PPT

Document Sample
PPT Powered By Docstoc
					  Nonprescription Drugs And
Reproductive Health Drugs Joint
 Advisory Committee Meeting

      December 16, 2003
     Plan B® (LEVONORGESTREL)
     For Emergency Contraception
         RX-to-OTC SWITCH



                                   1
Plan   B®:   RX-to-OTC Switch
      Carole S. Ben-Maimon, M.D.
   President and COO, Barr Research


On behalf of Women’s Capital Corporation


                                           2
                           Agenda
 Background Review
 How Plan B Prevents Pregnancy
 Rationale for OTC Switch
 Risk/Benefit Assessment
   – Vivian Dickerson, M.D., President-Elect, American College of
     Obstetricians and Gynecologists and Director, Obstetrics and
     Gynecology, University of California Irvine Medical Center
 Clinical Trials
   – Label Comprehension
   – Actual Use
 Health Consequences of Plan B OTC
   – David Grimes, M.D., FACOG, FACPM, Vice President of
     Biomedical Affairs, Family Health International and Clinical
     Professor, Department of Obstetrics and Gynecology,
     University of North Carolina School of Medicine
 CARE Program
                                                                    3
 What Is Emergency Contraception?

Emergency contraception is:

Therapy for women who do not wish to become
 pregnant and who have had unprotected
 sexual intercourse
  – Contraceptive accident
  – Sexual assault




                                               4
                Contraceptive Accident
53% of unintended pregnancies resulted from
 contraceptive accident
Contraceptive accidents include method
 accidents and user accidents
Many contraceptive accidents are immediately
 recognizable:
    – Condom break/slip
    – Missed/late OCs
    – Late injection
    – Dislodgment of patch, ring, diaphragm
    – Failure of spermicide to melt
    – Failed withdrawal
Source: Henshaw 1998
                                                5
                  Public Health Problem
Unintended Pregnancies:
Over 3,000,000/year in US;
  – Condom failure 15%, OC failure 8%
    (first year typical use)
  – ~800,000 unintended pregnancies in teens
  – In 2002, 215,000 US women were victims of rape,
    attempted rape, or sexual assault;
Half result in abortion;
Up to 50% of unintended pregnancies could be
 prevented by greater use of EC
   Source: Trussell 2004, Nat’l Vital Statistics Report 2003, Nat’l Crime Victimization Survey, 2002,
   Henshaw 1998, Trussell 1992
                                                                                                        6
Approved Emergency Contraceptives
Two FDA Approved RX ECs:
Preven – Approved 1998, Based on Yuzpe
        ®


 method
  – 2 x Levonorgestrel 0.25mg/Ethinyl Estradiol 0.05mg
    tablets within 72 hrs of unprotected sex followed by
    2 more tablets 12 hrs later


Plan B – Approved 1999
        ®



  – 1 x Levonorgestrel 0.75mg tablet within 72 hrs of
    unprotected sex followed by 1 more tablet 12 hrs
    later
                                                           7
      How Plan B Prevents Pregnancy
 Risk of pregnancy highest in the days leading up to
 and including the day of ovulation
              Probability of Conception on Specific Days Near
                              the Day of Ovulation




                                                     (Wilcox 1995)
Sources: Wilcox 1995, Trussell 2003, Croxatto 2002
                                                                     8
   How Plan B Prevents Pregnancy
Direct Evidence:
Interference with the ovulatory process –
 demonstrated in several studies
Hypothetical Mechanisms:
Interference with fertilization by affecting
 sperm migration – no direct evidence
Interference with implantation – no direct
 evidence

                                                9
Early Use of Plan B Increases Efficacy
                   WHO Trial: LNG Regimen




Source: WHO 1998
                                            10
          Barriers With RX Use
         RX Setting           OTC Setting

       Locate prescriber
                               Identify need
      available and willing
        to prescribe EC


       Contact prescriber


Additional potential
requirements:
• Office visit
• Pregnancy test
• Medical exam
• Counseling

       Obtain prescription

        Locate pharmacy
                              Purchase product
         that stocks EC
                                                 11
   Plan B® Has a Compelling
   Risk/Benefit Assessment
            Vivian Dickerson, M.D.,
     President-Elect, American College of
     Obstetricians and Gynecologists and
Director, Obstetrics and Gynecology, University
       of California Irvine Medical Center

