TA882 · STA
Only recommended if the company provides voclosporin with mycophenolate mofetil according to the commercial arrangement (simple discount patient access scheme)
Source documents
Intervention
Conditions
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| mycophenolate mofetil alone | standard of care | Yes | Yes |
| tacrolimus with mycophenolate mofetil | active drug | Yes | Yes |
| tacrolimus | active drug | Yes | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| AURORA 1 | RCT | Phase 3 | Yes |
| AURORA 2 | RCT | Phase 3 | Yes |
Economic model
ICER
Methodological decisions (12)
Additional monitoring costs for voclosporin versus tacrolimus
Company: voclosporin does not require additional monitoring because it has predictable pharmacokinetics allowing fixed dosing
ERG: inconsistent with costs modelled for tacrolimus
Committee: extra monitoring costs for voclosporin not appropriate; voclosporin does not need therapeutic drug monitoring like tacrolimus
ICER impact: negligible
Treatment discontinuation for non-trial comparators (tacrolimus, standard of care)
Company: initially assumed no discontinuation due to lack of evidence
ERG: clinically implausible; preferred to assume discontinuation equal to mycophenolate mofetil
Committee: company updated to assume discontinuation equal to voclosporin; assumptions did not have significant impact on cost-effectiveness
ICER impact: negligible
Fixed effects vs random effects network meta-analysis
Company: Fixed effects network meta-analysis justified because random effects estimates were not converging
ERG: Random effects network meta-analysis should be implemented using informative priors to account for considerable variation across trials
Committee: Random effects network meta-analysis was preferred and implemented in company's updated base case
ICER impact: negligible
Network meta-analysis heterogeneity across populations and trial outcomes
Company: network meta-analysis was appropriate
ERG: appropriate but heterogeneity increased uncertainty
Committee: heterogeneity noted; longer-term extrapolations particularly uncertain when associated with heterogeneity
ICER impact: increases
Whether people with stages 3b to 4 CKD could have a response
Company: People with stages 3b to 4 CKD modelled as unable to have response; provided scenario analyses showing 2.5% response rate but did not implement in base case
ERG: Clinical experts agreed response rate should not be zero and this should be reflected in base case
Committee: Assumption that people with stages 3b to 4 CKD could not have a response was acceptable; cost-effectiveness estimates insensitive to this assumption
ICER impact: negligible
Method for deriving transition probabilities from AURORA trials
Company: Used 'count method' due to limitations with alternative statistical methods which provided unrealistic outcomes
ERG: Acknowledged company's efforts but noted inherent uncertainties remain with count method
Committee: Company's explanation accepted; uncertainty remains
ICER impact: uncertain_direction
Company modelled people with stages 3b to 4 CKD as unable to have a response; EAG and clinical experts disagreed. Company provided scenario analyses allowing 2.5% response but did not implement in base case.
Company: no response for stages 3b to 4 CKD is reasonable; impact is small
ERG: clinical experts agreed number with response was not zero and should be reflected in base case
Committee: cost-effectiveness estimates were insensitive to this assumption; not a key uncertainty
ICER impact: negligible
Proportion of people with stage 5 CKD receiving kidney transplant
Company: Original base case used estimate considered too high
ERG: 65% transplantation rate based on clinical advice
Committee: 65% transplantation rate accepted
ICER impact: uncertain_direction
Corticosteroid doses used in AURORA trials compared to NHS clinical practice
Company: Lower doses used in trials are effective and in line with guidelines
ERG: Agreed steroid doses were lower than clinical practice but still effective
Committee: AURORA trials generalisable to UK but steroid doses may not reflect established NHS clinical practice
ICER impact: uncertain_direction
39.5% of AURORA 1 participants did not enrol in AURORA 2; impact on discontinuation analysis
Company: Provided scenario analyses with different assumptions for discontinuation (last observation carried forward, and two alternative scenarios)
ERG: Only last observation carried forward scenario was appropriate
Committee: Company efforts satisfactory; last observation carried forward scenario likely clinically plausible and slightly reduces cost-effectiveness
ICER impact: decreases
Treatment duration modelled at 36 months in line with AURORA data
Company: clinical experts supported stopping at 36 months; provided scenarios for 12 and 18 month durations
ERG: scenarios helpful but uncertain because retreatment not included
Committee: 36 months assumption arbitrary; almost half of people stopped by this point; clinical experts suggested ~9-12 months expected; key uncertainty is that retreatment not included in model
ICER impact: increases
Long-term treatment effect extrapolation beyond 36 months of trial data
Company: assumed long-term transition probabilities equal average of month 30 and 36 data with treatment waning; for active disease and partial response, voclosporin effect equals mycophenolate mofetil alone after 36 months; for complete response, equals average of both
ERG: considerable uncertainty using short-term data to predict off-treatment long-term outcomes; preferred to assume voclosporin plus mycophenolate and mycophenolate alone equal based on average transition probabilities
Committee: longer-term efficacy difficult to establish from short-term data; uncertainty with both approaches; model flexibility prevented EAG implementing preferred base case
ICER impact: increases
Evidence gaps
Commercial arrangement
Special considerations