COMBO, an interactive computer program for the analysis of drug combination assays is to be developed. Drug combinations play an important role in cancer therapy and anti-microbial therapy, and are increasingly recognized as important in AIDS therapy, and other anti-viral therapy. Assay of drug combinations is a major tool for the identification of new combinations, improving existing combinations, and determination of therapeutic index. Drug combination assays are currently performed at hundreds of sites in medical research institutions and pharmaceutical-biotechnology companies, where COMBO will be equally applicable to efficacy, toxicity, and therapeutic index analysis. COMBO will combine biochemically-motivated model selection of analysis options, effective graphical and tabular presentation of relevant results. COMBO will be programmed in the flexible MLAB environment, permitting the user either to remain within the context of the program or to generalize the data analysis in his own manner, through the provision of the MLAB programming language. The program will contain modules for calibration, data entry and editing, model selection, parameter estimation, graphical and tabular display of residuals, computation of pharmacologically-relevant parameters from the assay. The applicant will develop models for drug interaction which are motivated by practical experience, and analyze them by modern statistical methodologies.
