The FDA, Politics, and Plan B
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《新英格兰医药杂志》
The recent decision by the Food and Drug Administration (FDA) to postpone a decision on the proposal to switch levonorgestrel emergency contraception (sold under the brand name Plan B) to over-the-counter status suggests that the FDA's decision-making process is being influenced by political considerations. The data overwhelmingly demonstrate that emergency contraception is safe and effective when available without a prescription. Moreover, the evidence shows that the availability of emergency contraception does not result in a change in the usual behavior or contraceptive practices of the women who are its potential users. A treatment for any other condition, from hangnail to headache to heart disease, with a similar record of safety and efficacy would be approved quickly. Why has the FDA adopted its own plan B with respect to approval for over-the-counter use, instead of going ahead with the recommended approval?
Plan B consists of two 0.75-mg tablets of levonorgestrel, which should be taken as soon as possible, and within 72 hours, after an episode of unprotected intercourse. This drug is currently marketed with the recommendation that the two tablets be taken 12 hours apart, but studies have shown that they are equally efficacious if taken together as a single 1.5-mg oral dose. Thousands of women in several countries have been treated in safety and efficacy studies, which have found a pregnancy rate of about 1 percent when levonorgestrel is used after a single act of unprotected intercourse, as compared with a rate of 8 percent without treatment. The reduction in the risk of pregnancy after treatment is thus about 85 percent. Side effects are generally minor and include nausea (in 15 percent of women), vomiting (1 percent), and delayed menses (5 percent). Even if this method of contraception is "abused" — by repeated use — the consequences are minimal, consisting mostly of menstrual irregularities.
Pregnancy rates increase from 0.4 percent when treatment is initiated within 24 hours of unprotected intercourse to 2.7 percent when treatment begins 48 to 72 hours after the event. If a woman does not have the medication on hand when needed, the delay entailed in obtaining a prescription — and thus in initiating therapy — can seriously reduce its efficacy. Given traditional patterns of sexual behavior, many of the exposures that necessitate treatment occur at night or on weekends, when access to physicians and other health care providers may be limited. Furthermore, requiring a prescription poses a barrier to use and will increase the cost of obtaining the medication, putting it beyond the reach of many women. Studies of sexually active young women and adolescents have shown that having emergency contraception on hand does not result in higher rates of unprotected intercourse.
Under U.S. law, the FDA has the responsibility to approve drugs for sale once their efficacy and safety have been demonstrated. Until now, approval has been based on scientific evidence from well-designed clinical trials with adequate power to establish efficacy and rule out toxicity at some reasonable level of confidence. Political considerations have wisely been kept out of the decision-making process. Although the FDA is frequently criticized by politicians and others for being either too lenient or too tough (depending on one's political or commercial perspective), the integrity of the process has seldom been questioned.
This record has given people in the United States justified confidence in the medicines they take and has resulted in the FDA's enviable international reputation. To squander that trust by allowing political pressure to delay a decision to make safe and effective emergency contraception available over the counter seems to us a serious error. It is also likely to mean that both physicians and patients will wonder whether future drug-approval decisions are based on the evidence with regard to efficacy and safety or, rather, on political considerations. How will we know? How will we find out? The current delay in the process of FDA approval for the use of levonorgestrel as contraceptive Plan B may be followed by approval with restrictions on its over-the-counter sale that are designed to intimidate women who require access to this medication. Such steps have already been suggested: demanding evidence of the age of the purchaser, for example, and putting the medication "behind the counter" or in direct view of the pharmacist. Such suggestions were rejected by the FDA advisory committee that reviewed the science behind the application for approval. They should not now be reinstituted on political grounds. In this case there is no medical dispute. Rather, the delay results from the concern of some groups, without any supporting data, that the availability of the drug may have a corrupting influence on sexual behavior. If easy access to the drug could have such an influence, it would seem that the battle had already been lost.
Over-the-counter availability of Plan B emergency contraception makes good medical sense. It will improve access to an already approved medication, prevent unwanted pregnancies, reduce the need for induced abortions, and put women in the United States on a par with women in many other countries around the world, to whom such medication is already available. We urge the FDA to revert to its plan A and move ahead swiftly with approval for Plan B.
