plan b ® actual use and behavior studies nda 21-045 ndac & acrhd joint meeting december 16,...

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


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


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


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


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


Subject EnrollmentSubject EnrollmentSubject EnrollmentSubject Enrollment

665Screened subjects

80 (12%)

Not Enrolled 585 585 (88%)(88%)

EnrolledEnrolled

94%94%from clinicsfrom clinics

6% from6% frompharmaciespharmacies


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%


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


ResultsResultsResultsResults

• Self-Selection

• Timing of Dosing

• Adverse Events

• Contraceptive Behavior

• Pregnancy Rate

• Self-Selection


• Adverse Events


• Pregnancy Rate



• Self-Selection


• Adverse Events


• Pregnancy Rate

• Self-Selection


• Adverse Events


• Pregnancy Rate


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%)


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



• Self-Selection

• Timing of Doses

• Adverse Events


• Pregnancy Rate

• Self-Selection

• Timing of Doses

• Adverse Events


• Pregnancy Rate


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


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



• Self-Selection

• Timing of Dosing/use

• Adverse Events


• Pregnancy Rate

• Self-Selection


• Adverse Events


• Pregnancy Rate


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%)



• Self-Selection


• Adverse Events

• Contraceptive Behaviors

• Pregnancy Rate

• Self-Selection


• Adverse Events

• Contraceptive Behaviors

• Pregnancy Rate


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%


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



• Self-Selection


• Adverse Events


• Pregnancy Rate

• Self-Selection


• Adverse Events


• Pregnancy Rate


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)


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


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


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


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


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


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


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


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


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

plan b ® actual use and behavior studies nda 21-045 ndac & acrhd joint meeting december 16,...

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