| Sumario: | Attention to publication diversity calls for broader topic inclusion by journals. Although general medical journals have distinct editorial policies, cross-journal differences remain underexplored. To compare trends of major research topics of clinical trials among leading general medical journals indexed in PubMed. A meta-research study was conducted for clinical trials in Lancet, NEJM, JAMA and BMJ from 1966 to 2022. Clinical trial numbers and their associated MeSH major topic categories were compared among journals, analyzing annual trends. We employed the Cochran-Armitage test for trend analysis. We discovered a total of 18925, 13899, 8630, and 5429 MeSH major topic categories from 7377, 5302, 2785, and 1853 published clinical trials in Lancet, NEJM, JAMA, and BMJ, respectively. Notable variations in topics were observed in 14 out of 19 MeSH major topic categories. Lancet and NEJM published approximately 30% of their clinical trials in the Chemicals and Drugs category and Disease category, surpassing JAMA's percentages of 22.5% and 27.7%, and BMJ's 14.0 and 25.4%, respectively (p < 0.0001). In contrast, NEJM published 3.1% of its clinical trials in the Health Care category, which was lower than Lancet's 4.5%, JAMA's 6.8%, and BMJ's 12.9% (p < 0.0001). There were distinct publication trends between NEJM and Lancet in seven MeSH major topic categories (p for trend < 0.0001). The topic mix of clinical trials differs systematically across four leading general medical journals from 1966 to 2022. These differences likely shape what evidence readers encounter in education. KEY MESSAGES: The NEJM published 34.7% of its clinical trials in the Disease category and 29.2% in the Chemicals and Drugs category, followed by Lancet, JAMA, and BMJ, which published 25.4% and 14.0% of their clinical trials in the same categories, respectively NEJM published only 3.1% of its clinical trials within the Health Care category, which was lower than 4.5% of Lancet, 6.8% for JAMA, and 12.9% for BMJ. When comparing all clinical trials in the PubMed database, NEJM demonstrated a higher-than-average proportion and an increasing trend of published trials in the Disease and Chemicals and Drugs categories, while BMJ exceeded the average publication in the Health Care category.
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