                                                  12
         Regulatory Requirements for
         Non-Prescription Marketing
The drug must:
 Have an acceptable safety profile based on RX history
 Have a low potential for abuse and misuse
 Have an appropriate therapeutic index for safety
 Have a positive benefit to risk ratio
 Treat a condition that is self-recognizable, self-limiting
  and requires minimal HCP intervention




                                                               13
Plan B Meets Requirements for OTC Use
 Post-marketing and clinical trial safety data
  demonstrate an acceptable safety profile
 There is a low potential for abuse or misuse
 The benefits of OTC availability strongly
  outweigh the risks
 Consumers can properly self-select the
  product for its intended use and can correctly
  use the product
   – Label Comprehension Study
   – Actual Use Study
                                                   14
 Plan B: Safety and Efficacy Studies
Over 7,000 subjects have participated in clinical
studies:
                                                     Evaluable
            Study                    LNG Dose (mg)   Subjects
       Ho & Kwan 1993*                  0.75 x 2        410
         WHO 1998**                     0.75 x 2        976
           Wu 1999                      0.75 x 2        643
                                        0.75 x 2        545
        Arowojolu 2002
                                        1.5 x 1         573
                                        0.75 x 2       1,356
           WHO 2002
                                        1.5 x 1        1,356
             Ho 2003                    0.75 x 2       2,030
             TOTAL                                     7,889
     * Plan B NDA Supportive Study
     ** Plan B NDA Pivotal Study
                                                                 15
            Plan B is Safe & Effective
 Plan B is 89% effective in preventing pregnancy if used
  as labeled within 72 hours of unprotected sex
 Plan B has a well characterized safety profile, common
  AEs include:
   –   Nausea
   –   Abdominal pain
   –   Fatigue
   –   Headache
   –   Menstrual changes
 No deaths associated with Plan B regimen
 No increased risk of ectopic pregnancy with Plan B
 Professional screening does not impact efficacy or
  safety
                                                            16
     Ectopic Pregnancy and Plan B
Plan B is a progestin-only EC
6 trials of Plan B with systematic follow-up of
 pregnancies
  – 7,889 evaluable participants
  – 133 pregnancies
  – 2 ectopic (1.5%, consistent with background rate)
Post-marketing information for Plan B confirms
 low incidence of ectopic pregnancy



                                                        17
               Plan B:
       RX-to-OTC Switch Studies
The Plan B RX-to-OTC application is supported
by two studies:

                            Number of
           Study         Subjects Enrolled
           Label
                               663
        Comprehension
          Actual Use           585




                                                18
      Label Comprehension Study
                    DESIGN
PURPOSE:      To evaluate comprehension of a
               prototype label of the Plan B OTC
               product

POPULATION: Women ages 12 to 50 surveyed in
               eight U.S. cities
               – Sampling included minority women and
                 those at high risk for poor label
                 comprehension

INSTRUMENT: Questionnaire
                                                        19
      Label Comprehension Study
        Demographics of Eligible Subjects
Age                n (%)
 12-16            76 (11.6)
 17-25           355 (54.1)
                                 REALM* n=395
 26-50           225 (34.3)      Literacy Level             n (%)
Race/Ethnicity
                                   ≤ 8th Grade           139 (35.2)
 White           324   (49.4)       Literacy
 Black           155   (23.6)      > 8th Grade           254 (64.3)
                                    Literacy
 Asian or PI      30   (4.6)
                                   missing                   2     (0.5)
 Native            6   (0.9)
                                * Rapid Estimate of Adult Literacy in Medicine
  American
                                  (Davis 1993 )
 Hispanic        154 (23.5)

                                                                                 20
       Label Comprehension Study
               Objectives
1.  Prevention of pregnancy after unprotected sex
2.  Back up method (not regular contraceptive)
3.  Does not prevent STIs/AIDS
4.  1st pill taken within 72 hours
5.  1st pill taken ASAP
6.  2nd pill taken 12 hours after 1st
7.  Not for use in pregnant women
8.  Not for use in women with unexplained vaginal
    bleeding
9. Not for use in women with allergy to product
10. Side effects include nausea and vomiting
11. If severe abdominal pain develops, seek immediate
    medical care
                                                        21
Label Comprehension Study




