# Presentation: 079881

## Targeted Pregnancy Prevention ProgramSM for Women on Accutane® (isotretinoin)

- Eileen Enny Leach, MPH
- September 18, 2000

## Targeted Pregnancy Prevention Program

- Created from an analysis and revision of the 1988 Pregnancy Prevention ProgramSM
- Revised program targeted to both:
- small percentage of patients who do notavoid pregnancy
- physicians who are having difficulty assessingand predicting an individual patient’s behavior
- Goal: Prevention of pregnancy

## Accutane Product Labeling

- 1982 - 1987
- Launched with Category X with strong **Warnings** based on animal data
- Revised to include data as it became available
- 1988 Risk Management Pregnancy Prevention ProgramSM for Women on Accutane® (isotretinoin) (PPP)

**Notes:**
Expected US rate vs. Accutane rate.

## Pregnancy test required 7 days beforestarting Accutane
Two reliable forms of birth control
Begin therapy on 2nd or 3rd day of next menses
One month prescription only
Monthly pregnancy testing
Monthly contraceptive counseling

- Two reliable forms of birth control
- Begin therapy on 2nd or 3rd day of next menses
- One month prescription only
- Monthly pregnancy testing
- Monthly contraceptive counseling

**1988 Label Change**** *****Elements***

## 1988 Accutane Package Elements

- Blister pack for 10, 20, 40mg

**1988 Accutane Package Elements**

## 1988 Accutane Package Elements

- Blister pack for 10, 20, 40mg
- “Avoid pregnancy” logo at each pill site

**1988 Accutane Package Elements**

## 1988 Accutane Package Elements

- “Avoid pregnancy” logo at each pill site
- Black box warnings

**1988 Accutane Package Elements**

## 1988 Accutane Package Elements

- “Avoid pregnancy” logo at each pill site
- Black box warnings
- Line drawings of birth defects

**1988 Accutane Package Elements**

## 1988 Risk Management SystemPregnancy Prevention ProgramSM (PPP)for Women on Accutane® (isotretinoin)

**1988 Risk Management System*****Pregnancy Prevention Program******SM****** (PPP)******for Women on Accutane******®****** *****(isotretinoin)**

## 1988 Risk Management SystemPregnancy Prevention ProgramSM (PPP) for Women on Accutane® (isotretinoin)

**1988 Risk Management System*****Pregnancy Prevention Program******SM****** (PPP) ******for Women on Accutane******®****** *****(isotretinoin)**

- Assists in meeting requirements of label
- Developed in cooperation with the American College of Obstetrics and Gynecology
- Initiated Accutane Survey (patient survey)
- Accutane Tracking Survey (prescriber survey)

## Pregnancy Prevention ProgramSM  for Women on Accutane® (isotretinoin)

- 97% of prescribers use at least one component of the PPP*
- Reduced pregnancy rate from†
- 1989	4.0 per 1000
- 1998	2.1 per 1000

- *	Accutane Prescriber Tracking Survey
- †	Accutane Survey (incidence rate based on 1000 140-day courses)

**Notes:**
Consent Form 91%
Checklist 78%
Patient Brochure 97%
Patient Self Test 71%
Contraceptive Pamphlet 73%
Serum Pregnancy Test 83%
Gyn Referral Program 44%

## Review of Individual Reports3 Pregnancies per 1000 Female Patients

- Confusion about timing of pregnancy test
- False negatives
- Did not wait until 2nd or 3rd day of menses
- Misinformation about contraceptive methods
- Received more than one month supply
- No monthly pregnancy testing orcontraceptive counseling

- Accutane Survey and Roche Accutane Drug Safety Database

## Review of Individual ReportsWomen Who Reported Pregnancy During Accutane Therapy 3 Pregnancies per 1000 Female Patients 

- Reasons Women Became Pregnant
- Unsuccessful at abstinence
- Used ineffective contraception
- Used contraception inconsistently
- Had unexpected sexual activity
- Had a failure of the contraceptive method

## All Pregnancies Reported in the US (annually)

**45%**
**Women who reported ****unwanted or mistimed **
**pregnancies**

**Women, in the US, who****became pregnant**
**(3.6 million)**

**All Pregnancies Reported in the US ****(annually)**

## All Pregnancies Reported in the US (annually)

**45%**
**Women who reported ****unwanted or mistimed **
**pregnancies**

**Women, in the US, who****became pregnant**
**(3.6 million)**

**All Pregnancies Reported in the US ****(annually)**

## Accutane-Exposed Pregnancies

- Pregnancy rate for women taking Accutane
- 3 pregnancies per 1000
- Pregnancy rate 0.3%

