UNASSIGNED: Renal cell carcinoma is the most common type of kidney cancer, comprising approximately 85% of all renal malignancies. Patients with advanced renal cell carcinoma are the focus of this National Institute for Health and Care Excellence multiple technology appraisal. A patient\'s risk of disease progression depends on a number of prognostic risk factors; patients are categorised as having intermediate/poor risk or favourable risk of disease progression.
UNASSIGNED: The objectives of this multiple technology appraisal were to appraise the clinical effectiveness and cost-effectiveness of lenvatinib plus pembrolizumab versus relevant comparators listed in the final scope issued by the National Institute for Health and Care Excellence: sunitinib, pazopanib, tivozanib, cabozantinib and nivolumab plus ipilimumab.
UNASSIGNED: The assessment group carried out clinical and economic systematic reviews and assessed the clinical and cost-effectiveness evidence submitted by Eisai, Hatfield, Hertfordshire, UK (the manufacturer of lenvatinib) and Merck Sharp & Dohme, Whitehouse Station, NJ, USA (the manufacturer of pembrolizumab). The assessment group carried out fixed-effects network meta-analyses using a Bayesian framework to generate evidence for clinical effectiveness. As convergence issues occurred due to sparse data, random-effects network meta-analysis results were unusable. The assessment group did not develop a de novo economic model, but instead modified the partitioned survival model provided by Merck Sharp & Dohme.
UNASSIGNED: The assessment group clinical systematic review identified one relevant randomised controlled trial (CLEAR trial). The CLEAR trial is a good-quality, phase III, multicentre, open-label trial that provided evidence for the efficacy and safety of lenvatinib plus pembrolizumab compared with sunitinib. The assessment group progression-free survival network meta-analysis results for all three risk groups should not be used to infer any statistically significant difference (or lack of statistically significant difference) for any of the treatment comparisons owing to within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption. The assessment group overall survival network meta-analysis results for the intermediate-/poor-risk subgroup suggested that there was a numerical, but not statistically significant, improvement in the overall survival for patients treated with lenvatinib plus pembrolizumab compared with patients treated with cabozantinib or nivolumab plus ipilimumab. Because of within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption, the assessment group overall survival network meta-analysis results for the favourable-risk subgroup and the all-risk population should not be used to infer any statistically significant difference (or lack of statistically significant difference) for any of the treatment comparisons. Only one cost-effectiveness study was included in the assessment group review of cost-effectiveness evidence. The study was limited to the all-risk population, undertaken from the perspective of the US healthcare system and included comparators that are not recommended by the National Institute for Health and Care Excellence for patients with untreated advanced renal cell carcinoma. Therefore, the extent to which resource use and results are generalisable to the NHS is unclear. The assessment group cost-effectiveness results from the modified partitioned survival model focused on the intermediate-/poor-risk and favourable-risk subgroups. The assessment group cost-effectiveness results, generated using list prices for all drugs, showed that, for all comparisons in the favourable-risk subgroup, treatment with lenvatinib plus pembrolizumab costs more and generated fewer benefits than all other treatments available to NHS patients. For the intermediate-/poor-risk subgroup, treatment with lenvatinib plus pembrolizumab costs more and generated more benefits than treatment with cabozantinib and nivolumab plus ipilimumab.
UNASSIGNED: Good-quality clinical effectiveness evidence for the comparison of lenvatinib plus pembrolizumab with sunitinib is available from the CLEAR trial. For most of the assessment group Bayesian hazard ratio network meta-analysis comparisons, it is difficult to reach conclusions due to within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption. However, the data (clinical effectiveness and cost-effectiveness) used to populate the economic model are relevant to NHS clinical practice and can be used to inform National Institute for Health and Care Excellence decision-making. The assessment group cost-effectiveness results, generated using list prices for all drugs, show that lenvatinib plus pembrolizumab is less cost-effective than all other treatment options.
UNASSIGNED: This study is registered as PROSPERO CRD4202128587.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis Programme (NIHR award ref: NIHR134985) and is published in full in Health Technology Assessment; Vol. 28, No. 49. See the NIHR Funding and Awards website for further award information.
Renal cell carcinoma is the most common type of kidney cancer. Several drug treatment options are available for NHS patients with advanced or metastatic disease, and the choice of treatment varies depending on a patient’s risk of disease progression. A new drug combination, lenvatinib plus pembrolizumab, may soon become available to treat NHS patients. This review explored whether treatment with lenvatinib plus pembrolizumab offered value for money to the NHS. We reviewed the effectiveness of treatment with lenvatinib plus pembrolizumab versus other NHS treatment options. We also estimated the costs and benefits of treatment with lenvatinib plus pembrolizumab versus current NHS treatments for patients with higher and lower risks of disease progression. Compared with current NHS treatments, treatment with lenvatinib plus pembrolizumab may increase the time that people with a higher risk of disease progression (i.e. worsening disease) were alive. However, for patients with a lower risk of disease progression, the available evidence is limited and only shows that treatment with lenvatinib plus pembrolizumab may prolong the time that patients have a stable level of disease. For all patients, compared to all current NHS treatments, treatment with lenvatinib plus pembrolizumab is very expensive. Compared with current NHS treatments for untreated renal cell carcinoma, using published prices (which do not include any discounts that are offered to the NHS), treatment with lenvatinib plus pembrolizumab may not provide good value for money to the NHS.