                            22
Label Comprehension Study




                            23
Label Comprehension Study




                            24
 Plan B is Intended as a Back up Method &
       not for Regular Contraception
                                                       12-16   17-25 26-50 Total
OBJECTIVE 2: (Age)                                     n=76    n=355 n=225 n=656
           Overall (≥3 Questions) Correct: 57.9                67.6 71.6 67.8
9. According to the label, should Plan B be used
as regular birth control? (NO)                         77.6 87.0 85.3 85.4
21. A woman is planning to have sex tonight. She
usually uses condoms to prevent pregnancy. This
time she plans to use Plan B instead because her       50.0 49.6 40.9 46.6
husband complains about using condoms. Is this
a correct use of Plan B ? (NO)
22. A woman used Plan B every day instead of her
usual birth control pills. Was this a correct use of   90.8 91.0 89.8 90.5
Plan B ? (NO)
25. A woman and her husband do not like using
condoms, and the woman does not want to take
birth control pills. They decide to use Plan B as      59.2 65.6 75.6 68.3
their main contraceptive method. Is this a correct
use of Plan B? (NO)
                                                                                   25
 Plan B is Intended as a Back up Method &
       not for Regular Contraception
                                                             ≤ 8th    > 8th   Total
OBJECTIVE 2: (REALM)                                        n=139    n=254    n=656
                 Overall (≥3 Questions) Correct:            46.0     78.7     67.8
9. According to the label, should Plan B be used as
regular birth control? (NO)                                 70.5     92.5     85.4
21. A woman is planning to have sex tonight. She
usually uses condoms to prevent pregnancy. This time
she plans to use Plan B instead because her husband         36.7     53.5     46.6
complains about using condoms. Is this a correct use
of Plan B ? (NO)

22. A woman used Plan B every day instead of her
usual birth control pills. Was this a correct use of Plan   75.5     94.5     90.5
B ? (NO)
25. A woman and her husband do not like using
condoms, and the woman does not want to take birth
control pills. They decide to use Plan B as their main      50.4     78.3     68.3
contraceptive method. Is this a correct use of Plan B?
(NO)
                                                                                      26
  Plan B Label Changes
         PANEL 2



BOLDED




                         27
The First Pill Should be Taken within 72 Hours
                after Intercourse
                                                                   ≤ 8th    > 8th   Total
 OBJECTIVE 4:                                                     n=139    n=254    n=656
               Overall (≥2 Questions) Correct: 71.9                        90.2     85.7
 10. After unprotected sex, when is the best
 time to take the first tablet?*                                  44.6     62.2     54.3
                          ASAP and within 3 days                    20.9     25.6     23.5
                                  Within 3 days                     23.7     36.6     30.8
 19. A woman had unprotected sex 2 days ago
 and then used Plan B to prevent pregnancy.                       78.4     89.8     86.7
 Was this a correct use of Plan B? (YES)
 20. A woman had unprotected sex a week ago
 and then used Plan B to prevent pregnancy.                       87.8     95.7     94.5
 Was this a correct use of Plan B? (NO)
 29. How many days does the label say is the
 longest after sex a woman should wait before                     84.2     94.9     91.3
 taking the first Plan B tablet? (3 DAYS OR 72
 HOURS)

    *ASAP 23.7% (≤8th grade); 36.6% (>8th grade); 26.4% (total)                              28
       Label Comprehension Study
                        Results
 Intent to treat analysis shows:
   – Satisfactory response rates for all objectives
   – 80% or greater response rate for 9 of 11 objectives

                     Conclusion
 Study demonstrates adequate label comprehension in
  all populations evaluated
 Based on the results, the label was modified to
  enhance comprehension in the Actual Use Study
                                                           29
          Plan B Label Changes
                        PANEL 1


                 ENLARGED




Label Comprehension Study         Actual Use Study
                                                     30
Plan B Label Changes
       PANEL 4




