Fig. 1. IDACombo allows drug combination efficacy predictions to be made using monotherapy cell line screening data, and these predictions can be validated against measured efficacies or used to identify novel efficacious drug combinations.

a Example calculations demonstrating how IDACombo predicts drug combination efficacies based on IDA. In this example, three cell lines (1–3) with measured efficacies for three monotherapies (A–C) at their selected concentrations are used to predict the efficacy of the combination of drugs A + B + C. Highlighted cells indicate the best monotherapy for that cell line (i.e. provides greatest reduction in viability). b Strategy for validating IDACombo efficacy predictions using in vitro measurements of efficacy. Measured and predicted average efficacies for each treatment can be directly compared by calculating their correlation and calculating prediction errors. c Strategy for validating IDACombo efficacy predictions using published clinical trial results. Combination efficacies which have been predicted using cell line data are used to predict study HRs, and these predicted HRs are used, along with the number of events observed in each clinical trial, to predict study powers. Predicted HRs can be compared to reported HRs, and a power threshold (80%) can be set to classify trials as likely or unlikely to detect a significant improvement in a trial outcome (i.e. PFS), which can then be compared to observed trial outcomes. d Analysis techniques available for using IDACombo predictions to identify novel efficacious drug combinations. High-throughput analyses using summary statistics can be used to compare efficacy predictions for many drug combinations at once, or detailed analyses can be used to explore the efficacy of a single drug combination at varying concentrations of each drug in the combination.