Drug Safety Oversight Board: Recent Activities

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Drug Safety Oversight BoardRecent Activities

• FDA Science Board
• Advisory Committee Meeting
• March 31st, 2006

Douglas C. Throckmorton, MD Deputy Director
Center for Drug Evaluation and Research US Food
and Drug Administration
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Todays Talk

• Update Science Board on Drug Safety Oversight
  Board (DSB) activities and its relationship to
  other safety activity in CDER. Focus on
• Roles of DSB and Advisory Committee (AC) meetings
  in CDER deliberations on drug safety
• DSB Activities
• Safety Communications
• Internal CDER process development

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Drug Safety Oversight Board (DSB)

• Formed in 2005 as part of CDER response to new
  needs to communicate and manage product safety
• Task provide independent oversight and advice to
  the CDER Center Director on management of
• Important drug safety issues and policies
• Dissemination of certain safety information
  through FDAs website to healthcare professionals
  and patients

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DSB Membership

• Chair Deputy Director, CDER
• Executive Director Dr. Susan Cummins
• Membership - representatives from CDER offices,
  CBER, CDRH, NIH, VAH

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CDER Response to Drug Safety Issues
Complimentary Roles of DSB and AC Meetings
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DSB does Not Replace AC Meetings or Reduce Public
Input

• DSB Meetings
• Review of information on many products at each
  meeting
• CDER Process oriented
• What steps should CDER take to evaluate, resolve
  and communicate a complex safety issue?
• How should CDER track and address emerging safety
  issues?

• AC Meetings
• Review of information on single drug or class of
  drugs
• Regulatory Action oriented
• Should a new product be approved for marketing?
• Is there evidence of a new important risk?

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DSB does Not Replace AC Meetings or Reduce Public
Input (cont)

• DSB Meetings
• Venue for resolving CDER organizational drug
  safety disputes
• Venue for discussing need for AC meetings about
  emerging safety information

• AC Meetings
• Venue for obtaining public input where needed to
  assist decision-making
• Discussing safety and efficacy of new products
  prior to marketing publicly
• Discussing emerging safety concerns for marketed
  products
• Discussing risk management for identified safety
  concerns both pre- and post-marketing

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AC Members have Access to Detailed Information

• Examples
• Product developers data and analyses
• CDER efficacy and safety evaluations
• CDER review from other disciplines pre-clinical
  toxicology, clinical pharmacology, statistical
• CDER reviews of post-marketing Adverse Event
  reports
• Summary information on drug use

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CDER AC Meetings Discuss Drug Safety Issues

• Drug safety a frequent part of (or sole reason
  for) AC discussions
• Examples
• Tysabri for Multiple Sclerosis
• Drugs for ADHD (2 ACs)

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CDER Outreach for Public Input on Drug Safety
Communications beyond AC Meetings

• December 7th 8th 2005 Part 15 Hearing FDAs
  public communications about drug safety
• Public supports goals of new FDA communications,
  but
• Many types of communications
• Sometimes confusing
• Navigating the FDA website
• Difficult for various groups to locate documents
  directed to them patients, health care
  providers, regulators

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Summary

• DSB and AC Meetings have separate, vital roles in
  CDER responses to drug safety
• CDER uses available venues to assure appropriate
  public input into safety decisions

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Current Focus of DSB Activities
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DSB Focus on Emerging Safety Issues

• Since last Science Board, 11 safety
  communications discussed with DSB before or after
  posting. Examples
• Nimodipine (Nimotop) alert about added Black Box
  warning about cardiovascular risks of
  inappropriate intravenous use of product approved
  for oral use
• Aprotinin (Trasylol) alert about serious renal
  toxicity ischemic events in patients undergoing
  CABG or cardiac surgery with CP bypass
• Technetium 99m Tc fanolesomab (NeutroSpec)
  market suspension following reports of serious
  life-threatening cardiopulmonary adverse events
• Norlegstromin/ethinyl estradiol (Ortho Evra)
  alert about ongoing studies to define clinical
  consequences of total estrogen levels for users
  that average 60 higher than oral contraceptives
  containing 35 micrograms of estrogen

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DSB Focus on Process Development

• Work on CDER process for addressing emerging
  safety issues
• Discussion of a CDER-wide tracking system for
  identified safety issues
• Work on Guidance for DSB conduct
• Revision of Proposed Drug Watch Guidance
• Addressing public comments
• Revising Guidance where needed
• Work on Guidance for DSB staff activity
• Creation of Standard Operating Procedures (MaPP)
  for
• DSB meetings
• DSB information sheet development
• Other routine DSB operations

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DSB Focus on Process Development (from MaPP)

• Identify, track and oversee management of
  important drug safety issues
• Adjudicate organizational disputes concerning
  management of drug safety issues
• Select drugs to be placed on Drug Watch and
  update their status as appropriate
• Establish policies regarding management of drug
  safety issues in CDER
• Oversee the development of patient and
  professional information sheets in CDER
• Track important emerging safety issues and ensure
  they are resolved in a timely manner
• Ensure CDER decisions about a drugs safety
  benefit from the input and perspective or 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 the drug

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Summary

• DSB continues to develop its role in CDER
• Continued role in assisting effective safety
  communication
• Focus on process development for drug safety
  tracking and oversight

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Conclusions

• DSB does not replace or diminish the importance
  of AC meetings, or reduce the discussion of
  safety in public venues
• DSB continues to be a valued, new voice to assist
  CDER decision-making on drug safety