{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T21:57:23Z","timestamp":1747173443856,"version":"3.40.5"},"reference-count":40,"publisher":"Cambridge University Press (CUP)","issue":"1","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"unspecified","delay-in-days":66,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J Technol Assess Health Care"],"published-print":{"date-parts":[[2023]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:sec id=\"S0266462323000119_sec1\">\n\t    <jats:title>Objectives<\/jats:title>\n\t    <jats:p>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.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0266462323000119_sec2\" sec-type=\"methods\">\n\t    <jats:title>Methods<\/jats:title>\n\t    <jats:p>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).<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0266462323000119_sec3\" sec-type=\"results\">\n\t    <jats:title>Results<\/jats:title>\n\t    <jats:p>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).<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0266462323000119_sec4\" sec-type=\"conclusions\">\n\t    <jats:title>Conclusions<\/jats:title>\n\t    <jats:p>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.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1017\/s0266462323000119","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T08:26:03Z","timestamp":1678263963000},"source":"Crossref","is-referenced-by-count":2,"title":["Clinical effectiveness reporting of novel cancer drugs in the context of non-proportional hazards: a review of nice single technology appraisals"],"prefix":"10.1017","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-7616","authenticated-orcid":false,"given":"David","family":"Salmon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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National Institute for Health and Care Excellence (NICE). Nivolumab for advanced non-squamous non-small-cell lung cancer after chemotherapy. Technology appraisal guidance [TA713] [Internet]. NICE website. 2021. Available from: https:\/\/www.nice.org.uk\/guidance\/ta713."},{"key":"S0266462323000119_r14","doi-asserted-by":"crossref","DOI":"10.1201\/b18041","volume-title":"Modelling survival data in medical research","author":"Collett","year":"2015"},{"key":"S0266462323000119_r2","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/69.1.239"},{"key":"S0266462323000119_r16","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1093\/biomet\/52.3-4.650","article-title":"A generalized two-sample wilcoxon test for doubly censored data","volume":"52","author":"Gehan","year":"1965","journal-title":"Biometrika [Internet]"},{"key":"S0266462323000119_r10","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.publhealth.20.1.145"},{"key":"S0266462323000119_r7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810699"},{"key":"S0266462323000119_r26","unstructured":"26. National Institute for Health and Care Excellence (NICE). Palbociclib with fulvestrant for treating hormone receptor-positive, HER2-negative, advanced breast cancer. Technology appraisal guidance [TA619] [Internet]. NICE website. 2020. Available from: https:\/\/www.nice.org.uk\/guidance\/ta619."},{"key":"S0266462323000119_r19","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1093\/annonc\/mdy075","article-title":"Treatment effects measured by restricted mean survival time in trials of immune checkpoint inhibitors for cancer","volume":"29","author":"Liang","year":"2018","journal-title":"Ann Oncol"},{"key":"S0266462323000119_r17","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/1471-2288-13-152","article-title":"Restricted mean survival time: An alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome","volume":"13","author":"Royston","year":"2013","journal-title":"BMC Med Res Methodol"},{"key":"S0266462323000119_r15","unstructured":"15. 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