                 BOLDED




                          31
Plan B Label Changes
       PANEL 6




                 BOLD




                        32
          Plan B Label Changes
          PANEL 13          Contraception  Control




Label Comprehension Study              Actual Use Study
                                                          33
            Actual Use Study
PURPOSE:     To determine if women seeking
              EC could self-select and use the
              product appropriately and safely
              when labeled for OTC
              distribution
OBJECTIVE: Estimate the frequency of
            contraindicated and incorrect
            use of Plan B
DESIGN:      Non-comparative case series
              study
LOCATIONS: – 5 Planned Parenthood affiliates
            – 5 pharmacies (Seattle, WA)
                                                 34
              Actual Use Study
               Study Procedures
Initial Screening –
  – Given information about the study, not the product
  – Reviewed ―Drug Facts Panel‖ on a sealed prototype
    product
  – Decided to receive or not receive Plan B without
    counseling
Signed Informed Consent
Received study product and Study Data Card
Follow-up contact at 1 week and 4 weeks
                                                         35
Actual Use and Label Comprehension
              Studies
                                     Enrolled       Enrolled
 Demographics (%)                    AU Study       LC Study        U.S. Women*
                                      N=585         N=656**          (Aged 14-44)
Age (years)
   14-16                                 5.0             9.8               9.2
   17-25                                74.4            59.0              26.8
   26-30                                14.0             7.8              15.5
   31-35                                 4.1            11.3              16.2
   36-44                                 2.6            12.1              32.2
Race
   Asian                                 6.3             4.8               4.3
   Black (African American)              9.9            23.5              13.7
   White                                76.4            48.8              72.0
   Hispanic                             14.2            23.5              13.9
   Other                                10.1            22.9               —
     * Data from U.S. Census 2002   ** Label Comprehension Study  women aged 14-44   36
                       Actual Use Study
      Analysis Cohorts
                                     665 Screened


                         585 Enrolled                   80 Not Enrolled


42 Lost-to-Follow-Up                         543 Provide Follow-
                                               up Information

      509 Time between sex and 1st pill


       523 Time between 1st and 2nd pill            540 Used Plan B


                          506 All Times
                                                                          37
              Actual Use Study
              Contraindicated Use
Was Plan B used according to outer package
 label?

Contraindications to use included:
  – Already pregnant
  – Allergy to any ingredient in Plan B
  – Any unusual vaginal bleeding




                                              38
              Actual Use Study
              Contraindicated Use

99% of classifiable study subjects did not have
 contraindications to Plan B

7 subjects with contraindications to Plan B:
  – 1 pregnant at time of Plan B use
  – 6 unexplained vaginal bleeding
       3 prior emergency contraceptive users



                                                   39
                      Actual Use Study
                               Correct Use
Using Plan B according to strict interpretation
 of directions:
                      Correct Use:        Classifiable   Correct Use
         Both pills taken correctly           506         366 (72%)
       1st pill ≤ 72hrs. after sex act        509         499 (98%)
 2nd pill exactly 12hrs. after 1st pill       523         387 (74%)




                                                                       40
                      Actual Use Study
             Time From Sex Act to 1st Pill
                                   Actual Use
                                     Study                        WHO 1998*
    Time (Hours)                     N=509                         N=974
                   ≤ 24                  37%                            46%
              25 – 48                    39%                            35%
              49 – 72                    22%                            19%
                   > 72                   2%                            0.2%
* Source: Reanalysis of study data submitted in approved NDA 21-045 (WHO 92908)



                                                                                  41
                      Actual Use Study
   Time Interval Between 1st and 2nd Pill
                                   Actual Use
                                     Study                        WHO 1998*
    Time (Hours)                     N=523                         N=974
                   < 12                  10%                             9%
                      12                 74%                            74%
          >12 to 16                      12%                            13%
                    >16                   4%                             5%
* Source: Reanalysis of study data submitted in approved NDA 21-045 (WHO 92908)



                                                                                  42
              Actual Use Study
              Pregnancy Analysis
10 Pregnancies (of 526)
  – Pregnancy Rate: 1.9%
  – 95% Confidence Interval (0.92%, 3.47%)
Of 10 pregnancies:
  – 4 elective abortions
      1 called study pregnancy registry
  – 6 lost to follow-up
WHO (#92908) Clinical Trial 1.1%
                                             43
    Actual Use Study: Conclusions
Study design simulated OTC environment
Subjects were representative of the OTC
 population likely to use Plan B
Subjects were able to self-select and use the
 product correctly
The results are similar to the WHO pivotal trial

Plan B should be as safe and effective in an
 OTC setting as it is in the current RX setting
                                                    44
Health Consequences Of Over-
 the-Counter Levonorgestrel
  Emergency Contraception
    David Grimes, M.D., FACOG, FACPM
  Vice President of Biomedical Affairs, Family Health
         International and Clinical Professor,
 Department of Obstetrics and Gynecology, University
         of North Carolina School of Medicine



                                                        45
     Take-Home Message

Access to and use of emergency
contraception improves the health
of women.
Emergency contraception helps
prevent unintended pregnancy,
which carries substantial medical
risks.