BACKGROUND: Vision impairment and blindness are significant global public health challenges, particularly in low- and middle-income countries, where access to eye care services remains limited. India has significantly reduced the prevalence of Blindness and Vision Impairment (VI) over the last two decades. This was achieved with the help of greater investments towards blindness control programs. The use of utility values helps in conducting economic evaluations of various eye health programs and empirically justify investing in these programs. This study aimed to estimate utility values for various childhood eye conditions in central India using the EuroQol-Five-Dimension-Youth (EQ-5D-Y) instrument.
METHODS: This is a before and after study with data collected at two time points for few participants and at only one time point for others. This study was undertaken at Shri Sadguru Netra Chikitsalaya (SNC) and included children representing central and north India. Participants were randomly sampled in the hospital. After comprehensive eye examination, participants completed the EuroQol-Five-Dimension-Youth (EQ-5D-Y) questionnaire along with EuroQol Visual Analogue Scale (EQ VAS) measurement to elicit their health state for their condition which was repeated after six months post-intervention to measure the change in utility value. We have used Indonesian value set to analyze the preference scores of each dimension of EQ-5D-Y.
RESULTS: Utility values of 16 eye conditions were estimated at baseline and seven conditions were followed up for post-intervention utility value estimation. There is a statistically significant improvement in the utility values post-intervention amongst six conditions. Blindness and Pediatric cataract had the greatest change (0.23 and 0.2 respectively) in utility value whereas mild Vision Impairment (VI) showed the least change (0.02) in the utility value post-intervention. Blindness had the lowest baseline (0.62) and post-intervention (0.85) utility value.
CONCLUSIONS: The utility values estimated in this study showed that generic measures such as EQ-5D-Y may be used to elicit health states for various eye conditions amongst children. These estimates are helpful in undertaking cost-utility analyses of eye health programs and interventions aimed at these eye conditions.

OBJECTIVE: The present analysis estimated the cost-effectiveness of treatment with the Tandem t: slim X2 insulin pump with Control IQ technology (CIQ) in children with type 1 diabetes in Sweden.
METHODS: A four-state Markov model and probabilistic sensitivity analyses (PSA) were used to assess the cost-effectiveness of CIQ use compared with treatment with multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII) in conjunction with CGM. Data sources included clinical input data from a recent retrospective, observational study, cost data from local diabetes supply companies and government agencies, and published literature. Outcomes measures were quality adjusted life years (QALYs) at 10, 20 and 30-year time horizons based on cost per QALY and incremental cost-effectiveness ratio (ICER).
RESULTS: A total of 84 type 1 diabetes children were included (CIQ, n = 37; MDI, n = 19; CSII, n = 28). For all time horizons, the use of CIQ was a dominant strategy (e.g. more effective and less costly) compared with MDI or CSII use: 10-year ICER, SEK -88,010.37 and SEK -91,723.92; 20-year ICER, SEK -72,095.33 and SEK -87,707.79; and 30-year ICER, SEK -65,573.01 and SEK -85,495.68, respectively. PSA confirmed that CIQ use was less costly compared with MDI and CSII.
CONCLUSIONS: Initiation of CIQ use in children with type 1 diabetes is cost-saving, besides previously shown improved glycaemic control, and increased quality of life. Further investigations are needed to more fully elucidate the cost-effectiveness of these technologies in different countries with existing differences in payment models.

