The Evaluation of Surrogate Endpoints

Setting the Scene.- Regulatory Aspects in Using Surrogate Markers in Clinical Trials.- Notation and Motivating Studies.- The History of Surrogate Endpoint Validation.- Validation Using Single-trial Data: Mixed Binary and Continuous Outcomes.- A Meta-analytic Validation Framework for Continuous Outcomes.- The Choice of Units.- Extensions of the Meta-analytic Approach to Surrogate Endpoints.- Meta-analytic Validation with Binary Outcomes.- Validation in the Case of Two Failure-time Endpoints.- An Ordinal Surrogate for a Survival True Endpoint.- A Combination of Longitudinal and Survival Endpoints.- Repeated Measures and Surrogate Endpoint Validation.- Bayesian Evaluation of Surrogate Endpoints.- Surrogate Marker Validation in Mental Health.- The Evaluation of Surrogate Endpoints in Practice: Experience in HIV.- An Alternative Measure for Meta-analytic Surrogate Endpoint Validation.- Discussion: Surrogate Endpoint Definition and Evaluation.- The Promise and Peril of Surrogate Endpoints in Cancer Research.

Both humanitarian and commercial considerations have spurred intensive search for methods to reduce the time and cost required to develop new therapies. The identification and use of surrogate endpoints, i.e., measures that can replace or supplement other endpoints in evaluations of experimental treatments or other interventions, is a general strategy that has stimulated both enthusiasm and skepticism.
This book offers a balanced account on this controversial topic. The text presents major developments of the last couple of decades, together with a unified, meta-analytic framework within which surrogates can be evaluated from several angles. Methodological development is coupled with perspectives on various therapeutic areas. Academic views are juxtaposed with standpoints of scientists working in the biopharmaceutical industry as well as of colleagues from the regulatory authorities.

From the reviews:

"A strength of this book is its comprehensive and up-to-date presentation of issues pertinent to the evaluation of surrgoate endpoints...This book makes an important contribution to the clinical trials literature..." Journal of Biopharmaceutical Statistics, 2006

"Many of the chapters deal with real-life data examples and studies involving surrogate outcomes, many written by authors who were directly involved in these studies...The editors have written nice background sections...until a more concise manuscript on this topic is written, this book will remain the most important resource for biostatisticians and researchers in this area." Debajyoti Sinha for the Journal of the American Statistical Association, December 2006

"This book is a reflection of the ongoing debate on the definition and use of surrogate markers...I see the book as an invitation to join the debate. There is much work to be done and reading the book might inspire many to participate. It will be useful for researchers in this and related fields, such as joint modeling of longitudinal and survival data and multivariate meta-analysis. The book is well organized, is a pleasure to read, and is very well documented with up-to-date references." Hans C. Van Houwelingen for Bioometrics, September 2006

"This edited volume deals with a topic that has been the subject of much debate since publication of Prentice's 1989 attempt to formalize the definition of a surrogate marker or endpoint. ... This work focuses on evaluation of a surrogate endpoint. ... an attempt has been made to maintain common notations whenever possible. The editors have succeeded in producing a very useful book." (V. T. Farewell, Short Book Reviews, Vol. 25 (2), 2005)

"I enjoyed readhing the book and I certainly learned a lot about these fascinating areas. The book is suitable as a textbook for a postgraduate course in statistics but is also aninvaluable reference for the