## 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
- Mean age 26.3 years*

- *Roche Accutane Drug Safety Database (1991-1998)

## Considerations for Risk Managementfor Accutane

- Accutane is a known teratogen
- Female Accutane patients are usually of childbearing potential
- 91% of surveyed women believe they know about contraception*
- 37% chose the least effective birth control method*

- * Lewin Survey 2000

## Risk Management Options

- Selective and targeted
- Should not negatively impact:
- the compliant patient
- the current success of the program

## Risk ManagementModel

**Source:  Presidential/Congressional Commission on Risk Assessment and Risk Management, *****Framework for Environmental Health Risk Management — Final Report*****, Vol. 1, 1997.**

## Women Who Reported Pregnancies*3 Pregnancies per 1000 Female Patients

**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

## 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%**

**Issue:  Pregnancy testing**

## 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
- 34% reported failure to use contraception on the perceived day of conception
- 33% occurred while using *one form of contraception*
- 51% reported contraception failure
- 61% occurred while using *one form of contraception*

**= ****64%**

## Targeted Pregnancy Prevention ProgramProvisions

- Revise Accutane labeling
- two safe, effective forms of birth control
- negative results from two pregnancy tests
- Provide urine pregnancy test kits
- Introduce an Office Implementation System
- Package for one month supply using unit dosing
- Encourage enrollment in Accutane Survey
- Provide educational materials for prescribersand patients

## 1988 LabelElements of Label

**1988 Label*****Elements of Label***

**2000 Label Change*****Elements of Label***

- Two pregnancy tests required at specified times
- No Rx until confirmation of a negative result from a second pregnancy test
- Two safe, effective forms of contraception
- One primary and one secondary

## Effective Forms of Contraception

**Effective Forms of Contraception**

- Primary
- Tubal ligation
- Partner’s vasectomy
- Birth control pills
- Injectable/implantablebirth control products
- IUD

- Secondary
- Diaphragms with spermicide
- Latex condoms with spermicide
- Cervical caps withspermicide

## Two pregnancy tests required at specified times 
No Rx until confirmation of a negative result from a second pregnancy test 
Two safe, effective forms of contraception
One primary and one secondary
Reinforce one month prescription only

- No Rx until confirmation of a negative result from a second pregnancy test
- Two safe, effective forms of contraception
- One primary and one secondary
- Reinforce one month prescription only

**2000 Label Change*****Elements of Label***

## One Month Supply with Unit Dosing

**One Month Supply with Unit Dosing**

## Two pregnancy tests required at specified times 
No Rx until confirmation of a negative result from a second pregnancy test 
Two safe, effective forms of contraception
One primary and one secondary
Reinforce one month prescription only
Reinforce monthly pregnancy testing and monthly contraceptive counseling

- No Rx until confirmation of a negative result from a second pregnancy test
- Two safe, effective forms of contraception
- One primary and one secondary
- Reinforce one month prescription only
- Reinforce monthly pregnancy testing and monthly contraceptive counseling

**2000 Label Change*****Elements of Label***

## Progress Notes

**Progress Notes**

## Office Implementation System

## Office Implementation System

## Office Implementation System

**Office Implementation System**

## Office Implementation System

## The 10-Step Office Implementation System

- 	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**

**NEW**

**NEW**

**NEW**

- Steps

- SelectingAppropriatePatients

- PatientEducation

**REVISED**

**Notes:**
Limiting Access

## Targeted Pregnancy Prevention ProgramSM  for Women on Accutane® (isotretinoin)Prescriber Assessment and Intervention Skills

*Guide to Best Practices for*
*Prescribers*
- Contraception education
- Assessment and intervention skills
- How to initiate and have a conversation about sexual activity
- Method for using support materials

**Notes:**
counseling skills, staff awareness, patient information, algorithm on reproduction beliefs

## Targeted Pregnancy Prevention ProgramContraception Knowledge and Behavior

*Be Smart, Be Safe, Be Sure*
- Provides step-by-step process for:
- Qualification checklist
- Accutane information
- Self-evaluation Quiz
- Contraception CounselingReferral Program
- Information/Consent Form
- Accutane Patient Survey
- Contraception Knowledge Test

**Notes:**
counseling skills, staff awareness, patient information, algorithm on reproduction beliefs

## Pregnancy Test KitInstructions

- Monoclonal and polyclonal antibodies(> 25 mIU/mL hCG)
- Easy to perform,easy to evaluate
- Standardized against WHO International Reference Preparation
- 99% accurate at 11 days post conception

