Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 0 Targeted Pregnancy Prevention Program SM for Women on Accutane ® (isotretinoin) Eileen Enny Leach, MPH September 18, 2000

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 1 Targeted Pregnancy Prevention Program Created from an analysis and revision of the 1988 Pregnancy Prevention Program SM Created from an analysis and revision of the 1988 Pregnancy Prevention Program SM Revised program targeted to both: Revised program targeted to both: –small percentage of patients who do not avoid pregnancy –physicians who are having difficulty assessing and predicting an individual patient’s behavior Goal: Prevention of pregnancy Goal: Prevention of pregnancy

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 2 Accutane Product Labeling –Launched with Category X with strong Warnings based on animal data –Revised to include data as it became available 1988 Risk Management Pregnancy Prevention Program SM for Women on Accutane ® (isotretinoin) (PPP) 1988 Risk Management Pregnancy Prevention Program SM for Women on Accutane ® (isotretinoin) (PPP)

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 3 Pregnancy test required 7 days before starting Accutane Pregnancy test required 7 days before starting Accutane Two reliable forms of birth control Two reliable forms of birth control Begin therapy on 2nd or 3rd day of next menses Begin therapy on 2nd or 3rd day of next menses One month prescription only One month prescription only Monthly pregnancy testing Monthly pregnancy testing Monthly contraceptive counseling Monthly contraceptive counseling 1988 Label Change Elements

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 4 Blister pack for 10, 20, 40mg Blister pack for 10, 20, 40mg 1988 Accutane Package Elements

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 5 Blister pack for 10, 20, 40mg Blister pack for 10, 20, 40mg “Avoid pregnancy” logo at each pill site “Avoid pregnancy” logo at each pill site 1988 Accutane Package Elements

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 6 Blister pack for 10, 20, 40mg Blister pack for 10, 20, 40mg “Avoid pregnancy” logo at each pill site “Avoid pregnancy” logo at each pill site Black box warnings Black box warnings 1988 Accutane Package Elements

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 7 Blister pack for 10, 20, 40mg Blister pack for 10, 20, 40mg “Avoid pregnancy” logo at each pill site “Avoid pregnancy” logo at each pill site Black box warnings Black box warnings Line drawings of birth defects Line drawings of birth defects 1988 Accutane Package Elements

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/ Risk Management System Pregnancy Prevention Program SM (PPP) for Women on Accutane ® (isotretinoin)

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/ Risk Management System Pregnancy Prevention Program SM (PPP) for Women on Accutane ® (isotretinoin) Assists in meeting requirements of label Assists in meeting requirements of label Developed in cooperation with the American College of Obstetrics and Gynecology Developed in cooperation with the American College of Obstetrics and Gynecology Initiated Accutane Survey (patient survey) Initiated Accutane Survey (patient survey) Accutane Tracking Survey (prescriber survey) Accutane Tracking Survey (prescriber survey)

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 10 Pregnancy Prevention Program SM for Women on Accutane ® (isotretinoin) 97% of prescribers use at least one component of the PPP* 97% of prescribers use at least one component of the PPP* Reduced pregnancy rate from † Reduced pregnancy rate from † – per 1000 – per 1000 *Accutane Prescriber Tracking Survey Accutane Survey (incidence rate based on day courses) † Accutane Survey (incidence rate based on day courses)

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 11 Review of Individual Reports 3 Pregnancies per 1000 Female Patients Confusion about timing of pregnancy test Confusion about timing of pregnancy test –False negatives –Did not wait until 2nd or 3rd day of menses Misinformation about contraceptive methods Misinformation about contraceptive methods Received more than one month supply Received more than one month supply No monthly pregnancy testing or contraceptive counseling No monthly pregnancy testing or contraceptive counseling Accutane Survey and Roche Accutane Drug Safety Database

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 12 Review of Individual Reports Women Who Reported Pregnancy During Accutane Therapy 3 Pregnancies per 1000 Female Patients Reasons Women Became Pregnant Unsuccessful at abstinence Unsuccessful at abstinence Used ineffective contraception Used ineffective contraception Used contraception inconsistently Used contraception inconsistently Had unexpected sexual activity Had unexpected sexual activity Had a failure of the contraceptive method Had a failure of the contraceptive method