                                    46
                    Maternal Mortality
Pregnancy remains a risky business
U.S. maternal mortality rate in 1999: 13 deaths
 per 100,000 live births
4200 deaths reported to CDC from 1991 to 1999




   Source: Chang et al. MMWR Surveill Summ 2003; 21:1

                                                        47
                    Maternal Morbidity
In the U.S.:
43% of women have some type of morbidity
 during childbirth hospitalization
25% of women are hospitalized during
 pregnancy for a complication of the pregnancy




     Sources: Danel et al. Am J Public Health 2003;93:631
              Scott et al. Obstet Gynecol 1997;90:225

                                                            48
                   In Contrast…

Emergency
contraception has
no important
medical harms,
either in terms of
morbidity or
mortality

   Source: Grimes. N Engl J Med 2002;347:846


                                               49
     Induced Abortion: an Index of
         Unwanted Pregnancy

862,000 abortions reported to CDC in 1999
Ratio: 256 abortions per 1000 live births
 (1 in 5 pregnancies)
Rate: 17 abortions per 1000 women
 aged 15-44 yr (about 2%)




    Source: Elam-Evans et al. MMWR Surveill Summ 2002;51:1

                                                             50
                       Social Benefits
Emergency contraception helps eliminate the
 need for abortion.
In the U.S. in 2000, about 51,000 induced
 abortions were averted by use of emergency
 contraception, which is still not widespread.




      Source: Jones et al. Perspect Sex Reprod Health 2002;34:294



                                                                    51
  Impact on Existing Contraception


Easy access to
emergency
contraception does
not undermine use of
ongoing
contraception.

Grimes and Raymond. Ann Intern Med 2002;137:180



                                                  52
 Rationale for Over-the-Counter
           Availability


Levonorgestrel emergency
contraception is not toxic,
addictive, or complex to use.
It clearly meets the requirements of
the Durham-Humphrey Amendment
(1951).
    Source: 21 CFR 310.200(b)
                                       53
Social Benefits


       Peace of mind for
       women and their
       families
       •Unplanned coitus
       •Coercive coitus
       •Failed or missed
             contraception

                             54
         For Women in Crisis



The net effect is
fewer unintended
pregnancies, fewer
induced abortions,
and fewer
unplanned births.



                               55
           Conclusion


The FDA today has a unique
opportunity to improve the health of
women and their families by dropping
medically unjustified obstacles to
levonorgestrel emergency
contraception.


                                       56
         The Alternative

Restricted access to levonorgestrel
emergency contraception indirectly
causes unintended pregnancies,
induced abortions, and preventable
morbidity and mortality.


The public health choice is clear.

                                      57
U.S. Pregnancy Rates: 1990 – 1999




 Source: Nat Vital Stat Rpts 52:7 (10/31/03)   58
U.S. Abortion Rates: 1990 – 1999




Source: Nat Vital Stat Rpts 52:7 (10/31/03)   59
 OC and Condom Use in the United States in 1982,
1988 and 1995, for Contracepting Women 15-19 and
                20-24 Years of Age




 Source: CDC Health 2002 (DHHS Pub 1232)
                                                   60
                 Contracepting Women




Source: CDC Health 2002 (DHHS Pub 1232)
                                          61
        Education & Awareness
Education and awareness programs work
Despite these programs, over 3,000,000
 unintended pregnancies still occur
50% of unintended pregnancies could be
 prevented by greater use of EC
Awareness of and access to EC needs to be
 enhanced



                                             62
 Plan B Retail Pharmacy Prescriptions




Source: IMS Health Data
                                        63
        Plan B: Pharmacy Access
In five states Plan B is available directly from a
 pharmacist without an advance prescription:
  – Washington State (since 1997)
  – California (pilot program – 2000)
  – Alaska (2002)
  – New Mexico (2003)
  – Hawaii (2003)




                                                      64
                             Pharmacy Access
                                    Washington State
                                           >1,000 RX/month                          ~2,000 RX/month


