TA1110 · STA
Source documents
Intervention
Condition
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| androgen deprivation therapy (adt) alone | standard of care | Yes | — |
| docetaxel plus adt plus prednisolone | active drug | Yes | — |
| adt alone | standard of care | Yes | — |
| docetaxel in combination | active drug | Yes | Yes |
| enzalutamide plus adt | active drug | Yes | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| LATITUDE | RCT | not stated | Yes |
| STAMPEDE | RCT | not stated | Yes |
Economic model
ICER
Methodological decisions (20)
Committee recognized need to consider separate analysis for population where docetaxel is contraindicated or unsuitable, but acknowledged that defining this population clinically is complex
Committee: For whole population: both ADT alone and docetaxel in combination are appropriate comparators; separate consideration possible for chemotherapy-ineligible group if cost-effective for whole population not demonstrated
Whether ADT alone is an appropriate comparator for people for whom docetaxel is contraindicated or unsuitable versus the general population
Company: presented single modelled comparison with ADT alone for the docetaxel-contraindicated population
Committee: concluded company's modelled comparison with ADT alone was not a valid estimate for people for whom docetaxel is contraindicated or unsuitable but used it in absence of specific data
ICER impact: increases
Modelling of costs and benefits of follow-on treatments in hormone-relapsed phase
Company: Company modelled treatment pathways based on opinion of 4 clinicians regarding NHS market shares; assumed 80% had abiraterone or enzalutamide after progression; modelled costs of multiple follow-on treatments
ERG: not stated
Committee: Committee noted mismatch between modelled treatments and proportions in trials; noted model accounted for costs but potentially not all life-extending benefits; concluded accounting for costs but not benefits could bias ICER upwards
ICER impact: increases
Whether abiraterone in combination and docetaxel in combination can be assumed equivalent in overall survival
Company: Company used indirect comparison with hazard ratio from NMA (academic in confidence)
ERG: not stated
Committee: Committee considered useful scenario assuming equal hazard of overall survival (HR 1.00) between abiraterone in combination and docetaxel; also considered scenario using HR 1.13 from STAMPEDE direct comparison metastatic subgroup
ICER impact: uncertain_direction
Company developed network meta-analysis to compare abiraterone with docetaxel in combination, incorporating STAMPEDE and additional trials, arguing STAMPEDE subgroup analysis was underpowered and did not reflect licensed population
Company: Network meta-analysis incorporating multiple trials is more appropriate than STAMPEDE subgroup analysis
Committee: Direct data from STAMPEDE is preferred for comparing abiraterone with docetaxel
Company developed network meta-analysis for abiraterone vs docetaxel comparison, incorporating LATITUDE, STAMPEDE, CHAARTED, and GETUG-AFU 15. Committee preferred direct comparison from STAMPEDE metastatic subgroup.
Company: Network meta-analysis should be used as it includes multiple trials and contributes additional information on treatment effect
Committee: Direct randomised comparison from STAMPEDE is preferred as less likely to be biased
ICER impact: uncertain_direction
Original multistate Markov model did not provide plausible estimates. Company revised to partitioned survival model.
Committee: Partitioned survival model is appropriate
ICER impact: negligible
Choice between Markov vs partitioned survival model structure
Company: Company initially submitted multistate Markov model; revised to partitioned survival model after committee feedback
ERG: not stated
Committee: Committee deemed Markov model did not provide plausible estimates of post-progression or overall survival and did not generate valid cost-effectiveness estimates; agreed partitioned survival model was appropriate
ICER impact: uncertain_direction
LATITUDE and STAMPEDE included only people with adequate haematological function and ECOG/WHO performance status 0-2. No specific data for people for whom docetaxel is contraindicated or unsuitable.
