Post on 02-Apr-2015
Plan BPlan B® ® Actual UseActual Useand Behavior Studiesand Behavior Studies
NDA 21-045NDA 21-045
Plan BPlan B® ® Actual UseActual Useand Behavior Studiesand Behavior Studies
NDA 21-045NDA 21-045
NDAC & ACRHD Joint MeetingNDAC & ACRHD Joint MeetingDecember 16, 2003December 16, 2003
Jin Chen, MD, PhDJin Chen, MD, PhDDivision of OTC Drug ProductsDivision of OTC Drug Products
NDAC & ACRHD Joint MeetingNDAC & ACRHD Joint MeetingDecember 16, 2003December 16, 2003
Jin Chen, MD, PhDJin Chen, MD, PhDDivision of OTC Drug ProductsDivision of OTC Drug Products
Center for Drug Evaluation and ResearchCenter for Drug Evaluation and Research
2NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
OutlineOutlineOutlineOutline
• Plan B Actual Use Study
• Behavior studies associated with emergency contraception
• Plan B Actual Use Study
• Behavior studies associated with emergency contraception
3NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Actual Use StudyActual Use StudyPrinciplesPrinciples
Actual Use StudyActual Use StudyPrinciplesPrinciples
• Simulate OTC setting• Assess
– self-diagnosis– self-selection– self-medication– safety– efficacy (rarely)
• Multi-center, open-label, single-arm, uncontrolled trial
• Simulate OTC setting• Assess
– self-diagnosis– self-selection– self-medication– safety– efficacy (rarely)
• Multi-center, open-label, single-arm, uncontrolled trial
4NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Actual Use StudyActual Use StudyPrinciplesPrinciples (cont.) (cont.)
Actual Use StudyActual Use StudyPrinciplesPrinciples (cont.) (cont.)
Study Population: anticipated OTC users
• Geographically diverse OTC-like settings
• Minimal exclusion criteria
• Subgroups (low literacy, age)
• Unlimited product access
• Minimal intervention from healthcare professionals
Study Population: anticipated OTC users
• Geographically diverse OTC-like settings
• Minimal exclusion criteria
• Subgroups (low literacy, age)
• Unlimited product access
• Minimal intervention from healthcare professionals
5NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Plan B Actual Use StudyObjectives
Plan B Actual Use StudyObjectives
• Primary Objectives:– Self-selection– Timing of doses
• Secondary Objectives:– Adverse events– Multiple use– Pregnancy rate
• Additional Observation:– Contraceptive behaviors
• Primary Objectives:– Self-selection– Timing of doses
• Secondary Objectives:– Adverse events– Multiple use– Pregnancy rate
• Additional Observation:– Contraceptive behaviors
6NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Plan B Actual Use StudyPlan B Actual Use StudyDesign/ProcedureDesign/Procedure
Plan B Actual Use StudyPlan B Actual Use StudyDesign/ProcedureDesign/Procedure
• Conducted in 5 family planning clinics across US & 5 pharmacies in WA
• Female subjects of reproductive age
• Purchased 1 package of Plan B
• 4-week Follow-up (2 contacts)
• Data collection by phone and diary card
• Conducted in 5 family planning clinics across US & 5 pharmacies in WA
• Female subjects of reproductive age
• Purchased 1 package of Plan B
• 4-week Follow-up (2 contacts)
• Data collection by phone and diary card
7NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Subject EnrollmentSubject EnrollmentSubject EnrollmentSubject Enrollment
665Screened subjects
80 (12%)
Not Enrolled 585 585 (88%)(88%)
EnrolledEnrolled
94%94%from clinicsfrom clinics
6% from6% frompharmaciespharmacies
8NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Demographics of Enrolled SubjectsDemographics of Enrolled Subjects(n=585)(n=585)
Demographics of Enrolled SubjectsDemographics of Enrolled Subjects(n=585)(n=585)
• Age: 14-44 yrs (22±5)
• Education:– 87% ≥ HS education– 13% had 9th-11th grade education
• Prior EC experience: 40%
• Age: 14-44 yrs (22±5)
• Education:– 87% ≥ HS education– 13% had 9th-11th grade education
• Prior EC experience: 40%
9NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Subject Follow-UpSubject Follow-Up(n=585)(n=585)
Subject Follow-UpSubject Follow-Up(n=585)(n=585)
• 93% (n=543) at least one follow-up contact
– 86% (n=501): 2 follow-up contacts– 2% (n=12): ≥ 3 follow-up– 5% (n=30): only 1 follow-up
• 7% (n=42) lost to follow-up
• 92% (n=540) used Plan B
• 93% (n=543) at least one follow-up contact
– 86% (n=501): 2 follow-up contacts– 2% (n=12): ≥ 3 follow-up– 5% (n=30): only 1 follow-up
• 7% (n=42) lost to follow-up
• 92% (n=540) used Plan B
10NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
ResultsResultsResultsResults
• Self-Selection
• Timing of Dosing
• Adverse Events
• Contraceptive Behavior
• Pregnancy Rate
• Self-Selection
• Timing of Dosing
• Adverse Events
• Contraceptive Behavior
• Pregnancy Rate
11NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
ResultsResultsResultsResults
• Self-Selection
• Timing of Dosing
• Adverse Events
• Contraceptive Behavior
• Pregnancy Rate
• Self-Selection
• Timing of Dosing
• Adverse Events
• Contraceptive Behavior
• Pregnancy Rate
12NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Self-SelectionSelf-Selection(n=540)(n=540)
Self-SelectionSelf-Selection(n=540)(n=540)
95% of users (n=514) correctly self-selected:
• Unprotected intercourse (40%)
• Condom broke or slipped (45%)
• Missed taking OC pills (7%)
• Withdrawal method (4%)
95% of users (n=514) correctly self-selected:
• Unprotected intercourse (40%)
• Condom broke or slipped (45%)
• Missed taking OC pills (7%)
• Withdrawal method (4%)
13NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Self-Selection Self-Selection (cont.)(cont.)
