COMBO: A NEW APPROACH TO THE DESIGN AND ANALYSIS OF EXPERIMENTS ON COMBINATION THERAPY (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

COMBO: A NEW APPROACH TO THE DESIGN AND ANALYSIS OF EXPERIMENTS ON COMBINATION THERAPY (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 32:A2036 1991. Unique Identifier : AIDSLINE ICDB/91674834
Weinstein JN; Bunow B; NCI, Bldg. 10 Room 4B-56, Bethesda, MD 20892

Abstract: Prompted by the need to analyze data from our own experiments, we have taken a fresh look at the problem of identifying potentiation, synergy, antagonism, enhancement of therapeutic index, and other types of drug interactions. This investigation has revealed a need for the following capabilities: (i) flexible choice of interaction models; (ii) parametric and nonparametric (Monte Carlo) statistical methods to estimate p-values and confidence limits (a sound statistical basis is critical in this field); (iii) flexibility with respect to experimental design (eg, checkerboard, constant-ratio, etc); and (iv) statistical techniques to reduce the size of experiments by reducing the number of replicates required. These requirements motivated the development of a computer program package, COMBO, that operates in the MLAB computing environment on PC's. It provides a variety of models, eg, 'robust potentiation,' 'robust antagonism,' 'pure potentiation,' and 'eff-tox' (the latter for instances in which both efficacy and toxicity are observed simultaneously). COMBO can also be used for experiments on single drugs. Graphical displays, multiple statistical diagnostics, and identifiers of aberrant data are included. We have used COMBO to analyze data on combinations that include doxorubicin, suramin, tumor necrosis factor, dipyridamole, AZT, ddl, ddC, and CD4-pseudomonas exotoxin, inter alia. Preliminary descriptions are in PNAS 87:8889, 1990 and in Annals NY Acad Sci 616, 1990, in press (Bunow and Weinstein, et al).

Keywords: Acquired Immunodeficiency Syndrome/*DRUG THERAPY Drug Therapy, Combination *Drug Therapy, Computer-Assisted Human *Software ABSTRACT

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