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/ % Women who reported unwanted or mistimed pregnancies Women, in the US, who became pregnant (3.6 million) All Pregnancies Reported in the US (annually)

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/ % Women who reported unwanted or mistimed pregnancies Women, in the US, who became pregnant (3.6 million) 5% Women who reported pregnancies with typical use of birth control pills All Pregnancies Reported in the US (annually)

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 15 Accutane-Exposed Pregnancies Pregnancy rate for women taking Accutane Pregnancy rate for women taking Accutane –3 pregnancies per 1000 –Pregnancy rate 0.3%

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 16 Women Who Reported Pregnancies 3 Pregnancies per 1000 Female Patients 91% reported receiving warnings prior to start of treatment that the drug could cause birth defects if used during pregnancy 91% reported receiving warnings prior to start of treatment that the drug could cause birth defects if used during pregnancy Mean age 26.3 years* Mean age 26.3 years* *Roche Accutane Drug Safety Database ( )

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 17 Considerations for Risk Management for Accutane Accutane is a known teratogen Accutane is a known teratogen Female Accutane patients are usually of childbearing potential Female Accutane patients are usually of childbearing potential 91% of surveyed women believe they know about contraception* 91% of surveyed women believe they know about contraception* –37% chose the least effective birth control method* * Lewin Survey 2000

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 18 Risk Management Options Selective and targeted Selective and targeted Should not negatively impact: Should not negatively impact: –the compliant patient –the current success of the program

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 19 Risk Management Model Engage Partners and Other Stakeholders Select a Strategy Identify Issues and Put Them into Context Assess Risk/ Assess Benefits Identify and Analyze Options Evaluate Results Implement the Strategy Source: Presidential/Congressional Commission on Risk Assessment and Risk Management, Framework for Environmental Health Risk Management — Final Report, Vol. 1, 1997.

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 20 Women Who Reported Pregnancies* 3 Pregnancies per 1000 Female Patients Became pregnant during therapy Did not wait to begin therapy before next menstrual cycle Pregnant at time of initial office visit Information not available *Roche Accutane Drug Safety Database

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 21 Targeting Patients at Risk 3 Pregnancies per 1000 Female Patients Pregnant at the time of initial visit (14%) or did not wait unit the next menses (12%) 26% = 26% Issue: Pregnancy testing

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 22 Targeting Patients at Risk 3 Pregnancies per 1000 Female Patients Pregnancy occurred during therapy 11% reported they believed they would be able to maintain abstinence 11% reported they believed they would be able to maintain abstinence 34% reported failure to use contraception on the perceived day of conception 34% reported failure to use contraception on the perceived day of conception –33% occurred while using one form of contraception 51% reported contraception failure 51% reported contraception failure –61% occurred while using one form of contraception 64% = 64%

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 23 Targeted Pregnancy Prevention Program Provisions Revise Accutane labeling Revise Accutane labeling –two safe, effective forms of birth control –negative results from two pregnancy tests Provide urine pregnancy test kits Provide urine pregnancy test kits Introduce an Office Implementation System Introduce an Office Implementation System Package for one month supply using unit dosing Package for one month supply using unit dosing Encourage enrollment in Accutane Survey Encourage enrollment in Accutane Survey Provide educational materials for prescribers and patients Provide educational materials for prescribers and patients

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/ Label Elements of Label 2000 Label Change Elements of Label Two pregnancy tests required at specified times Two pregnancy tests required at specified times No Rx until confirmation of a negative result from a second pregnancy test No Rx until confirmation of a negative result from a second pregnancy test Two safe, effective forms of contraception Two safe, effective forms of contraception –One primary and one secondary 100%

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 25 Accutane Package Insert, May 2000 Effective Forms of Contraception Primary Tubal ligation Tubal ligation Partner’s vasectomy Partner’s vasectomy Birth control pills Birth control pills Injectable/implantable birth control products Injectable/implantable birth control products IUD IUDSecondary Diaphragms with spermicide Diaphragms with spermicide Latex condoms with spermicide Latex condoms with spermicide Cervical caps with spermicide Cervical caps with spermicide

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 26 Two pregnancy tests required at specified times Two pregnancy tests required at specified times No Rx until confirmation of a negative result from a second pregnancy test No Rx until confirmation of a negative result from a second pregnancy test Two safe, effective forms of contraception Two safe, effective forms of contraception –One primary and one secondary Reinforce one month prescription only Reinforce one month prescription only 100% 2000 Label Change Elements of Label

