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Clinical effectiveness reporting of novel cancer drugs in the context of non-proportional hazards: a review of nice single technology appraisals

Part of: Special Collection - Methods

Published online by Cambridge University Press:  08 March 2023

David Salmon Open the ORCID record for David Salmon [Opens in a new window]  and
G. J. Melendez-Torres
David Salmon*
Affiliation:
Faculty of Health and Life Sciences, University of Exeter, Devon, UK
G. J. Melendez-Torres
Affiliation:
Peninsula Technology Assessment Group (PenTAG), Faculty of Health and Life Sciences, University of Exeter, Devon, UK
*
*Author for correspondence: David Salmon, E-mail: david.salmon1@nhs.net
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Abstract

Objectives

The hazard ratio (HR) is a commonly used summary statistic when comparing time to event (TTE) data between trial arms, but assumes the presence of proportional hazards (PH). Non-proportional hazards (NPH) are increasingly common in NICE technology appraisals (TAs) due to an abundance of novel cancer treatments, which have differing mechanisms of action compared with traditional chemotherapies. The goal of this study is to understand how pharmaceutical companies, evidence review groups (ERGs) and appraisal committees (ACs) test for PH and report clinical effectiveness in the context of NPH.

Methods

A thematic analysis of NICE TAs concerning novel cancer treatments published between 1 January 2020 and 31 December 2021 was undertaken. Data on PH testing and clinical effectiveness reporting for overall survival (OS) and progression-free survival (PFS) were obtained from company submissions, ERG reports, and final appraisal determinations (FADs).

Results

NPH were present for OS or PFS in 28/40 appraisals, with log-cumulative hazard plots the most common testing methodology (40/40), supplemented by Schoenfeld residuals (20/40) and/or other statistical methods (6/40). In the context of NPH, the HR was ubiquitously reported by companies, inconsistently critiqued by ERGs (10/28), and commonly reported in FADs (23/28).

Conclusions

There is inconsistency in PH testing methodology used in TAs. ERGs are inconsistent in critiquing use of the HR in the context of NPH, and even when critiqued it remains a commonly reported outcome measure in FADs. Other measures of clinical effectiveness should be considered, along with guidance on clinical effectiveness reporting when NPH are present.

Keywords

non-proportional hazardsNational Institute for Health and Care Excellencehealth technology assessmentsurvival analysiscancer
Type
Method
Information
International Journal of Technology Assessment in Health Care , Volume 39 , Issue 1 , 2023 , e16
Copyright
© The Author(s), 2023. Published by Cambridge University Press

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