TA886 · STA
Only recommended if the company provides it according to the commercial arrangement (commercial access agreement with confidential discount)
Source documents
Intervention
Condition
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| routine monitoring for cancer recurrence | no treatment | Yes | — |
| placebo | placebo | — | — |
| routine monitoring | standard of care | — | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| OlympiA | RCT | Phase 3 | Yes |
Economic model
ICER
Methodological decisions (10)
Company assumed BRCA testing costs were zero, arguing most people with HER2-negative high-risk early breast cancer undergo routine BRCA screening. EAG questioned this for hormone receptor-positive HER2-negative population.
Company: No additional BRCA testing costs as routine BRCA screening already performed for eligible patients under National Genetic Test Directory criteria
ERG: BRCA testing costs should be included for hormone receptor-positive HER2-negative population
Committee: Company position accepted; most patients with HER2-negative early breast cancer at high risk meet current testing criteria
ICER impact: negligible
Risk of recurrence assumption in triple-negative breast cancer population after 5 years
Company: 0% chance of recurrence after 5 years
ERG: 5% risk from year 5 to year 15
Committee: 2% to 3% risk of recurrence between years 5 and 8, while uncertain, was reasonable
ICER impact: uncertain direction
Company proposed 1.5% discount rates for costs and outcomes for triple-negative population instead of standard 3.5%, arguing immature long-term data.
Company: Discount rates of 1.5% for costs and outcomes in triple-negative population
ERG: Standard 3.5% discount rates appropriate; immaturity and uncertainty of data means olaparib unlikely to restore full health or provide sustained benefits to justify reduced rate
Committee: Standard 3.5% discount rates apply; olaparib does not meet criteria for reduced rate (75.4% of placebo arm had no invasive DFS event by 4 years)
ICER impact: increases
Committee noted concern about company's utility values being unrealistically high and not consistent with other TA estimates for triple-negative breast cancer. Also questioned whether mapped values from OlympiA were plausible.
Company: Utility values estimated from OlympiA trial data are appropriate
Committee: Company's estimates implausibly high; disease-free value (0.869) only slightly lower than age-matched general population (0.877), unrealistic for patients post-surgery and chemotherapy
ICER impact: decreases
Choice of distribution for extrapolating recurrence in hormone receptor-positive HER2-negative breast cancer population beyond trial data
Company: log-normal distribution
ERG: generalised gamma distribution
Committee: Insufficient evidence to determine; noted clinical experts' opinion that little difference between distributions for long-term invasive disease-free survival
ICER impact: small effect on ICERs
Choice of distribution for extrapolating survival after early metastatic recurrence
Company: exponential distribution
ERG: Gompertz distribution (due to non-proportional hazards)
Committee: Did not discuss further given small effect on ICER
ICER impact: small effect on ICER
Source and values for health-related quality of life in health states, particularly disease-free state
Company: EORTC QLQ-C30 data from OlympiA mapped to EQ-5D-3L using Crott and Briggs algorithm; utility values 0.869 (disease-free and non-metastatic), 0.685 (metastatic)
ERG: Verrill et al. 2020 UK study in HER2-positive breast cancer population; utility values 0.732 (disease-free), 0.668 (non-metastatic), 0.603 (metastatic); with age-adjustment: 0.770, 0.702, 0.634
Committee: EAG's age-adjusted utility values from Verrill et al. were most appropriate
ICER impact: increases
Company used EQ-5D-3L mapped from EORTC QLQ-C30 in OlympiA. EAG used UK study (Verrill et al. 2020) with direct EQ-5D measurement in HER2-positive breast cancer populations.
Company: Health-related quality-of-life data from EORTC QLQ-C30 in OlympiA, mapped to EQ-5D-3L; utility values 0.869 (disease-free and non-metastatic), 0.685 (metastatic)
ERG: External UK study (Verrill et al. 2020) with age-adjusted estimates: 0.770 (disease-free), 0.702 (non-metastatic), 0.634 (metastatic)
Committee: EAG's age-adjusted estimates from Verrill et al. were most appropriate
ICER impact: decreases
Whether to use same utility value for disease-free and non-metastatic breast cancer (local recurrence) health states
Company: Same utility value (0.869) for both disease-free and non-metastatic breast cancer health states based on non-significant difference in trial
ERG: Different utilities warranted
Committee: Different utilities should be used; same utility value was unrealistic given anxiety of local recurrence and probable further surgery
ICER impact: increases
Company assumed non-metastatic breast cancer utility equal to disease-free utility (difference non-significant). Committee concerned this was unrealistic given anxiety associated with local recurrence and possible further surgery.
Company: Non-metastatic breast cancer utility set equal to disease-free utility value (0.869) as difference was non-significant
Committee: Separate utility value for non-metastatic breast cancer reflecting anxiety and probable further surgery
ICER impact: decreases
Evidence gaps
Commercial arrangement
Special considerations