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/ % One Month Supply with Unit Dosing

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 28 Two pregnancy tests required at specified times Two pregnancy tests required at specified times No Rx until confirmation of a negative result from a second pregnancy test No Rx until confirmation of a negative result from a second pregnancy test Two safe, effective forms of contraception Two safe, effective forms of contraception –One primary and one secondary Reinforce one month prescription only Reinforce one month prescription only Reinforce monthly pregnancy testing and monthly contraceptive counseling Reinforce monthly pregnancy testing and monthly contraceptive counseling 100% 2000 Label Change Elements of Label

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 29 Progress Notes Please check as completed Initial pregnancy test–Negative 2nd pregnancy test–Negative Monthly pregnancy test–Negative Patient has joined the Survey Patient has seen the Be Prepared, Be Protected video Patient has been counseled about avoiding pregnancy Patient is not sexually active Monthly Contraception Assessment Patient is sexually active LMP: Choice of contraception: PrimarySecondary Change in method/new method Counseling on contraception failure rates

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 30 Office Implementation System ContraceptionRx Consider Accutane Therapy Sexually Active Without Contraception Pregnancy Prevention Program 10 Steps Yes (1) (2) Sexually Active With Contraception Counseling either Prescriber or Contraceptive Counseling Primary and Secondary Method (3) Contraceptive Counseling

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 31 Office Implementation System Contraception Rx Consider Accutane Therapy Sexually Active Without Contraception PPP 10 Steps Yes (1) (2) Sexually Active With Contraception Counseling either Prescriber or Contraceptive Counseling Primary and Secondary Method (3) Contraceptive Counseling Pos. 2nd Urine Pregnancy Test 1st Urine Pregnancy Test Neg. Pos. No Rx for Accutane (2nd Day of Menses or 11 Days Post Sexual Activity with No Birth Control) (4)(5) Send for Contraceptive Counseling No Rx for Accutane

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/ nd Urine Pregnancy Test 1st Urine Pregnancy Test Contraception Rx Consider Accutane Therapy Sexually Active Without Contraception PPP 10 Steps Yes Neg. Pos. No Rx for Accutane (2nd Day of Menses or 11 Days Post Sexual Activity with No Birth Control) Pos. No Rx for Accutane No (1) (2) (4)(5) Send for Contraceptive Counseling Sexually Active With Contraception Counseling either Prescriber or Contraceptive Counseling (3) Contraceptive Counseling Primary and Secondary Method Office Implementation System –Assess acne –Review patient Musts, check contraceptive use –Pregnancy Tests = Neg Accutane Prescription Given Pharmacist Dispenses Take Accutane (30 days) Revisit Monthly 2-5 Accutane Patient Survey SEU Patient Enrolls (6) (8) (9) (7)

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 33 Office Implementation System –Assess acne –Review patient Musts, check contraceptive use –Pregnancy Tests = Neg Lab Monitoring 2nd Urine Pregnancy Test 1st Urine Pregnancy Test ContraceptionRx Consider Accutane Therapy Sexually Active Without Contraception PPP 10 Steps Yes Neg. Pos. No Rx for Accutane (2nd Day of Menses or 11 Days Post Sexual Activity with No Birth Control) Pos. No Rx for Accutane Accutane Prescription Given Neg. Pharmacist Dispenses Take Accutane (30 days) No Revisit Monthly 2-5 Accutane Patient Survey SEU Patient Enrolls (1) (2) (4)(5) (6) (8) (9) Send for Contraceptive Counseling Sexually Active With Contraception Counseling either Prescriber or Contraceptive Counseling (7) (3) Contraceptive Counseling Primary and Secondary Method

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/ Qualification checklist 2.Important Information About Your Treatment with Accutane (isotretinoin) 3.Self-evaluation Quiz 4.Contraceptive Counseling Referral Program 5.Information/Consent Form 6.Accutane Patient Survey 7.Be Prepared, Be Protected video 8.Preventing Pregnancy, a Guide to Contraception 9.Contraception Knowledge Test 10.Accutane InfoLine and Confidential Contraceptive Counseling Line The 10-Step Office Implementation System REVISED NEW Steps Selecting Appropriate Patients Patient Education REVISED

