Prescription Compliance Survey

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee Advisory Committee February 26 & 27, 2004February 26 & 27, 2004

Isotretinoin Pregnancy Prevention Isotretinoin Pregnancy Prevention Program EvaluationProgram Evaluation

Prescription Compliance Surveyand

Patient Surveys

Allen Brinker, MD, MSFebruary 26, 2004



Collaborators -Cynthia Kornegay, Ph.D.

Primary reviewer for prescription compliance survey

Parivash Nourjah, Ph.D.Primary analyst for a patient survey dataset supplied by Hoffmann-LaRoche



Order of topics:

Prescription Compliance Program (PCS)

Patient Survey

4Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee Advisory Committee February 26 & 27, 2004February 26 & 27, 2004

Prescription Compliance Survey (PCS)Prescription Compliance Survey (PCS)OverviewOverview

• Survey Design• Survey Results• Methodological Issues

– Response Rate– Number of Prescriptions Captured– Participation by Stores

• Survey Audit– Recruiting Strategy/Response Rate

• Conclusions


PCS GoalsPCS Goals

• Primary Outcome: Compliance with

Qualification sticker use

• Secondary Outcomes: Completeness

and correctness of Qualification stickers

• Inference

– presence of a Qualification sticker

does not imply adherence to all parts

of the current RMP


PCS DesignPCS Design

• Retrospective, repeated-measures survey

• 6,000 selected U.S. pharmacies

• Stratified, random sample

• Data collected in March, June, September,

and December for 2 years

• 750 Stores selected for each collection period

• Stores can only be included once


PCS ResultsPCS Results

• High rate of compliance (>90%) across all survey waves for both PCS and audit

• Results consistent across age, gender, and payer type

• Some differences across prescription volume and population density– both high volume and rural pharmacies

more likely to receive prescriptions with incomplete stickers


Methodological IssuesMethodological Issues

• Minimum necessary response rate for each wave

was 60% of the sample, or 450 stores

– response rates ranged from 25% to 59%

• In December 2002, CVS, Eckerd, Rite Aid,

Walgreens and Wal-Mart asked and were removed

from the survey pool

– 33% of stores, or 15,200

– probably represented more than 33% of Rxs


Methodological IssuesMethodological IssuesPCS Prescriptions CapturedPCS Prescriptions Captured

Number of Prescriptions: Estimated Actual

Average no. per QTR 2.55 0.84

Total per QTR 1,150 268


PCS AuditPCS AuditRecruitingRecruiting

• Proposed strategy: random sample of

15% of PCS respondents– does not appear to have been

implemented as proposed

– consistently high response rates (>20%)• recruiting strategy may not be random

– utility and/or applicability of audit results is

questionable


PCS Overall ConclusionsPCS Overall Conclusions

• High rate of compliance with

Qualification stickers

– not the same as high rate of compliance

with SMART program in total


PCS Overall ConclusionsPCS Overall Conclusions

• Insufficient pharmacy sample size

• Generalizability compromised

– low pharmacy response rate

– 23% of expected prescriptions captured

– five largest U.S. chains dropped out

• Alternate study designs should be considered

for future studies with similar goals


Patient Surveys Patient Surveys OverviewOverview

• Purpose of Patient Survey

• Methods

– Limitations

• Survey Population

– Representativeness / Generalizability

• Results

• Summary Conclusions


Patient Survey - PurposePatient Survey - Purpose

• Isotretinoin Patient Surveys

– Implemented in 1989 to “assess the

compliance of physicians and patients with

the Accutane Pregnancy Prevention

Program and to identify the rate of

pregnancy during treatment with

isotretinoin.”


Patient Survey - Reports and Analysis Patient Survey - Reports and Analysis OverviewOverview

• FDA data include:

– Slone Epidemiology Group Quarterly

Reports

• year prior and continuing in year following

– Primary FDA analysis of an Accutane-

brand patient survey• started in 3rd QTR following implementation of

the current RMP


Patient Survey - MethodsPatient Survey - Methods

Two versions of survey instrument:

–Old survey instrument–no questions on Qualification sticker

–no questions related to MedGuide

–pregnancy test question limited to

whether a pregnancy test was

performed


Patient Survey - MethodsPatient Survey - MethodsNew survey instrument

• Current RMP-specific questions–Qualification sticker present on Rx ?–date and number of pregnancy tests

performed

• Not introduced until 3rd QTR following implementation of the current RMP

–enrolled ~6,000 participants through the end of first year


Patient Survey - MethodsPatient Survey - MethodsSelected LimitationsSelected Limitations

•Mailed survey–some are surveyed by telephone

•Follow-up survey–cannot be anonymous

•Generalizability limited due to–low enrollment rate–voluntary survey participation


Patient Survey - MethodsPatient Survey - MethodsSelected LimitationsSelected Limitations

•Important issues - continued

•Measurement errors• Recall bias

• Social desirability bias

• Poor questionnaire design– complex questions and question skip

patterns to be followed


ResultsResultsSurvey PopulationSurvey Population

• Absolute participation in Isotretinoin Patient

Surveys based on FDA models:

–16% to 19% in year before current RMP

–22% to 26% in the first year current RMP

Trends in Enrollment in Isotretinoin Trends in Enrollment in Isotretinoin Patient SurveysPatient Surveys

15.5 17.3 15.418.6 21.4 22.6

26 23.4

0

20

40

60

80

100

QTR1 QTR2 QTR3 QTR4 QTR5 QTR6 QTR7 QTR8

pe

rce

nt e

nro

llme

nt

Arrow separates the 4 QTR’s before implementation of the current RMP and the 4 QTR's following its implementation



Age group

(years)

Degge/SI

cohort*

(as submitted)

AdvancePC

S*

(4/02-3/03)

