Sexual
and Contraceptive Behavior studies on Plan B
A Literature Review
The sponsor submitted five
published and three unpublished studies of varying quality that assess the
effects of advance provision of emergency contraception on sexual and contraceptive
behaviors. When reviewing these studies as a body of evidence, the quality or
applicability of each study must be considered.
While most of the studies state that they were randomized, only one
study (Ellertson) used a random number generator as the method of
randomization. The other studies used systems such as date of clinic visit or
other less desirable systems. The two unpublished studies would not have
received peer review (although Gold et. al was recently accepted for
publication by the Journal Of Pediatric and Adolescent Gynecology). Three of the studies were performed in
foreign countries and may have limited generalizability to the
STUDY DESIGN
1.
Study Location: Five studies were
conducted in the
2. Subjects: All subjects in the eight studies were recruited from family planning clinics (the purposes for visiting the clinics were EC consultation, post-abortion follow-up and postpartum evaluation). The age range was 15-45 years with most enrollees being around 20 years old.
3. Study Groups: Subjects were randomly (in most studies) assigned to the following 2 or 3 groups. All subjects received education regarding emergency contraception use (this is in contradistinction to the actual use study submitted by the sponsor where education was not given to the subjects enrolled in the study, thereby more closely mimicking an OTC environment).
Advance EC
Group:
Subjects received in advance one course of EC pills in six studies and three
courses of EC pills in two studies (one in US and one on India);
Control
Group:
Subjects received EC education only (including advice on where to get and how
to use EC) except for one study where EC education was not given in the control
group;
Pharmacy
EC Access Group: Subjects received EC when needed from pharmacy in one US study (in
4.
Sample Size: Number of subjects
ranged from 160 to 1020 in the five
5. Follow-up Period: Subjects were followed from 8 weeks up to 1 year after admission to the studies.
RESULTS
1. EC Use: All studies suggest that the advance EC provision increase EC use. This supported the hypothesis of the studies that easier access would translate into increased use.
2. Unprotected Sex: In these studies, unprotected sex was defined as lack of use of a contraceptive. All studies demonstrated that compared to baseline, the advance EC group and control group had decreased frequency of unprotected sex. In some studies, the decrease in unprotected sex was greater in the control group.
3.
Condom Use: One
4. Consistent Use of Regular Contraception: Most of the studies demonstrate that women in both the treatment and control groups increase their use of a regular contraception compared to baseline. One US study suggest that women with advance EC access are more likely to use less-effective contraception (although they had less unprotected sex compared to baseline and increased “condom use every time” from 12% at baseline to 47% at study completion), and another US study showed higher frequency of missing oral contraceptive pills in subjects provided with advance EC than those in control.
COMMENTS
1. These studies were not conducted in a simulated OTC setting. However, several of the studies would have recruited a similar subject population as that used in the actual use study. The main difference in design would be that subjects in the literature review would have received education compared to the subjects in the actual use study and would have received an advanced provision of EC.
2. Subjects were recruited exclusively from clinic sites and received EC education during enrollment (except one study in which control subjects did not receive EC education), which can not be generalizable to the OTC population.
3. Study population in each study was a subset of general population and was heterogeneous among all these studies. This diversity is desirable reflecting many subgroups and capturing the many aspects of an OTC population. The similarity of results is also reassuring in that the different subsets tend to exhibit the same behavioral trends.
4. Most studies provided only one course of advance EC. In those studies, after the one course of EC pills were used, subjects in the advance EC group would have the same accessibility to EC as the control group.
5.
Subjects recruited and studies conducted outside US may
not be extrapolated to
6. There were limitations of design and/or methodology of the studies and conclusions should be considered in that context.
CONCLUSION
1. The literature review studies suggests that the advance access of emergency contraception did not increase the likelihood of unprotected sex in women populations who visited family planning clinics. The study duration’s ranged from 4-12 months in follow-up. The results may provide certain supportive evidence to resolve some issues raised from the actual use study (such as whether consistent use of routine contraception persist greater than the one month of observation in the actual use study data submitted by the sponsors).
