FDA approved vs. Pharmacy compounded 17-OHPC—current issues for obstetricians to consider in reducing recurrent preterm birth

Resistance to Change

“…A large multicenter international study under the direction of the Pregnancy Research Branch of NIH based at Wayne State University demonstrated significant efficacy of such suppositories [69][70][71][72][73][74][75]. Despite that, the US Preventative Services Task Force (USPTF) refused to endorse their use after performing a very unconventional and convoluted statistical analysis in which the USPTF ignored significant components of the study data and focused on only a subset (following the findings of one US-based center rather than the findings of three European centers) [69][70][71][72][73][74][75]. Concurrently, a company produced Makena and obtained FDA approval for weekly injections of 17α-hydroxyprogesterone caproate under an Accelerated Approval Program -set up to permit rapid development of drugs that addressed serious medical problems.…”

“…Assessment of PTB treatments requires multiple levels of queries. First, the idea that a serious problem like PTB, with risks in part determined by a multitude of social determinants of health, could be treated as a single problem amenable to any single therapy is certainly not a given [69][70][71][72][73][74][75]. Second, the variability in quality of compounded treatments (which are not as tightly controlled as pharmaceutical company products but in which physicians had considerable confidence) needed to be understood.…”

“…Furthermore, the study ran almost 5 years longer than the average for such studies. The FDA emphasized the need for standardization, cited the recall problems of compounded 17-OHPC, and downplayed the utility of vaginal suppositories [76][77][78]. These approaches conflicted with the confidence that many physicians had developed in these treatments.…”

17-Alpha-Hydroxyprogesterone vs. Placebo for Preventing of Recurrent Preterm Birth: A Systematic Review and Meta-Analysis of Randomized Trials

“…The use of vaginal progesterone demonstrated a significant reduction in the risk of PTB ( 3 ), and also the use of 17-alpha-hydroxyprogesterone caproate (17-OHPC), which showed promising results ( 4 ). In 2011, the Food and Drug Administration (FDA) approved 17-OHPC for reducing the risk of PTB among pregnant women with a singleton pregnancy who have a history of singleton spontaneous PTB, and it was the only approved medication for this indication ( 5 ). However, in 2020, 17-OHPC (Makena) was recommended to be withdrawn from the market after failing the PROLONG trial to confirm the clinical benefit in reducing the risk of PTB and the benefit to neonates ( 6 , 7 ).…”