Public Workshop on Risk Management Day 2 Risk Management Programs Washington DC, April 10

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Public Workshop on Risk ManagementDay 2 Risk
Management ProgramsWashington DC, April 10

• International Society for Pharmacoepidemiology
• S. Pérez-Gutthann, MD, MPD, PhD

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ISPE Backgroundwww.pharmacoepi.org

• Non-profit international professional membership
  organization
• Mission to foster the science of
  pharmacoepidemiology, applying epidemiologic
  approaches to studying the use, effectiveness,
  value and safety of therapeuticals.
• International forum for sharing knowledge and
  scientific approaches
• Over 700 members, 45 countries.
• Working in academia, pharmaceutical industry,
  government agencies, non-profit and for-profit
  research organizations.
• Background epidemiology, biostatistics,
  medicine, nursing, pharmacology, pharmacy, law,
  health economics, and journalism.
• Comments are based on the feedback provided by
  senior members

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General

• This concept paper is useful in the overview of
  the Agencys views
• initiating and designing a RMP
• selection and development of tools,
• evaluation of RMP
• web based catalog of programs and tools
• We have identified a number of suggestions and
  clarifications.

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Section I - C DWhat is Risk Management
Planning, What is a Risk Management Program and
what are its goals and objectives

• The three concept papers suggest a fragmented
  view of Risk Management.
• Danger of consolidating institutional divisions
  between those working in safety pre and post
  approval.
• Integration of specialists in both areas from
  early development through post market is needed.
• PVP and RMP definitions - overlap and partially
  contradict each other in concept papers II III
• RMP, Concept Paper III, line 65 a risk
  management program (RMP) would be a submission to
  FDA that comprehensively analyzes a products
  risk profile and proposes active interventions to
  minimize them.
• RMP, Concept Paper II, line 62 FDA is defining
  a risk management program (RMP) as a strategic
  safety program designed to decrease product risk
  by using one or more interventions or tools
  beyond the package insert.
• PVP, Concept Paper II, line 55. We envision a
  pharmacovigilance plan as being a plan proposed
  by a sponsor for the ongoing evaluation of
  identified safety signals through enhanced
  pharmacovigilance practices.

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Section I - C DWhat is Risk Management
Planning, What is a Risk Management Program and
what are its goals and objectives

• Gaps in current RMP
• Risk management prior to launch
• Activities, timelines, interactions with Agency,
  relation to other development planning documents
  and meetings
• Determination of background risks based on
  epidemiologic analysis of the patient population
  anticipated to be exposed to the therapeutic
  agent
• Formal document to provide overall overview of
  risks and decisions about moving or not beyond
  risk communication in IB/PI
• Guidance for therapeutic agents other than
  medications

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Section I - C DWhat is Risk Management
Planning, What is a Risk Management Program and
what are its goals and objectives

• Proposal
• A dynamic Risk Management Plan - broader sense
  that the targeted Risk Management Program in this
  concept paper
• Initiated at the moment of entry into humans,
  based on data from toxicology, etc.
• Moving with the drug along development milestones
  
• With a specific Pharmacovigilance Plan section
  prior to approval
• Moving with the drug in the postapproval periodic
  safety review process
• A specific Risk Management Program would be then
  initiated when moving beyond IB/PI for a specific
  issue (s).

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Section IV A, B, CIntervention or tools
available

• Assumptions for use of tools
• Use of tools is based on the assumption that risk
  factors for the target adverse event have been
  identified and that there is some understanding
  of how the medication should be used to minimize
  this risk.
• This point could be made clearer at the front of
  the document
• Effectiveness of tools wide range in results
• Educational / academic detailing programs.
• Flag warning systems in pharmacy computers
• PI as risk communication/minimization tool
• Content E.g. describing risks as crude
  percentages without specifying the exposure
  duration, balance common adverse events versus
  rarer serious adverse events
• Target prescribers, patients

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IV DChoice of tools and RMP Levels

• Broad categorization helpful in providing
  overview of level of concern and action for
  specific agents and accross therapeutic class
• Clarification What are the views on guiding
  criteria to move from level 1 to level 2, etc.
• Frequency of event, public health impact,
  effectiveness of tool
• Web catalog of programs tools plus
  categorization in levels is very useful

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Section VHow and when can risk management
programs be evaluated

• P 9, lines 304, 320 Evaluation of an RMP might
  involve a metric of reducing the occurrence of an
  adverse event
• Goal of any program, but may be very difficult to
  measure.
• Mention that for most drugs, the frequency of
  serious adverse events, which are usually the
  focus of RMPs, the evaluation of such events
  might be problematic because of sample size
  considerations.
• For an event, which occurs at 1/1000, for
  example, it would take tens of thousands of
  patients to detect a halving of this frequency.
• p.4, lines 119-120 No ready formula currently
  exists to determine when risks exceed benefits.
• P 10, lines 368-372. Limitations of SR
• Given above, a more prominent role of formal
  pharmacoepidemiologic studies in assessing risk
  and evaluating risk interventions is proposed

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Special Considerations

• Impact on health delivery systems
• Impact on prescriber and pharmacist workload
• Particularly if Level 2-4 RM programs are running
  simultaneously
• Therapeutic class balance
• Avoid that only new drugs within a TC with
  similar safety profile are focus of RMP  
• International coordination
• EMEA, ICH work in progress. Opportunity to
  coordinate internationally objectives, process
  and documents early on.
• Collaboration among stakeholders
• Guidelines should emphasize the important role of
  close collaboration between the Agency, Sponsor
  and Experts in the decision to move beyond Level
  1 RM, choice of tools, evaluations, etc.

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Next stepswww.pharmacoepi.org

• ISPE is firmly committed to providing an unbiased
  scientific forum to the views of all parties with
  interests in the safety of therapeuticals, and as
  such is deeply committed to the advancement of
  Risk Management Sciences.
• Welcome opportunity to work together with the
  Agency
• Full membership to provide feedback on paper.
• Annual conference will be focused on Risk
  Management.
• Several workshops and sessions are being planned
  jointly with FDA staff.
• 1st International Conference on Therapeutic Risk
  Management and the 19th International Conference
  on PharmacoepidemiologyAugust 21-24 in
  Philadelphia.
• Thank you