The FDA, Politics, and Plan B
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In response to the editorial by Drazen and colleagues (April 8 issue)1: It is a terrible message that the findings of scientists can be subject to the pressure of politicians, especially when the goal is the same — to prevent undesired pregnancies and to minimize the need for abortion. Levonorgestrel emergency contraception (Plan B) is amazingly free of severe adverse effects and is very effective. Condoms are openly displayed and sold over the counter in many large pharmacies. There is no reason why Plan B should not be treated similarly. The message should be that if one engages in sexual activities, they should be consensual and safe and engaged in with forethought. In case that fails, prevention of pregnancy should be available in a timely fashion. Over-the-counter status would be medically smart and socially responsible.
Paul D. Burstein, M.D.
University of Wisconsin Medical School
Milwaukee, WI 53211
References
Drazen JM, Greene MF, Wood AJJ. The FDA, politics, and Plan B. N Engl J Med 2004;350:1561-1562.
To the Editor: Drazen and colleagues assert that there are no scientific concerns in considering over-the-counter status for levonorgestrel emergency contraception. In fact, the Food and Drug Administration (FDA) advisory committees raised a number of issues, both from panel members opposing over-the-counter status and from some of those supporting it.1 Label comprehension and the effects of unrestricted access for young adolescents (especially those younger than 15 years of age) have not been studied. The effectiveness rates in package information need to be estimated by the best methods currently available and should include rates of typical-use effectiveness, not just perfect-use effectiveness.2 Package labeling needs to be modified to state adequately that Plan B may at times act after fertilization and thus allow informed consent for women who personally believe that life begins at fertilization.3 There are also public health concerns that unrestricted over-the-counter status might be accompanied by increased reliance on Plan B that could reduce the use of reproductive health care by adolescent women, increase rates of sexually transmitted infection, and negate the proposed reduction in unwanted pregnancies.
Joseph B. Stanford, M.D.
University of Utah
Salt Lake City, UT 84108
jstanford@dfpm.utah.edu
W. David Hager, M.D.
University of Kentucky
Lexington, KY 40503
Susan A. Crockett, M.D.
14427 Brook Hollow
San Antonio, TX 78232
References
Nonprescription Drugs Advisory Committee (NDAC) in joint session with the Advisory Committee for Reproductive Health Drugs (ACRHD). Meeting transcript. (Accessed May 14, 2004, at http://www.fda.gov/ohrms/dockets/ac/03/transcripts/4015T1.pdf.)
Trussell J, Ellertson C, von Hertzen H, et al. Estimating the effectiveness of emergency contraceptive pills. Contraception 2003;67:259-265.
Kahlenborn C, Stanford JB, Larimore WL. Postfertilization effect of hormonal emergency contraception. Ann Pharmacother 2002;36:465-470.
The editorialists reply: We received letters both supporting and condemning our editorial concerning the FDA's delay in approving the proposal to switch Plan B from prescription status to over-the-counter availability. The letter from Dr. Stanford and colleagues raises several important issues; each of these was considered by the FDA's joint advisory committees, which voted 23 to 4 for approval on December 16, 2003.
Dr. Stanford and colleagues object, stating that label comprehension among adolescents "especially those younger than 15 years of age" has "not been studied." Label-comprehension data collected from 656 girls and women 12 to 50 years of age, including 76 subjects 12 to 16 years of age (11.6 percent), were presented at the meeting. Of all U.S. girls and women 12 to 50 years of age, 12.6 percent are 12 to 16 years of age. The adolescents understood 60 to 97 percent of the label's communication objectives. These results were very similar to the results for the group as a whole and are well within the standards previously accepted for the approval of other over-the-counter drugs.
The mechanisms of action of levonorgestrel are not fully defined. It clearly can interfere with ovulation, and it clearly will not interfere with an implanted pregnancy. It may interfere with implantation of a blastocyst. Those who consider "life" to begin at fertilization may consider this medication an unacceptable option for this reason. We support appropriate labeling to allow persons to make informed decisions. Such labeling changes are part of the usual negotiation process that occurs between a company and the FDA before approval.
Finally, the concern that over-the-counter availability of emergency contraception will lead to "public health" problems, including increased rates of sexually transmitted infections due to irresponsible sexual behavior and decreased use of proper primary contraceptive methods, is just not supported by credible available data. The actual-use study data presented to the committees demonstrated that women with ready access to emergency contraception used condoms more frequently, had intercourse without any contraception less frequently, and used more efficacious methods of contraception more frequently than other women.
We understand and respect the fact that some have moral objections to contraception. However, as we explain in our editorial, the statutory duty of the FDA is to review the data evaluating the safety and efficacy of drugs and, when safety and efficacy are demonstrated, to approve such drugs for sale. If groups with moral objections wish to prevent the sale of a class of drugs, they should proceed through the legislative process. They should not corrupt the scientific-review process of the FDA to achieve their ends. We believe that it will be very hard to put this genie back in the bottle. We squander public trust at our peril.
