pharmacoepidemiology and drug safety 2014; 23: 439
Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/pds.3573
LETTER TO THE EDITOR
Comments on: Are Food and Drug Administration prescription drug safety plans working? A case study of isotretinoin† Fain and Alexander1 commented on the database study by Pinheiro et al.2 that evaluated the effectiveness of iPledge, the Risk Evaluation and Mitigation Strategy (REMS) for isotretinoin, noting several limitations to the approach used. They also suggested that surveybased analyses are “fraught with methodological challenges.” Although their latter point may be true for some surveys, we believe that it is feasible to design and perform scientifically rigorous surveys to evaluate REMS. Indeed, from 1989 to 2003, the Slone Epidemiology Center conducted the Accutane Survey, an independent evaluation of the Pregnancy Prevention Program for Accutane (the first risk management program directed at pregnancy prevention), which was initiated in 1988. In our 1995 report in the New England Journal of Medicine on over 177 000 women3 (and in subsequent reports to the Food and Drug Administration on over 492 000 women4) who were followed during their isotretinoin treatment and for 6 months thereafter, we provided the distribution of the contraceptive methods reported by women in the Survey. In addition, the Survey asked about sexual activity, which allowed us to identify the proportion of women who reported abstinence. Importantly, because the Survey captured information on the primary outcome of interest—pregnancy—we were also able to estimate method-specific pregnancy rates, which were lower than those for typical use of each method.5 Motivation is a well-established predictor of successful contraception,5 and in the context of a REMS targeted toward pregnancy prevention, women may be more highly motivated to use contraception properly. Our findings suggest that method-specific failure rates derived from the population at large should not be generalized to REMS participants, making survey-specific rates a critical element in evaluating the effectiveness of a REMS. A carefully designed and rigorously executed Survey can provide information on pregnancies as well as the wide range of pregnancy prevention behaviors and
Copyright © 2014 John Wiley & Sons, Ltd.
thereby overcome one of the limitations Pinheiro faced in using surrogate measures. CONFLICT OF INTEREST The Slone Epidemiology Center received research support from Roche for the conduct of the Accutane Survey, but the support ended a decade ago, and no support was received related to this letter. REFERENCES 1. Fain K, Alexander GC. Are Food and Drug Administration prescription drug safety plans working? A case study of isotretinoin. Pharmacoepidemiol Drug Saf 2013. doi:10.1002/pds.3514. 2. Pinheiro SP, Kang EM, Kim CY, Governale LA, Zhou EH, Hammad TA. Concomitant use of isotretinoin and contraceptives before and after iPledge in the United States. Pharmacoepidemiol Drug Saf 2013. doi:10.1002/pds.3481. 3. Mitchell AA, Van Bennekom CM, Louik C. A pregnancy-prevention program in women of childbearing age receiving isotretinoin. N Engl J Med 1995; 333: 101–6. 4. Proceedings of the FDA Dermatologic and Ophthalmic Drugs Advisory Committee Meeting September 2000. Mitchell AA, Van Bennekom CM. An assessment of the Accutane (isotretinoin) pregnancy-prevention program. http://www.fda. gov/ohrms/dockets/ac/00/slides/3639s1i.ppt (accessed 5 November 2013). 5. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology (16th edn). Irvington Publishers, Inc.: New York, 1994.
CARLA M. VAN BENNEKOM* ALLEN A. MITCHELL Slone Epidemiology Center at Boston University, Boston, Ma, USA *C. M. Van Bennekom, Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA 02215. E-mail: [email protected] †
The study cited in the letter to the editor was supported by Hoffmann-La Roche and was approved by the Boston University Medical Campus Institutional Review Board.
Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/pds.3573
LETTER TO THE EDITOR
Comments on: Are Food and Drug Administration prescription drug safety plans working? A case study of isotretinoin† Fain and Alexander1 commented on the database study by Pinheiro et al.2 that evaluated the effectiveness of iPledge, the Risk Evaluation and Mitigation Strategy (REMS) for isotretinoin, noting several limitations to the approach used. They also suggested that surveybased analyses are “fraught with methodological challenges.” Although their latter point may be true for some surveys, we believe that it is feasible to design and perform scientifically rigorous surveys to evaluate REMS. Indeed, from 1989 to 2003, the Slone Epidemiology Center conducted the Accutane Survey, an independent evaluation of the Pregnancy Prevention Program for Accutane (the first risk management program directed at pregnancy prevention), which was initiated in 1988. In our 1995 report in the New England Journal of Medicine on over 177 000 women3 (and in subsequent reports to the Food and Drug Administration on over 492 000 women4) who were followed during their isotretinoin treatment and for 6 months thereafter, we provided the distribution of the contraceptive methods reported by women in the Survey. In addition, the Survey asked about sexual activity, which allowed us to identify the proportion of women who reported abstinence. Importantly, because the Survey captured information on the primary outcome of interest—pregnancy—we were also able to estimate method-specific pregnancy rates, which were lower than those for typical use of each method.5 Motivation is a well-established predictor of successful contraception,5 and in the context of a REMS targeted toward pregnancy prevention, women may be more highly motivated to use contraception properly. Our findings suggest that method-specific failure rates derived from the population at large should not be generalized to REMS participants, making survey-specific rates a critical element in evaluating the effectiveness of a REMS. A carefully designed and rigorously executed Survey can provide information on pregnancies as well as the wide range of pregnancy prevention behaviors and
Copyright © 2014 John Wiley & Sons, Ltd.
thereby overcome one of the limitations Pinheiro faced in using surrogate measures. CONFLICT OF INTEREST The Slone Epidemiology Center received research support from Roche for the conduct of the Accutane Survey, but the support ended a decade ago, and no support was received related to this letter. REFERENCES 1. Fain K, Alexander GC. Are Food and Drug Administration prescription drug safety plans working? A case study of isotretinoin. Pharmacoepidemiol Drug Saf 2013. doi:10.1002/pds.3514. 2. Pinheiro SP, Kang EM, Kim CY, Governale LA, Zhou EH, Hammad TA. Concomitant use of isotretinoin and contraceptives before and after iPledge in the United States. Pharmacoepidemiol Drug Saf 2013. doi:10.1002/pds.3481. 3. Mitchell AA, Van Bennekom CM, Louik C. A pregnancy-prevention program in women of childbearing age receiving isotretinoin. N Engl J Med 1995; 333: 101–6. 4. Proceedings of the FDA Dermatologic and Ophthalmic Drugs Advisory Committee Meeting September 2000. Mitchell AA, Van Bennekom CM. An assessment of the Accutane (isotretinoin) pregnancy-prevention program. http://www.fda. gov/ohrms/dockets/ac/00/slides/3639s1i.ppt (accessed 5 November 2013). 5. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology (16th edn). Irvington Publishers, Inc.: New York, 1994.
CARLA M. VAN BENNEKOM* ALLEN A. MITCHELL Slone Epidemiology Center at Boston University, Boston, Ma, USA *C. M. Van Bennekom, Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA 02215. E-mail: [email protected] †
The study cited in the letter to the editor was supported by Hoffmann-La Roche and was approved by the Boston University Medical Campus Institutional Review Board.