Company: Treatment effect from whole LATITUDE population can be used to represent people for whom docetaxel is contraindicated or unsuitable
Committee: Data specific to docetaxel-ineligible population is preferred, but acknowledges unavailability and uses LATITUDE whole population with uncertainty acknowledged
ICER impact: increases
Whether trial data from LATITUDE (whole population including those able to have docetaxel) can be generalised to people for whom docetaxel is contraindicated or unsuitable
Company: Company considered results of LATITUDE could be generalised to people who cannot or should not have docetaxel
ERG: not stated
Committee: Committee agreed it was not possible to determine the size of effectiveness for people for whom docetaxel is contraindicated or unsuitable; not presented with data on effectiveness in this subgroup
ICER impact: uncertain_direction
Whether LATITUDE trial population data represent people for whom docetaxel is contraindicated or unsuitable. Committee acknowledged considerable uncertainty when using whole LATITUDE population to estimate cost-effectiveness for this subgroup due to lack of specific data
Company: presented modelled comparison with ADT using whole LATITUDE population
ERG: presented scenarios removing chemotherapy follow-on treatment and associated survival benefit to model the docetaxel-contraindicated subgroup
Committee: acknowledged uncertainty and noted that even in company's base case and ERG scenarios, ICERs for this subgroup exceeded £30,000 per QALY
ICER impact: increases
Whether hazards of progression and death are proportional between arms
Company: Company agreed hazards were not proportional
ERG: not stated
Committee: Committee agreed with company that hazards were not proportional; appropriate to fit curves to each arm separately
ICER impact: negligible
Choice of parametric distribution for extrapolating progression-free and overall survival from LATITUDE
Company: Company presented both log-logistic (considered plausible but optimistic) and Weibull (considered plausible but pessimistic) distributions
ERG: ERG highlighted that model assumed treatment effect maintained long-term; may wane in clinical practice; provided scenarios for adjustment
Committee: Weibull distribution broadly appropriate for progression-free survival; log-logistic distribution plausible for overall survival in full trial population. Would have preferred further extrapolations for subgroup of people unable to have docetaxel
ICER impact: uncertain_direction
Committee considered scenarios for overall survival hazard ratios for abiraterone in combination compared with docetaxel in combination: direct comparison HR of 1.13 from STAMPEDE metastatic subgroup, company's indirect comparison (confidential), and assumption of equal hazards at various time points
Company: presented indirect comparison with confidential HR
Committee: approved use of direct comparison HR of 1.13 from STAMPEDE metastatic subgroup and equal hazards scenarios to account for potential treatment waning
ICER impact: uncertain_direction
Whether treatment effect of abiraterone compared with comparators is maintained long-term or wanes over time
Company: Company model assumed treatment effect maintained over long term
ERG: ERG provided scenarios to adjust for potential treatment waning
Committee: Committee noted longer-term STAMPEDE data (8-year follow-up) supported ongoing benefit; agreed scenarios exploring alternative time points for treatment waning were useful
ICER impact: decreases
Use of abiraterone in first-line hormone-sensitive disease limits follow-on treatment options because abiraterone and enzalutamide are commissioned only once in treatment pathway, whereas docetaxel or ADT-first approaches preserve more options
Committee: First-choice treatment affects follow-on treatments; abiraterone in combination limits options compared to ADT alone or docetaxel in combination
Trials included follow-on treatments (docetaxel, abiraterone, enzalutamide for hormone-relapsed disease) that would not be available to people who cannot have docetaxel, but this was reflected in trial survival estimates.
Company: LATITUDE results can be generalised to docetaxel-ineligible people
Committee: LATITUDE survival estimates include docetaxel-based follow-on treatments not applicable to docetaxel-ineligible patients; STAMPEDE estimates more relevant to NHS practice
ICER impact: increases
Whether treatment pathway in LATITUDE (including docetaxel for hormone-relapsed disease) reflects real-world pathway for people who cannot have docetaxel
Company: Company based modelling on LATITUDE results assuming follow-on docetaxel use
ERG: not stated
Committee: Committee concluded that overall survival estimates from LATITUDE included effect of docetaxel in hormone-relapsed phase which would not apply to people who cannot have docetaxel; preferred a model reflecting actual treatment pathway
ICER impact: increases
Modelling of subsequent treatment (chemotherapy as follow-on) and associated survival benefit for people in whom docetaxel is contraindicated or unsuitable
Company: included chemotherapy follow-on treatment in base case
ERG: removed chemotherapy follow-on treatment and survival benefit in scenario analyses
Committee: acknowledged validity concern with company's approach for docetaxel-contraindicated population but used it as best available evidence
ICER impact: uncertain_direction
Source of health-related quality of life data for utility values in the model
Company: Company used EQ-5D from LATITUDE for ADT and abiraterone in combination; used separate preference study (general public) for docetaxel disutility
ERG: ERG derived docetaxel disutility from EQ-5D data in STAMPEDE and carried out scenario; stated consistent with company approach
Committee: Committee preferred EQ-5D data from STAMPEDE metastatic subgroup (high-risk hormone-sensitive) where data available for all three arms (abiraterone in combination, docetaxel in combination, ADT alone). In absence of company access to STAMPEDE EQ-5D, company's and ERG's approaches were broadly consistent and acceptable
ICER impact: negligible
Evidence gaps
Commercial arrangement
Special considerations
Cross-references