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iPLEDGE Allegiance to the Pill: Evaluation of Year 1 of a Birth Defect Prevention and Monitoring System

Published online by Cambridge University Press:  01 January 2021

Toby L. Schonfeld ,
N. Jean Amoura  and
Christopher J. Kratochvil
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Extract

Following the widespread occurrence of birth defects from the use of thalidomide to treat nausea during pregnancy in the 1960s and 1970s, the Food and Drug Administration (FDA) became particularly vigilant about the use of therapeutic agents during pregnancy and in women of childbearing potential. The FDA developed a list that categorizes an agent according to the known (and potential unknown) risks to a fetus. The drug thalidomide falls into Category X: agents that have demonstrated clear risk of fetal abnormalities and whose risks outweigh the benefits of use during pregnancy.

Another Category X drug is isotretinoin, commonly known by its trade name Accutane. Isotretinoin is an oral medication prescribed for severe recalcitrant, nodular acne in patients who are unresponsive to conventional therapy. Isotretinoin has been available since 1982, and it remains the only effective treatment for this condition.

Type
Symposium
Information
Journal of Law, Medicine & Ethics , Volume 37 , Issue 1 , Spring 2009 , pp. 104 - 117
Copyright
Copyright © American Society of Law, Medicine and Ethics 2009

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References

Food and Drug Administration, “Labeling and prescription drug advertising: Content and format for labeling for human prescription drugs,” Federal Register 44 (1979): 37434–37467.Google Scholar
Schonfeld, T. L. Gordon, B. G., “Contraception in Research: A Policy Suggestion,” IRB: Ethics and Human Research 27, no. 2 (March-April 2005): 15–20.10.2307/3564482CrossRefGoogle Scholar
Thalidomide has been reintroduced to the market as a chemotherapeutic agent, but retains its Category X standing. This demonstrates that the categorization is not simply an incremental list of risks; instead it is a weighing of both risks to the fetus and benefit to the mother. Doering, P. L. Boothby, L. A. Cheok, M., “Review of Pregnancy Labeling of Prescription Drugs: Is the Current System Adequate to Inform of Risks?” American Journal of Obstetrics and Gynecology 187, no. 2 (2002): 333–339.CrossRefGoogle Scholar
Food and Drug Administration, Briefing Document for iPLEDGE Year One Update, United States Department of Health and Human Services, available at <http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007–4311b1–02-ipledge.pdf> (last visited December 16, 2008).+(last+visited+December+16,+2008).>Google Scholar
According to reports, greater than 35% of fetuses exposed to isotretinoin will have some measure of “isotretinoin embryopathy.” Of those fetuses that are affected, approximately 70% will have significant ear abnormalities, 25% will have jaw abnormalities, 10% will have cleft palate, 40% will have heart defects, 30% will have thymic defects, and 20% will have eye abnormalities. In addition, central nervous system deficiencies are common (∼80% of affected cases), which may lead to poor cognitive performance and learning disabilities, even in those children who have no other structural defects. Finally, the risk of miscarriage or stillbirth is 40% in women taking isotretinoin, and the risk for delivering a baby prematurely is doubled in isotretinoin-exposed pregnancies. Robertson, J. Polifka, J. D. Avner, M. Chambers, C. Delevan, G. Koren, G. Lavigne, D. V. Martinez, L. P. Miller, R. K. Carey, J. C., “A Survey of Pregnant Women Using Isotretinoin,” Birth Defects Research (Part A) 73 (2005): 881–887.CrossRefGoogle Scholar
