Evidence map›Paper›PMID 28728605›Full record

ArticleBMC medicine2017

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

Robert Kemp, Vinay Prasad

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 16 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

117 citing papers in PubMed, 16 syntheses or guidelines pooled it.

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  4. Entecavir for children and adults with chronic hepatitis B.The Cochrane database of systematic reviews · 2025
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  10. Xiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B.The Cochrane database of systematic reviews · 2019
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  11. Acupuncture for chronic hepatitis B.The Cochrane database of systematic reviews · 2019
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  16. Direct-acting antivirals for chronic hepatitis C.The Cochrane database of systematic reviews · 2017
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57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Robert KempSchool of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Vinay PrasadDivision of Hematology Oncology, Knight Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA. prasad@ohsu.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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. DISCUSSION: In 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.

Indexed as

Antineoplastic AgentsBiomarkersMedical OncologyDrug ApprovalHumansQuality of LifeAntineoplastic AgentsBiomarkersCancerOutcomesRegulationSurrogate endpointsUS Food and Drug Administration (FDA)

Identifiers

PMID28728605
PMCPMC5520356

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.