OBJECTIVE: This study aimed to produce Sri Lankan population norms of utility values, EuroQol visual analog scale scores, and reported problems in each domain of the EQ-5D-5L, as well as a disutility catalog, based on a representative set of Sri Lankan preferences.
METHODS: Data from a nationally representative sample of 6415 adults from the Sri Lanka Health and Ageing Study in 2018 to 2019 were used. Sri Lankan preferences were applied to EQ-5D-5L scores to produce utility values. Descriptive statistics were produced for responses by EQ-5D-5L dimension, mean utility values, and EuroQol visual analog scale scores, disaggregated by demographic and disease group. Multivariable logistic regression assessed associations with problems in each dimension, and demographic and chronic diseases. Robust ordinary least squares and tobit regressions were performed to estimate the marginal disutility of demographic covariates and disease conditions.
RESULTS: The mean utility value for the overall population was 0.867. Utility values decreased with age and increased with increasing education and richer socioeconomic quintiles. Males had higher utility values than females (0.89 vs 0.84; P < .001). Utility values declined by 0.007 with each year increase in age (P < .001) and statistically significant differences (P < .05) in utility were found by ethnicity, socioeconomic quintile, and disease conditions such as stroke, diabetes, cancer, depression, and musculoskeletal conditions, using a tobit regression.
CONCLUSIONS: This study provides the first nationally representative set of population norms based on a local value set for key demographic groups and selected chronic disease conditions for Sri Lanka. It also provides a catalog that can be easily used to calculate quality-adjusted life-years for cost-utility analysis when modeling public health interventions.

The pursuit of value and equity have been put on a legal footing in the NHS with the arrival of the legal duty for all in the NHS to improve health and well-being of the population served, to provide fair access to high quality healthcare, and to use resources sustainably and efficiently. Recognising this we used analysis of variation to help us understand the degree to which we were fulfilling our new duty for people with back pain in Mid-Nottinghamshire and where there might be opportunities for value improvement.MSK Together is a group of clinical and managerial representatives from providers, purchasers, local government, and patients who work collectively to optimise the use of resources for people with MSK conditions in Mid-Nottinghamshire. Back pain is the third largest burden of disease in the locality, and the largest cause of disability, so it is of strategic importance to MSK Together-we wanted to know about, and act on, opportunities for value improvement across the population of people with back pain.In 2019/20, after adjusting for age and sex, we found a greater than three-fold variation among general practices in age-sex standardised rates of all hospital service usage for back pain conditions. When looking at a four-year period (2016/17-2019/20), the observed variation increased to eight-fold for (with narrow 95% confidence intervals). When looking at procedures (e.g., surgery or injections), the standardised variation among general practices was six-fold in 2019/20. The deprivation score of the general practice (a heterogenous measure given the mixed neighbourhoods many general practices serve) showed little correlation to the rates observed and did not appear to justify the variation.When we looked at the deprivation of the neighbourhood from which the individuals receiving back pain procedures came, there appeared to be a weak correlation in terms of lower rates of intervention in the least-deprived compared with the most-deprived communities. This correlation was not tested statistically. People receiving hospital services for back pain appeared to receive the first episode of care most often in their 40s (working age), compared with people from the least-deprived areas who received care most commonly in their 60s (approaching retirement).When we looked at the interventions provided in Mid-Nottinghamshire for back pain, 29 interventions were provided to 17,225 people. Using a recent NICE evaluation of cost-effectiveness of back pain interventions, we established that, of these 29 interventions, 16 have evidence of improving the quality of life, for nine there was no evidence of benefit or harm, for three there was evidence that they do not provide an improvement in quality of life, and for one there was possible evidence of harm. The total cost of interventions was estimated at £4.5 million and, using the evidence from the NICE review, the total quality adjusted life year (QALY) gain to the treated population of people with back pain was calculated to be 4,571 QALYs.After discussions among the MSK Together group, it was agreed that some interventions could be stopped or scaled down, and new interventions introduced (in particular, in more-deprived neighbourhoods). Within the same estimated cost envelope of £4.5 million, the QALY gain was predicted to increase to 7702 QALYs and, by targeting QALY-related interventions to people from deprived neighbourhoods, reduce inequity (and therefore health inequalities).Using variation helped us identify areas for improvement and generated a momentum for change among the MSK Together group. By examining what we were doing, the associated costs, and the likely QALY benefits (from research evidence), we identified lower value interventions to stop or reduce and new interventions to introduce, achieving greater health gain for people with back pain with no additional resource requirements.