See FDA, supra note 4, at 5.Google Scholar
Abroms, L. Maibach, E. Lyon-Daniel, K. Feldman, S. R., “What Is the Best Approach to Reducing Birth Defects Associated with Isotretinoin?” PLoS Medicine 3, no. 11 (2006): 1978–1983, at 1979.CrossRefGoogle Scholar
Ellison, R. H. Leach, E. E., “Isotretinoin and Pregnancy,” JAMA 285, no. 16 (April 25, 2001): 2080–2081.CrossRefGoogle Scholar
Brinker, A. Kornegay, C. Nourjah, P., “Trends in Adherence to a Revised Risk Management Program Designed to Decrease or Eliminate Isotretinoin-Exposed Pregnancies: Evaluation of the Accutane SMART program,” Archives of Dermatology 141, no. 5 (May 2005): 563–569.CrossRefGoogle Scholar
Id., at 564.Google Scholar
Honein, M. A. Moore, C. A. Erickson, J. D., “Can We Ensure the Safe Use of Known Human Teratogens? Introduction of Generic Isotretinoin in the US as an Example,” Drug Safety 27, no. 14 (2004): 1069–1080, at 1075.10.2165/00002018-200427140-00001CrossRefGoogle Scholar
Id.Google Scholar
Id., at 1078.Google Scholar
See FDA, supra note 4.Google Scholar
Hatcher, R. A. Trussell, J. Stewart, F., Contraceptive Technology, 18th rev. ed. (New York: Ardent Media, 2004).Google Scholar
Cheetham, T. C. Wagner, R. A. Chiu, G. Day, J. M. Yoshinaga, M. S. Wong, L., “A Risk Management Program Aimed at Preventing Fetal Exposure to Isotretinoin: Retrospective Cohort Study,” Journal of the American Academy of Dermatology 55, no. 3 (September 2006): 442–448.CrossRefGoogle Scholar
See FDA, supra note 4.Google Scholar
Berard, A. Azoulay, L. Koren, G. Blais, L. Perreault, S. Oraichi, D., “Isotretinoin, Pregnancies, Abortions and Birth Defects: A Population-Based Perspective,” British Journal of Clinical Pharmacology 63, no. 2 (2007): 195–205.CrossRefGoogle Scholar
See Hatcher, , supra note 15.Google Scholar
Chandra, A. Martinez, G. M. Mosher, W. D. Abma, J. C. Jones, J., and National Center for Health Statistics, “Fertility, Family Planning, and Reproductive Health of US Women: Data from the 2002 National Survey of Family Growth,” Vital Health Statistics 23, no. 25 (2005).Google Scholar
See Hatcher, , supra note 15.Google Scholar
Finer, L. B. Henshaw, S. K., “Disparities in Rates of Unintended Pregnancy in the United States 1994–2001,” Perspectives on Sexual and Reproductive Health 38, no. 2 (2006): 90–96.CrossRefGoogle Scholar
Alan Guttmacher Institute, Into a New World: Young Women's Sexual and Reproductive Lives, New York, 1998.Google Scholar
Id. See also Finer, Henshaw, , supra note 22.Google Scholar
Farley, T. M., “Life-Table Methods for Contraceptive Research,” Statistics in Medicine 5, no. 5 (September-October 1986): 475–489; Helmerhorst, F. M. Belfield, T. Kulier, R. Maitra, N. O'Brien, P. Grimes, D. A., “The Cochrane Fertility Regulation Group: Synthesizing the Best Evidence about Family Planning,” Contraception 74, no. 4 (October 2006): 280–286; Trussell, J., “Methodological Pitfalls in the Analysis of Contraceptive Failure,” Statistics in Medicine 10, no. 2 (February 1991): 201–220.10.1002/sim.4780050512CrossRefGoogle Scholar
See FDA, supra note 4, at 5.Google Scholar