Related Letters:
The FDA, Politics, and Plan B
Burstein P. D., Stanford J. B., Hager W. D., Crockett S. A., Drazen J. M., Greene M. F., Wood A. J.J.
Extract | Full Text | PDF
N Engl J Med 2004; 350:2413-2414, Jun 3, 2004. Correspondence(Jeffrey M. Drazen, M.D., )
Plan B consists of two 0.75-mg tablets of levonorgestrel, which should be taken as soon as possible, and within 72 hours, after an episode of unprotected intercourse. This drug is currently marketed with the recommendation that the two tablets be taken 12 hours apart, but studies have shown that they are equally efficacious if taken together as a single 1.5-mg oral dose. Thousands of women in several countries have been treated in safety and efficacy studies, which have found a pregnancy rate of about 1 percent when levonorgestrel is used after a single act of unprotected intercourse, as compared with a rate of 8 percent without treatment. The reduction in the risk of pregnancy after treatment is thus about 85 percent. Side effects are generally minor and include nausea (in 15 percent of women), vomiting (1 percent), and delayed menses (5 percent). Even if this method of contraception is "abused" — by repeated use — the consequences are minimal, consisting mostly of menstrual irregularities.
Pregnancy rates increase from 0.4 percent when treatment is initiated within 24 hours of unprotected intercourse to 2.7 percent when treatment begins 48 to 72 hours after the event. If a woman does not have the medication on hand when needed, the delay entailed in obtaining a prescription — and thus in initiating therapy — can seriously reduce its efficacy. Given traditional patterns of sexual behavior, many of the exposures that necessitate treatment occur at night or on weekends, when access to physicians and other health care providers may be limited. Furthermore, requiring a prescription poses a barrier to use and will increase the cost of obtaining the medication, putting it beyond the reach of many women. Studies of sexually active young women and adolescents have shown that having emergency contraception on hand does not result in higher rates of unprotected intercourse.
Under U.S. law, the FDA has the responsibility to approve drugs for sale once their efficacy and safety have been demonstrated. Until now, approval has been based on scientific evidence from well-designed clinical trials with adequate power to establish efficacy and rule out toxicity at some reasonable level of confidence. Political considerations have wisely been kept out of the decision-making process. Although the FDA is frequently criticized by politicians and others for being either too lenient or too tough (depending on one's political or commercial perspective), the integrity of the process has seldom been questioned.
This record has given people in the United States justified confidence in the medicines they take and has resulted in the FDA's enviable international reputation. To squander that trust by allowing political pressure to delay a decision to make safe and effective emergency contraception available over the counter seems to us a serious error. It is also likely to mean that both physicians and patients will wonder whether future drug-approval decisions are based on the evidence with regard to efficacy and safety or, rather, on political considerations. How will we know? How will we find out? The current delay in the process of FDA approval for the use of levonorgestrel as contraceptive Plan B may be followed by approval with restrictions on its over-the-counter sale that are designed to intimidate women who require access to this medication. Such steps have already been suggested: demanding evidence of the age of the purchaser, for example, and putting the medication "behind the counter" or in direct view of the pharmacist. Such suggestions were rejected by the FDA advisory committee that reviewed the science behind the application for approval. They should not now be reinstituted on political grounds. In this case there is no medical dispute. Rather, the delay results from the concern of some groups, without any supporting data, that the availability of the drug may have a corrupting influence on sexual behavior. If easy access to the drug could have such an influence, it would seem that the battle had already been lost.
Over-the-counter availability of Plan B emergency contraception makes good medical sense. It will improve access to an already approved medication, prevent unwanted pregnancies, reduce the need for induced abortions, and put women in the United States on a par with women in many other countries around the world, to whom such medication is already available. We urge the FDA to revert to its plan A and move ahead swiftly with approval for Plan B.
Related Letters:
The FDA, Politics, and Plan B
Burstein P. D., Stanford J. B., Hager W. D., Crockett S. A., Drazen J. M., Greene M. F., Wood A. J.J.
Extract | Full Text | PDF
N Engl J Med 2004; 350:2413-2414, Jun 3, 2004. Correspondence(Jeffrey M. Drazen, M.D., )