OBJECTIVE: Quality-adjusted life years (QALYs) have been challenged as a measure of benefit for people with disabilities, particularly for those in low-utility health states or with irreversible disability. This study examined the impact of a QALY-based assessment on the price for a hypothetical treatment for Duchenne muscular dystrophy (DMD), a progressive, genetic neuromuscular disease.
METHODS: A previously published, 5-state model, which analyzed treatments for early ambulatory (EA) DMD patients, was replicated, validated, and adapted to include early nonambulatory (ENA) DMD patients. The model was used to assess a QALY-based threshold price (maximum cost-effective price) for a hypothetical treatment for 13-year-old ENA and 5-year-old EA patients (initial health states with lower and higher utility, respectively). All inputs were replicated including willingness-to-pay thresholds of $50 000 to $200 000/QALY.
RESULTS: In contrast to EA patients, ENA patients had a 98% modeled decline in QALY-based threshold price at a willingness-to-pay of $150 000/QALY or higher, despite equal treatment benefit (delayed progression/death). At $100 000/QALY or lower, net nontreatment costs exceeded health benefits, implying any treatment for ENA patients would not be considered cost-effective, even at $0 price, including an indefinite pause in disease progression.
CONCLUSIONS: For certain severe, disabling conditions, traditional approaches are likely to conclude that treatments are not cost-effective at any price once a patient progresses to a disabled health state with low utility value. These findings elucidate theoretical/ethical concerns regarding potential discriminatory properties of traditional QALY assessments for people with disabilities, particularly those who have lost ambulation or have other physical limitations.

Rehabilitation technologies offer promising opportunities for interventions for patients with motor disabilities. However, their use in routine care remains limited due to their high cost and persistent doubts about their cost-effectiveness. Providing solid evidence of the economic efficiency of rehabilitation technologies would help dispel these doubts in order to better take advantage of these technologies. In this context, this systematic review aimed to examine the cost-effectiveness of rehabilitation interventions based on the use of digital technologies. In total, 660 articles published between 2011 and 2021 were identified, of which eleven studies met all the inclusion criteria. Of these eleven studies, seven proved to be cost-effective, while four were not. Four studies used cost-utility analyses (CUAs) and seven used cost-minimization analyses (CMAs). The majority (ten studies) focused on the rehabilitation of the upper and/or lower limbs after a stroke, while only one study examined the rehabilitation of the lower limbs after knee arthroplasty. Regarding the evaluated devices, seven studies analyzed the cost-effectiveness of robotic rehabilitation and four analyzed rehabilitation with virtual reality.The assessment of the quality of the included studies using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) suggested that the quality was related to the economic analysis method: all studies that adopted a cost-utility analysis obtained a high quality score (above 80%), while the quality scores of the cost-minimization analyses were average, with the highest score obtained by a CMA being 72%. The average quality score of all the articles was 75%, ranging between 52 and 100. Of the four studies with a considering score, two concluded that there was equivalence between the intervention and conventional care in terms of cost-effectiveness, one concluded that the intervention dominated, while the last one concluded that usual care dominated. This suggests that even considering the quality of the included studies, rehabilitation interventions based on digital technologies remain cost-effective, they improved health outcomes and quality of life for patients with motor disorders while also allowing cost savings.

