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Accelerated Approval of 17α-Hydroxyprogesterone Caproate: A Cautionary Tale.
Obstet Gynecol. 2020 May; 135(5):1207-1213.OG

Abstract

Before 2011, 17α-hydroxyprogesterone caproate (17P) was used to prevent recurrent preterm birth in women with singleton pregnancies and was compounded at a low cost (∼$15 per injection). In 2011, the U.S. Food and Drug Administration (FDA) approved a commercial version of 17P (trade name "Makena") through their Accelerated Approval Program, and the price of 17P subsequently increased by nearly 100-fold. This approval was largely based on a methodologically limited, placebo-controlled trial, which found that although 17P significantly reduced preterm births, the placebo group had significantly more participants with a history of preterm birth, potentially confounding the results. The FDA required a confirmatory trial for continued approval that demonstrated clinical benefit. Eight years after accelerated approval, the confirmatory trial, PROLONG (Progestin's Role in Optimizing Neonatal Gestation), found no evidence of an effect of Makena for reducing recurrent preterm birth or perinatal mortality. Trial completion triggered an automatic review of Makena by an advisory committee, which voted 9-7 to recommend revoking approval of Makena for preterm birth. Although the FDA created the Accelerated Approval Program to introduce therapies for serious conditions that lacked treatment options, Makena is an example of the limitations of this program. We encourage the FDA to re-evaluate their program and consider improvements, such as shorter timeframes to complete confirmatory trials, potentially revoking approval if the studies are not completed within a predefined timeframe, and to hold manufacturers responsible, in part, for the costs of therapy if they cannot prove a clinical benefit.

Authors+Show Affiliations

Center for Evidence-based Policy at Oregon Health & Science University, Portland, Oregon.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32282587

Citation

Godlewski, Bethany J., et al. "Accelerated Approval of 17α-Hydroxyprogesterone Caproate: a Cautionary Tale." Obstetrics and Gynecology, vol. 135, no. 5, 2020, pp. 1207-1213.
Godlewski BJ, Sobolik LI, King VJ, et al. Accelerated Approval of 17α-Hydroxyprogesterone Caproate: A Cautionary Tale. Obstet Gynecol. 2020;135(5):1207-1213.
Godlewski, B. J., Sobolik, L. I., King, V. J., & Harrod, C. S. (2020). Accelerated Approval of 17α-Hydroxyprogesterone Caproate: A Cautionary Tale. Obstetrics and Gynecology, 135(5), 1207-1213. https://doi.org/10.1097/AOG.0000000000003787
Godlewski BJ, et al. Accelerated Approval of 17α-Hydroxyprogesterone Caproate: a Cautionary Tale. Obstet Gynecol. 2020;135(5):1207-1213. PubMed PMID: 32282587.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Accelerated Approval of 17α-Hydroxyprogesterone Caproate: A Cautionary Tale. AU - Godlewski,Bethany J, AU - Sobolik,Lily I, AU - King,Valerie J, AU - Harrod,Curtis S, PY - 2020/4/14/pubmed PY - 2020/9/9/medline PY - 2020/4/14/entrez SP - 1207 EP - 1213 JF - Obstetrics and gynecology JO - Obstet Gynecol VL - 135 IS - 5 N2 - Before 2011, 17α-hydroxyprogesterone caproate (17P) was used to prevent recurrent preterm birth in women with singleton pregnancies and was compounded at a low cost (∼$15 per injection). In 2011, the U.S. Food and Drug Administration (FDA) approved a commercial version of 17P (trade name "Makena") through their Accelerated Approval Program, and the price of 17P subsequently increased by nearly 100-fold. This approval was largely based on a methodologically limited, placebo-controlled trial, which found that although 17P significantly reduced preterm births, the placebo group had significantly more participants with a history of preterm birth, potentially confounding the results. The FDA required a confirmatory trial for continued approval that demonstrated clinical benefit. Eight years after accelerated approval, the confirmatory trial, PROLONG (Progestin's Role in Optimizing Neonatal Gestation), found no evidence of an effect of Makena for reducing recurrent preterm birth or perinatal mortality. Trial completion triggered an automatic review of Makena by an advisory committee, which voted 9-7 to recommend revoking approval of Makena for preterm birth. Although the FDA created the Accelerated Approval Program to introduce therapies for serious conditions that lacked treatment options, Makena is an example of the limitations of this program. We encourage the FDA to re-evaluate their program and consider improvements, such as shorter timeframes to complete confirmatory trials, potentially revoking approval if the studies are not completed within a predefined timeframe, and to hold manufacturers responsible, in part, for the costs of therapy if they cannot prove a clinical benefit. SN - 1873-233X UR - https://www.unboundmedicine.com/medline/citation/32282587/Accelerated_Approval_of_17α_Hydroxyprogesterone_Caproate:_A_Cautionary_Tale_ L2 - https://doi.org/10.1097/AOG.0000000000003787 DB - PRIME DP - Unbound Medicine ER -