Oncology clinical trials are increasingly conducted globally, with recent trends indicating a growing share of trial activity outside of the U.S. In 2025, 80% of patients in pivotal trials supporting novel cancer drug approvals by the FDA were enrolled outside of the U.S.1 Such global trials are critical for generating data across distinct regional and country-specific patient populations and care settings, ensuring the evidence underlying global regulatory approvals reflects these varied contexts. With the globalization of oncology research, it is increasingly important to ensure that the U.S. continues to be a reliable and competitive environment in which global trials can be initiated, scaled, and completed. This requires examining factors driving the shift in trial conduct, including site activation and trial start-up processes, and identifying opportunities to streamline U.S. trial implementation and operations. Doing so can help innovative treatments reach patients here while ensuring that the evidence generated is sufficiently representative of U.S. patients to support regulatory review and decision-making.
Characterizing Site Activation & Trial Start-Up Dynamics
To characterize trial start-up dynamics across different regions, Friends of Cancer Research (Friends) conducted a survey of eight pharmaceutical companies with global oncology drug development programs. Survey milestones and metrics were selected and defined based on industry feedback to accurately reflect trial start-up dynamics. (Figure 1) Companies submitted aggregated trial start-up timeline data for pivotal oncology clinical trials conducted globally from 2020 to 2025. The analysis evaluated not only how quickly the first trial site was opened, but also how efficiently sponsors were able to expand from initial activation to a broader network of operational sites.
Timelines
The U.S. excels at initial site activation, opening first clinical trial sites faster than in any other country or region. The first U.S. sites were activated a median of 124 days after final protocol approval, compared to 308 days for all ex-U.S. sites. However, the U.S. lagged in scaling up site activation, requiring substantially longer than other regions to activate 75% of planned sites and to reach the first patient in (FPI). After first-site activation, U.S. trials required a median of 309 days to activate 75% of planned sites, compared with 34-126 days across other regions. U.S. sites also required a median of 93 days to enroll the first patient, compared with 43-60 days in other regions. (Figure 2) These findings suggest that a primary challenge for U.S. trials is achieving efficient activation across a broad network of sites.
Bottlenecks in U.S. Site Activation
Sponsors reported the primary bottlenecks for U.S. trial start-up were prolonged budget negotiations, redundant/iterative local review processes, and site resource limitations. In particular, continued reliance on local IRBs and independent committees for reviewing protocol amendments and other trial documentation introduces redundant, sequential steps that delay U.S. site activation.Implications for Future U.S. Trial Infrastructure and Innovation
These bottlenecks contribute to delayed start-up timelines and may influence where sponsors prioritize trial activation, enrollment, and longer-term investment in clinical research infrastructure. The U.S. has long been the leader in approving innovative treatments, including global first-in-class medicines. For these drugs to reach patients early in the U.S., regulators require trials and data representative of U.S. patients and care settings. Recent studies indicate trial activity and approval volume are shifting globally 2,3,4, and survey results indicate ex-U.S. regions scale sites faster. Potential opportunities include broader and more consistent use of central IRBs and centralized amendment review, standardized contracting and budgeting approaches, parallel rather than sequential institutional reviews, and clearer expectations for site readiness. Examining trial implementation and operations will be essential to ensuring that innovative treatments continue to be studied and reach patients in the U.S.1 Drug Trials Snapshots Summary Report 2025. FDA Center for Drug Evaluation and Research. https://www.fda.gov/media/193285/download?attachment
2 Grace Collins, Divita Pandita, Hillary Andrews, Bernat Navarro-Serer, Elena Levi-D’Ancona, Jeff Allen, Mark Stewart, A cross-national review of novel oncology approvals in the United States and China (2020-2025), Health Affairs Scholar, Volume 4, Issue 7, July 2026, qxag183, https://doi.org/10.1093/haschl/qxag183
3 Pazdur R, Usdin S. The Geography of Pharmaceutical Innovation: The US and China in a New World Order. JAMA. 2026;335(15):1309–1310. doi:10.1001/jama.2026.2390
4 Zhu, X. and Xiao, D. (2026), Innovative Drugs Approved in China After Registration Classification Reform: Current Status, Disparities, and Challenges. Clin Pharmacol Ther, 119: 470-479. https://doi.org/10.1002/cpt.70084