Quality-adjusted Life-year Threshold Research Articles

Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.

In the United States, costs of antidiabetes medications exceed $327 billion. To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes. Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English. Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer. Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative. Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE). Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established. Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions. American College of Physicians. (PROSPERO: CRD42022382315).

The impact of willingness-to-pay threshold on price reduction recommendations for oncology drugs: a review of assessments conducted by the Canadian Agency for Drugs and Technologies in Health.

Since late 2020, the Canadian Agency of Drugs and Technologies in Health (CADTH) has been using a threshold of $50,000(CAD)per quality-adjusted life-year (QALY) for both oncology and non-oncology drugs. When used for oncology products, this threshold is hypothesized to have a higher impact on the time to access these drugs in Canada. We studied the impact of price reductions on time to engagement and negotiation with the pan-Canadian Pharmaceutical Alliance for oncology drugs reviewed by CADTH between January 2020 and December 2022. Overall, 103 assessments reported data on price reductions recommended by CADTH to meet the cost-effectiveness threshold for reimbursement. Of these assessments, 57% (59/103) recommendations included a price reduction of greater than 70% off the list price. Eight percent (8/103) were not cost-effective even at a 100% price reduction. Of the 47 assessments that had a clear benefit, in 21 (45%) CADTH recommended a price reduction of at least 70%. The median time to price negotiation (not including time to engagement) for assessments that received at least 70% vs >70% price reduction was 2.6vs 4.8months. This study showed that there is a divergence between drug sponsor's incremental cost-effectiveness ratio (ICER) and CADTH revised ICER leading to a price reduction to meet the $50,000/QALY threshold. For the submissions with clear clinical benefit the median length of engagement (2.5 vs 3.3months) and median length of negotiation (3.1 vs 3.6months) were slightly shorter compared with the submissions where uncertainties were noted in the clinical benefit according to CADTH. This study shows that using a $50,000 per QALY threshold for oncology products potentially impacts timely access to life saving medications.

Cost-effectiveness of therapist-assisted internet-delivered psychological therapies for PTSD differing in trauma focus in England: an economic evaluation based on the STOP-PTSD trial

Although there are effective psychological treatments for post-traumatic stress disorder (PTSD), they remain inaccessible for many people. Digitally enabled therapy is a way to overcome this problem; however, there is little evidence on which forms of these therapies are most cost effective in PTSD. We aimed to assess the cost-effectiveness of the STOP-PTSD trial, which evaluated two therapist-assisted, internet-delivered cognitive behavioural therapies: cognitive therapy for PTSD (iCT-PTSD) and a programme focusing on stress management (iStress-PTSD). In this health economic evaluation, we used data from the STOP-PTSD trial (n=217), a single-blind, randomised controlled trial, to compare iCT-PTSD and iStress-PTSD in terms of resource use and health outcomes. In the trial, participants (aged ≥18 years) who met DSM-5 criteria for PTSD were recruited from primary care therapy services in South East England. The interventions were delivered online with therapist support for the first 12 weeks, and three telephone calls over the next 3 months. Participants completed questionnaires on symptoms, wellbeing, quality of life, and resource use at baseline, 13 weeks, 26 weeks, and 39 weeks after randomisation. We used a cost-effectiveness analysis to assess cost per quality-adjusted life year (QALY) at 39 weeks post-randomisation, from the perspective of the English National Health Service (NHS) and personal social services and on the basis of intention-to-treat for complete cases. Treatment modules and the platform design were developed with extensive input from service users: service users also advised on the trial protocol and methods, including the health economic measures. This is a pre-planned analysis of the STOP-PTSD trial; the trial was registered prospectively on the ISRCTN Registry (ISRCTN16806208). NHS costs were similar across treatment groups, but clinical outcomes were superior for iCT-PTSD compared with iStress-PTSD. The incremental cost-effectiveness ratio for NHS costs and personal social services was estimated as £1921 per QALY. iCT-PTSD had an estimated 91·6% chance of being cost effective at the £20 000 per QALY threshold. From the societal perspective, iCT-PTSD was cost saving compared with iStress-PTSD. iCT-PTSD is a cost-effective form of therapist-assisted, internet-delivered psychological therapy relative to iStress-PTSD, and it could be considered for clinical implementation. Wellcome Trust and National Institute of Health Research Oxford Health Biomedical Research Centre.

Dehydrated human amnion/chorion membrane to treat venous leg ulcers: a cost-effectiveness analysis.

