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CHALLENGES AND METHODOLOGIES IN USING PROGRESSION FREE SURVIVAL AS A SURROGATE FOR OVERALL SURVIVAL IN ONCOLOGY

Part of: Special Collection - Methods

Published online by Cambridge University Press:  10 July 2018

Karla Hernandez-Villafuerte ,
Alastair Fischer  and
Nicholas Latimer
Karla Hernandez-Villafuerte
Affiliation:
German Cancer Research Center (DKFZ)k.hernandezvillafuerte@dkfz.de
Alastair Fischer
Affiliation:
Office of Health Economics
Nicholas Latimer
Affiliation:
ScHARR, University of Sheffield
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Abstract

Objectives:

A primary outcome in oncology trials is overall survival (OS). However, to estimate OS accurately requires a sufficient number of patients to have died, which may take a long time. If an alternative end point is sufficiently highly correlated with OS, it can be used as a surrogate. Progression-free survival (PFS) is the surrogate most often used in oncology, but does not always satisfy the correlation conditions for surrogacy. We analyze the methodologies used when extrapolating from PFS to OS.

Methods:

Davis et al. previously reviewed the use of surrogate end points in oncology, using papers published between 2001 and 2011. We extend this, reviewing papers published between 2012 and 2016. We also examine the reporting of statistical methods to assess the strength of surrogacy.

Results:

The findings from 2012 to 2016 do not differ substantially from those of 2001 to 2011: the same factors are shown to affect the relationship between PFS and OS. The proportion of papers reporting individual patient data (IPD), strongly recommended for full assessment of surrogacy, remains low: 33 percent. A wide range of methods has been used to determine the appropriateness of surrogates. While usually adhering to reporting standards, the standard of scholarship appears sometimes to be questionable and the reporting of results often haphazard.

Conclusions:

Standards of analysis and reporting PFS to OS surrogate studies should be improved by increasing the rigor of statistical reporting and by agreeing to a minimum set of reporting guidelines. Moreover, the use of IPD to assess surrogacy should increase.

Keywords

CancerSurrogate end pointsOverall survival (OS)Progression-free survival (PFS)Postprogression survival (PPS)
Type
Method
Information
International Journal of Technology Assessment in Health Care , Volume 34 , Issue 3 , 2018 , pp. 300 - 316
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

Funding: The Pharmaceutical Oncology Initiative (POI) of the Association of the British Pharmaceutical Industry (ABPI) commissioned the Office of Health Economics (OHE) in April 2016 to undertake a landscape study on methods and approaches to extrapolation from clinical endpoints measured in trials involving overall survival. We gratefully acknowledge the contributions of Francesco Pignatti (EMA), Eli Gavraj and Ian Watson (NICE), Prof Andrew Stevens (Chair of a NICE Appraisal Committee), Oriana Ciani and Prof Rod Taylor (University of Exeter Medical School), and POI member organizations. Nevertheless, views expressed in this paper are those of the authors and are not necessarily those of POI, EMA, NICE or the University of Exeter. Karla Hernandez-Villafuerte's previous affiliation was Office of Health Economics. Southside, 7th Floor, 105 Victoria Street, London SW1E 6QT.

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