Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School-UTHealth, Houston, and the Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, Texas; and Das Consulting, Guerneville, California.
Obstet Gynecol. 2020 Sep;136(3):622-627. doi: 10.1097/AOG.0000000000003991.
U.S. Food and Drug Administration (FDA)-approved 17α-hydroxyprogesterone caproate therapy is currently available to reduce recurrent preterm birth in the United States. This commentary reviews the original landmark Meis trial ("Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate"), which led to conditional approval of 17α-hydroxyprogesterone caproate by the FDA in 2011. The recent PROLONG (Progestin's Role in Optimizing Neonatal Gestation) trial failed to confirm the original findings. The Meis trial was rigorously designed and conducted, with highly statistically significant results that should not be undermined by the negative results of PROLONG. Given that the United States has among the highest preterm birth rates in the world and that the predominant enrollment in PROLONG was outside the United States, the results of the "old" Meis trial should not be summarily dismissed. It would be detrimental to high-risk pregnant patients to inappropriately prioritize results of PROLONG over the Maternal-Fetal Medicine Units Network's Meis trial (funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development). We assert PROLONG was underpowered, based on substantially lower observed preterm birth rates than anticipated, and therefore was a false-negative study, rather than the Meis trial being a false-positive study. Careful assessment of these two trials is critical as removal of 17α-hydroxyprogesterone caproate from the U.S. marketplace may have substantial effects on public health.
美国食品和药物管理局（FDA）批准的 17α-羟孕酮己酸酯治疗目前可用于减少美国的复发性早产。本评论回顾了最初的里程碑式 Meis 试验（“通过 17α-羟孕酮己酸酯预防复发性早产”），该试验导致 FDA 在 2011 年有条件批准 17α-羟孕酮己酸酯。最近的 PROLONG（孕激素在优化新生儿胎龄中的作用）试验未能证实最初的发现。Meis 试验设计严谨，结果具有高度统计学意义，不应因 PROLONG 的负面结果而受到损害。鉴于美国的早产率在世界上最高，而且 PROLONG 的主要入组人群在美国之外，“旧”Meis 试验的结果不应被草率驳回。如果不恰当地将 PROLONG 的结果置于 Maternal-Fetal Medicine Units Network 的 Meis 试验（由 Eunice Kennedy Shriver National Institute of Child Health and Human Development 资助）之上，对高危孕妇患者是有害的。我们断言 PROLONG 的效力不足，这是基于观察到的早产率远低于预期，因此是一项假阴性研究，而不是 Meis 试验是一项假阳性研究。对这两项试验进行仔细评估至关重要，因为将 17α-羟孕酮己酸酯从美国市场撤出可能对公共卫生产生重大影响。
