Surrogate endpoints in oncology: when are they acceptable for regulatory and clinical decisions, and are they currently overused?

BMC Medicine

Opinion

Vinay Prasad¹  Robert Kemp² 

[1] Division of Hematology Oncology, Knight Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, 97239, Portland, OR, USA;Department of Public Health and Preventive Medicine, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, 97239, Portland, OR, USA;Center for Health Care Ethics, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, 97239, Portland, OR, USA;School of Medicine, University of Oxford, John Radcliffe Hospital, OX3 9DU, Oxford, UK;

关键词: Surrogate endpoints;    Outcomes;    Cancer;    Regulation;    US Food and Drug Administration (FDA);   

DOI  :  10.1186/s12916-017-0902-9

 received in 2017-03-07, accepted in 2017-06-26,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundSurrogate outcomes are not intrinsically beneficial to patients, but are designed to be easier and faster to measure than clinically meaningful outcomes. The use of surrogates as an endpoint in clinical trials and basis for regulatory approval is common, and frequently exceeds the guidance given by regulatory bodies.DiscussionIn this article, we demonstrate that the use of surrogates in oncology is widespread and increasing. At the same time, the strength of association between the surrogates used and clinically meaningful outcomes is often unknown or weak. Attempts to validate surrogates are rarely undertaken. When this is done, validation relies on only a fraction of available data, and often concludes that the surrogate is poor. Post-marketing studies, designed to ensure drugs have meaningful benefits, are often not performed. Alternatively, if a drug fails to improve quality of life or overall survival, market authorization is rarely revoked.We suggest this reliance on surrogates, and the imprecision surrounding their acceptable use, means that numerous drugs are now approved based on small yet statistically significant increases in surrogates of questionable reliability. In turn, this means the benefits of many approved drugs are uncertain. This is an unacceptable situation for patients and professionals, as prior experience has shown that such uncertainty can be associated with significant harm.ConclusionThe use of surrogate outcomes should be limited to situations where a surrogate has demonstrated robust ability to predict meaningful benefits, or where cases are dire, rare or with few treatment options. In both cases, surrogates must be used only when continuing studies examining hard endpoints have been fully recruited.

【 授权许可】

CC BY   
© The Author(s). 2017