(n=540)(n=540)Self-Selection Self-Selection (cont.)(cont.)
(n=540)(n=540)
5% of users (n=26) incorrectly self-selected:
• 1.3% (n=7) had label contraindication:
– 6 unexplained vaginal bleeding
– 1 pregnancy
• 0.4% (n=2) took Plan B before unprotected intercourse
• 3% (n=17) provided non-specific reasons
5% of users (n=26) incorrectly self-selected:
• 1.3% (n=7) had label contraindication:
– 6 unexplained vaginal bleeding
– 1 pregnancy
• 0.4% (n=2) took Plan B before unprotected intercourse
• 3% (n=17) provided non-specific reasons
14NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
ResultsResultsResultsResults
• Self-Selection
• Timing of Doses
• Adverse Events
• Contraceptive Behavior
• Pregnancy Rate
• Self-Selection
• Timing of Doses
• Adverse Events
• Contraceptive Behavior
• Pregnancy Rate
15NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Timing of Dose per LabelTiming of Dose per Label(n=540)(n=540)
Timing of Dose per LabelTiming of Dose per Label(n=540)(n=540)
• 92% (n=499) – 1st pill < 72 hours
• 72% (n=387) – 2nd pill at 12 hours after 1st pill
• 68% (n=366) – both pills according to the label dosing regimen
• 92% (n=499) – 1st pill < 72 hours
• 72% (n=387) – 2nd pill at 12 hours after 1st pill
• 68% (n=366) – both pills according to the label dosing regimen
16NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Timing of DoseTiming of Dose(Alternate 2(Alternate 2ndnd Dosing Analysis) Dosing Analysis)
Timing of DoseTiming of Dose(Alternate 2(Alternate 2ndnd Dosing Analysis) Dosing Analysis)
• 92% (n=499) – 1st pill < 72 hours
• 93% (n=500) – 2nd pill between 6-18 hours after 1st pill
• 87% (n=469) – both pills according to the alternate 2nd dosing interval
• 92% (n=499) – 1st pill < 72 hours
• 93% (n=500) – 2nd pill between 6-18 hours after 1st pill
• 87% (n=469) – both pills according to the alternate 2nd dosing interval
17NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
ResultsResultsResultsResults
• Self-Selection
• Timing of Dosing/use
• Adverse Events
• Contraceptive Behavior
• Pregnancy Rate
• Self-Selection
• Timing of Dosing/use
• Adverse Events
• Contraceptive Behavior
• Pregnancy Rate
18NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Adverse Events (AEs) Adverse Events (AEs) (n=540)(n=540)
Adverse Events (AEs) Adverse Events (AEs) (n=540)(n=540)
• No serious AEs
• No new safety signals
• Most common AEs (transient):– Abdominal pain (14%)– Nausea (12%)– Headache (11%)– Fatigue/tiredness (8%)
• No serious AEs
• No new safety signals
• Most common AEs (transient):– Abdominal pain (14%)– Nausea (12%)– Headache (11%)– Fatigue/tiredness (8%)
19NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
ResultsResultsResultsResults
• Self-Selection
• Timing of Dosing/use
• Adverse Events
• Contraceptive Behaviors
• Pregnancy Rate
• Self-Selection
• Timing of Dosing/use
• Adverse Events
• Contraceptive Behaviors
• Pregnancy Rate
20NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Contraceptive BehaviorsContraceptive Behaviors(n=543)(n=543)
Contraceptive BehaviorsContraceptive Behaviors(n=543)(n=543)
Behavior1 month
before study1 month
during study
≥ 1 sex act w/o contraception
60% 20%
Withdrawal method
28% 10%
Condom use 79% 90%
21NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Contraceptive Behaviors Contraceptive Behaviors (cont.)(cont.)Contraceptive Behaviors Contraceptive Behaviors (cont.)(cont.)
