Stuart G Baker1, Barnett S Kramer2. 1. Division of Cancer Prevention, National Cancer Institute, Bethesda MD, USA sb16i@nih.gov. 2. Division of Cancer Prevention, National Cancer Institute, Bethesda MD, USA.
Abstract
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. CONCLUSION: The simple themes provide a general guideline for evaluation of surrogate endpoints, prognostic markers, and predictive markers.
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. CONCLUSION: The simple themes provide a general guideline for evaluation of surrogate endpoints, prognostic markers, and predictive markers.
Authors: Stephen Lam; Jean C leRiche; Annette McWilliams; Calum Macaulay; Yulia Dyachkova; Eva Szabo; John Mayo; Robert Schellenberg; Andy Coldman; Ernest Hawk; Adi Gazdar Journal: Clin Cancer Res Date: 2004-10-01 Impact factor: 12.531
Authors: Dinesh Singh; Phillip G Febbo; Kenneth Ross; Donald G Jackson; Judith Manola; Christine Ladd; Pablo Tamayo; Andrew A Renshaw; Anthony V D'Amico; Jerome P Richie; Eric S Lander; Massimo Loda; Philip W Kantoff; Todd R Golub; William R Sellers Journal: Cancer Cell Date: 2002-03 Impact factor: 31.743
Authors: Vittorio Stumpo; Lelio Guida; Jacopo Bellomo; Christiaan Hendrik Bas Van Niftrik; Martina Sebök; Moncef Berhouma; Andrea Bink; Michael Weller; Zsolt Kulcsar; Luca Regli; Jorn Fierstra Journal: Cancers (Basel) Date: 2022-03-05 Impact factor: 6.639