Table 1.
Estimation of HSUVs in RDs: a review of NICE TA/HST guidance documents
| Report code (ref.) | Drug | Manufacturer’s approach | NICE/ERG’s notes/recommendations |
|---|---|---|---|
| Report date | Disease | ||
| HST6 [25] | Asfotase alfa | Mean utility values included in the company’s economic model were estimated by 9 clinical experts who completed the EQ-5D-5L for vignettes for each health state based on the 6MWT severity levels | The ERG felt that deriving HSUVs from clinical experts rather than from clinical studies is a limitation. Moreover, the 6MWT does not capture all the symptoms of hypophosphatasia and the EQ-5D domains, although clinicians may have considered these when providing HSUVs for the illustrative vignettes. However, the HSUVs obtained by the experts seem reasonable. |
| 2/8/2017 | Paediatric-onset hypophosphatasia | ||
| HST1 [26] | Eculizumab | EQ-5D was collected from 37 patients within two clinical studies (C08-002A/B and C08-003A/B) | None |
| 28/1/2015 | Atypical haemolytic uremic syndrome | ||
| HST4 [27] | Migalastat | Complication-related disutilities were derived from a group with Fabry diseases. Infusion-related disutilities were derived from a DCE performed with 506 people from the UK general population. | The ERG noted uncertainty about the comparability of infusion disutilities with those of disease complications given the differences in the methods used for estimation. The ERG did a scenario analysis with utilities derived from alternative sources and reduced infusion-related disutilities. |
| 22/2/2017 | Fabry Disease | ||
| HST9 [28] | Inotersen |
Original approach: published literature (Stewart 2017, which reports EQ-5D utilities using a Brazilian value set). Revised approach: using one or two EQ-5D health states in which the values from the Brazilian data were closest to the mean disease stage values for patients in the preferred THAOS registry (i.e., a global registry owned by another company). |
The ERG argued that using EQ-5D values based on Brazilian general population preferences was questionable because there are important differences in preferences for health states between the UK and Brazilian population. The revised approach, although not optimal, was acceptable for decision-making. |
| 22/5/2019 | Hereditary transthyretin amyloidosis | ||
| HST10 [29] | Patisiran | The company used the EQ-5D-5L utility values collected in APOLLO trial mapped to EQ-5D-3L (using Van Hout 2012) for a regression model relating HRQoL to PND scores and the interaction between time and treatment | The ERG considered the regression to be unreliable because it excluded important parameters (e.g., cardiac involvement) and included the interaction between time and treatment without the main terms (i.e., time and treatment). |
| 14/8/2019 | Hereditary transthyretin amyloidosis | ||
| HST11 [30] | Voretigene neparvovec | Vignettes were developed for each health state using clinicians and patient input. The company then asked six clinicians to complete HUI3 and EQ-5D for each health state in the economic model. The company preferred to use HUI3 because it contains a visual component. | The committee noted that the company’s methods have several serious limitations: (1) small number of clinicians taking part in the vignette study; (2) ophthalmologists may focus on issues related to vision loss, which may have underestimated the overall HRQoL. The ERG suggested using utilities from Rentz 2014, a general public time trade-off study that looked at 8 health states with varying degree of vision problems defined by the NEI VFQ-25 items. The committee considered that neither source of data was sufficiently robust but the HSUVs in the models are likely to fall between the values from Rentz et al. and the EQ-5D company values. |
| 9/10/2019 | Inherited retinal dystrophies | ||
| TA266 [31] | Mannitol dry powder | HUI2 was collected from patients in a clinical trial (DPM-CF-302); literature values were also included for lung transplantation and pulmonary exacerbations. | The committee was concerned by the use of HUI2 instead of EQ-5D that is the preferred measure by NICE and was not convinced that HRQoL of patients had been valued with any certainty. |
| 28/11/2012 | Cystic fibrosis | ||
| TA398 [32] | Lumacaftor–ivacaftor | A multivariate mixed-model repeated measures regression analysis was used to model the relationship between EQ-5D utility values, lung function (ppFEV1) and pulmonary exacerbations reported in TRAFFIC and TRANSPORT trials. Utility values for lung transplants were taken from Whiting 2014. | The committee appreciated that the company had included EQ-5D data, as preferred by NICE. There was no evidence to suggest that the EQ-5D was inappropriate and it generally captured the effects of having cystic fibrosis and its treatment. |
