In silico prediction of clinical efficacy

Development of an Optimized Dose for Coformulation of Zidovudine with Drugs That Select for the K65R Mutation Using a Population Pharmacokinetic and Enzyme Kinetic Simulation Model

“…Pharmacokinetic and pharmacodynamic simulations are useful tools for consolidating all available drug information into a usable form and are gaining favor in the pharmaceutical industry to design clinical trials, since they allow detailed analyses of dosage regimens in silico before the actual studies are conducted (13,21,56,57,63,64). Rosario et al recently utilized clinical trial simulations to streamline the phase 2a development of the CCR5 receptor blocking agent maraviroc (75).…”

Harnessing Systems Biology Approaches to Engineer Functional Microvascular Networks

“…The development of new drugs is a risky and costly process; approximately half of all compounds entering phase II clinical trials will fail, resulting in SYSTEMS BIOLOGY AND ANGIOGENESISover $8 million per drug in amortized costs. 11 Thus, the application of systems biology approaches to drug discovery could streamline the entire process and save time, money, and resources. In this review, we have discussed both bottom-up and top-down systems biology approaches that have already been taken to identify pro-angiogenic drug candidates and engineer microvascular networks.…”

“…Even so, much attention is presently focused on preclinical studies that identify combinations of promising angiogenic agents, including the fibroblast growth factors (FGFs), platelet-derived growth factors (PDGFs), angiopoeitins (Ang-), and the transforming growth factors (TGFs). 6,9,10 However, as screening libraries of potential drug candidates and drug combinations experimentally is prohibitively time consuming, expensive, and relatively limitless in scope, 11 many researchers have begun to turn to computational approaches. 12 Over the past 20 years or more, numerous mathematical and computational models of angiogenesis have been built to enhance our understanding of the process (for detailed reviews of the subject, see Refs.…”

Clinical Trial Simulations for Dosage Optimization of Docetaxel in Patients with Liver Dysfunction, Based on a Log-binominal Regression for Febrile Neutropenia

“…Recently, clinical trial simulations, which is a Monte Carlo prediction technique based on population pharmacokinetic/pharmacodynamic (PPK/PD) models, have been utilized to estimate the outcome of clinical trials before embarking on an expensive clinical trial. 13,14) Therefore, this study carried out, for theˆrst time, clinical trial simulations in which the Japanese standard dose of docetaxel was compared with the reduced dose of the drug in cancer patients with liver dysfunction, from the standpoints of survival and the number of safety events (e.g., febrile neutropenia (FN)) as the primary and secondary endpoints, respectively. Several dose-response models (i.e., time to death, time to progression, time to drop-out, FN occurrence and neutropenia occurrence), when combined with models for the distribution of covariates in a target population and a particular study design, allow for the clinical trial simulations for that design.…”