ABSTRACT
Quantitative systems pharmacology (QSP) models are often implemented using a wide variety of technical workflows and methodologies. To facilitate reproducibility, transparency, portability, and reuse for QSP models, we have developed gQSPSim, a graphical user interface-based MATLAB application that performs key steps in QSP model development and analyses. The capabilities of gQSPSim include (i) model calibration using global and local optimization methods, (ii) development of virtual subjects to explore variability and uncertainty in the represented biology, and (iii) simulations of virtual populations for different interventions. gQSPSim works with SimBiology-built models using components such as species, doses, variants, and rules. All functionalities are equipped with an interactive visualization interface and the ability to generate presentation-ready figures. In addition, standardized gQSPSim sessions can be shared and saved for future extension and reuse. In this work, we demonstrate gQSPSim's capabilities with a standard target-mediated drug disposition model and a published model of anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) treatment of hypercholesterolemia.
Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , Hypercholesterolemia/drug therapy , Proprotein Convertase 9/drug effects , Antibodies, Monoclonal, Humanized/pharmacokinetics , Antibodies, Monoclonal, Humanized/therapeutic use , Computer Simulation , Drug Development/instrumentation , Drug Discovery/instrumentation , Humans , Hypercholesterolemia/metabolism , Models, Biological , PCSK9 Inhibitors , Reference Standards , Reproducibility of Results , Software , Uncertainty , User-Computer Interface , WorkflowABSTRACT
Modeling and simulation (M&S) is increasingly used in drug development to characterize pharmacokinetic-pharmacodynamic (PKPD) relationships and support various efforts such as target feasibility assessment, molecule selection, human PK projection, and preclinical and clinical dose and schedule determination. While model development typically require mathematical modeling expertise, model exploration and simulations could in many cases be performed by scientists in various disciplines to support the design, analysis and interpretation of experimental studies. To this end, we have developed a versatile graphical user interface (GUI) application to enable easy use of any model constructed in SimBiology® to execute various common PKPD analyses. The MATLAB®-based GUI application, called gPKPDSim, has a single screen interface and provides functionalities including simulation, data fitting (parameter estimation), population simulation (exploring the impact of parameter variability on the outputs of interest), and non-compartmental PK analysis. Further, gPKPDSim is a user-friendly tool with capabilities including interactive visualization, exporting of results and generation of presentation-ready figures. gPKPDSim was designed primarily for use in preclinical and translational drug development, although broader applications exist. gPKPDSim is a MATLAB®-based open-source application and is publicly available to download from MATLAB® Central™. We illustrate the use and features of gPKPDSim using multiple PKPD models to demonstrate the wide applications of this tool in pharmaceutical sciences. Overall, gPKPDSim provides an integrated, multi-purpose user-friendly GUI application to enable efficient use of PKPD models by scientists from various disciplines, regardless of their modeling expertise.
Subject(s)
Drug Development/methods , Pharmaceutical Preparations/metabolism , Computer Simulation , Humans , Models, Biological , SoftwareABSTRACT
A variety of wound measurement techniques are available to clinicians. Options range from relatively simple and inexpensive to complex, expensive devices. An iterative design approach was used to evaluate and improve performance and clinical utility of a new wound measurement device (WMD). The design was based upon a commercially available Smartphone. Accuracy was assessed using bench testing and reliability of area measurements was determined using multiple evaluators. Clinical utility was investigated by deploying the WMD during wound rounds in a rehabilitation hospital. Accuracy testing revealed an average error <2% at 0° or skew and an average error of 4.28% at 10° of skew. The intra-rater reliability exceeded 0.975 for all raters and inter-rater reliability was 0.966. Clinical utility testing provided the opportunity to address several usability concerns including the software interface and computation times. The accuracy and reliability of a new, non-contact wound measurement device exceeded that of other manual techniques and were, at least, equivocal to other computer-based technologies. Some limitations of using a Smartphone were identified by the clinicians that can be addressed by the more advanced processing power of newer technology. Overall, the WMD was shown to have the potential as a useful clinical tool.
