Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory autoimmune disease in childhood, significantly contributing to both short- and long-term disability. While certain human leukocyte antigen (HLA) class II alleles are known to be associated with specific subgroups of JIA, emerging evidence suggests a strong correlation between these alleles and treatment response. This study involved 143 JIA patients diagnosed according to International League of Associations for Rheumatology criteria. Each patient underwent HLA class II typing, including HLA-B27, as well as tests for rheumatoid factor (RF) and antinuclear antibodies (ANA). Comprehensive rheumatological assessments were conducted at diagnosis, with follow-ups at three and six months post-onset. After six months of methotrexate (MTX) treatment, patients were categorized as responders or non-responders. Responders achieved clinically inactive disease based on the American College of Rheumatology Provisional Criteria for Defining Clinical Inactive Disease and Clinical Remission. Non-responders, who did not reach clinically inactive disease after six months of treatment, required the addition of another non-biological disease-modifying antirheumatic drug (DMARD) or a biological DMARD. Our analysis revealed that the HLA-DRB1*01 allele is a significant prognostic marker for therapeutic response, predicting therapeutic resistance (P=0.01). The most prevalent HLA-DRB1 alleles in the treatment-resistant group were HLA-DRB1*08:11 (11.3%), HLA-DRB1*01:01 (8.5%), HLA-DRB1*01:13, HLA-DRB1*04:11 (7%), HLA-DRB1*08:13, and HLA-DRB1*08:15 (4.2%). These findings highlight the critical role of HLA class II alleles in pediatric rheumatology, particularly in relation to treatment response and disease prognosis. In the era of personalized medicine, understanding the genetic contributions to treatment response and outcomes in JIA patients is essential. A key limitation of this study was the lack of comparison of treatment responses across different JIA subtypes. Future studies should prioritize evaluating MTX efficacy within specific JIA subgroups to enable a more tailored understanding of its effectiveness.

Background Non-publication, incomplete publication and excessively slow publication of clinical trial outcomes contribute to research waste and can harm patients. While research waste in German academic trials is well documented, research waste in Germany related to a specific disease area across non-commercial and commercial sponsors has not previously been assessed. Methods In this cohort study, we used public records from three clinical trial registries to identify 70 completed or terminated clinical trials involving women with metastatic breast cancer with trial sites in Germany. We then searched registries and the literature for trial outcomes and contacted sponsors about unreported studies. Results We found that 66/70 trials (94.3%) had made their results public. Only 13/70 (18.6%) trials had reported results within one year of completion as recommended by the World Health Organisation (WHO). The outcomes of 4/70 trials (5.7%) had not been made public at all, but only one of those trials had recruited a significant number of patients. Conclusions Discussions about research waste in clinical trials commonly focus on weakly designed or unreported trials. We believe that late reporting of results is another important form of research waste. In addition, a discussion regarding the appropriate ethical and legal rules for reporting the results of terminated trials might add value. German legislation now requires sponsors to upload the results of some clinical trials onto a trial registry within one year of trial completion, but these laws only cover around half of all trials. Our findings highlight the potential benefits of extending the scope of national legislation to cover all interventional clinical trials involving German patients.

Abstract Objectives: Assess the extent to which the clinical trial registration and reporting policies of 25 of the world’s largest public and philanthropic medical research funders meet best practice benchmarks as stipulated by the 2017 WHO Joint Statement, and document changes in the policies and monitoring systems of 19 European funders over the past year. Design, Setting, Participants: Cross-sectional study, based on assessments of each funder’s publicly available documentation plus validation of results by funders. Our cohort includes 25 of the largest medical research funders in Europe, Oceania, South Asia, and Canada. Interventions: Scoring all 25 funders using an 11-item assessment tool based on WHO best practice benchmarks, grouped into three primary categories: trial registries, academic publication, and monitoring, plus validation of results by funders. Main outcome measures: How many of the 11 WHO best practice items each of the 25 funders has put into place, and changes in the performance of 19 previously assessed funders over the preceding year. Results: The 25 funders we assessed had put into place an average of 5/11 (49%) WHO best practices. Only 6/25 funders (24%) took the PI’s past reporting record into account during grant application reviews. Funders’ performance varied widely from 0/11 to 11/11 WHO best practices adopted. Of the 19 funders for which 2021(2) baseline data was available, 10/19 (53%) had strengthened their policies over the preceding year. Conclusions: Most medical research funders need to do more to curb research waste and publication bias by strengthening their clinical trial policies.

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