Jordan, A. Y. Parks, L. Chen, S. Higgins, K. Fleischer, A. B. Feldman, S. R., “Does the Teratogenicity of Isotretinoin Outweigh Its Benefits?” Journal of Dermatological Treatment 16, no. 4 (2005): 190–192; Mitchell, A. A. Van Bennekom, C. Louik, C., “An Assessment of the Accutane (Isotreinoin) Pregnancy Prevention Program,” presentation, September 18–19 2000, available at <http://www.fda.gov/ohrms/dockets/ac/00/slides/3639s1.htm> (last visited December 16, 2008).10.1080/09546630510044904CrossRefGoogle Scholar
See Cheetham, , supra note 16.Google Scholar
Goldsmith, L. A. Bolognia, J. L. Callen, J. P. Chen, S. C. Feldman, S. R. Lim, H. W. Lucky, A. W., “American Academy of Dermatology Consensus Conference on the Safe and Optimal Use of Isotretinoin: Summary and Recommendations,” Journal of the American Academy of Dermatology 50, no. 6 (2004): 900–906.10.1016/j.jaad.2004.02.012CrossRefGoogle Scholar
See Cheetham, , supra note 16, at 446.Google Scholar
See Berard, , supra note 18.Google Scholar
See Finer, , supra note 22.Google Scholar
Nava-Ocampo, A. A. Koren, G., “Human Teratogens and Evidence-Based Teratogen Risk Counseling: The Motherisk Approach,” Clinical Obstetrics and Gynecology 50, no. 1 (March 2007): 123–131, at 125.CrossRefGoogle Scholar
Id.Google Scholar
Koren, G. Levichek, Z., “The Teratogenicity of Drugs for Nausea and Vomiting of Pregnancy: Perceived Versus True Risk,” American Journal of Obstetrics and Gynecology 186, no. 5, Supplement (May 2002): S248–S252; Pole, M. Einarson, A. Pairaudeau, N. Einarson, T. Koren, G., “Drug Labeling and Risk Perceptions of Teratogenicity: A Survey of Pregnant Canadian Women and Their Health Professionals,” Journal of Clinical Pharmacology 40, no. 6 (June 2000): 573–577; Williams, J. Myson, V. Steward, S. Jones, G. Wilson, J. F. Kerr, M. P. Smith, P. E., “Self-discontinuation of Antiepileptic Medication in Pregnancy: Detection by Hair Analysis,” Epilepsia 43, no. 8 (August 2002): 824–831; Williams, J. Lawthom, C. Dunstan, F. D. Dawson, T. P. Kerr, M. P. Wilson, J. F. Smith, P. E., “Variability of Antiepileptic Medication Taking Behaviour in Sudden Unexplained Death in Epilepsy: Hair Analysis at Autopsy,” Journal of Neurology, Neurosurgery, and Psychiatry 77, no. 4 (April 2006): 481–484.CrossRefGoogle Scholar
Friedman, J. M. Little, B. B. Brent, R. L. Cordero, J. F. Hanson, J. W. Shepard, T. H., “Potential Human Teratogenicity of Frequently Prescribed Drugs,” Obstetrics and Gynecology 75, no. 4 (April 1990): 594–599.Google Scholar
See Honein, , supra note 11, at 1070.Google Scholar
Anderson, J. R. Schonfeld, T. L. Kelso, T. K. Prentice, E. D., “An IRB's Deliberations Regarding Restrictions on Women of Child-Bearing Potential as Subjects for an Early Phase Clinical Trial,” IRB: Ethics and Human Research 25, no. 4 (July-August 2003): 7–11.CrossRefGoogle Scholar
Newport, D. J. Viguera, A. C. Beach, A. J. Ritchie, J. C. Cohen, L. S. Stowe, Z. N., “Lithium Placental Passage and Obstetrical Outcome: Implications for Clinical Management during Late Pregnancy,” American Journal of Psychiatry 162, no. 11 (November 2005): 2162–2170; Yonkers, K. A. Wisner, K. L. Stowe, Z. Leibenluft, E. Cohen, L. Miller, L. Manber, R. Viguera, A. Suppes, T. Altshuler, L., “Management of Bipolar Disorder during Pregnancy and the Postpartum Period,” American Journal of Psychiatry 161, no. 4 (April 2003): 608–620.CrossRefGoogle Scholar