| 27/07/2016 | Cystic fibrosis | ||
| TA276 [33] | Colistimethate sodium and tobramycin dry powders for inhalation | CFQ data collected in a clinical trial were mapped to EQ-5D using published coefficients (Eidt-Koch 2009) | The Assessment Group highlighted the shortcomings in the use of the mapping approach to produce HSUVs. The ERG developed a de novo model deriving HSUVs from the Bradley (2010) study. |
| 27/3/2013 | Pseudomonas lung infection in cystic fibrosis | ||
| HST2 [34] | Elosulfase alfa |
Original approach: HSUVs were based on the general population (asymptomatic state), an observational study of the natural history of MPS IVa using EQ-5D-5L, and cross-sectional surveys of people with the conditions and their families. Revised approach: HSUVs were obtained from the literature. |
The committee noted that the effect of the condition on HRQoL had been assessed using EQ-5D-5L in a natural history study, while the clinical trials on elosulfase alfa collected only limited evidence on HRQoL and did not collect EQ-5D. Therefore, although it was reasonable to include a utility increment with elosulfase alfa, the existing evidence did not allow this benefit to be estimated robustly. |
| 16/12/2015 | Mucopolysaccharidosis type IVa | ||
| HST8 [24] | Burosumab | The company conducted a utility study in which vignettes describing the modelled health states were developed. The vignettes were valued using EQ-5D-5L by 6 clinical experts. An additional value was inferred for the healed health state. | The committed noted that the utilities were scored by clinicians not patients, and were not taken directly from trials, which were limitations of the data. It concluded that the utility values were uncertain but, in the absence of an alternative, were acceptable for decision-making. |
| 10/10/2018 | X-linked hypophosphatemia | ||
| HST7 [35] | Strimvelis | Quality of life data collected in the STRIMVELIS clinical trials were too limited to be included in the model. The company instead used utilities from the literature. No disutility was considered for people having intravenous immunoglobulin (IVIG) or for those who had severe infections. The impact of these assumptions was explored in sensitivity and scenario analyses. | The ERG preferred to incorporate the company's scenario analysis in which a utility weight was applied to people who had IVIG. The committee concluded that, because the ERG's preferred assumptions were based on available evidence, they were preferable for decision-making. |
| 7/2/2018 | Adenosine deaminase deficiency-severe combined immunodeficiency | ||
| TA588 [36] | Nusinersen | The company generated patient utilities from the clinical advisers. The carer-related utilities used by the company assumed that the best health state was associated with general population utility, and the worst health state was the average carer utility from a literature source. | The committee recognised that identifying robust utility values in babies and young children is exceptionally challenging. The ERG considered the company’s approach as the most appropriate. However, it noted that the utility estimates should be considered cautiously because they are not based on formal elicitation methods, may be different if other clinicians valued the health states and may not accurately reflect the view of people with SMA or their carers. Moreover, the estimates of carer utilities used in the model should be treated with caution because most were driven by assumptions rather than by evidence. |
| 24/7/2019 | Spinal muscular atrophy | ||
| TA431 [37] | Mepolizumab | EQ-5D was collected in DREAM trial | The committee noted that the company did not adjust utilities by age because DREAM showed there was no difference between age and utility. The committee considered the ERG's comment that DREAM was not powered to detect age-dependent utilities and noted that there were fewer patients underpinning the data for utilities in older people. The committee concluded that it preferred the ERG's base case, which applied age-adjusted utilities. |
| 25/1/2017 | Severe refractory eosinophilic asthma | ||
| HST5 [38] | Eliglustat | The SF-36 collected in the GD-DS3 score study was mapped to EQ-5D using a published algorithm. The utility increment (0.12) of oral therapy over infusion therapy was taken from a vignette study | The ERG agreed that the GD-DS3 score study provided the most complete set of utility values. It also agreed that oral therapy would provide a clear quality-of-life benefit but questioned the extent of the benefit assumed by the company, even though this was based on a vignette study, and proposed the alternative utility increment of 0.5. The committee concluded that, although the true value was uncertain, the alternative value used by the ERG was more appropriate. |
| 28/6/2017 | Gaucher disease (type 1) | ||
