TA876 · STA
It is only recommended if the company provides it according to the commercial arrangement (simple discount patient access scheme)
Source documents
Intervention
Condition
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| neoadjuvant chemoradiotherapy | active drug | Yes | — |
| surgery alone | standard of care | Yes | — |
| adjuvant chemotherapy | active drug | Yes | — |
| neoadjuvant chemotherapy alone | active drug | Yes | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| CheckMate-816 | RCT | 3 | Yes |
Economic model
ICER
Methodological decisions (9)
Company applied a 'cure assumption' in the economic model. There is no convincing clinical evidence to support how the cure assumption was modelled. General consensus that cure occurs between years 5 and 8, but no consensus on rates of cure and lack of empirical evidence.
Company: Company applied cure assumption in the model
ERG: EAG considered no convincing clinical evidence to support the cure assumption as modelled
Committee: Cure assumption applied was uncertain; scenario analysis removing the assumption had small effect on cost-effectiveness results
ICER impact: negligible
CheckMate-816 had no UK recruitment and about 50% Asian family background. Resection types and minimally invasive surgery rates differ from NHS practice. Neoadjuvant nivolumab plus chemotherapy was less effective in North American and European populations compared with Asian population.
Company: Company submitted CheckMate-816 data as primary evidence
ERG: EAG noted generalisability concerns regarding ethnic composition, resection types (higher thoracotomy/pneumonectomy vs. NHS minimally invasive surgery practice), and conducted subgroup analyses by family background
Committee: Trial likely representative of NHS clinical practice; most baseline characteristics were well balanced; clinical evidence from CheckMate-816 was uncertain but suitable for decision making
ICER impact: uncertain_direction
Retreatment restrictions applied for people who had neoadjuvant nivolumab plus chemotherapy and progressed within 6 months, making them ineligible for further immuno-oncology treatment.
Company: Company applied 6-month immuno-oncology retreatment restriction and redistributed treatments in distant metastasis state accordingly
ERG: EAG noted uncertainty in proportion ineligible for retreatment and timelines; conducted additional scenario analyses including 12-month restriction and no restriction scenarios
Committee: Application of retreatment restrictions in the economic model was uncertain
ICER impact: uncertain_direction
Application of immuno-oncology therapy retreatment restrictions for people who progressed within 6 months of neoadjuvant nivolumab plus chemotherapy
Company: Applied 6-month retreatment restriction
ERG: Considered uncertainty in proportion ineligible and timeline; noted company did scenario analysis with 12-month restriction
ICER impact: uncertain_direction
Parametric models used to extrapolate time to any progression (TTaP) and time to locoregional recurrence (TTLR) beyond CheckMate-816 follow-up. Considerable uncertainty around extrapolation of TTaP and TTLR curves.
Company: Company provided extrapolation approach for TTaP and TTLR
ERG: EAG's approach to modelling long-term TTLR and event-free mortality was uncertain but plausible
Committee: Both company and EAG approaches were considered plausible and produced cost-effectiveness estimates well below NICE's threshold; optimal approach to modelling survival was uncertain
ICER impact: negligible
Treatment redistribution in distant metastasis health state accounting for people who had events on neoadjuvant treatment
Company: Redistributed treatments across remaining options for those ineligible for immuno-oncology
ERG: Conducted additional scenario analyses assuming same distribution of chemotherapies for both immuno-oncology and non-immuno-oncology treatments
ICER impact: uncertain_direction
Health-state utility values for event-free and locoregional recurrence states were higher than expected for NSCLC population. Other issues: using overall rather than treatment-specific utilities from CheckMate-816, using linear mixed models for non-linear EQ-5D-3L data, age-sex adjustment process.
Company: Company used overall utilities from CheckMate-816 with age-sex adjustment
ERG: EAG presented 4 scenarios to explore utility value uncertainty
Committee: Uncertainty sufficiently explored given available evidence
ICER impact: uncertain_direction
Use of overall rather than treatment-specific utilities from CheckMate-816 in the economic model
Company: Used overall utilities
ERG: Identified this as a minor issue but noted it would be difficult to resolve given lack of evidence
ICER impact: negligible
Concerns that utility values for event-free and locoregional recurrence health states were higher than expected in NSCLC population
Company: Applied utility values from the model
ERG: Presented 4 scenarios to explore this uncertainty
ICER impact: uncertain_direction
Evidence gaps
Commercial arrangement
Special considerations
Cross-references