IMS Health

NDTI™***

(4/02-3/03)

Up to age 19 1917 (35%) 43% 45%

20-29 2092 (38%) 28% 30%

30-39 918 (17%) 16% 16%

40+ 536 (10%) 13% 9%

Total 5463 100% 100%

*excludes 6 records where age was missing + 432 records on generic isotretinoin **Advance PCS™ Dimension Rx, accessed 11 December 2003 ***IMS Health, IMS National Disease and Therapeutic IndexTM, 4/2002-3/2003, accessed 15 December 2003; FDA custom calculations were based on IMS Health data



• Prescriber

–94% of isotretinoin recipients within Degge/SI

cohort indicated prescriber was a dermatologist

–80% of recent isotretinoin prescriptions*

associated with a dermatologist

*Source: IMS Health National Prescription Audit PlusTM (3 Dec 2003)


Results - Initiation of TherapyResults - Initiation of TherapyConsent formConsent form

• Analyses of Degge/SI cohort:

– 76% signed two consent forms (as required)

– 4% signed only one form

– 9% reported signing no consent forms

– 11% were uncertain / did not answer


Results - Initiation of TherapyResults - Initiation of TherapyQualification stickerQualification sticker

• Analyses of Degge/SI cohort:

– 92% reported Rx with Qualification Sticker

• Consistent with findings from the PCS

– 2.5% reported no sticker

– 5.5% did not know / did not answer


Results - Initiation of TherapyResults - Initiation of TherapyPregnancy TestingPregnancy Testing

•Analyses of apparently fertile, 15-45

year-old participants in Degge/SI cohort:•91% reported at least one pregnancy test

•66% reported two tests

•Performance increased only slightly with restriction to sexually active

•Performance decreased only slightly with restriction to sexually INactive


Results - Initiation of Therapy Results - Initiation of Therapy Trends in Pregnancy TestingTrends in Pregnancy Testing

•Slone Epi Group Quarterly reports

•ANY pregnancy testing

•77%-85% for year prior to the current RMP

•91%-92% in first year of current RMP

Results - Initiation of TherapyResults - Initiation of TherapyTrends in ANY Pregnancy Testing in Slone SurveyTrends in ANY Pregnancy Testing in Slone Survey

0

20

40

60

80

100


pe

rce

nt

Arrow separates the 4 QTRs before implementation of the current RMP and the 4 QTRs following its implementation


Results - Initiation of TherapyResults - Initiation of TherapyContraception PracticesContraception Practices

• Analyses of apparently fertile and sexually

active women among the Degge/SI cohort:– 95.4% reported use of some form of

birth control– 48.9% reported use of appropriate birth

control per the revised RMP• one primary and one secondary birth

control method


Results - Initiation of TherapyResults - Initiation of TherapySexual Activity - Univariate FocusSexual Activity - Univariate Focus

N

Total 4596

Sexually active since starting Accutane therapy

1806

Sexually active before but not during Accutane therapy 993

Not sexually active before or during Accutane therapy 1797


Results - Initiation of TherapyResults - Initiation of TherapyBivariate AnalysesBivariate Analyses

• Conducted to address the relationship

between the presence or absence of a

Qualification sticker and

•any pregnancy testing

•any birth control


Results - Initiation of TherapyResults - Initiation of TherapyQualification Sticker and Pregnancy TestingQualification Sticker and Pregnancy Testing

n=4400n=4400

NoYesPregnancy

Test

Qualification Sticker

90(90%)

3908(91%) Yes

10(10%)

392(9%)No


Results - Initiation of TherapyResults - Initiation of TherapyQualification Sticker and Birth Control (any)Qualification Sticker and Birth Control (any)

n=1788n=1788

NoYesAny Birth Control

Use

Qualification Sticker

70(96%)

1671(97%) Yes

3(4%)

44(3%) No


ResultsResultsDuring TherapyDuring Therapy

• Analyses of Degge/SI participants

during therapy:

– 95% report use of a Qualification

sticker

– 81% report monthly pregnancy

testing


Results - During Therapy Results - During Therapy Trends in Report of Pregnancy TestingTrends in Report of Pregnancy Testing

• Slone Epi Group Quarterly reports

• ANY pregnancy testing during therapy with isotretinoin

• ~70% in year prior to revised RMP

• ~85% in first year of revised RMP

Results - During TherapyResults - During TherapyTrends in ANY Pregnancy Testing in Slone SurveyTrends in ANY Pregnancy Testing in Slone Survey

0

20

40

60

80

100


perc

ent

Arrow separates the 4 QTRs before implementation of the current RMP and the 4 QTRs following its implementation


Pregnancy RatePregnancy Rate

• 15 pregnancies were identified among 4277

first-time users within the Degge/Si cohort

– pregnancy rate: 3.5/1000 women

– the rate is likely an underestimate as it is

censored as of the data lock date

• Similar to that reported for participants in the

Slone Survey of Accutane recipients


AddendumAddendumGeneric Isotretinoin DataGeneric Isotretinoin Data

• Any pregnancy testing prior to initiation: ~90%

• Two pregnancy tests prior to initiation: ~65%

• NO birth control among apparently fertile,

sexually active respondents: ~3%

• Any pregnancy testing during therapy: ~82%


Overall SummaryOverall Summary

• Isotretinoin-exposed pregnancies continue to

occur after implementation of the current RMP

• Enrollment in isotretinoin patient surveys

increased only modestly after implementation of

the current RMP



• Despite their wide utilization,

Qualification stickers have been

issued to patients who have not

undergone pregnancy testing



• The observed pregnancy rate for the

Degge/SI cohort recruited following

implementation of the current RMP

appears similar to that reported for

cohorts recruited before

implementation of the current RMP

Documents

Prescription Compliance Survey