                                                                      >50,000 RX
                                                                     (cumulative)


  1998            1999              2000         2001           2002           2003           2004


                          140                          >1,500
                       pharmacies                    pharmacists
                                                                                      ~300 pharmacies
                                                                                     (of 1150 total, 26%)
                                                                                     ~1,700 pharmacists
                                                                                     (of 5350 total, 32%)




Sources: Washington States Dept of Health 2003, Boggess 2002, Gardner 2001, Hayes 2000, www.go2ec.org
                                                                                                        65
      Pharmacy Access: EC Educational
                Programs
                                         California
  Largest program had estimated reach of ~10
  million consumers and professionals:
  ~991,000 women with print material
  1 million women and men through paid media
  70,000 healthcare providers with print material
  ~8 million people through free media


Source: Pharmacy Access Partnership (www.go2ec.org)
                                                      66
                           Pharmacy Access
                                        California

Pilot programs begin in
     San Francisco




2000                 2001                 2002                 2003                 2004

                                                                             ~800 pharmacies
                                                                            (of 5,700 total, 14%)
                                                                        ~ 2,500-3,000 pharmacists
                                                                            (of 22,000 total, <14%)

                                    Pharmacy access
                                    legislation passed




Source: Pharmacy Access Partnership 2003, Boggess 2002, www.go2ec.org
                                                                                                      67
Pharmacies and Pharmacist in the US
More than 200,000 Pharmacists (in 2000)
Almost 53,000 Pharmacies (in 2002)
Pharmacists must be recruited and educated
 about EC
In Washington, only 26% of pharmacies are
 participating in the pharmacy access program
 after 5 years and 14% in California after 2 years

 Source: Pharmacy Access Partnership 2003, Washington State Dept of Health 2003, IMS 2002, US
 Dept of Labor 2000
                                                                                                68
                   Barriers With RX Use and
                      Pharmacy Access
         RX Setting           OTC Setting            Pharmacy
                                                      Access
       Locate prescriber
                               Identify need
      available and willing
        to prescribe EC


       Contact prescriber                         Locate pharmacist
                                                    authorized to
                                                     provide EC
Additional potential
requirements:
• Office visit
• Pregnancy test
• Medical exam                                    Consultation with
• Counseling                                        Pharmacist


       Obtain prescription

        Locate pharmacy
                               Purchase product
         that stocks EC
                                                                      69
                                    ®
                 Plan B :
              CARE ProgramSM




Convenient Availability Responsible Education


An informational program to ensure that Healthcare Providers and
Consumers understand what EC is, when it can and should be used
and where to get it



                                                               70
               CARE Program
Designed to:
Increase Awareness through Education
  – Programs will include a comprehensive approach to
    education
  – Consumers, physicians, physician’s assistants,
    nurse practitioners, and pharmacists
Increase Availability through OTC Distribution
  – Minimize delay
  – Lower barriers in order to maximize appropriate use
  – Ensure availability


                                                          71
          CARE Program:
       Communication Objectives
―Plan A‖ is abstinence, family planning, routine
 contraception
Plan B is used when a woman has concerns
 about the effectiveness of ―Plan A‖
Plan B does not replace routine forms of birth
 control
Plan B does not treat nor prevent sexually
 transmitted diseases
Follow-up with HCP is strongly encouraged

                                                    72
 CARE Program: Need for Education
Problem:
Only 43% of women know EC is available in US
Only 6% of women have used EC
Only 1.3% of women who had an abortion
 reported taking EC to prevent the pregnancy




   Sources:Kaiser 2000, Kaiser 2003, Jones 2002   73
                CARE Program:
              Consumer Awareness

 Educational brochures at HCP offices
   – 250 sales reps visiting ~30,000 physicians
 Educational brochures at point of purchase
 No trial offers (coupons, samples, rebates)
 Print and radio will be educational and will be the
  primary initial consumer media
   – Women’s magazines (e.g. Health, Cosmopolitan, Glamour,
     Self)
 Advertising designed to educate
   – Similar to Public Service Announcements
   – Advertorials that introduce and explain diagnosis/responsible
     use
                                                                     74
Proposed OTC Label – Outer Carton