To evaluate the cost-effectiveness of dehydrated human amnion/chorion membrane (DHACM) in Medicare enrolees who developed a venous leg ulcer (VLU). This economic evaluation used a four-state Markov model to simulate the disease progression of VLUs for patients receiving advanced treatment (AT) with DHACM or no advanced treatment (NAT) over a three-year time horizon from a US Medicare perspective. DHACM treatments were assessed when following parameters for use (FPFU), whereby applications were initiated 30-45 days after the initial VLU diagnosis claim, and reapplications occurred on a weekly to biweekly basis until completion of the treatment episode. The cohort was modelled on the claims of 530,220 Medicare enrolees who developed a VLU between 2015-2019. Direct medical costs, quality-adjusted life years (QALYs), and the net monetary benefit (NMB) at a willingness-to-pay threshold of $100,000/QALY were applied. Univariate and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty of model results. DHACM applied FPFU dominated NAT, yielding a lower per-patient cost of $170 and an increase of 0.010 QALYs over three years. The resulting NMB was $1178 per patient in favour of DHACM FPFU over the same time horizon. The rate of VLU recurrence had a notable impact on model uncertainty. In the PSA, DHACM FPFU was cost-effective in 63.01% of simulations at the $100,000/QALY threshold. In this analysis, DHACM FPFU was the dominant strategy compared to NAT, as it was cost-saving and generated a greater number of QALYs over three years from the US Medicare perspective. A companion VLU Medicare outcomes analysis revealed that patients who received AT with a cellular, acellular and matrix-like product (CAMP) compared to patients who received NAT had the best outcomes. Given the added clinical benefits to patients at lower cost, providers should recommend DHACM FPFU to patients with VLU who qualify. Decision-makers for public insurers (e.g., Medicare and Medicaid) and commercial payers should establish preferential formulary placement for reimbursement of DHACM to reduce budget impact and improve the long-term health of their patient populations dealing with these chronic wounds. Support for this analysis was provided by MiMedx Group, Inc., US. JLD, and RAF are employees of MiMedx Group, Inc. WHT, BH, PS, BGC and WVP were consultants to MiMedx Group, Inc. VD, AO, MRK, JAN, NW and GAM served on the MiMedx Group, Inc. Advisory Board. MRK and JAN served on a speaker's bureau. WVP declares personal fees and equity holdings from Stage Analytics, US.

Understanding the National Institute for Health and Care Excellence Severity Premium: Exploring Its Implementation and the Implications for Decision Making and Patient Access

ObjectivesThis study aimed to evaluate the impact of the National Institute for Health and Care Excellence’s (NICE) new severity modifier, which has replaced the end-of-life (EoL) premium, on future NICE recommendations, considering past decision-making patterns. MethodsNICE technology appraisals (TAs) published between January 2020 and December 2022 were reviewed. Summary statistics were generated to assess how the new severity modifier might affect hypothetical decision making in historical TAs. ResultsA total of 138 data points were identified from 132 TAs. Although the EoL premium was applied in 46 appraisals (33%), 57 (39%) qualify for a severity-based quality-adjusted life-year (QALY) multiplier. Only 19 appraisals (14.6%) not receiving an EoL premium met the severity criteria, the majority (17) qualifying for a 1.2× multiplier. In appraisals predicted to meet the severity criteria, 45 (79%) were in oncology, making them 4.04 times (95% CI 1.91-9.02) more likely to qualify for a severity modifier than nononcology indications. Among historically EoL indications, 42 (91%) were predicted to meet the severity criteria, making them 14.8 times (95% CI 6.37-37.6) more likely to qualify for a severity modifier. ConclusionsThe new severity modifier will predominantly benefit oncology indications, continuing their previous explicit prioritization under the EoL decision modifier. However, the new severity modifier is harder to achieve and less generous; only a fraction of appraisals qualify for the highest effective £51 000 per QALY threshold. The vast majority of indications previously approved at £50 000 per QALY would now need to meet a cost-effectiveness threshold of <£36 000. This may necessitate greater pricing flexibility from manufacturers and increase the likelihood of negative recommendations.

Cost-effectiveness of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing and isolation strategies in nursing homes.

