TA137 · STA
Source documents
Intervention
Conditions
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| chop chemotherapy | active drug | Yes | — |
| best supportive care | best supportive care | — | — |
| observation only | no treatment | — | — |
| fludarabine-containing regimens | active drug | — | — |
| rituximab maintenance therapy | active drug | — | — |
| no use of rituximab | no treatment | — | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| EORTC trial | RCT | — | Yes |
| GLSG-FCM trial | RCT | — | Yes |
| GLSG trial | RCT | — | — |
Economic model
ICER
Methodological decisions (16)
Selection of appropriate comparator for dual-use strategy
Company: Comparison with chemotherapy alone
Committee: Appropriate comparator is single use of rituximab as maintenance therapy, as maintenance therapy is expected to become standard
ICER impact: increases
Administration costs for rituximab infusions
Company: Assumed outpatient setting at £86 per visit
ERG: More appropriate for day-case setting at £504 per visit
Committee: Accepted ERG recalculation
ICER impact: uncertain_direction
Post-progression treatment costs
Company: Used average costs from trial, including wide variation
ERG: Aggregated treatments into meaningful categories (chemotherapy, rituximab, other) to avoid skewing from expensive outliers
Committee: Accepted ERG approach
ICER impact: decreases
Cost of rituximab administration
Company: Not specified in detail
Committee: Cost as day-case procedure rather than outpatient visit, reflecting current rapid administration practice
ICER impact: decreases
Aggregation of post-progression treatment costs
Company: Individual itemisation of treatments
ERG: Aggregate treatments into categories
Committee: Aggregate treatments into categories
ICER impact: decreases
Treatment of event-free period in model fitting
Company: Lack of initial period of non-zero hazards for groups randomised at maintenance
ERG: Should account for protocol-driven event-free period
Committee: Accepted ERG correction; excluding event-free period changed model fit
ICER impact: decreases
Treatment of event-free period when fitting survival distributions
Company: Excluded protocol-driven event-free period when fitting Weibull model
ERG: Event-free period should be included to avoid changing goodness-of-fit and influencing cost-effectiveness estimates
Committee: Event-free period should not be excluded; excluding it can change distribution fit and bias results
ICER impact: decreases
Whether proportional hazards assumption holds for comparing treatment groups
Company: Estimated three parameters assuming common parameters across patient groups
ERG: Assumption not substantiated; should estimate four parameters independently
Committee: Accepted ERG concern; independent fitting resulted in lower ICER of £15,775
ICER impact: decreases
Assumption that treatment pairs share common parameters in Weibull model
Company: Shared common parameters across patient groups, estimating three parameters rather than four
ERG: Proportional hazards assumption not substantiated; should fit functions independently
Committee: Independent fitting of Weibull functions without proportional hazards assumption
ICER impact: decreases
Manufacturer initially assumed proportional hazards with only treatment effect differences between fitted distributions. Committee noted this strong assumption was not substantiated by RCT data and could overestimate clinical and cost effectiveness.
Company: Assumed proportional hazards such that only treatment effect differed between distributions
Committee: Relax the proportional hazards assumption and independently fit Weibull functions, resulting in ICER of £15,775 per QALY gained
ICER impact: decreases
Choice of Weibull model for extrapolating survival data to 30 years
Company: Used Weibull function to extrapolate hazard rates from trial data (limited to 1500 days) to 30 years
ERG: Weibull choice not sufficiently justified; proportional hazards assumption not substantiated; proposed limiting extrapolation to Kaplan-Meier estimates to 1500 days only
Committee: Accepted ERG concerns but allowed exploration of multiple survival models; manufacturer provided additional analyses with exponential and independently fitted Weibull functions
ICER impact: increases
Choice of parametric model for extrapolating survival beyond trial follow-up
Company: Weibull model with proportional hazards assumption across groups
ERG: Weibull model choice not justified; proportional hazards assumption not substantiated by trial data
Committee: Exponential model shown to be best fit; independent fitting of Weibull without proportional hazards assumption
ICER impact: decreases
Manufacturer initially excluded the protocol-driven event-free period when fitting parametric distributions to trial data. Committee rejected this approach as excluding the event-free period could change goodness-of-fit and influence cost-effectiveness results.
Company: Excluded the protocol-driven event-free period when initially fitting distributions
Committee: Include the event-free period when fitting distributions; additional manufacturer analysis using Weibull and exponential models resulted in ICERs of £21,379 (Weibull) and £16,183 (exponential) respectively
Duration of benefit from rituximab treatment
Company: Assumed benefit equivalent to baseline risk after 5 years
ERG: Suggested limiting to observed trial period (1500 days)
Committee: Sensitivity analyses conducted with varying durations (2-5 years)
ICER impact: increases
Duration of treatment benefit assumed in extrapolation
Company: Not explicitly stated
Committee: 5-year duration of treatment benefit over lifetime horizon is reasonable
ICER impact: uncertain_direction
Duration of treatment benefit assumption in survival extrapolation model
Committee: 5 years treatment benefit duration, which was considered reasonable
ICER impact: uncertain_direction
Evidence gaps
Special considerations
Cross-references