Studies of Artificial Intelligence/Machine Learning Registered on ClinicalTrials.gov: Cross-Sectional Study With Temporal Trends, 2010-2023.

Background: The rapid growth of research in artificial intelligence (AI) and machine learning (ML) continues. However, it is unclear whether this growth reflects an increase in desirable study attributes or merely perpetuates the same issues previously raised in the literature.

Objective: This study aims to evaluate temporal trends in AI/ML studies over time and identify variations that are not apparent from aggregated totals at a single point in time.

Methods: We identified AI/ML studies registered on ClinicalTrials.gov with start dates between January 1, 2010, and December 31, 2023. Studies were included if AI/ML-specific terms appeared in the official title, detailed description, brief summary, intervention, primary outcome, or sponsors' keywords. Studies registered as systematic reviews and meta-analyses were excluded. We reported trends in AI/ML studies over time, along with study characteristics that were fast-growing and those that remained unchanged during 2010-2023.

Results: Of 3106 AI/ML studies, only 7.6% (n=235) were regulated by the US Food and Drug Administration. The most common study characteristics were randomized (56.2%; 670/1193; interventional) and prospective (58.9%; 1126/1913; observational) designs; a focus on diagnosis (28.2%; 335/1190) and treatment (24.4%; 290/1190); hospital/clinic (44.2%; 1373/3106) or academic (28%; 869/3106) sponsorship; and neoplasm (12.9%; 420/3245), nervous system (12.2%; 395/3245), cardiovascular (11.1%; 356/3245) or pathological conditions (10%; 325/3245; multiple counts per study possible). Enrollment data were skewed to the right: maximum 13,977,257; mean 16,962 (SD 288,155); median 255 (IQR 80-1000). The most common size category was 101-1000 (44.8%; 1372/3061; excluding withdrawn or missing), but large studies (n>1000) represented 24.1% (738/3061) of all studies: 29% (551/1898) of observational studies and 16.1% (187/1163) of trials. Study locations were predominantly in high-income countries (75.3%; 2340/3106), followed by upper-middle-income (21.7%; 675/3106), lower-middle-income (2.8%; 88/3106), and low-income countries (0.1%; 3/3106). The fastest-growing characteristics over time were high-income countries (location); Europe, Asia, and North America (location); diagnosis and treatment (primary purpose); hospital/clinic and academia (lead sponsor); randomized and prospective designs; and the 1-100 and 101-1000 size categories. Only 5.6% (47/842) of completed studies had results available on ClinicalTrials.gov, and this pattern persisted. Over time, there was an increase in not only the number of newly initiated studies, but also the number of completed studies without posted results.

Conclusions: Much of the rapid growth in AI/ML studies comes from high-income countries in high-resource settings, albeit with a modest increase in upper-middle-income countries (mostly China). Lower-middle-income or low-income countries remain poorly represented. The increase in randomized or prospective designs, along with 738 large studies (n>1000), mostly ongoing, may indicate that enough studies are shifting from an in silico evaluation stage toward a prospective comparative evaluation stage. However, the ongoing limited availability of basic results on ClinicalTrials.gov contrasts with this field's rapid advancements and the public registry's role in reducing publication and outcome reporting biases.