Efficacy and Safety of a Transdermal Contraceptive System Geoffrey H. Smallwood, MD, Mary L. Meador, MD, John P. Lenihan, Jr, MD, Gary A. Shangold, MD, Alan C. Fisher, DrPH, George W. Creasy, MD, for the ORTHO EVRA/EVRA 002 Study Group OBJECTIVES: To evaluate the efficacy, cycle control, compli- ance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 g and ethinyl estradiol 20 g daily. METHODS: In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n  1171) or 13 cycles (n  501). The treatment regimen for each cycle was three con- secutive 7-day patches (21 days) followed by 1 patch-free week. RESULTS: The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respec- tively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached com- pletely. Adverse events were typical of hormonal contra- ception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). CONCLUSIONS: The transdermal contraceptive patch pro- vides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contracep- tive patch is associated with excellent compliance and wearability characteristics. (Obstet Gynecol 2001;98: 799 – 805. © 2001 by the American College of Obstetri- cians and Gynecologists.) Hormonal contraception is used by over 100 million women worldwide, 1 and by over 12 million women in the United States. 2,3 The introduction of lower-dose combination oral contraceptives (OCs) (50 g ethinyl estradiol) has provided many women a highly effective, safe, and tolerable method of contraception. However, the 1995 National Survey of Family Growth (NSFG) (US data) estimated that the failure rates of OCs were as high as 8.3% during the first year of typical use. 4 This rate of failure is quite different from failure rates of 0.1% observed in clinical trials in which OCs were used cor- rectly and consistently. 5 Noncompliance is the primary reason cited for the difference between these rates. 6–8 Although OCs provide effective birth control when used correctly, there is a need for effective, readily reversible hormonal contraception that will enhance user compli- ance by providing a simpler dosing schedule. Transdermal systems for the delivery of estrogens and estrogen–progestin combinations have been developed for hormone replacement therapy. 9,10 Until recently, the transdermal delivery of sufficient amounts of progestin and estrogen for effective contraception had not been possible. A new transdermal contraceptive patch (OR- THO EVRA (US trademark)/EVRA (worldwide trade- mark) containing norelgestromin (formerly known as 17-deacetyl norgestimate), the active metabolite of norg- estimate, and ethinyl estradiol has been developed by The R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ. The combination of norgestimate and ethi- nyl estradiol has been used effectively in leading OCs From private practice clinics in Nashville, Tennessee; Bend, Oregon; Tacoma, Washington; and the R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey. This study was conducted at 73 centers: the United States (31), the United Kingdom (13), the Netherlands (7), France (5), Switzerland (5), Israel (4), Sweden (4), Australia (2), Austria (1), and Belgium (1). This study was supported by The R.W. Johnson Pharmaceutical Research Institute. Principal investigators: B.M. Sibai, V.L. Odlind, T. Lefton, Marilyn Short, J.S. Brigham, F.D. Fingerhut, E. Weisberg, B. Satterfield, D.A. Sund- wall, U. Gaspard, B.R. Kurtz, S.A. Funk, A. Bigrigg, L. Hopkins, K.K. Leonhardt, M. Weerasinghe, D.-M. Gruber, J. Adelglass, R.L. Holly, M. McCartney, T. Ba ¨ckstro ¨m, E.G. Garner, G. Berg, G.M. Bouw, A. Van Zanten, H. Resnick, F. Sargos, S. Craft, M.-C. Jourdan, B.-M. Landgren, J.F. Peipert, P. Farrington, R. Kroll, S. Randall, D. Stucki, A. Youssoupov-Labatut, I. Zordan, A. Glasier, M.A. Macsalka, B. Soltes, M. Birkha ¨user, D.H. Bogchel- man, R. de Boer, A.L. Troostwijk, F.J.M. Broekmans, D. Hochner-Celnikier, G.S. Merki, J. Bitzer, J. Itzkovitz, D.F. Archer, A. Kubba, P.H.M. van de Weijer, E. Weisberg, R.W. Ke, R. Kirkman, M. Boyce, A. Brzezinski, F. Dargacha-Sable ´, J. Guillebaud, M. Walling, H.A. Zacur, S. Jones, D. Man- sour, Y. Rabinovici, R.D. Crist, Dr. Eberhard, C. Wilkinson, and M. Kishen. 799 VOL. 98, NO. 5, PART 1, NOVEMBER 2001 0029-7844/01/$20.00 © 2001 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc. PII S0029-7844(01)01534-4