1. 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

2. Risk Minimization (RiskMAP) Guidance Goal: minimize a product’s 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 2

3. 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 3

4. 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 4

5. 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 5

6. 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 6

7. 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. Categories of RiskMAP Tools 7

8. RiskMAP “Tools” Targeted education and outreach –Health care provider letters –Training programs –Continuing education –Patient package inserts –Medication Guides –Promotional techniques 8

9. 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 9

10. 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 10

11. 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 11

12. 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? 12

13. 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 13

14. 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 14

15. 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 15

16. 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 16

17. 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 17

18. Evaluation Strategies Root Cause Analysis Spontaneous AE report monitoring (Medication errors) Record review Stakeholder surveys –Knowledge, Attitude and Behavior Program audits System audit trail 18

19. 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 19

20. What Works in Risk Minimization? Really don’t have enough history to know Involves changing behaviors and/or systems—education? marketing? Limited/controlled distribution works –“No blood, no drug” Attestation, testing, limiting access in other ways –Lotronex ® 20

21. What Doesn’t Work in Risk Minimization? Severe restriction of use via complex program –Dofetilide ® –Plenaxis ® Unintended consequences Unrealistic study size or expectations 21