2. The studies did not simulate an OTC setting although some of the studies have recruited similar subject populations as those enrolled in the actual use study.
3. Most of the studies demonstrate that women in both the treatment and control groups increase their use of a routine contraception (less unprotected sex) compared to baseline.
4. Most of the studies either demonstrated no significant decrease in condom use with advance EC provision and control groups or demonstrated that “used condoms every time” increased in treatment and control groups when compared to baseline
Table
1. Effects of Emergency Contraception under Advance Provision on Sexual
and Contraceptive Behavior
|
Author
& Publication |
Study
Design |
Study
Location |
Subjects |
Follow-up Periods |
Advance EC Access caused changes in |
|
|
Sexual
Behavior |
Contraceptive
Behavior |
|||||
|
Raine
et al: Obstet Gynecol 2000 Literature
#1 |
Non-randomized
2 groups: Advance
EC (one EC course) & Control (EC education) |
|
263
women age
16-24 (64% adolescents); 32% Excluded
subjects presenting for EC |
4
months |
Decrease in unprotected sex in both groups vs. baseline
(Control>Tx) |
More
likely to use less effective contraception (increased condom use) Increased
EC use; |
|
Raine
et al: UCSF
Study (NDA: vol 13, p134) Unpublished Literature
#2 |
Randomized
3 groups: Advance
EC Provision (3
EC courses), Pharmacy
EC Access; Standard
EC Access |
|
1020
women age
15-24 years (20±3 yrs); 20%
17%
AA Excluded
subjects presenting for EC |
6
months |
Decrease
in unprotected sex in all 3 groups vs.
baseline (SA>PA>AP(p<0.05 in PA & SA groups) No
increase in incidence of STDs compared to Stnd EC Access |
Increase
in OC use in all 3 groups with an offset decrease in condom use in all 3
groups Decrease in condom use greatest in AP & PA groups |
|
Jackson et al, Obstet
Gynecol 2003 Literature
#3 |
Randomized
2 groups by date of hospital admin: Advance
EC (one EC course) & Control (but no EC education) |
|
370
Postpartum women age
26±6 yrs 72%
43%
Married |
6
months & 12
months |
Increased
consistent use contraception and more effective method in both groups. No increase in report of unprotected sex |
No change in routine contraception and condom
use; Increase in EC use. |
|
Belzer
et al: J Adol Health (Abstract), 2003 Literature
#4 |
Randomized
2 groups: Advance
EC (one EC course) & Control |
(unknown
site) |
160
adolescent mothers age
14-20 yrs; 83%
16%
AA |
6
months |
No
increase in unprotected sex (but limited data available) |
No
decrease in condom use and primary contraception between groups. No data provided on within group changes; (limited
data available) Increase
in EC use |
|
Gold: Unpublished Manuscript Literature
#5 |
Randomized
2 groups: Advance
EC (one EC course) & Control |
|
301
adolescent women age
15-20 (17±2); 58%
AA |
8
months |
No
increase in unprotected intercourse No
increase in STDs compared to control |
No
decrease in condom use; Other
info not available |
|
Glasier
& Baird: New Eng J Med 1998 Literature
#6 |
Randomized
2 groups by birth date: Advance
EC (one EC course) & Control (EC education) |
|
1083
women age
16-44 (23% age 16-20), 20%>30 y/o Post
EC or Therapeutic abortion |
1-year |
Decrease
in unprotected sex in both groups vs. baseline. |
Increase
in OC use in both groups with decrease in condom use similar changes between
2 groups. Increase
EC use. |
|
Lovvorn et al: Contraception 2000 Literature #7 |
Non-randomized
2 groups: Advance
EC (one EC course) & Control (EC education) |
|
211
women (spermicide users) age
18-45 yrs |
8
weeks |
Decrease
in unprotected sex compared to
baseline in both groups (Control>AEC) Significant
limitations in study design. |
Increase
EC use; Other
info not reported. Significant
flaws in study design. |
|
Ellertson et al: Obetet
Gynecol 2001 Literature
#8 |
Randomized
2 group: Advance
EC (3 EC course) & Control |
|
411
women (condom
users); age
25±4 yrs (83% 20-29 yr); Barrier
method users |
12
months (38% 12-month; 90% 3-month); pts off study if switched to more
reliable method (23%) |
Similar
proportion having unprotected sex vs. the control |
Increase
EC use. |
Information
in the table is extracted and summarized from the individual literature reviews
as attached in the following pages.
