Objective To know the current status of multinational clinical trials (MNCTs) in East Asia, and to find the characters of MNCTs in countries/regions. Methods We downloaded the trial records of East Asia on May 8, 2008 from ClinicalTrials.gov and analyzed the data. Results The number of clinical trials sponsored by industry was 125 in China Mainland, 196 in Taiwan, 134 in Hong Kong, 264 in Korea, and 231 in Japan, respectively. Of the total 654 clinical trials in East Asia, 307 (47%) trials were MNCTs, most of which were conducted by Euro-American pharmaceutical companies, such as Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi-Aventis and Bristol-Myers Squibb. Main therapeutic areas were cancer, followed by CNS diseases, cardiovascular diseases, infectious diseases, diabetes mellitus and respiratory diseases. Trials in phaseⅢwere 198 (65%), in phaseⅣ32 (10%), others in phaseⅡorⅠ. One hundred and ninety trials (62%) were double-blind clinical trials, about half of them using placebo. The characters of clinical trials in China were: ① Most of MNCTs were large scale trials with big sample size and many study sites; ② Most of local trials were phase Ⅲ trials; ③ There were no phase Ⅰ trials. The characters in Taiwan, Hong Kong and Korea were: 1) Most of the trials (84% in Taiwan and 93% in Hong Kong, 72% in Korea) were MNCTs, 2) A lot of large scale trials were conducted with each other. The characters of clinical trials in Japan were: ① MNCTs were only 17%, ② Large scale trials were fewer. Conclusion In East Asia, MNCTs are developing because of the initiation of the Europe and America pharmaceutical giants. It seems that the regulation in each country influence the development pattern of East Asia.
ObjectiveTo investigate the potential causal relationships between blood metabolites and diabetic kidney disease (DKD) in East Asian populations and to identify ethnicity-specific metabolic risk factors. MethodsWe utilized summary-level data from genome-wide association studies (GWAS) comprising 112 blood metabolites in a Chinese population and DKD in an East Asian population. Genetic variants significantly associated with metabolites were selected as instrumental variables. We performed bidirectional two-sample Mendelian randomization (MR) analyses, with primary causal estimates derived using the inverse variance weighted (IVW) method. Sensitivity analyses included MR-Egger, weighted median, and Bayesian-weighted MR (BWMR). Metabolites showing suggestive evidence of association were further investigated using multivariable MR and colocalization analysis. Robustness of findings was assessed via Cochran’s Q test for heterogeneity, the MR-Egger intercept test for horizontal pleiotropy, and leave-one-out analysis. ResultsForward MR analysis identified suggestive associations between elevated levels of tyrosine, glutamine, leucine, and the albumin-to-globulin ratio with DKD risk. In multivariable MR analysis, leucine (OR=0.084, P=0.026) and the albumin-to-globulin ratio (OR=0.161, P=0.048) retained statistically significant independent protective effects against DKD, whereas the associations for tyrosine and glutamine were attenuated. Colocalization analysis did not support the presence of shared underlying causal genetic variants between the identified metabolites and DKD. Sensitivity analyses revealed no significant evidence of heterogeneity or horizontal pleiotropy. Reverse MR analysis did not suggest the presence of reverse causation. ConclusionOur findings suggest that leucine and the albumin-to-globulin ratio may act as independent protective factors against DKD in East Asian populations. These results provide new genetic insights into the ethnicity-specific metabolic mechanisms contributing to DKD.