Evidence map›Paper›PMID 27236424›Full record

ArticleMayo Clinic proceedings2016

Strength of Validation for Surrogate End Points Used in the US Food and Drug Administration's Approval of Oncology Drugs.

Chul Kim, Vinay Prasad

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PubMed Full text at PMC Publisher
In one paragraph

Article in Mayo Clinic proceedings, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 5 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

56 citing papers in PubMed, 5 syntheses or guidelines pooled it.

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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.

Chul KimMedical Oncology Service, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Vinay PrasadDepartment of Medicine, Division of Hematology Oncology/Knight Cancer Institute, Oregon Health & Science University, Portland. Electronic address: prasad@ohsu.edu.

Funding

Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

objectiveTo determine the strength of the surrogate-survival correlation for cancer drug approvals based on a surrogate. PARTICIPANTS AND

methodsWe performed a retrospective study of the US Food and Drug Administration (FDA) database, with focused searches of MEDLINE and Google Scholar. Among cancer drugs approved based on a surrogate end point, we examined previous publications assessing the strength of the surrogate-survival correlation. Specifically, we identified the percentage of surrogate approvals lacking any formal analysis of the strength of the surrogate-survival correlation, and when conducted, the strength of such correlations.

resultsBetween January 1, 2009, and December 31, 2014, the FDA approved marketing applications for 55 indications based on a surrogate, of which 25 were accelerated approvals and 30 were traditional approvals. We could not find any formal analyses of the strength of the surrogate-survival correlation in 14 out of 25 accelerated approvals (56%) and 11 out of 30 traditional approvals (37%). For accelerated approvals, just 4 approvals (16%) were made where a level 1 analysis (the most robust way to validate a surrogate) had been performed, with all 4 studies reporting low correlation (r≤0.7). For traditional approvals, a level 1 analysis had been performed for 15 approvals (50%): 8 (53%) reported low correlation (r≤0.7), 4 (27%) medium correlation (r>0.7 to r<0.85), and 3 (20%) high correlation (r≥0.85) with survival.

conclusionsThe use of surrogate end points for drug approval often lacks formal empirical verification of the strength of the surrogate-survival association.

Identifiers

PMID27236424
PMCPMC5104665

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