抗菌药物临床试验入组的地域变化：对普遍性的影响。

Geographic Shifts in Antibacterial Drug Clinical Trial Enrollment: Implications for Generalizability.

机构信息

Office of Infectious Diseases, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, USA.

出版信息

Clin Infect Dis. 2021 Apr 26;72(8):1422-1428. doi: 10.1093/cid/ciaa246.

DOI:10.1093/cid/ciaa246

PMID:32161946

Abstract

BACKGROUND

As drug development has globalized, trials have increasingly enrolled participants from all parts of the world rather than just the United States and Western Europe. For antibacterial drug trials, understanding enrollment trends and regional differences is important for generalizability considerations.

METHODS

We retrospectively analyzed 42 phase 3 trials submitted to the US Food and Drug Administration after 2001 for complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), community-acquired bacterial pneumonia (CABP), and acute bacterial skin and skin structure infection (ABSSSI) (n = 29 282 participants). Enrollment numbers, demographics, clinical characteristics, and microbiological data were compared to identify temporal and geographic trends.

RESULTS

For cUTI, cIAI, and CABP trials, Eastern European enrollment greatly increased over the study period. For ABSSSI trials, North American enrollment increased. Demographic characteristics and regional microbiology among regions were broadly similar with several exceptions. For cIAI trials, Eastern European participants had the lowest proportion of participants with prior antibacterial drug therapy. For ABSSSI trials, North American participants more commonly reported intravenous drug use. Microbiological differences relative to North America included a greater proportion of Klebsiella pneumoniae among Asian cIAI isolates (17.8% vs 9.0%, P = .0057), a higher proportion of cephalosporin resistance in South American Enterobacteriaceae cUTI isolates (26.8% vs 15.7%, P = .044), and a lower proportion of Staphylococcus aureus in Eastern European ABSSSI isolates (43.7% vs 61.9%, P < .0001).

CONCLUSIONS

Geographic trends in recruitment for recent antibacterial clinical trials differ by indication. Regional similarities in demographic characteristics and microbiology across regions lessen concerns regarding generalizability due to shifting enrollment trends.

摘要

背景

随着药物研发的全球化，临床试验越来越多地招募来自世界各地的参与者，而不仅仅是美国和西欧。对于抗菌药物试验，了解招募趋势和区域差异对于考虑推广性非常重要。

方法

我们回顾性分析了 2001 年后向美国食品和药物管理局提交的 42 项 3 期临床试验，用于治疗复杂尿路感染（cUTI）、复杂腹腔内感染（cIAI）、社区获得性细菌性肺炎（CABP）和急性细菌性皮肤和皮肤结构感染（ABSSSI）（n=29282 名参与者）。比较了招募人数、人口统计学特征、临床特征和微生物学数据，以确定时间和地理趋势。

结果

对于 cUTI、cIAI 和 CABP 试验，东欧的招募人数在研究期间大幅增加。对于 ABSSSI 试验，北美招募人数增加。各地区的人口统计学特征和区域微生物学基本相似，但也存在一些例外。对于 cIAI 试验，东欧参与者接受过抗菌药物治疗的比例最低。对于 ABSSSI 试验，北美的参与者更常报告静脉内药物使用。与北美相比，微生物学差异包括亚洲 cIAI 分离株中肺炎克雷伯菌的比例更高（17.8%比 9.0%，P=0.0057），南美肠杆菌科 cUTI 分离株中头孢菌素耐药的比例更高（26.8%比 15.7%，P=0.044），东欧 ABSSSI 分离株中金黄色葡萄球菌的比例更低（43.7%比 61.9%，P<0.0001）。