Azoulay, L. Oraichi, D. Berard, A., “Patterns and Utilization of Isotretinoin for Acne from 1984 to 2003: Is There Need for Concern?” European Journal of Clinical Pharmacology 62, no. 8 (2006): 667–674; also see Robertson, , supra note 5. There are data to suggest that isotretinoin is being used in some contexts inappropriately: As a first-line agent, for those with less-severe forms of disease, or for longer than the recommended course of treatment. There is a sex difference in prescription use as well, which suggests that men may be underutilizing this therapy or women may be overutilizing it. See Honein, , supra note 11. One reasonable way to reduce the overall risk of fetal exposure is to ensure that only those patients whose disease meets the clinical indications for isotretinoin (broadly considered to include not just physical indications) begin isotretinoin therapy. See Jones, K. L. Adams, J. Chambers, C. D. Erickson, J. D. Lammer, E. Polifka, J., “Isotretinoin and Pregnancy,” JAMA 285, no. 16 (April 25, 2001): 2079–2080.CrossRefGoogle Scholar
Anderson, C. John, O. P. Keltner, D. Kring King, A. M., “Who Attains Social Status? Effects of Personality and Physical Attractiveness in Social Groups,” Journal of Personal and Social Psychology 81, no. 1 (2001): 116–132; Jackson, L. Ervin, K., “Height Stereotypes of Women and Men: The Liabilities of Shortness for Both Sexes,” Journal of Social Psychology 132, no. 4 (1992): 433–445.10.1037/0022-3514.81.1.116CrossRefGoogle Scholar
Hull, P. R. D'Arcy, C., “Acne, Depression, and Suicide,” Dermatologic Clinics 23, no. 4 (October 2005): 665–674.10.1016/j.det.2005.05.008CrossRefGoogle Scholar
See Goldsmith, , supra note 29.Google Scholar
See Jordan, , supra note 27.Google Scholar
Doshi, A. E., “The Cost of Clear Skin: Balancing the Social and Safety Costs of iPLEDGE with the Efficacy of Accutane (Isotretinoin),” Seton Hall Law Review 37, no. 2 (2007): 625–660, at 647.Google Scholar
Id.Google Scholar
Id., at 651.Google Scholar
Pseudotumor cerebri: Increased intracranial pressure, often unknown etiology, that may cause headaches, visual changes, or even vision loss.Google Scholar
See Goldsmith, , supra note 29. Studies investigating a causal link between isotretinoin and psychological risks are just beginning to appear in the literature. It remains unclear how much of the psychological risk is attributable to isotretinoin, and how much relates to the underlying disease and/or age group. See Magin, P. Pond, D. Smith, W., “Isotretinoin, Depression and Suicide: A Review of the Evidence,” British Journal of General Practice: The Journal of the Royal College of General Practitioners 55, no. 511 (February 2005): 134–138; Marqueling, A. L. Zane, L. T., “Depression and Suicidal Behavior in Acne Patients Treated with Isotretinoin: A Systematic Review,” Seminars in Cutaneous Medicine and Surgery 24, no. 2 (June 2005): 92–102; Strahanand, J. E. Raimer, S., “Isotretinoin and the Controversy of Psychiatric Adverse Effects,” International Journal of Dermatology 45, no. 7 (July 2006): 789–799.Google Scholar
See Berard, , supra note 18.Google Scholar
Assuming, of course, that the program achieves this goal satisfactorily.Google Scholar
See Cheetham, , supra note 16; also Doshi, , supra note 45.Google Scholar
See Doshi, , supra note 45, at 659.Google Scholar
Potter, L., “Measuring Compliance among Oral Contraceptive Users,” Family Planning Perspectives 28, no. 4 (1996): 154–158.10.2307/2136191CrossRefGoogle Scholar
See Berard, , supra note 18.Google Scholar
Id., at 203.Google Scholar
