TA892 · STA
Source documents
Intervention
Condition
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| rituximab plus lenalidomide | active drug | Yes | — |
| rituximab plus bendamustine | active drug | Yes | — |
| rituximab plus chemotherapy | active drug | Yes | — |
| r-chop | active drug | — | — |
| r-cvp | active drug | — | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| GO29781 | single_arm | 2 | Yes |
Economic model
ICER
Methodological decisions (14)
Whether rituximab plus bendamustine is representative of other rituximab plus chemotherapy combinations
Company: Rituximab plus bendamustine used as proxy for other chemotherapy combinations due to lack of comparative data
ERG: Agreement that direct comparison with R-CHOP not feasible
Committee: Rituximab plus bendamustine is reasonable comparator but whether it is representative of other rituximab plus chemotherapy highly uncertain; may set bar high as these patients typically younger and fitter
ICER impact: uncertain_direction
Uncertainty about whether rituximab plus bendamustine is representative of other types of rituximab plus chemotherapy (R-CHOP, R-CVP).
Committee: Need direct comparison with all relevant standard care comparators
ICER impact: uncertain_direction
MAIC approach for rituximab plus lenalidomide comparison missing important prognostic factors
Company: Important variables excluded because data not available from AUGMENT study (number of previous therapies, refractory status, prior stem cell transplant, lymph node size)
ERG: Missing important prognostic factors including number of previous therapies leads to high uncertainty and potential for bias
Committee: Indirect comparison with rituximab plus lenalidomide is highly uncertain with potential for bias due to unmatched variables
ICER impact: increases
Propensity score analysis for rituximab plus bendamustine comparison includes double-refractory status with unclear clinical plausibility
Company: Variables selected based on improving overall balance of covariates
ERG: Unclear whether double-refractory status should be included; has wide standard errors and shows unclear clinical plausibility in interaction analysis
Committee: Some uncertainty associated with rituximab plus bendamustine indirect comparison
ICER impact: uncertain_direction
Reliability and plausibility of MAIC and propensity score analyses for indirect treatment comparisons
Company: Results of indirect treatment comparisons considered highly uncertain by EAG. Company noted that in AUGMENT study used in MAIC, less than 50% had third-line or later treatment and none had rituximab-refractory follicular lymphoma. Company also noted differences in propensity score analysis between study populations.
ERG: EAG noted inconsistent results within the 2 indirect comparisons, making them highly uncertain. Results favoured mosunetuzumab for some endpoints but comparator for others. Differences in results across the 2 indirect comparisons made them difficult to interpret.
Committee: Committee concluded that results of the indirect treatment comparisons were highly uncertain and inconsistencies within them made them very unreliable.
ICER impact: uncertain_direction
Indirect treatment comparisons were highly uncertain. The committee highlighted that a trial comparing mosunetuzumab with standard care comparators is needed rather than relying on indirect comparisons.
Company: Proposed alternative confidential source of evidence for comparator treatments
Committee: Direct comparative trial needed to resolve uncertainty
ICER impact: increases
Partitioned survival model vs response-based modelling approach
Company: Used partitioned survival model with 3 health states
ERG: Not explicitly stated
Committee: Partitioned survival is standard but response-based approach could be more suitable for mosunetuzumab vs rituximab plus lenalidomide; would better capture benefits of complete response but has own uncertainties
ICER impact: uncertain_direction
Partitioned survival model versus response-based modelling approach for comparison with rituximab plus lenalidomide
Company: Used partitioned survival model with 3 health states (progression-free, post-progression, dead)
ERG: Not explicitly stated as disagreement
Committee: Committee considered partitioned survival model standard but noted that response-based modelling approach could be more suitable for comparing mosunetuzumab with rituximab plus lenalidomide. This may have avoided some problems with survival modelling and more fully captured complete response benefits. However, acknowledged own uncertainties.
ICER impact: uncertain_direction
Overall survival modelling approach - whether to pool treatment arms or model separately
Company: Modelled mosunetuzumab and comparator arms separately
ERG: Preferred to pool mosunetuzumab and comparator arms, which removed treatment difference for OS from both comparisons. Noted overall survival data from single-arm mosunetuzumab study was very immature and there was no clear OS benefit.
Committee: Noted EAG's pooling changed cost-effectiveness estimate substantially for both comparisons. Noted EAG's approach assumed both treatments have same OS whereas clinical experts expected people to live longer with mosunetuzumab. Concluded would consider both approaches.
ICER impact: increases
Whether GO29781 study cohort generalises to UK patients. SACT would provide useful UK-based data but would not sufficiently resolve the high uncertainty associated with indirect treatment comparisons.
Committee: SACT data would help but cannot fully resolve generalisability concerns
ICER impact: uncertain_direction
Choice of parametric distributions for progression-free and overall survival modelling
Company: For rituximab plus lenalidomide comparison: Weibull for mosunetuzumab PFS, log normal for rituximab plus lenalidomide PFS, Weibull for OS both arms. For rituximab plus bendamustine comparison: log normal for both arms PFS, exponential for OS both arms.
ERG: For rituximab plus lenalidomide comparison: log normal for rituximab plus lenalidomide PFS, preferred log normal for mosunetuzumab arm using available data and switched to log normal when observed data unavailable, Weibull for OS both arms. For rituximab plus bendamustine comparison: same as company.
Committee: Committee concluded company and EAG agreed on most survival distributions and all would be considered.
ICER impact: uncertain_direction
Overall survival is a key uncertainty. The timeframe for data collection with managed access may not be long enough to show an overall survival benefit.
Committee: Longer-term data from GO29781 study needed but unlikely to resolve uncertainty within managed access timeframe
ICER impact: uncertain_direction
Distribution of subsequent treatments after disease progression
Company: Applied subsequent treatment costs from point of disease progression for all arms. After first meeting, agreed with EAG on distribution: rituximab plus lenalidomide (35%), rituximab plus chemotherapy (25%), other non-rituximab chemotherapy (10%) for mosunetuzumab and rituximab plus bendamustine arms.
ERG: Noted approach produced bias towards lower costs in favour of mosunetuzumab. Agreed on distribution after first meeting.
Committee: Noted subsequent therapy assumptions informed by clinical advice. Concluded company's subsequent treatment assumptions likely to reflect clinical practice.
ICER impact: decreases
Source of health-state utility values for progression-free and post-progression states
Company: Originally based on GO29781 study cohort. Company changed approach during consultation to use Wild et al. 2006 literature values from 222 UK patients, previously used in idelalisib TA guidance.
ERG: At first meeting agreed company's approach acceptable. For updated base case, noted Wild et al. published as abstract only and values cannot be validated. Noted Wild data has much larger difference in utility between progression-free and post-progression states than GO29781. Preferred not to change utility values in base case, which remain GO29781 cohort values.
Committee: Considered company and EAG took different approaches, both associated with uncertainty. Preferred GO29781 study cohort values because from clinical study of mosunetuzumab patients, while Wild et al. may not be robust source and could not be validated.
ICER impact: decreases
Evidence gaps
Commercial arrangement
Special considerations
Cross-references