# Presentation: 552933

## Plan B® Actual Useand Behavior StudiesNDA 21-045

**NDAC & ACRHD Joint Meeting**
**December 16, 2003**
**Jin Chen, MD, PhD**
**Division of OTC Drug Products**

- Center for Drug Evaluation and Research

## Outline

**Plan B Actual Use Study**
**Behavior studies associated with emergency contraception**

## Actual Use StudyPrinciples

- Simulate OTC setting
- Assess
- self-diagnosis
- self-selection
- self-medication
- safety
- efficacy (rarely)
- Multi-center, open-label, single-arm, uncontrolled trial

## Actual Use StudyPrinciples (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

## Plan B Actual Use StudyObjectives

**Primary Objectives:**
- Self-selection
- Timing of doses
**Secondary Objectives:**
- Adverse events
- Multiple use
- Pregnancy rate
**Additional Observation:**
- Contraceptive behaviors

## Plan B Actual Use StudyDesign/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**

## Subject Enrollment

**665**
**Screened subjects**

**80 ****(12%)**
**Not Enrolled**

## Demographics of Enrolled Subjects(n=585)

**Age: 14-44 yrs (22±5)**
**Education:**
- 87% ≥ HS education
- 13% had 9th-11th grade education
**Prior EC experience: **40%

## Subject Follow-Up(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**

## Results

**Self-Selection**
**Timing of Dosing**
**Adverse Events**
**Contraceptive Behavior**
**Pregnancy Rate**

## Results

**Self-Selection**
**Timing of Dosing**
**Adverse Events**
**Contraceptive Behavior**
**Pregnancy Rate**

## Self-Selection(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%)**

## Self-Selection (cont.)(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**

## Results

**Self-Selection**
**Timing of Doses**
**Adverse Events**
**Contraceptive Behavior**
**Pregnancy Rate**

## Timing of Dose per Label(n=540)

**92% (n=499) – 1****st**** pill < 72 hours**
**72% (n=387) – 2****nd**** pill at 12 hours after 1****st ****pill**
**68%**** (n=366) – both pills according to the label dosing regimen**

## Timing of Dose(Alternate 2nd Dosing Analysis)

**92% (n=499) – 1****st**** pill < 72 hours**
**93% (n=500) – 2****nd**** pill between ****6-18 hours**** after 1****st ****pill**
**87% ****(n=469)**** ****– both pills according to the alternate 2****nd**** dosing interval**

## Results

**Self-Selection**
**Timing of Dosing/use**
**Adverse Events**
**Contraceptive Behavior**
**Pregnancy Rate**

## Adverse Events (AEs) (n=540)

**No serious AEs**
**No new safety signals**
**Most common AEs (transient):**
- Abdominal pain (14%)
- Nausea (12%)
- Headache (11%)
- Fatigue/tiredness (8%)

## Results

**Self-Selection**
**Timing of Dosing/use**
**Adverse Events**
**Contraceptive Behaviors**
**Pregnancy Rate**

## Contraceptive Behaviors(n=543)

| Behavior | 1 month before study | 1 month during study |
| --- | --- | --- |
| ≥ 1 sex act w/o contraception  | 60% | 20% |
| Withdrawal method | 28% | 10% |
| Condom use | 79% | 90% |

## Contraceptive Behaviors (cont.)

**Subjects tended to use more effective**
**	****contraception methods**
**1.7% ****of enrolled subjects (n=10) requested Plan B more than once during 3-month enrollment period**

## Results

**Self-Selection**
**Timing of Dosing/use**
**Adverse Events**
**Contraceptive Behavior**
**Pregnancy Rate**

## Pregnancy Rate(n=540)

**Confirmed pregnancy (n=10):****	****1.9%**
**Unknown pregnancy status:****	****	****2.6%**
**	****(n=14, at the end of the study)****	****	**

## Summary

**95% of users correctly self-selected Plan B**
**68% of users took 1****st**** pill within 72 hours and 2****nd**** pill at 12 hours after the 1****st**** pill**
** ****87% of users took 1****st**** pill within 72 hours and 2****nd**** pill between 6-18 hours**

## Summary (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

## Limitations ofPlan B Actual Use Study

**Short follow-up period**
**Purchased only 1 package of Plan B**
**No literacy testing**
**94% of subjects from clinics**

## Contraceptive Behavior Studiesin Literature

**8 behavior studies on  advance provision**
**of emergency contraception**
**5 published, 2 unpublished and 1 abstract**
**5 studies conducted in US**
**1 study each from UK, India, and Ghana**

## Contraceptive Behavior StudiesStudy Design

***Study Populations:***
- Family planning clinics/hospital-based clinics
- Ages 15-45 years
- Sample size from 160 to 1083 subjects

## Contraceptive Behavior StudiesStudy Design (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**

## Contraceptive Behavior StudiesResults

**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 Studies

***Complement the AU Study:***
**Longer follow-up period**
**Relative large sample size**
**Advance EC provision**

## Limitations ofContraceptive Behavior Studies

**Conducted in clinics**
**EC education (verbal and written)**
**3 foreign studies**
**6 studies provided 1 course of EC**