prescription compliance survey
TRANSCRIPT
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
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
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
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
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
5Joint 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
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
6Joint 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
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
7Joint 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
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
8Joint 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
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
9Joint 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
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
10Joint 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
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
11Joint 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
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
12Joint 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
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
13Joint 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
Patient Surveys Patient Surveys OverviewOverview
• Purpose of Patient Survey
• Methods
– Limitations
• Survey Population
– Representativeness / Generalizability
• Results
• Summary Conclusions
14Joint 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
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.”
15Joint 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
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
16Joint 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
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
17Joint 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
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
18Joint 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
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
19Joint 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
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
20Joint 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
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
22Joint 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
ResultsResultsSurvey PopulationSurvey Population
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
23Joint 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
ResultsResultsSurvey PopulationSurvey Population
• 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)
24Joint 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
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
25Joint 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
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
26Joint 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
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
27Joint 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
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
QTR1 QTR2 QTR3 QTR4 QTR5 QTR6 QTR7 QTR8
pe
rce
nt
Arrow separates the 4 QTRs before implementation of the current RMP and the 4 QTRs following its implementation
29Joint 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
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
30Joint 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
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
31Joint 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
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
32Joint 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
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
33Joint 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
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
34Joint 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
ResultsResultsDuring TherapyDuring Therapy
• Analyses of Degge/SI participants
during therapy:
– 95% report use of a Qualification
sticker
– 81% report monthly pregnancy
testing
35Joint 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
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
QTR1 QTR2 QTR3 QTR4 QTR5 QTR6 QTR7 QTR8
perc
ent
Arrow separates the 4 QTRs before implementation of the current RMP and the 4 QTRs following its implementation
37Joint 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
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
38Joint 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
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%
39Joint 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
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
40Joint 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
Overall SummaryOverall Summary
• Despite their wide utilization,
Qualification stickers have been
issued to patients who have not
undergone pregnancy testing
41Joint 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
Overall SummaryOverall Summary
• 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