The
Advance EC (AEC) or the Advance EC Provision (AP) or Treatment(Tx) group : Subjects received EC pills in advance plus EC
education at the enrollment.
The
Control or Standard EC access (SA)
group: Subjects received only EC
education (except the
The
Pharmacy EC Access (PA) group: Subjects received EC pills from pharmacy without
prescription.
OC:
Oral Birth Control Pills; AA: Africa
American; EC: Emergency Contraception; STDs: sexually transmitted diseases;
Table 1 (Cont). Effects of
Emergency Contraception under Advance Provision on Sexual and Contraceptive
Behavior
Literature #1 (vol. 13, page 068)
Emergency Contraception:
Advance Provision in a Young, High-Risk Clinic Population
Author: Tina Raine, Cynthia Harper, Kathleen Leon, and Philip Darney
Affiliate: Department of Obstetrics, Gynecology, and Reproductive Sciences
Center for Reproductive Health Research and Policy
Sponsor:
Fred Gellert
Family Foundation,
Study Location:
From June to November 1998
Publication: Obstet Gynecol 96:1–7, 2000
Design: Single-center, non-randomized, clinical trial;
4-month follow-up
Single course of Advance EC Provision
METHODS
Subject
A total of 263 female subjects were recruited and enrolled
from a family planning clinic of
Inclusion criteria:
Women age 16–24 years
Able to speak English or Spanish
Available for follow-up in 4 months.
Exclusion criteria:
Pregnancy
Using contraceptive implants
Using intrauterine devices
Presentation for emergency contraception
Contraindications to oral contraceptive (OC) pills.
The subjects were assigned on an alternating basis into the following 2 groups:
Treatment groups: 130 subjects received EC education and one course of EC pills (comprised 8 OC pills; each contained 0.15 mg of levonorgestrel and 30 ug of ethinyl estradiol).
Control group: 133 subjects received EC education alone.
Data Collection
Research assistants interviewed subjects at enrollment and at follow-up (at 4 month by telephone or clinic visit) using a questionnaire to obtain demographic information and to measure outcomes, including contraceptive methods and patterns of use.
Data Analysis
All analyses were conducted using the intent-to-treat population, with all study subjects analyzed according to their initial group assignment. Differences between Treatment and Control were analyzed with a Chi-square test for categorical variables and t tests for continuous variables. A multiple logistic regression analysis was used to determine the effect of advance provision of emergency contraception on use at follow-up.
RESULTS
Subject Demographics
Only age and race/ethnicity were reported in the article, as summarized in Table 1. The mean age was 19 years (64% adolescents). Most subjects were minorities. The demographic distribution between 2 groups was similar.
Table 1. Demographics of Subjects
(% of enrolled subjects)
|
Demographic |
Treatment n=130 |
Control n=133 |
Total n=263 |
|
Mean
age (years) |
19.2 |
18.8 |
19.0 |
|
Race
or ethnicity |
|
|
|
|
Hispanic |
33.1 |
30.1 |
31.6 |
|
Black |
26.2 |
31.6 |
28.9 |
|
White |
16.9 |
12.8 |
14.8 |
|
Asian |
14.6 |
16.5 |
15.6 |
|
Other
(biracial) |
9.2 |
9.0 |
9.1 |
|
Primary
language Spanish |