PMID- 36883316
OWN - NLM
STAT- MEDLINE
DCOM- 20230309
LR  - 20230309
IS  - 1471-6348 (Electronic)
IS  - 0266-4623 (Linking)
VI  - 39
IP  - 1
DP  - 2023 Mar 8
TI  - Clinical effectiveness reporting of novel cancer drugs in the context of 
      non-proportional hazards: a review of nice single technology appraisals.
PG  - e16
LID - 10.1017/S0266462323000119 [doi]
AB  - 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.
FAU - Salmon, David
AU  - Salmon D
AUID- ORCID: 0000-0002-3411-7616
AD  - Faculty of Health and Life Sciences, University of Exeter, Devon, UK.
FAU - Melendez-Torres, G J
AU  - Melendez-Torres GJ
AD  - Peninsula Technology Assessment Group (PenTAG), Faculty of Health and Life 
      Sciences, University of Exeter, Devon, UK.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230308
PL  - England
TA  - Int J Technol Assess Health Care
JT  - International journal of technology assessment in health care
JID - 8508113
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Treatment Outcome
MH  - *Antineoplastic Agents/therapeutic use
MH  - Dietary Supplements
MH  - Technology
MH  - *Neoplasms/drug therapy
OTO - NOTNLM
OT  - National Institute for Health and Care Excellence
OT  - cancer
OT  - health technology assessment
OT  - non-proportional hazards
OT  - survival analysis
EDAT- 2023/03/09 06:00
MHDA- 2023/03/10 06:00
CRDT- 2023/03/08 03:33
PHST- 2023/03/08 03:33 [entrez]
PHST- 2023/03/09 06:00 [pubmed]
PHST- 2023/03/10 06:00 [medline]
AID - S0266462323000119 [pii]
AID - 10.1017/S0266462323000119 [doi]
PST - epublish
SO  - Int J Technol Assess Health Care. 2023 Mar 8;39(1):e16. doi: 
      10.1017/S0266462323000119.