                                    75
Proposed OTC Label – Inner Carton




                                    76
Proposed OTC Label – Inner Carton




                                    77
Proposed OTC Label – Inner Carton




                                    78
Dose Reminder Card




                     79
            CARE Program:
     Toll-Free Number and Website
Toll free number
  – Staffed by healthcare professionals 24 hours a day
Website
  – Links about Plan B and associated issues for HCPs
    and consumers
Phone number and website included on
 outside package and interior labeling
Encourage consumers to initiate discussions
 with HCPs


                                                         80
           CARE Program:
   Healthcare Practitioner Education
Physicians, physician’s assistants and nurse
 practitioners
  – Professional journal advertising
  – Continuing education
  – Major medical meetings
Retail pharmacists
  – National account managers
  – Pharmacy journals
  – Continuing education
  – Interaction with state pharmacy boards
  – Major pharmacy meetings
                                                81
             CARE Program – Distribution
  Problem: Pharmacies currently do not carry EC


  Only 35% of pharmacies in Pennsylvania able
   to fill RX within 24 hours


  89% of pharmacies in Albuquerque, New
   Mexico did not stock EC
     – Only 53% could obtain EC within 24 hours


Sources: Bennett 2003, Espey 2003
                                                  82
               CARE Program:
                 Distribution
Sell only to drug wholesalers, clinics, or retail
 chains and stores with valid pharmacy or drug
 wholesaler licenses
Display unit product information will be made
 available
Plan B will continue to be made available to
 clinics at a discount
For consideration:
  – Should the sponsor recommend to pharmacists that
    Plan B be placed on shelves near the pharmacist or
    behind the counter?
                                                         83
              CARE Program
                Summary
CARE is intended to:
Encourage appropriate use of Plan B through
 healthcare professional and consumer
 education
Ensure awareness that Plan B is conveniently
 available
Reinforce safe and effective use with
 appropriate packaging and labeling
Monitor through surveys and adjust to improve
 meeting the CARE objectives where
 appropriate
                                                 84
Conclusion: Plan B RX-to-OTC Switch
Over 3,000,000 unintended pregnancies occur
 in the US each year
  – Condom failure 15%, OC failure 8%
    (first year typical use)
  – ~800,000 unintended pregnancies in teens
  – In 2002, 215,000 US women were victims of rape, attempted
    rape, or sexual assault
Half result in abortion
Up to 50% of unintended pregnancies could be
 prevented by greater use of EC
Plan B for OTC use will ensure that those who
 need EC will have convenient availability with
 responsible education
   Source: Trussell 2004, Nat’l Vital Statistics Report 2003, Nat’l Crime Victimization Survey, 2002,
   Henshaw 1998, Trussell 1992                                                                          85
 Plan B is Safe and Effective for OTC
Plan B has demonstrated safety and efficacy
 suitable for OTC use
Early use of EC is critical to reduce chance of
 unintended pregnancy
Prescription requirement presents barriers that
 delay chance for early use of EC
Plan B meets an important unmet medical need
The Plan B CARE program ensures responsible
 and appropriate education and distribution

                                                   86
             Final Conclusion
Plan B for OTC use along with CARE Program
 will:
Provide important benefit to consumer
Enhance availability and minimize delay
Reduce unintended pregnancies




                                             87
Back-up Slides Shown
                             Ectopic Pregnancies
                                  Post-marketing Reports
                              Estimated              Total                   Ectopic     Expected
                              Patient                Pregnancies             Pregnanices Ectopics
      Country                 Exposure               Reported                Reported    (2% risk)*
      United
      Kingdom                   2,100,000                     29                    8        195
      France                    1,800,000                    201                    12       167
      United States             2,400,000                    110                    1        223
      Totals                   6,300,000                    340                     21       585
   *Assume 3.1% risk of pregnancy with unprotected intercourse not occurring
   mid-cycle and and 85% reduction in pregnancies with use of Plan B

Wilcox et al. Contraception 2001; 63: 211-215; MMWR, January 27, 1995; 44: 46-48.