| TA467 [39] | Holoclar | The value of the utility decrement for disfigurement used in the company’s model was taken from a bespoke standard gamble (SG) stated preference exercise in 520 UK participants who were presented with various clinical scenarios describing moderate to severe LSCD, including an image of a patient’s eye with this condition. The estimated utility decrement for disfigurement was consistent with the opinion of clinical experts. | The committee noted that the utility values used in the company’s model were far lower than any used in previous appraisals for eye treatments, noting that ERG had used alternative values. For disfigurement, it used a decrement of 0.140 (rather than the company's assumption of 0.318), using cataracts as a proxy. The committee recognised that cataract disutilities were used as a proxy for disfigurement, and although uncertainty remained in the utilities, the ERG's values were a more realistic reflection of the impact on HRQoL. |
| 16/8/2017 | Limbal stem cell deficiency after eye burns | ||
| TA606 [40] | Lanadelumab | The company used utility values from Nordenfelt 2014, which is a Swedish study that included EQ-5D-5L values for both the attack-free and the attack health states. The company explained that the EQ-5D-5L values collected in the HELP-03 trial were limited and could not be used in the model. | The committee concluded that the company's preferred utility values that included a benefit for lanadelumab subcutaneous administration were acceptable for decision-making |
| 16/10/2019 | Hereditary angioedema | ||
| TA443 [41] | Obeticholic acid | HRQoL data were not collected in POISE trial so the company used utility values from published literature (Younossi 2001 and Wright 2006, used in NICE's technology appraisal guidance on sofosbuvir for treating chronic hepatitis C) | The committee acknowledged the uncertainty associated with the utility values but accepted that they had been derived from published sources |
| 26/4/2017 | Primary biliary cholangitis | ||
| TA491 [42] | Ibrutinib | EQ-5D-5L data were collected in the RESONATE CLL trial. The utility decrements associated with progression and adverse events were based on published literature (Beusterien 2010, Tolley 2013). | Clinical advisors to the ERG noted that given the lack of HRQoL data available for patients with WM, the use of utilities from a CLL study by proxy may be reasonable |
| 22/11/2017 | Waldenstrom’s macroglobulinaemia | ||
| TA379 [43] | Nintedanib | The company assigned utility values to each health state in the model using EQ-5D data collected in the INPULSIS trials | The committee approved of the company using trial-based EQ-5D data to estimate HSUVs |
| 27/1/2016 | Idiopathic pulmonary fibrosis | ||
| HST3 [44] | Ataluren | The company model included HRQoL data from the literature (Landfeldt et al. 2014) to inform the utility values for patients and carers | The committee concluded that it is imperative that its future review includes carer utility data |
| 20/7/2016 | Duchenne muscular dystrophy | ||
| HST12 [45] | Cerliponase alfa | The company commissioned a utility study in which vignettes describing health states for both cerliponase alfa and standard care were developed. The vignettes were validated by a clinical expert and sent to 8 clinical experts who completed the EQ-5D-5L questionnaire as a proxy for patients. These were mapped to the EQ-5D-3L before being applied in the model. The company also included disutilities for carers and siblings. | The committee was concerned about the robustness of the vignettes used to elicit these utility values. It noted that they contained additional disease elements that had an unclear association with the motor and language scale that defined the health states. However, it concluded that, in the absence of further evidence, it would consider EQ-5D-3L values estimated from the utility study using vignettes. The committee was satisfied with the principle of including disutility values for carers and siblings but agreed with the ERG that applying them for the whole 95-year time horizon was unrealistic given the life expectancy of parents, and also because disutility may change as siblings grow up and move on. |
| 27/11/2019 | Neuronal ceroid lipofuscinosis type 2 |
6MWT 6-min walk test, CFQ cystic fibrosis questionnaire, CLL chronic lymphocytic leukaemia, EQ-5D EuroQol-5 Dimension, EQ-5D-Y EuroQol-5 Dimension-Youth, ERG Evidence Review Group, HRQoL health-related quality of life, HST highly specialized technology, HSUVs health state utility values, HUI Health Utility Index, LSCD limbal stem cell deficiency, SMA spinal muscular atrophy, NEI VFQ National Eye Institute Visual Function Questionnaire, NICE National Institute for Health and Care Excellence, PND polyneuropathy disability, TA technology appraisal