The document discusses the FDA's review process for approving Plan B as an over-the-counter contraceptive. The science showed Plan B was safe and effective for over-the-counter use, but political concerns over reproductive rights led the FDA to deny over-the-counter status. After lawsuits and congressional pressure, Plan B was approved for over-the-counter sale with age restrictions. However, the FDA's review of Plan B was less scientific and more political than for other drugs.

1. The Case of the FDA and Plan B The Politics of Drug Regulation and the Implications for Consumer Welfare

2. Plan B: Emergency Contraception Contraception after intercourse Levonorgestrel 0.75 mg x 2 (12 hrs) or 1.5 mg x1 “Plan B” approved by FDA in 1999 as a prescription Has fewer side effects than combo estrogen progestin pills

3. How long after? FDA: within 72 hours Advocates: within 120 hours, but more effective with earlier administration, so take as soon as possible

4. FDA Criteria for OTC Status Acceptable safety profile based on prescription use and experience Low potential to be abused Appropriate safety and therapeutic index Positive benefit-risk assessment Needed for a condition or illness that is self-recognizable, self-limiting, and requires minimal intervention by a health care practitioner for treatment

5. Did Plan B Meet these Criteria? Safety Side effects with Plan B include nausea, abdominal pain, fatigue, headache, menstrual changes, dizziness, breast tenderness, vomiting, and diarrhea. Menstrual bleeding may be heavier or lighter, earlier or later, after taking Plan B. Benefit/risk assessment – generally high with some disagreement

6. Perfect use and typical use pregnancy rate - EC Perfect use Excludes anyone with intercourse after EC use, not completing dose, etc. (Anyone not following directions excluded) Typical Use All users, all kinds of use

7. Randomized trials of EC Nearly all reported studies are randomized clinical trials, but… Unethical to randomize women to placebo Comparison has been another regimen of EC Most often estrogen/progestin regimen

8. Perfect use and typical use pregnancy rates -EC World Health Organization 1998 Study (n=997) Randomized trial of estrogen/progesterin vs. Plan B

9. WHO 1998

10. The Politics: How does EC work? Before fertilization? Prevent ovulation Prevent sperm migration After fertilization? Prevent implantation

11. Abbreviated time line for Plan B July 1999: Women’s Capital Corporation's application for Plan B to be a prescription drug is approved February 2001: American College of Obstetricians and Gynecologists issues a statement in support of Plan B OTC status. More than 70 medical, public health and other organizations file a citizens’ petition asking the FDA to grant Plan B OTC status April 2002: WCC’s request approval to do two pediatric studies on the use of Plan B denied by FDA (wanted to see how adolescents would use the drug) April 2003: WCC applies for OTC status

12. Time Line Continued May 2003: FDA Commissioner Mark McClelland discusses Plan B application with White House officials December 2003: 44 members of Congress send letter t0 the FDA urging it to reject WCC’s application for OTC status for Plan B

13. FDA Hearing: December 2003 Advisory committee for reproductive health drugs: 11 members Advisory committee for OTC drugs: 13 members Special consultants: 4 persons Mix of science, theater, and politics End of day: vote 23 approve, 4 against move to OTC status, 1 extension Vote 27-1 that Plan B can be safely used – even by adolescents – as recommended by the label

14. Dissenting Votes Stanford: Overestimated effectiveness information and inadequate information for informed consent of post fertilization effects Hager: Insufficient information regarding OTC safety for adolescents Crockett: Should remain prescription for physician counseling for contraception Cantilena (Chair): Label comprehension studies inadequate

15. Abbreviated time line for Plan B January 2004: FDA Commissioner’s Office recommends that the Office of Drug Evaluation NOT approve OTC sale January 2004: Office of Drug Evaluation concludes Plan B is safe for OTC sales January 2004: 76 members of Congress send letter to Commissioner McClelland expressing support for the panel’s decision and recommending OTC status

16. February 2004: Office of Drug Evaluation staff ask for more data on Plan B and adolescents. But also recommends Plan B for unrestricted OTC sale May 2004: Against internal advice of staff, the FDA director of CDER denies OTC status, citing (only) concerns about safety of use in adolescents Investigations begin of decision being for political reasons July 2004: Company applies for OTC status for women age 16 and older (if adolescents are issue) January 2005: The FDA fails to issue a decision on the Plan B application within the previously scheduled time. The Center for Reproductive Rights files a lawsuit against FDA on behalf of reproductive health groups and activists for its continued failure to grant Plan B OTC status. Suit claims that the FDA broke its own rules and regulations by ignoring science and holding Plan B to a different standard than other OTC drugs

17. January 2005: JAMA publishes study that shows increased access to EC does not lead to increased pregnancy rates, increase in unprotected sex, or cause women to give up regular birth control July 2005: Senators Patty Murray and Hilary Clinton allow the nomination of Lester Crawford as FDA Commissioner to proceed with promise from HHS Secretary Mike Leavitt that Plan B decision will be made by September 1 August 2005: FDA announces it will not make a decision but will wait for 60-day comment period with no specified deadline August 2005: Susan Wood, Director of FDA Office of Women’s Health, resigns September 2005: Lester Crawford resigns

18. Fall 2005: Andrew von Eschenbach nominated for FDA Commissioner; nomination placed on hold by Senators Patty Murray and Hilary Clinton until FDA acts on Plan B OTC application August 24, 2006: An FDA memo from acting FDA Commissioner Dr. von Eschenbach approves the application of Plan B for OTC status for women age 18 and over – the day before the Senate confirmation hearings Commissioner von Exchenbach approved by senate

19. Conditions for marketing Plan B Only sold in facilities that can sell prescription drugs Sold from behind the counter OTC upon ID proof of 18 and over Company will Engage in educational campaigns for health professionals and public Do annual survey of health professionals Use existing data sources to monitor pregnancy rates, abortion rates, STI rates Monitor point of purchase with anonymous shoppers

20. GAO Report: Unusual Aspects of FDA’s Review Process FDA’s high level management was more involved in review of Plan B than in those of other OTC switch applications Conflicting accounts within the FDA about whether the decision to not approve was made before the reviews were complete Rationale for the acting director’s decision was novel – never before had behavioral implications due to cognitive differences by age been considered

21. Implications for Consumer Welfare? When does life begin? What are women’s reproductive rights? Are young girls capable of making their own reproductive decisions?

22. Reviewing… Plan B Science regarding effectiveness and safety quite clear Science regarding how it works not so clear FDA’s authority to approve drugs for OTC sale Case of Plan B, politics of reproductive rights overshadowed the science of how effective it was