Acetyl Salicylic Acid [OVA]

Introduction: In biomarker-driven clinical trials, translational strategies typically involve moving findings from animal experiments to human trials. Typically, the translation is static, using a fixed model derived from animal experiments for the duration of the trial. Bayesian designs, capable of incorporating information external to the experiment, provide a dynamic translational strategy. This article demonstrates an example of such a dynamic Bayesian strategy in a clinical trial. Methods: This study explored the effect of a personalized dose of fish oil for reducing prostaglandin E-2, an inflammatory marker linked to colorectal cancer. A Bayesian design was imple- mented for the dose-finding algorithm that adaptively updated a dose-response model derived from a previously completed animal study during the clinical trial. In the initial stages of the trial, the dose-response model parameters were estimated from the rodent data. The model was updated following a Bayesian algorithm after data on every 10-15 subjects were obtained until the model stabilized. Subjects were enrolled in the study between 2013 and 2015, and the data analysis was carried out in 2016. Results: The 3 dosing models were used for groups of 16, 15, and 15 subjects. The mean target dose significantly decreased from 6.63 g/day (Model 1) to 4.06 g/day (Model 3) (p=0.001). Com- pared with the static strategy of dosing with a single model, the dynamic modeling reduced the dose significantly by about 1.38 g/day on average. Conclusions: A Bayesian design was effective in adaptively revising the dosing algorithm, resulting in a lower pill burden. (C) 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Purpose Prior work has shown that higher circulating concentrations of fibroblast growth factor-21 (FGF-21) are associated with an increased likelihood of developing colorectal cancer. We conducted a prospective study to assess the relationship between circulating FGF-21 and odds of developing early neoplastic lesions in the colorectum. Methods A total of 94 study participants were included from the ursodeoxycholic acid (UDCA) trial, a phase III, randomized, double-blind, placebo-controlled clinical trial of the effect of 8-10 mg/kg of body weight UDCA vs. placebo. Logistic regression analyses were conducted to evaluate the association between baseline FGF-21 concentrations and odds of developing a metachronous adenoma. Results Of the characteristics compared across tertiles of FGF-21 concentrations, including age, race, sex, BMI, and other variables, only a previous personal history of colorectal polyps prior to entry into the UDCA trial was statistically significantly related to FGF-21 levels, with a proportion of 26.7%, 56.7%, and 50.0% across the first, second, and third tertiles, respectively (p < 0.05). Higher circulating concentrations of FGF-21 were statistically significantly associated with greater odds of developing a metachronous colorectal adenoma. After adjusting for potential confounders and when compared with the lowest tertile of FGF-21, the adjusted ORs (95% CIs) for metachronous colorectal adenoma in the second and third tertiles were 4.72 (95% CI, 1.42-15.72) and 3.82 (95% CI, 1.15-12.68), respectively (ptrend < 0.05). Conclusion Our results reveal for the first time that, in addition to a recently discovered association with colorectal cancer, circulating FGF-21 concentrations are significantly and directly associated with odds of developing metachronous colorectal adenoma.