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 35 Targeted Pregnancy Prevention Program SM for Women on Accutane ® (isotretinoin) Prescriber Assessment and Intervention Skills Guide to Best Practices for Prescribers Contraception education Contraception education Assessment and intervention skills Assessment and intervention skills How to initiate and have a conversation about sexual activity How to initiate and have a conversation about sexual activity Method for using support materials Method for using support materials

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 36 Targeted Pregnancy Prevention Program Contraception Knowledge and Behavior Be Smart, Be Safe, Be Sure Provides step-by-step process for: Provides step-by-step process for: –Qualification checklist –Accutane information –Self-evaluation Quiz –Contraception Counseling Referral Program –Information/Consent Form –Accutane Patient Survey –Contraception Knowledge Test

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 37 Pregnancy Test Kit Instructions Monoclonal and polyclonal antibodies (> 25 mIU/mL hCG) Monoclonal and polyclonal antibodies (> 25 mIU/mL hCG) Easy to perform, easy to evaluate Easy to perform, easy to evaluate Standardized against WHO International Reference Preparation Standardized against WHO International Reference Preparation 99% accurate at 11 days post conception 99% accurate at 11 days post conception

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 38 Women Who Reported Pregnancy During Accutane Therapy Reasons Women Became Pregnant Unsuccessful at abstinence Unsuccessful at abstinence Used ineffective contraception Used ineffective contraception Used contraception inconsistently Used contraception inconsistently Had unexpected sexual activity Had unexpected sexual activity Had a failure of the contraceptive method Had a failure of the contraceptive method

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 39 Targeted Pregnancy Prevention Program Knowledge About Contraception Preventing Pregnancy: A Guide to Contraception Patient responsibilities Patient responsibilities Birth defects Birth defects Avoiding pregnancy Avoiding pregnancy –Myths, methods and failure rates Contraceptive Counseling Line Contraceptive Counseling Line

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 40 New Birth Defect Line Drawings

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 41 Roche Education Initiatives Prescriber Prescriber Office Staff Office Staff Pharmacist Pharmacist

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 42 Prescriber Education Guide to Best Practices for Prescribers Guide to Best Practices for Prescribers –Database of registered prescribers (name, address, and CME number) Roche Professional Representatives – Office Visit Roche Professional Representatives – Office Visit Dermatology Resident Program Dermatology Resident Program Peer reviewed journal articles for CME Peer reviewed journal articles for CME Web site CME Web site CME

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 43 Office Staff Education Contraception Counseling Certificate Program Contraception Counseling Certificate Program –CEU for Registered Nurses –Certificate for RNs, LPNs, Medical Assistants Dermatology Nurses’ Association Dermatology Nurses’ Association –CEU provider unit –Presented at regional and state chapters levels

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 44 Pharmacist Education Distribution of professional materials to: Distribution of professional materials to: –Pharmacy Groups –Individual Pharmacists –Pharmaceutical Associations CEU articles in pharmacy journals CEU articles in pharmacy journals

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 45 Chronology of Actions March 1999: Roche submitted Targeted PPP to the FDA March 1999: Roche submitted Targeted PPP to the FDA March 2000: Roche announced Targeted PPP at the American Academy of Dermatology March 2000: Roche announced Targeted PPP at the American Academy of Dermatology April 2000: Roche distributed urine pregnancy test kits April 2000: Roche distributed urine pregnancy test kits –Immediately addressed 26% of pregnancies

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 46 Chronology of Actions May 2000: FDA approved label change May 2000: FDA approved label change June 2000: Distribution of “Dear Doctor” letter Distribution of contraception video June 2000: Distribution of “Dear Doctor” letter Distribution of contraception video July 2000: Individual prescriber and office staff training July 2000: Individual prescriber and office staff training

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 47 Chronology of Actions October 2000: Roche will launch educational materials October 2000: Roche will launch educational materials –Addresses prescriber assessment and intervention skills relative to contraception –Targets female Accutane patients’ contraception knowledge and behavior –Provides an “Office Implementation System”

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 48 Process Metrics – Achieving Goals Prescribers Prescribers Office Staff Office Staff Pharmacists Pharmacists Accutane Survey Accutane Survey Roche Call Center Roche Call Center Behavioral Research Behavioral Research

