Evaluation of surrogacy in the multi-trial setting based on information theory: an extension to ordinal outcomes

ABSTRACT

Summary: In clinical trials, surrogate outcomes are early measures of treatment effect that are used to predict treatment effect on a later primary outcome of interest: the primary outcome therefore does not need to be observed and trials can be shortened. Evaluating surrogates is a complex area as a given treatment can act through multiple pathways, some of which may circumvent the surrogate. One of the best established and practically sound approaches to surrogacy evaluation is based on information theory. We have extended this approach to the case of ordinal outcomes, which are used as primary outcomes in many medical areas. This extension provides researchers with the means of evaluating surrogates in this setting, which expands the usefulness of the information theory approach while also demonstrating its versatility.

KEYWORDS:

• Clinical trials
• information theory
• surrogacy evaluation

Acknowledgments

We would like to thank Cat Graham and Prof. Martin Dennis for their advice and permission to use the CLOTS3 (Dennis et al. 2013) trial data and Prof. Cathie Sudlow for her insights into the practical application of this work. Christopher Weir was supported in this work by NHS Lothian via the Edinburgh Clinical Trials Unit.

Supplementary material

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Additional information

Funding

This work was supported by the Medical Research Council; Rural and Environment Science and Analytical Services Division.