<p><strong>Importance: </strong>Timely access to clinically appropriate obstetric services is critical to the provision of high-quality perinatal care.</p>
<p><strong>Objective: </strong>To examine the geographic distribution, proximity, and urban adjacency of US obstetric hospitals by annual birth volume.</p>
<p><strong>Design, Setting, and Participants: </strong>This retrospective population-based cohort study identified US hospitals with obstetric services using the American Hospital Association (AHA) Annual Survey of Hospitals and Centers for Medicare & Medicaid provider of services data from 2010 to 2018. Obstetric hospitals with 10 or more births per year were included in the study. Data analysis was performed from November 6, 2020, to April 5, 2021.</p>
<p><strong>Exposure: </strong>Hospital birth volume, defined by annual birth volume categories of 10 to 500, 501 to 1000, 1001 to 2000, and more than 2000 births.</p>
<p><strong>Main Outcomes and Measures: </strong>Outcomes assessed by birth volume category were percentage of births (from annual AHA data), number of hospitals, geographic distribution of hospitals among states, proximity between obstetric hospitals, and urban adjacency defined by urban influence codes, which classify counties by population size and adjacency to a metropolitan area.</p>
<p><strong>Results: </strong>The study included 26 900 hospital-years of data from 3207 distinct US hospitals with obstetric services, reflecting 34 054 951 associated births. Most infants (19 327 487 [56.8%]) were born in hospitals with more than 2000 births/y, and 2 528 259 (7.4%) were born in low-volume (10-500 births/y) hospitals. More than one-third of obstetric hospitals (37.4%; 10 064 hospital-years) were low volume. A total of 46 states had obstetric hospitals in all volume categories. Among low-volume hospitals, 18.9% (1904 hospital-years) were not within 30 miles of any other obstetric hospital and 23.9% (2400 hospital-years) were within 30 miles of a hospital with more than 2000 deliveries/y. Isolated hospitals (those without another obstetric hospital within 30 miles) were more frequently low volume, with 58.4% (1112 hospital-years) located in noncore rural areas.</p>
<p><strong>Conclusions and Relevance: </strong>In this cohort study, marked variations were found in birth volume, geographic distribution, proximity, and urban adjacency among US obstetric hospitals from 2010 to 2018. The findings related to geographic isolation and rural-urban distribution of low-volume obstetric hospitals suggest the need to balance proximity with volume to optimize effective referral and access to high-quality perinatal care.</p>
<p><strong>BACKGROUND/AIMS: </strong>Noninferiority clinical trials are susceptible to false confirmation of noninferiority when the intention-to-treat principle is applied in the setting of incomplete trial protocol adherence. The risk increases as protocol adherence rates decrease. The objective of this study was to compare protocol adherence and hypothesis confirmation between superiority and noninferiority randomized clinical trials published in three high impact medical journals. We hypothesized that noninferiority trials have lower protocol adherence and greater hypothesis confirmation.</p>
<p><strong>METHODS: </strong>We conducted an observational study using published clinical trial data. We searched PubMed for active control, two-arm parallel group randomized clinical trials published in JAMA: The Journal of the American Medical Association, The New England Journal of Medicine, and The Lancet between 2007 and 2017. The primary exposure was trial type, superiority versus noninferiority, as determined by the hypothesis testing framework of the primary trial outcome. The primary outcome was trial protocol adherence rate, defined as the number of randomized subjects receiving the allocated intervention as described by the trial protocol and followed to primary outcome ascertainment (numerator), over the total number of subjects randomized (denominator). Hypothesis confirmation was defined as affirmation of noninferiority or the alternative hypothesis for noninferiority and superiority trials, respectively.</p>
<p><strong>RESULTS: </strong>Among 120 superiority and 120 noninferiority trials, median and interquartile protocol adherence rates were 91.5 [81.4-96.7] and 89.8 [83.6-95.2], respectively; = 0.47. Hypothesis confirmation was observed in 107/120 (89.2%) of noninferiority and 64/120 (53.3%) of superiority trials, risk difference (95% confidence interval): 35.8 (25.3-46.3), < 0.001.</p>
<p><strong>CONCLUSION: </strong>Protocol adherence rates are similar between superiority and noninferiority trials published in three high impact medical journals. Despite this, we observed greater hypothesis confirmation among noninferiority trials. We speculate that publication bias, lenient noninferiority margins and other sources of bias may contribute to this finding. Further study is needed to identify the reasons for this observed difference.</p>