Update on the Clinical Trials Landscape: Analysis of ClinicalTrials.gov Registration Data: 2000-2020

Abstract Background: The clinical trials landscape has evolved over the last two decades, shaped by advances in therapeutics and drug development, the emerging role of technology in trials, innovation in trial design and methods, and increased access to clinical trial information and data through registration. The ClinicalTrials.gov website was launched in 2000 by the NIH National Library of Medicine and is the largest clinical trials registry worldwide. The purpose of this cross-sectional analysis is to describe the composition and methodologic features of clinical trials as registered on ClinicalTrials.gov, and to identify key trends over time. Methods: We analyzed data from the publicly available CTTI AACT database, focusing on trials (interventional studies) started between 1 January, 2000 through 31 December, 2020. Characteristics of trial design (e.g., randomization, use of masking, sample size), eligibility criteria, outcome types, interventions, conditions, and results reporting were summarized over time. Results: There were 271,272 trials included in the analysis, of which 57% were completed. Most trials were randomized (66%), single site (68.7%), funded by other sources (69.0%) and had sample sizes less than 100 participants (62%). There was a significant increase in trials without FDA-defined phases ("Phase N/A") observed over time as a result of evolving trial designs, interventions and outcome types. Over 3,000 trials related to COVID-19 started in 2020 alone. Conclusions: ClinicalTrials.gov is a powerful tool that provides a window into the past, present, and future of the clinical research enterprise. Understanding characteristics and trends of trials can inform future trial design and clinical decision making.