Surrogate End Points: How Well do They Represent Patient-relevant End Points?

Abstract

This review takes a critical look at the concept of replacing patient-relevant end points, such as morbidity or mortality, with surrogate end points in clinical trials. Surrogate end points can be measured earlier in the course of a clinical trial and so are thought to accelerate the drug development process. Furthermore, they might be beneficial to the patients themselves by allowing faster adjustment of therapeutic strategies. However, the fact that in the past several promising surrogate end points have not fulfilled their expectations emphasizes the importance of applying strict evaluation criteria. The evaluation of the candidate surrogate end point prostate-specific antigen using the Prentice criteria and a meta-analytic approach is discussed. Prostate-specific antigen is often used to replace overall or progression-free survival in prostate cancer trials testing the benefit of medical interventions.

Keywords: :

• biomarker
• clinical end point
• clinical trials
• drug assessment
• meta-analysis
• narrative review
• patient-relevant end points
• Prentice criteria
• randomized-controlled trials
• surrogate end point

Acknowledgements

I am deeply grateful to Peter Sawicki, Thomas Kaiser (IQWiG, Cologne, Germany) and Petra Jost (Department of Radiology, University Clinic Bonn, Germany) for reviewing the manuscript. I would also like to thank the following IQWiG employees: Robert Grosselfinger for fruitful discussions about the Prentice criteria in the evaluation of surrogate end points, Sarah Schmitter and Elke Hausner for managing the Reference Manager database, Ulrich Gehrmann for reviewing the statistical section, and Natalie McGauran for editorial support.

The opinions expressed are those of the author and do not necessarily reflect those of the Institute for Quality and Efficiency in Health Care.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.