OBJECTIVE: The 2016 EQ-5D-3L value set for Trinidad and Tobago (T&T) allows for the calculation of EQ-5D-5L values via the crosswalk algorithm. The 2016 value set was based on methods predating the EQ-VT protocol, now considered the gold standard for developing EQ-5D value sets. Furthermore, direct elicitation of EQ-5D-5L is preferred over crosswalked values. This study aimed to produce an EQ-5D-5L value set for T&T.
METHODS: A representative sample (age, sex, geography) of adults each completed 10 composite Time Trade-Off (cTTO) tasks and 12 Discrete Choice Experiment (DCE) tasks in face-to-face interviews. The cTTO data were analyzed using a Tobit model that corrects for heteroskedasticity. DCE data were analyzed using a mixed logit model. The cTTO and DCE data were combined in hybrid models.
RESULTS: One thousand and seventy-nine adults completed the valuation interviews. Among the modelling approaches that were explored, the hybrid heteroskedastic Tobit model produced all internally consistent, statistically significant coefficients, and performed best in terms of out-of-sample predictivity for single states. Compared to the existing EQ-5D-5L crosswalk set, the new value set had a higher number of negative values (236 or 7.6% versus 21 or 0.7%). The mean absolute difference was 0.157 and the correlation coefficient between the two sets was 0.879.
CONCLUSIONS: This study provides a value set for the EQ-5D-5L for T&T using the EQ-VT protocol. We recommend this value set for QALY computations relating to T&T.

OBJECTIVE: The aim of this study is to investigate the cost-effectiveness of revision total knee arthroplasty compared to primary total knee arthroplasty in terms of cost-per-quality-adjusted life year (QALY).
METHODS: Data were retrieved for all primary and revision total knee replacement (TKA) procedures performed at a tertiary Swiss hospital between 2006 and 2019. A Markov model was created to evaluate revision risk and we calculated lifetime QALY gain and lifetime procedure costs through individual EuroQol 5 dimension (EQ-5D) scores, hospital costs, national life expectancy tables and standard discounting processes. Cost-per-QALY gain was calculated for primary and revision procedures.
RESULTS: EQ-5D data were available for 1343 primary and 103 revision procedures. Significant QALY gains were seen following surgery in all cases. Similar, but significantly more QALYs were gained following primary TKA (PTKA) (5.67 ± 3.98) than following revision TKA (RTKA) (4.67 ± 4.20). Cost-per-QALY was €4686 for PTKA and €10,364 for RTKA. The highest average cost-per-QALY was seen in two-stage RTKA (€12,292), followed by one-stage RTKA (€8982).
CONCLUSIONS: RTKA results in a similar QALY gain as PTKA. The costs of achieving health gain are two to three times higher in RTKA, but both procedures are highly cost-effective.
METHODS: Economic level II.

BACKGROUND: The joint evidence of the cost and the effectiveness of family-based therapies is modest.
OBJECTIVE: To study the cost-effectiveness of family therapy (FT) versus treatment-as-usual (TAU) for young people seen after self-harm combining data from an 18-month trial and hospital records up to 60-month from randomisation.
METHODS: We estimate the cost-effectiveness of FT compared to TAU over 5 years using a quasi-Markov state model based on self-harm hospitalisations where probabilities of belonging in a state are directly estimated from hospital data. The primary outcome is quality-adjusted life years (QALY). Cost perspective is NHS and PSS and includes treatment costs, health care use, and hospital attendances whether it is for self-harm or not. Incremental cost-effectiveness ratios are calculated and deterministic and probabilistic sensitivity analyses are conducted.
RESULTS: Both trial arms show a significant decrease in hospitalisations over the 60-month follow-up. In the base case scenario, FT participants incur higher costs (mean +£1,693) and negative incremental QALYs (-0.01) than TAU patients. The associated ICER at 5 years is dominated and the incremental health benefit at the £30,000 per QALY threshold is -0.067. Probabilistic Sensitivity Analysis finds the probability that FT is cost-effective is around 3 - 2% up to a maximum willingness to pay of £50,000 per QALY. This suggest that the extension of the data to 60 months show no difference in effectiveness between treatments.
CONCLUSIONS: Whilst extended trial follow-up from routinely collected statistics is useful to improve the modelling of longer-term cost-effectiveness, FT is not cost-effective relative to TAU and dominated in a cost-utility analysis.