Glei, D. A., “Measuring Contraceptive Use Patterns among Teenage and Adult Women,” Family Planning Perspectives 31, no. 2 (March-April 1999): 73–80; Severy, L. J. Silver, S. E., “Two Reasonable People: Joint Decision Making in Contraceptive Choice and Use,” Advances in Population: Psychosocial Perspectives 1, no. 3 (1993): 207–227.10.2307/2991642CrossRefGoogle Scholar
Johnsen, D., “From Driving to Drugs: Governmental Regulation of Pregnant Women's Lives after Webster,” University of Pennsylvania Law Review 138, no. 179 (1989): 179–215, at 192.CrossRefGoogle Scholar
Note that this is different once women become mothers. Child Protective Services will take custody of children who test positive for illegal substance after birth. Yet a woman with a positive drug screen during pregnancy receives no sanction other than counseling (scolding?) by her health care provider.Google Scholar
The State of Michigan does provide a set of “Driving Safety Tips for Pregnant Women,” which include how to wear a safety belt, how to position the steering wheel, and when to avoid driving (“When possible, ride as a passenger rather than drive to avoid potential contact with the steering wheel.”) (See www.michigan.gov).Google Scholar
Id., at 205.Google Scholar
Id.Google Scholar
Consider, for example, that the U.S. Supreme Court struck down policies that enabled employers to discriminate against hiring women of childbearing potential for well-paying jobs because of concerns about environmental toxins affecting future pregnancies (Minkoff, Paltrow, 2006), or the firestorm that was raised from the South Carolina action to jail pregnant recreational drug users.Google Scholar
Id., at 196.Google Scholar
Bottrell, M. M. Alpert, H. Fischbach, R. L. Emanuel, L. L., “Hospital Informed Consent for Procedure Forms: Facilitating Quality Patient-Physician Interaction,” Archives of Surgery 135, no. 1 (January 2000): 26–33; Paasche-Orlow, M. K. Taylor, H. A. Brancati, F. L., “Readability Standards for Informed-Consent Forms as Compared with Actual Readability,” New England Journal of Medicine 348, no. 8 (February 20, 2003): 721–726.CrossRefGoogle Scholar
See Abroms, , supra note 7, at 1981.10.1111/j.1752-0606.1981.tb01391.xCrossRefGoogle Scholar
Id.Google Scholar
Id.Google Scholar
Id.Google Scholar
However, it is important to remember the statistics reported earlier: The highest rates of pregnancy are in the 25–39-year-old age group, not with adolescents.Google Scholar
Bearinger, L. H. Sieving, R. E. Ferguson, J. Sharma, V., “Global Perspectives on the Sexual and Reproductive Health of Adolescents: Patterns, Prevention, and Potential,” The Lancet 369, no. 9568 (April 7, 2007): 1220–1231; Tylee, A. Haller, D. M. Graham, T. Churchill, R. Sanci, L. A., “Youth-Friendly Primary Care Services: How Are We Doing and What More Needs to Be Done?” The Lancet 369, no. 9572 (May 5, 2007): 1565–1573.CrossRefGoogle Scholar
See Alan Guttmacher Institute, supra note 23.Google Scholar
Mahowald, M., Women and Children in Health Care: An Unequal Majority (New York: Oxford University Press, 1996); Sherwin, S., No Longer Patient: Feminist Ethics and Health Care (Philadelphia: Temple University Press, 1992).Google Scholar
See Cheetham, , supra note 16, at 447.Google Scholar
See Doshi, , supra note 45, at 251.Google Scholar
Brent, R. L. Beckman, D. A., “Prescribed Drugs, Therapeutic Agents, and Fetal Teratogenesis,” in Medicine of the Fetus and Mother, Reece, E. A. Hobbins, J. C., eds., 2nd ed. (Philadelphia: Lippincott-Raven Publishers, 1999): At 289–313.Google Scholar