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Updated: May 18, 2026

Diagonal Method to Measure Synergy Among Any Number of Drugs
Published on: June 21, 2018
Calculating additive treatment effects from multiple randomized trials provides useful estimates of combination
Edward J Mills1, Kristian Thorlund, John P A Ioannidis
1Faculty of Health Sciences, University of Ottawa, 43 Templeton Street, Ottawa, Ontario, Canada. Edward.mills@uottawa.ca
Objective:
Many clinicians and decision makers want to know the combined effects of treatments that have not been evaluated in combination. It is possible to determine such treatment effects by making assumptions about the additive effects. We discuss here the prerequisites and methods of applying additivity assumptions in synthesizing the evidence from randomized trials and multiple treatment meta-analyses.
Study Design And Setting:
Using statistical approaches, we demonstrate the utility of additivity of both pairwise randomized trials and multiple treatment comparison meta-analyses.
Results:
We present illustratively an example on estimating the treatment effects of drug combinations for chronic obstructive pulmonary disease. We confirm the additive treatment effects by comparing with direct combination treatment trial results.
Conclusion:
Additive effects may be a useful tool to estimate the effectiveness of treatment combinations.
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