Statistical approaches for evaluating surrogate outcomes in clinical trials: A systematic review

ABSTRACT

The use of surrogate outcomes that predict treatment effect on an unobserved true outcome may have substantial economic and ethical advantages, through reducing the length and size of clinical trials. There has been extensive investigation of the best means of evaluating putative surrogates. We present a systematic review on the evolution of statistical methods for validating surrogates starting from the defining paper of Prentice (1989). We highlight the fundamental differences in the current statistical evaluation approaches, their advantages and disadvantages, and examine the understanding and perceptions of investigators in this area.

KEYWORDS:

• Clinical trials
• statistical methodology
• surrogate evaluation
• systematic review

Acknowledgments

We would like to thank the reviewers for their constructive comments which helped us improve the manuscript.

Funding

Hannah Ensor was supported in her work by a MRC Trials Methodology Studentship. Christopher Weir was supported in this work by NHS Lothian via the Edinburgh Health Services Research Unit.

Additional information

Funding

Hannah Ensor was supported in her work by a MRC Trials Methodology Studentship. Christopher Weir was supported in this work by NHS Lothian via the Edinburgh Health Services Research Unit.