• Subjects tended to use more effectivecontraception methods
• 1.7% of enrolled subjects (n=10) requested Plan B more than once during 3-month enrollment period
• Subjects tended to use more effectivecontraception methods
• 1.7% of enrolled subjects (n=10) requested Plan B more than once during 3-month enrollment period
22NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
ResultsResultsResultsResults
• Self-Selection
• Timing of Dosing/use
• Adverse Events
• Contraceptive Behavior
• Pregnancy Rate
• Self-Selection
• Timing of Dosing/use
• Adverse Events
• Contraceptive Behavior
• Pregnancy Rate
23NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Pregnancy RatePregnancy Rate(n=540)(n=540)
Pregnancy RatePregnancy Rate(n=540)(n=540)
• Confirmed pregnancy (n=10): 1.9%
• Unknown pregnancy status: 2.6%(n=14, at the end of the study)
• Confirmed pregnancy (n=10): 1.9%
• Unknown pregnancy status: 2.6%(n=14, at the end of the study)
24NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
SummarySummarySummarySummary
• 95% of users correctly self-selected Plan B
• 68% of users took 1st pill within 72 hours and 2nd pill at 12 hours after the 1st pill
• 87% of users took 1st pill within 72 hours and 2nd pill between 6-18 hours
• 95% of users correctly self-selected Plan B
• 68% of users took 1st pill within 72 hours and 2nd pill at 12 hours after the 1st pill
• 87% of users took 1st pill within 72 hours and 2nd pill between 6-18 hours
25NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Summary Summary (cont.)(cont.)Summary Summary (cont.)(cont.)
• No serious AEs and no new safety signals
• Subjects tended to use more effective contraception
• No significant differences among demographic subgroups:– Self-selection– Timing of dose/use– AEs– Adverse contraceptive behaviors
• No serious AEs and no new safety signals
• Subjects tended to use more effective contraception
• No significant differences among demographic subgroups:– Self-selection– Timing of dose/use– AEs– Adverse contraceptive behaviors
26NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Limitations ofLimitations ofPlan B Actual Use StudyPlan B Actual Use Study
Limitations ofLimitations ofPlan B Actual Use StudyPlan B Actual Use Study
• Short follow-up period
• Purchased only 1 package of Plan B
• No literacy testing
• 94% of subjects from clinics
• Short follow-up period
• Purchased only 1 package of Plan B
• No literacy testing
• 94% of subjects from clinics
27NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Contraceptive Behavior StudiesContraceptive Behavior Studiesin Literaturein Literature
Contraceptive Behavior StudiesContraceptive Behavior Studiesin Literaturein Literature
8 behavior studies on advance provisionof emergency contraception
• 5 published, 2 unpublished and 1 abstract
• 5 studies conducted in US
• 1 study each from UK, India, and Ghana
8 behavior studies on advance provisionof emergency contraception
• 5 published, 2 unpublished and 1 abstract
• 5 studies conducted in US
• 1 study each from UK, India, and Ghana
28NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Contraceptive Behavior StudiesContraceptive Behavior StudiesStudy DesignStudy Design
Contraceptive Behavior StudiesContraceptive Behavior StudiesStudy DesignStudy Design
Study Populations:
• Family planning clinics/hospital-based clinics
• Ages 15-45 years
• Sample size from 160 to 1083 subjects
Study Populations:
• Family planning clinics/hospital-based clinics
• Ages 15-45 years
• Sample size from 160 to 1083 subjects
29NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Contraceptive Behavior StudiesContraceptive Behavior StudiesStudy DesignStudy Design (cont.)(cont.)
Contraceptive Behavior StudiesContraceptive Behavior StudiesStudy DesignStudy Design (cont.)(cont.)
• Randomized controlled design
–Treatment group: advance provision of 1 or 3 courses of EC pills
–Control group: Rx EC access
• EC education for all subjects
• Follow-up period from 2-12 months
• Randomized controlled design
–Treatment group: advance provision of 1 or 3 courses of EC pills
–Control group: Rx EC access
• EC education for all subjects
• Follow-up period from 2-12 months
30NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Contraceptive Behavior StudiesContraceptive Behavior StudiesResultsResults
Contraceptive Behavior StudiesContraceptive Behavior StudiesResultsResults
Subjects with advanced EC provision
• were more likely to use EC
• did not have more unprotected sex
• did not decrease condom use
• did not switch to less effective contraception
Subjects with advanced EC provision
• were more likely to use EC
• did not have more unprotected sex
• did not decrease condom use
• did not switch to less effective contraception
31NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Contraceptive Behavior StudiesContraceptive Behavior StudiesContraceptive Behavior StudiesContraceptive Behavior Studies
Complement the AU Study:
• Longer follow-up period
• Relative large sample size
• Advance EC provision
Complement the AU Study:
• Longer follow-up period
• Relative large sample size
• Advance EC provision
32NDAC & ACRHDNDAC & ACRHDDecember 16, 2003December 16, 2003
Limitations ofLimitations ofContraceptive Behavior StudiesContraceptive Behavior Studies
Limitations ofLimitations ofContraceptive Behavior StudiesContraceptive Behavior Studies
• Conducted in clinics
• EC education (verbal and written)
• 3 foreign studies
• 6 studies provided 1 course of EC
• Conducted in clinics
• EC education (verbal and written)
• 3 foreign studies
• 6 studies provided 1 course of EC