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 49 Prescriber Metric Goals Prescriber notification of targeted programSept Prescriber notification of targeted programSept Roche professional representative office visit for message reinforcement Roche professional representative office visit for message reinforcement –90% of prescribing dermatologistsJan –Remaining prescribersMar CME credit programs dermatologists, primary care prescribers, reproductive health prescribers, pediatriciansJun CME credit programs dermatologists, primary care prescribers, reproductive health prescribers, pediatriciansJun Dermatology Resident Education ProgramsDec Dermatology Resident Education ProgramsDec. 2002

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 50 Office Staff Metric Goals Dermatology Nurses’ Association Members - 20 chaptersMar Dermatology Nurses’ Association Members - 20 chaptersMar All members will be educatedSept All members will be educatedSept completed, 5 additional planned completed, 5 additional planned2000

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 51 Pharmacist Metric Goals Distribution of professional materialsOct Distribution of professional materialsOct Publication of CEU articles in pharmacy journalsMar Publication of CEU articles in pharmacy journalsMar. 2001

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 52 Accutane Survey Metric Goals Increase enrollment to 60%Mar Increase enrollment to 60%Mar –Require prescribers to instruct their patients to join survey –Require prescribers to submit Survey Enrollment Forms –Frequent feedback of results directly to prescribers and through publications –Increase visibility of survey through patient education and promotional activities –Increase compensation to patients Substantially increase DAT arm2001 Substantially increase DAT arm2001 Modify questions to enhance utilityDec of survey Modify questions to enhance utilityDec of survey

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 53 Roche Call Center ~ 10,000 calls received annually from healthcare professionals, patients and family members regarding Accutane ~ 10,000 calls received annually from healthcare professionals, patients and family members regarding Accutane –Over 1,000 queries received annually in reference to pregnancy and teratogenicity Developing a database of femaleApr patients and HCP callers Developing a database of femaleApr patients and HCP callers –Comprised of demographics, risk behaviors, and PPP practices –Source to reinforce Targeted PPP

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 54 Continuous Improvement Behavioral Research Concentrate on identifying Specific knowledge Specific knowledge Attitudes and beliefs Attitudes and beliefs Behavioral intentions Behavioral intentions –Resulting in specific pregnancy risk behaviors

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 55 Continuous Improvement Behavioral Research Discriminant Behavioral Study Mar Participants Participants –Prescribers –Female Accutane patients Those who became pregnant Those who became pregnant Those who avoided pregnancy Those who avoided pregnancy Outcome Outcome –Identify risk factors for pregnancy

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 56 Engage Partners and Other Stakeholders Select a Strategy Identify Issues and Put Them into Context Assess Risk/ Assess Benefits Identify and Analyze Options Evaluate Results Implement the Strategy Risk Management Model

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 57 Engage Partners and Other Stakeholders Select a Strategy Identify Issues and Put Them into Context Assess Risk/ Assess Benefits Identify and Analyze Options Evaluate Results Implement the Strategy Dermatologists, Nurses/Med Assts, Reproductive HCPs, Promote risk-free behavior Pregnancy Prevention Women who become pregnant (26%, 64%) Uniquely efficacious Educate/ Select appropriate patients Accutane Survey/ Discriminant Behavioral Study Targeted Pregnancy Prevention Program Risk Management Model Accutane PATIENTS

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 58 Summary 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 59 Summary 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients Targeted Pregnancy Prevention Program Targeted Pregnancy Prevention Program –Ensures selection of appropriate patients –Addresses the education of women who are still at risk

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 60 Summary 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients Targeted Pregnancy Prevention Program Targeted Pregnancy Prevention Program –Ensures selection of appropriate patients –Addresses the education of women who are still at risk Increased enrollment in the Accutane Survey will enhance the validity of the data Increased enrollment in the Accutane Survey will enhance the validity of the data

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 61 Summary 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients Targeted Pregnancy Prevention Program Targeted Pregnancy Prevention Program –Ensures selection of appropriate patients –Addresses the education of women who are still at risk Increased enrollment in the Accutane Survey will enhance the validity of the data Increased enrollment in the Accutane Survey will enhance the validity of the data Continuing research will identify risk factors for pregnancy Continuing research will identify risk factors for pregnancy

Safe Frame for 35mm Slides (delete from both Title and Slide masters before imaging slides or printing) Accutane FDA (PPP) 9/17/00 62