Approving cancer treatments based on endpoints other than overall survival: an analysis of historical data using the PACE Continuous Innovation Indicators™ (CII)

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Abstract

Background: There is an active debate about the role that endpoints other than overall survival (OS) should play in the drug approval process. Yet the term ‘surrogate endpoint’ implies that OS is the only critical metric for regulatory approval of cancer treatments. We systematically analyzed the relationship between U.S. Food and Drug Administration (FDA) approval and publication of OS evidence to understand better the risks and benefits of delaying approval until OS evidence is available.

Scope: Using the PACE Continuous Innovation Indicators (CII) platform, we analyzed the effects of cancer type, treatment goal, and year of approval on the lag time between FDA approval and publication of first significant OS finding for 53 treatments approved between 1952 and 2016 for 10 cancer types (n = 71 approved indications).

Findings: Greater than 59% of treatments were approved before significant OS data for the approved indication were published. Of the drugs in the sample, 31% had lags between approval and first published OS evidence of 4 years or longer. The average number of years between approval and first OS evidence varied by cancer type and did not reliably predict the eventual amount of OS evidence accumulated.

Conclusions: Striking the right balance between early access and minimizing risk is a central challenge for regulators worldwide. We illustrate that endpoints other than OS have long helped to provide timely access to new medicines, including many current standards of care. We found that many critical drugs are approved many years before OS data are published, and that OS may not be the most appropriate endpoint in some treatment contexts. Our examination of approved treatments without significant OS data suggests contexts where OS may not be the most relevant endpoint and highlights the importance of using a wide variety of fit-forpurpose evidence types in the approval process.

Keywords: surrogate endpoints, survival, cancer, U.S. Food and Drug Administration, risks and benefits, standards of care, database, policy making.

Citation: Brooks N, Campone M, Paddock S, Shortenhaus S, Grainger D, Zummo J, Thomas S, Li R. Approving cancer treatments based on endpoints other than overall survival: an analysis of historical data using the PACE Continuous Innovation Indicators™ (CII). Drugs in Context 2017; 6: 212507. DOI: 10.7573/dic.212507

Contributions: Brooks contributed to conception and design of the work; acquisition, analysis, and interpretation of the data; and drafting and critical revisions of the manuscript. Campone contributed to interpretation of data and critical revisions of the manuscript. Paddock contributed to conception and design of the work; acquisition, analysis, and interpretation of the data; and drafting and critical revisions of the manuscript. Shortenhaus contributed to conception and interpretation of data and critical revisions of the manuscript. Grainger contributed to conception and interpretation of data and critical revisions of the manuscript. Zummo contributed to conception and interpretation of data and critical revisions of the manuscript. Li contributed to conception and interpretation of data and critical revisions of the manuscript. Thomas contributed to conception and design of the work; acquisition, analysis, and interpretation of the data; and drafting and critical revisions of the manuscript.

Disclosure and potential conflicts of interest: Grainger, Shortenhaus, and Zummo are, or were at the time of writing, employees of and own stock in Eli Lilly and Company. Brooks, Li, Paddock, and Thomas received remuneration by Rose Li and Associates, Inc. under contract to Eli Lilly and Company for their time and effort in conducting the analysis and preparing the manuscript. Brooks is now a full-time employee of the Kaiser Permanente Center for Health Research. Campone declares no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at: http://www.drugsincontext.com/wp-content/uploads/2017/10/dic.212507-COI.pdf

Acknowledgements: The authors gratefully acknowledge Nancy Tuvesson, Rose Li and Associates, Inc., for editorial support in the preparation of this manuscript.

Funding declaration: This study was funded by Eli Lilly and Company.

Copyright: Copyright © 2017 Brooks N, Campone M, Paddock S, Shortenhaus S, Grainger D, Zummo J, Thomas S, Li R. Distributed under the terms of the Creative Commons License Deed CC BY NC ND 4.0, which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2017 Brooks N, Campone M, Paddock S, Shortenhaus S, Grainger D, Zummo J, Thomas S, Li R. https://doi.org/10.7573/dic.212507. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: http://www.drugsincontext.com/approving-cancer-treatments-based-on-endpoints-other-than-overall-survival-an-analysis-of-historical-data-using-the-pace-continuous-innovation-indicators-cii

Correspondence: Samuel Thomas, Rose Li and Associates, Inc., 9501 Wadsworth Dr., Bethesda, MD 20740, USA. samuel.thomas@roseliassociates.com

Provenance: submitted; externally peer reviewed.

Submitted: 4 August 2017; Peer review comments to author: 14 September 2017; Revised manuscript received: 28 September 2017; Accepted: 29 September 2017; Publication date: 15 November 2017.

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