Developing, Pilot Testing

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Developing, Pilot Testing Evaluating RiskMAP
Interventions

• Annette Stemhagen, DrPH, FISPE
• Vice President
• UBC Epidemiology Risk Management
• The FDA Regulatory and Compliance Symposium
• August 25, 2005

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Risk Minimization (RiskMAP) Guidance

• Goal minimize a products risks while
  preserving its benefits.
• For the majority of products, routine risk
  minimization measures are sufficient
• RiskMAP -- strategic safety program minimizing
  known risks of a product while preserving its
  benefits.
• A RiskMAP uses tools to achieve goals.
• Development and Use of Risk Minimization Action
  Plans (RiskMAPs)http//www.fda.gov/cder/guidance/
  6358fnl.htm

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How to Design a Risk Minimization Program

• Complete risk and benefit assessment
• Define goals and objectives for risk minimization
  intervention
• Identify appropriate tools
• Conduct feasibility

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Risk and Benefit Assessment

• Quantify risks, if possible
• High risk populations?
• Specific doses?
• Inappropriate use?
• Off-label use?
• Misuse or abuse?
• Evaluate risk in context of benefit

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Goals and Objectives for Risk Minimization

• Ideal Goals
• No deaths
• No abuse
• No pregnancies
• No patients taking drug X also take Drug Y
• Specify objectives
• Inform all health care professionals
• Inform all patients
• Increase knowledge of appropriate use
• Require pregnancy test before each prescription
  fill

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RiskMAP Tool Selection

• Maintain widest accessibility with least burden
  to health care system
• Target key groups most likely to be able to
  minimize risk
• Determine the feasibility of proposed approach

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Categories of RiskMAP Tools

• Targeted Education and Outreach
• Increase appropriate knowledge and behaviors of
  stakeholders who have the capacity to prevent or
  mitigate risks
• Reminder Systems
• Systems that prompt, remind or guide in
  prescribing, dispensing, or using a product to
  minimize risk
• Performance-Linked Access Systems
• Link product access to laboratory testing or
  other documentation.

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RiskMAP Tools

• Targeted education and outreach
• Health care provider letters
• Training programs
• Continuing education
• Patient package inserts
• Medication Guides
• Promotional techniques

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RiskMAP Tools

• Reminder systems, processes or forms
• Patient agreement or acknowledgement forms
• Health care practitioner certification or
  attestation programs
• Limited Rx amount or refills
• Specialized packaging to enhance safety
• Prescription stickers
• Special prescription pads

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RiskMAP Tools

• Performance-linked access systems that guide
  prescribing, dispensing and use
• Compulsory reminder systems
• Certification of prescribers/dispensers
• Documentation of safe-use conditions
• blood tests for agranulocytosis
• pregnancy tests

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How Can You Determine if Your Approach Will
Succeed?

• Feasibility assessments prior to designing
  intervention
• Pilot testing prior to full implementation, if
  feasible
• Ongoing evaluation over the life of the program

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Initial Feasibility Assessments

• Determine likelihood of success with
• Stakeholders
• Physicians
• Pharmacists
• Patients and caregivers
• Wholesalers/distributors
• Others
• Program Design
• Fit busy practice routine?
• Represent actual clinical practice?
• Need no extraordinary testing?
• Requires minimal training?

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Assessing Feasibility Using Existing Data

• Medical chart review
• Natural history of disease
• Cross sectional surveys, e.g., NCHS
• Registries
• Large automated databases
• Market research data
• Competitive products
• Physician prescribing behavior
• ISS and ISE (particularly placebo groups)
• Literature
• Past experience

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Ad Hoc Data Collection for Assessing Feasibility

• Panel of experts
• Focus groups
• Stakeholder surveys
• Health Care Providers
• Patients
• General population sample
• Time and Motion studies

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Ongoing Feasibility Throughout the Program

• Conduct Failure Mode and Effects Analysis (FMEA)
• Test your assumptions
• How good were the data?
• How good were the assumptions?
• Projected vs. actual
• Implement mid-course corrections

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Pilot Test Tools

• Qualitative and quantitative testing of
  educational materials
• Health literacy
• Comprehension
• Randomized trial of educational programs
• User acceptance testing of systems
• Phased roll out of program to small group of
  physicians prior to widespread implementation
• Registry
• Large streamlined study

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RiskMAP Evaluation

• Continually assess modify
• Use evidence based performance measures
• At least two different approaches
• Quantitative, representative, minimally biased
• Measure health outcome goal
• Surrogates
• Process measures
• KAB

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Evaluation Strategies

• Root Cause Analysis
• Spontaneous AE report monitoring (Medication
  errors)
• Record review
• Stakeholder surveys
• Knowledge, Attitude and Behavior
• Program audits
• System audit trail

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Evaluation Strategies

• Large automated database study
• National surveys databases, e.g., DAWN, TESS
• Market research data, e.g., IMS-Health
• Registries
• Product exposure registry
• Pregnancy registry
• Large streamlined study

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What Works in Risk Minimization?

• Really dont have enough history to know
• Involves changing behaviors and/or
  systemseducation? marketing?
• Limited/controlled distribution works
• No blood, no drug
• Attestation, testing, limiting access in other
  ways
• Lotronex

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What Doesnt Work in Risk Minimization?

• Severe restriction of use via complex program
• Dofetilide
• Plenaxis
• Unintended consequences
• Unrealistic study size or expectations

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