The distribution of non-small cell lung cancer early phase clinical trial sites within and outside the United States

Recent regulatory guidance outlining considerations for bringing clinical trials into routine care and closer to where US patients live highlights the importance the U.S. Food and Drug Administration places on the applicability of trial data to real-world patient populations. However, recent Oncologic Drugs Advisory Committee meetings reveal that insufficient enrollment of US patients remains an issue in oncology trials, calling into question the relevance and representativeness of trial results to the US patient population. In addition to factors like long timelines to trial accrual and completion, trial site saturation has been anecdotally cited as a factor pushing trials outside of the US. To understand recent trends in the locations of clinical trial sites, LUNGevity Foundation used lung cancer as a use case to assess the distribution of early phase clinical trial sites within and outside of the US over time. This quantitative descriptive assessment utilized ClinicalTrials.gov data to analyze interventional, industry-sponsored clinical trials for non-small cell lung cancer (NSCLC) in early phase I or phase I opening in January 2020-December 2024. Unique sites were defined as a single address where at least one trial, identified by a unique NCT number, was located. Trial instances were defined as the initiation of a unique trial at a unique site. Overall, 555 trials opened within the study period for a total of 8,393 trial instances across all sites in 47 countries. Trial sites were largely located in the US (45%), China (11%), Spain (8%), Korea (5%), France (4%), and Australia (4%). While the number of trials opening increased until 2024, the number of unique trial sites and trial instances, both globally and within the US, started decreasing in 2022 and continued to decrease through 2024. Notably, the number of US sites with at least one trial opening markedly decreased during the entire study period (395 sites in 2020 to 223 sites in 2024). However, the sites with the highest trial volume (top 20 sites had at least 27 trials open in the study period) did not see this decrease over time. This analysis demonstrates a concerning trend towards trial consolidation at top performing sites in the US, further supporting concerns regarding site saturation and conflicting with appeals to decentralize and move trials into the community. Further work is needed to understand if these trends persist in later phase clinical trials and other tumor types.