Geographic shifts in antibacterial drug clinical trial enrollment: implications for generalizability.
Clin Infect Dis. 2020 Mar 12;:
Authors: Bart SM, Farley JJ, Bala S, Amini T, Cox E
BACKGROUND: As drug development has globalized, trials have increasingly enrolled subjects 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 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 subjects). 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 subjects had the lowest proportion of subjects with prior antibacterial drug therapy. For ABSSSI trials, North American subjects more commonly reported intravenous drug use. Microbiological differences relative to North America included a greater proportion of Klebsiella pneumoniae among Asian cIAI isolates (20.3% vs 9.0%, p=0.0057), a higher proportion of cephalosporin resistance in South American Enterobacteriaceae cUTI isolates (26.8% vs 15.7%, p=0.044), and a lower proportion of Staphylococcus aureus in Eastern European ABSSSI isolates (43.7% vs 61.9%, p<0.0001).
CONCLUSION: 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.
PMID: 32161946 [PubMed - as supplied by publisher]