August 15, 2006

Dr. Andrew von Eschenbach, M.D.
Acting Commissioner
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD  20857-0001

Dear Dr. von Eschenbach,

As the President of the American Association of Pro Life Obstetricians and  Gynecologists (AAPLOG), a special interest group of the American College of Obstetricians and Gynecologists (ACOG), I write to inform you that it is with great concern that AAPLOG members have recently learned of the Food and Drug Administration’s plans to approve Plan B as an over-the-counter (OTC) product for women aged 18 and over.  We strongly urge the FDA not to approve Plan B OTC.  Our recommendation is based on the scientific literature. If the FDA does approve Plan B, despite the scientific literature, AAPLOG has several suggestions as to labeling.

Two studies examining emergency contraception (EC) have demonstrated that ready availability of emergency contraception does not produce a reduction in either abortion rates or unintended pregnancy rates.  A study in Scotland1 yielded no decrease in abortion rates when free, advance access to emergency contraceptives was provided.  Another study conducted in San Francisco2 produced no decrease in unintended pregnancy rates when advance access to emergency contraceptives was provided at no cost to the patient and was accompanied by instruction on Plan B.  Thus, two studies in which EC access exceeded real-life conditions did not produce the desired public health effects of a reduction in number of unwanted pregnancies and/or a reduction in the number of induced abortions.

AAPLOG has an additional concern: it appears that the ectopic pregnancy rate following Plan B use can be as high as 6%.  In 2003, the United Kingdom’s Department of Health3 alerted British physicians to this possible complication based on post-marketing surveillance in which 201 EC failures were found to contain twelve ectopic pregnancies - or a 6% rate - triple the expected rate for both UK and US.   We can find no study which alleviates this concern.  Additionally, approximately 20% or more of Plan B label comprehension subjects did not understand the potential seriousness of severe abdominal pain that may occur after using Plan B4 ( a symptom of possible ectopic pregnancy). These two facts taken together argue strongly against OTC availability of Plan B, even for adults, since lack of physician involvement puts the burden of early diagnosis of ectopic pregnancy squarely on the patient. Clearly, physician involvement is essential for the patient considering this medication, since even small delays in diagnosing ectopic pregnancy can be fatal.

If the FDA does proceed to approve Plan B OTC despite the scientific literature, three labeling issues must be clearly addressed:

1)Ectopic pregnancy warnings must be on the outer label and inner package insert, cautioning that Plan B does not protect against ectopic pregnancy, a possibly life-threatening medical condition, and that women who have had a previous ectopic pregnancy, Fallopian tube surgery, pelvic inflammatory disease, etc. should not take Plan B, except under a physician’s careful monitoring.

2)Plan B’s labeling does not give adequate notice to a potential user that Plan B may prevent the implantation of a human embryo (e.g., a fertilized ovum) as one mechanism of action, thus acting as an abortificient.  The outer label and inner package insert should reflect that Plan B may destroy a human embryo, so that a woman can make a truly informed decision for herself,  and not use a potential abortificient inadvertently.

3)Many women who are “at risk” for sexually transmitted infections (STIs) will use Plan B OTC but will not see a physician for STI testing, including HIV testing, or for regular Pap smears.  This will place these women at greater risk for future infertility from STI’s or future cervical disease - including dysplasia and cancer, as well as HIV.  AAPLOG believes that competent Plan B self-medication must include understanding the necessity of follow-up exams for STIs and cervical disease, which should be reflected on the label. This is especially important for sexual assault victims who also need to be encouraged to seek medical and psychological care after an assault.

Finally, in the November 1, 2005 filing in the Plan B Federal Register proceeding, it was argued that the FDA does not have the statutory or regulatory authority to create a split OTC/Rx marketing plan for a drug.  That being said, if the FDA proceeds as planned, it should take steps to ensure that the drug is not being purchased by adults for the purpose of surreptiously aiding perpetrators of statutory rape.  Perhaps, then, only women should be allowed to purchase the drug OTC.

Based on the scientific literature, AAPLOG urges you to reconsider the current plans to allow Plan B to be sold OTC. If the FDA proceeds, the above labeling is mandatory. Thank you for your thoughtful consideration of all these issues. I and other AAPLOG physicians are available to answer any questions you or your colleagues may have in this matter.

Sincerely,

Elizabeth Shadigian, M.D.
President, AAPLOG

1 Glasier A, Fairhurst W et al. Advanced provision of emergency contraception does not reduce abortion rates. Contraception 69:361-366, 2004.

2 Raine T, Harper C, et al. Direct access to emergency contraception through pharmacies and effect on unintended pregnancy and STI’s: A randomized controlled trial. JAMA 293:54-62, 2005.

3 http://www.dh.gov.uk/PublicationsAndStatistics/LettersAndCirculars/CMOUpdate, #35, content #20, dated 4-2-03.

4 Actual Use Study, Volumes 27-30 of sNDA 21-045, Phase 3 Non-Comparative Case Series Study of Plan B Levonorgestrel Emergency Contraceptive Pills Provided Using a Simulated Over-The-Counter Approach;Women’s Capital Corporation(The sponsorship was transferred to the Barr Research in Nov, 03) Investigators:Family Health International (FHI), Research Triangle Park, NC, January, 2003.    
In addition, the sine qua non of an OTC-switch is that patients should be capable of self-medicating by reading the drug’s package insert.  The above label comprehension tests for Plan B indicate that safe self-medication is not possible for a significant segment of the population.  For example, only 75% of all respondents answered correctly that Plan B should not be taken in the presence of unexplained vaginal bleeding. Among the low-level literacy group that figure declined to 69%.  Furthermore, only 67% of all respondents understood that Plan B is designed to serve as a backup for regular contraception methods, not a replacement. Among those of low-literacy this figure dropped to 46%; whereas for women of high literacy the figure was 78%.  Obviously, many patients do not understand much of the drug’s package insert, which argues against FDA approval of EC OTC.