cardiovascular risk
• Erectile dysfunction drugsnon-arteritic anterior
  ischemic optic neuropathy
• Topical Immunosuppressant calcineurin
  inhibitorspotential cancer risk
• Long-acting beta agonistsincreased 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 CDERs initiative to improve
  management of drug safety inform the public
  about emerging medication risks