## Women Who Reported Pregnancy During Accutane Therapy

- Reasons Women Became Pregnant
- Unsuccessful at abstinence
- Used ineffective contraception
- Used contraception inconsistently
- Had unexpected sexual activity
- Had a failure of the contraceptive method

## Targeted Pregnancy Prevention Program  Knowledge About Contraception

*Preventing Pregnancy:*
*A Guide to Contraception*
- Patient responsibilities
- Birth defects
- Avoiding pregnancy
- Myths, methods and failure rates
- Contraceptive Counseling Line

**Notes:**
counseling skills, staff awareness, patient information, algorithm on reproduction beliefs

## New Birth Defect Line Drawings

**New Birth Defect Line Drawings**

## Roche Education Initiatives

- Prescriber
- Office Staff
- Pharmacist

## Prescriber Education

*Guide to Best Practices for Prescribers*
- Database of registered prescribers (name, address, and CME number)
- Roche Professional Representatives –Office Visit
- Dermatology Resident Program
- Peer reviewed journal articles for CME
- Web site CME

**Notes:**
Limited Access

## Office Staff Education

- Contraception Counseling Certificate Program
- CEU for Registered Nurses
- Certificate for RNs, LPNs, Medical Assistants
- Dermatology Nurses’ Association
- CEU provider unit
- Presented at regional and state chapters levels

## Pharmacist Education

- Distribution of professional materials to:
- Pharmacy Groups
- Individual Pharmacists
- Pharmaceutical Associations
- CEU articles in pharmacy journals

**Notes:**
Limited Access

## Chronology of Actions

- March 1999:Roche submitted Targeted PPP to the FDA
- March 2000:Roche announced Targeted PPP at the American Academy of Dermatology
- April 2000:Roche distributed urine pregnancy test kits
- Immediately addressed 26% of pregnancies

## Chronology of Actions

- May 2000:FDA approved label change
- June 2000:Distribution of “Dear Doctor” letterDistribution of contraception video
- July 2000:Individual prescriber and office staff training

## Chronology of Actions

- 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”

## Process Metrics – Achieving Goals

- Prescribers
- Office Staff
- Pharmacists
- Accutane Survey
- Roche Call Center
- Behavioral Research

## Prescriber Metric Goals

- Prescriber notification of targeted program	Sept. 2000
- Roche professional representative officevisit for message reinforcement
- 90% of prescribing dermatologists	Jan. 2001
- Remaining prescribers	Mar. 2001
- CME credit programs dermatologists, primary care prescribers, reproductive health prescribers, pediatricians	Jun. 2001
- Dermatology Resident Education Programs	Dec. 2002

## Office Staff Metric Goals

- Dermatology Nurses’ Association Members - 20 chapters	Mar. 2001
- All members will be educated	Sept. 2001
- 1 completed, 5 additional planned	2000

## Pharmacist Metric Goals

- Distribution ofprofessional materials	Oct. 2000
- Publication of CEU articlesin pharmacy journals	Mar. 2001

## Accutane Survey Metric Goals

- Increase enrollment to 60%	Mar. 2001
*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 arm	2001
- Modify questions to enhance utility	Dec. 2000of survey

## Roche Call Center

- ~ 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 female	Apr. 2001patients and HCP callers
- Comprised of demographics, risk behaviors, andPPP practices
- Source to reinforce Targeted PPP

## Continuous ImprovementBehavioral Research

- Concentrate on identifying
- Specific knowledge
- Attitudes and beliefs
- Behavioral intentions
- Resulting in specific pregnancy risk behaviors

## Continuous ImprovementBehavioral Research

- Discriminant Behavioral Study 	Mar. 2001
- Participants
- Prescribers
- Female Accutane patients
- Those who became pregnant
- Those who avoided pregnancy

- Outcome
- Identify risk factors for pregnancy

## Risk Management Model

**Risk Management Model**

## Risk Management Model

**Dermatologists,**
**Nurses/Med Assts,****Reproductive HCPs,**

- Promoterisk-free behavior

- Pregnancy Prevention

- Women whobecome pregnant(26%, 64%)
- Uniquely efficacious

- Educate/Select appropriate patients

- Accutane Survey/ Discriminant Behavioral Study

- Targeted Pregnancy Prevention Program

**Risk Management Model**

**Accutane**

***PATIENTS***

## Summary

- 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients

## Summary

- 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients
- Targeted Pregnancy Prevention Program
- Ensures selection of appropriate patients
- Addresses the education of women who are still at risk

## Summary

- 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients
- 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

## Summary

- 1988 Accutane Pregnancy Prevention Program works for majority of female Accutane patients
- 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
- Continuing research will identify risk factorsfor pregnancy

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