Jeffrey M. Drazen, M.D.
Michael F. Greene, M.D.
Alastair J.J. Wood, M.D.
Paul D. Burstein, M.D.
University of Wisconsin Medical School
Milwaukee, WI 53211
References
Drazen JM, Greene MF, Wood AJJ. The FDA, politics, and Plan B. N Engl J Med 2004;350:1561-1562.
To the Editor: Drazen and colleagues assert that there are no scientific concerns in considering over-the-counter status for levonorgestrel emergency contraception. In fact, the Food and Drug Administration (FDA) advisory committees raised a number of issues, both from panel members opposing over-the-counter status and from some of those supporting it.1 Label comprehension and the effects of unrestricted access for young adolescents (especially those younger than 15 years of age) have not been studied. The effectiveness rates in package information need to be estimated by the best methods currently available and should include rates of typical-use effectiveness, not just perfect-use effectiveness.2 Package labeling needs to be modified to state adequately that Plan B may at times act after fertilization and thus allow informed consent for women who personally believe that life begins at fertilization.3 There are also public health concerns that unrestricted over-the-counter status might be accompanied by increased reliance on Plan B that could reduce the use of reproductive health care by adolescent women, increase rates of sexually transmitted infection, and negate the proposed reduction in unwanted pregnancies.
Joseph B. Stanford, M.D.
University of Utah
Salt Lake City, UT 84108
jstanford@dfpm.utah.edu
W. David Hager, M.D.
University of Kentucky
Lexington, KY 40503
Susan A. Crockett, M.D.
14427 Brook Hollow
San Antonio, TX 78232
References
Nonprescription Drugs Advisory Committee (NDAC) in joint session with the Advisory Committee for Reproductive Health Drugs (ACRHD). Meeting transcript. (Accessed May 14, 2004, at http://www.fda.gov/ohrms/dockets/ac/03/transcripts/4015T1.pdf.)
Trussell J, Ellertson C, von Hertzen H, et al. Estimating the effectiveness of emergency contraceptive pills. Contraception 2003;67:259-265.
Kahlenborn C, Stanford JB, Larimore WL. Postfertilization effect of hormonal emergency contraception. Ann Pharmacother 2002;36:465-470.
The editorialists reply: We received letters both supporting and condemning our editorial concerning the FDA's delay in approving the proposal to switch Plan B from prescription status to over-the-counter availability. The letter from Dr. Stanford and colleagues raises several important issues; each of these was considered by the FDA's joint advisory committees, which voted 23 to 4 for approval on December 16, 2003.
Dr. Stanford and colleagues object, stating that label comprehension among adolescents "especially those younger than 15 years of age" has "not been studied." Label-comprehension data collected from 656 girls and women 12 to 50 years of age, including 76 subjects 12 to 16 years of age (11.6 percent), were presented at the meeting. Of all U.S. girls and women 12 to 50 years of age, 12.6 percent are 12 to 16 years of age. The adolescents understood 60 to 97 percent of the label's communication objectives. These results were very similar to the results for the group as a whole and are well within the standards previously accepted for the approval of other over-the-counter drugs.
The mechanisms of action of levonorgestrel are not fully defined. It clearly can interfere with ovulation, and it clearly will not interfere with an implanted pregnancy. It may interfere with implantation of a blastocyst. Those who consider "life" to begin at fertilization may consider this medication an unacceptable option for this reason. We support appropriate labeling to allow persons to make informed decisions. Such labeling changes are part of the usual negotiation process that occurs between a company and the FDA before approval.
Finally, the concern that over-the-counter availability of emergency contraception will lead to "public health" problems, including increased rates of sexually transmitted infections due to irresponsible sexual behavior and decreased use of proper primary contraceptive methods, is just not supported by credible available data. The actual-use study data presented to the committees demonstrated that women with ready access to emergency contraception used condoms more frequently, had intercourse without any contraception less frequently, and used more efficacious methods of contraception more frequently than other women.
We understand and respect the fact that some have moral objections to contraception. However, as we explain in our editorial, the statutory duty of the FDA is to review the data evaluating the safety and efficacy of drugs and, when safety and efficacy are demonstrated, to approve such drugs for sale. If groups with moral objections wish to prevent the sale of a class of drugs, they should proceed through the legislative process. They should not corrupt the scientific-review process of the FDA to achieve their ends. We believe that it will be very hard to put this genie back in the bottle. We squander public trust at our peril.
Jeffrey M. Drazen, M.D.
Michael F. Greene, M.D.
Alastair J.J. Wood, M.D.