                                                                                                      89
                          Repeat Use
                                  Safety
Trials of postcoital use of 0.75 mg LNG for
regular contraception:
 – >2,800 women followed for >13,000 cycles from 14
   studies
 – Most women took within 1 hr of unprotected
   intercourse
 – Up to 10 tablets/cycle
 – Many women discontinued due to menstrual
   disturbances
 – Only 1 ectopic pregnancy reported
 – No other serious adverse events reported
    Source: Multiple studies, see ISS                 90
      How Plan B Prevents Pregnancy
    The Cycle Day of Ovulation in 200 Cycles of
                 Fertile Women




Croxatto et al, unpublished

                                                  91
                 Actual Use Study

                     80 Not Enrolled (Not Eligible)


69 No Informed Consent                                11 Other Reasons
                                                         (1 unknown)
    9 Received Nothing

    2 Received Other Meds (Lo-Ovral, Ovral [4 tabs])

    58 Received Rx Plan B
    • did not meet eligibility criteria
    • did not sign informed consent




                                                                         92
 How Plan B Prevents Pregnancy
Things to Note:
Estrogen containing ECs have been the
 primary focus of investigation  limited data
 on Plan B
Progesterone is used to support pregnancy in
 cases of luteal phase defect
Anti-progestins have a well documented effect
 on the endometrium
Only clearly documented effect of LNG for EC
 is impact on ovulation, sperm motility, cervical
 mucous and pH
                                                    93
                         Actual Use Study
                           Prior vs. Naive Users
40% Prior Users of Emergency Contraception
Prior EC use did not affect Contraindicated use
 or Incorrect use
                                                Prior User         Naive User     Total*
                                                  N=213              N=327        N=540
 Contraindicated Use                                1.4%                   1.2%   1.3%
 Incorrect Use                                     29.6%               23.5%      25.9%
 Follow Instructions:
            1st pill  72hrs. after sex            95.3%               90.5%      92.4%
          2nd pill 12hrs. after 1st pill           68.5%               73.7%      71.7%
    * Denominator includes subjects both with and without available data                   94
     Actual Use: Timing of 2nd Pill
        (All Treated Subjects)
 Based on actual times reported by patients to
   the Interviewer (by phone contact):
73.8% of the subjects reported taking their 2nd
 pill exactly 12 hours after the first pill
86.1% of the subjects reported taking their 2nd
 pill within reported times of between 11.5 and
 12.5 hours after the first pill




                                                   95
              Actual Use Study
              Follow-up Compliance
543 (93%) Any follow-up information
  – 88% Two follow-up contacts
Pill Disposition
                                 Enrolled (N=585)
  Took both pills                  539 (92%)
  Took 1 pill                       1 (0.2%)
  Took no pills                      3 (1%)
  Lost-to-follow-up                 42 (7%)


                                                    96
                                  Efficacy
       How critical is 12-hr dosing to efficacy?
                                                         Crude pregnancy rate
      Study                  Dosing regimen
                                                            (obs preg/total)
                        2 x 0.75 mg LNG, 12 hrs                  1.1%
WHO 1998                          st
                          apart, 1 w/in 72 hrs                  (11/976)

Arowojolu 2002        1 x 1.5 mg LNG w/in 72 hrs                 0.7%
                                                                 (4/573)

WHO 2002              1 x 1.5 mg LNG w/in 72 hrs                 1.3%
                                                               (16/1,198)
                      2 x 0.75 mg LNG, 12 hrs or                 1.7%
Ho 2003                             st
                     24 hrs apart, 1 w/in 120 hrs              (35/2,071)

WHO 2000a              1 x 0.75 mg LNG w/in 1 hr
                         (ongoing postcoital use)
                                                         0.5% per treated cycle

                       1 x 0.75 mg LNG w/in 1 hr         0.7% per treated cycle
Chernev 1995
                         (ongoing postcoital use)
Sources: WHO 2002, Arowojolu 2002, WHO 2000a, WHO 1998
                                                                                  97
         OTC Prototype Labeling
               Effect on Implantation

Plan B works like other birth control pills.

  – If fertilization does occur, Plan B may prevent a
    fertilized egg from attaching to the womb
    (implantation). Plan B will not work after
    implantation of a fertilized egg.

  – Plan B is not the same as the early abortion pill,
    Mifeprex (RU486). Plan B cannot disrupt an
    established pregnancy.

                                                         98
                   Repeated Postcoital Use
        High level of menstrual disturbances after
             repeated use of 0.75 mg tablets




             Abbreviations: B=bleeding, S=spotting


Source: WHO 2002
                                                     99

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:53
posted:8/25/2011
language:English
pages:99