Evaluating surrogate endpoints, prognostic markers, and predictive markers: Some simple themes.
BACKGROUND
A surrogate endpoint is an endpoint observed earlier than the true endpoint (a health outcome) that is used to draw conclusions about the effect of treatment on the unobserved true endpoint. A prognostic marker is a marker for predicting the risk of an event given a control treatment; it informs treatment decisions when there is information on anticipated benefits and harms of a new treatment applied to persons at high risk. A predictive marker is a marker for predicting the effect of treatment on outcome in a subgroup of patients or study participants; it provides more rigorous information for treatment selection than a prognostic marker when it is based on estimated treatment effects in a randomized trial.


METHODS
We organized our discussion around a different theme for each topic.


RESULTS
"Fundamentally an extrapolation" refers to the non-statistical considerations and assumptions needed when using surrogate endpoints to evaluate a new treatment. "Decision analysis to the rescue" refers to use the use of decision analysis to evaluate an additional prognostic marker because it is not possible to choose between purely statistical measures of marker performance. "The appeal of simplicity" refers to a straightforward and efficient use of a single randomized trial to evaluate overall treatment effect and treatment effect within subgroups using predictive markers.


CONCLUSIONS
The simple themes provide a general guideline for evaluation of surrogate endpoints, prognostic markers, and predictive markers.
Division of Cancer Prevention, National Cancer Institute, Bethesda MD, USA sb16i@nih.gov.
Stuart G
SG
Baker
Division of Cancer Prevention, National Cancer Institute, Bethesda MD, USA.
Barnett S
BS
Kramer
D000465:Algorithms; D015415:Biomarkers / Q000032:analysis*; D003627:Data Interpretation, Statistical; D005544:Forecasting; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000379:methods
D015415:Biomarkers
Decision analysis; predictive marker; principal stratification; prognostic marker; randomized trial; relative utility curve; subgroup; treatment selection marker