Nursing home residents may be particularly vulnerable to coronavirus disease 2019 (COVID-19). Therefore, a question is when and how often nursing homes should test staff for COVID-19 and how this may change as severe acute respiratory coronavirus virus 2 (SARS-CoV-2) evolves. We developed an agent-based model representing a typical nursing home, COVID-19 spread, and its health and economic outcomes to determine the clinical and economic value of various screening and isolation strategies and how it may change under various circumstances. Under winter 2023-2024 SARS-CoV-2 omicron variant conditions, symptom-based antigen testing averted 4.5 COVID-19 cases compared to no testing, saving $191 in direct medical costs. Testing implementation costs far outweighed these savings, resulting in net costs of $990 from the Centers for Medicare & Medicaid Services perspective, $1,545 from the third-party payer perspective, and $57,155 from the societal perspective. Testing did not return sufficient positive health effects to make it cost-effective [$50,000 per quality-adjusted life-year (QALY) threshold], but it exceeded this threshold in ≥59% of simulation trials. Testing remained cost-ineffective when routinely testing staff and varying facemask compliance, vaccine efficacy, and booster coverage. However, all antigen testing strategies became cost-effective (≤$31,906 per QALY) or cost saving (saving ≤$18,372) when the severe outcome risk was ≥3 times higher than that of current omicron variants. SARS-CoV-2 testing costs outweighed benefits under winter 2023-2024 conditions; however, testing became cost-effective with increasingly severe clinical outcomes. Cost-effectiveness can change as the epidemic evolves because it depends on clinical severity and other intervention use. Thus, nursing home administrators and policy makers should monitor and evaluate viral virulence and other interventions over time.

Cost-effectiveness analysis of olaparib maintenance therapy for BRCA mutation ovarian cancer in the public sector in Malaysia.

Ovarian cancer is one of the most common cancer among women in Malaysia. Patients with ovarian cancer are often diagnosed at an advanced stage. Despite initial response to surgery and chemotherapy, most patients will experience a relapse. Olaparib has been reported have promising effects among BRCA mutated ovarian cancer patients. This study aimed to evaluate the cost-effectiveness of olaparib as a maintenance therapy for BRCA ovarian cancer in Malaysia. We developed a four-state partitioned survival model which compared treatment with olaparib versus routine surveillance (RS) from a Malaysian healthcare perspective. Mature overall survival (OS) data from the SOLO-1 study were used and extrapolated using parametric models. Medication costs and healthcare resource usage costs were derived from local inputs and publications. Deterministic and probabilistic sensitivity analyses (PSA) were performed to explore uncertainties. In Malaysia, treating patients with olaparib was found to be more costly compared to RS, with an incremental cost of RM149,858 (USD 33,213). Patients treated with olaparib increased life years by 3.05 years and increased quality adjusted life years (QALY) by 2.76 (9.45 years vs 6.40 years; 7.62 vs 4.86 QALY). This translated to an incremental cost-effectiveness ratio (ICER) of RM 49,159 (USD10,895) per life year gained and RM54,357 (USD 12,047) per QALY gained, respectively. ICERs were most sensitive to time horizon of treatment, discount rate for outcomes, cost of treatment and health state costs, but was above the RM53,770/QALY threshold. The use of olaparib is currently not a cost-effective strategy compared to routine surveillance based upon the current price in Malaysia for people with ovarian cancer with BRCA mutation, despite the improvement in overall survival.

Abstract 138: Cost-Effectiveness of Insertable Cardiac Monitors to Identify Atrial Fibrillation After Stroke Attributed to Large-Artery or Small-Vessel Disease

Introduction: Identification of atrial fibrillation (AF) in patients with stroke is critical for secondary stroke prevention with guideline-recommended oral anticoagulation (OAC). The randomized STROKE AF trial evaluating patients with ischemic stroke attributed to large-artery or small-vessel disease (LAD/SVD) found that insertable cardiac monitors (ICMs) were more likely to detect AF than standard of care (SoC) using intermittent external ECG monitors. However, the cost-effectiveness of ICMs in this population is not known. This study aimed to evaluate the cost-effectiveness of ICMs to detect new AF in patients with LAD/SVD stroke in the U.S. Methods: Using patient data from STROKE AF (N=492, median CHA 2 DS 2 -VASc=5.0), a lifetime Markov model was developed to assess the cost-effectiveness of ICM vs. SoC from a payer perspective. SoC was based on the frequency of ECG/Holter monitoring observed in the trial. AF detection was assumed to result in a switch from aspirin to OAC, unless precluded by prior bleeds. Lifetime risks of stroke and bleeding events were based on underlying presence of AF and the safety and efficacy of the treatment received. Future costs/effects were discounted at 3% annually to adjust to present values. Sensitivity analyses were conducted to assess uncertainty. Results: ICM was associated with a gain of 0.17 quality-adjusted life years (QALYs) versus SoC (6.63 vs. 6.46), driven by higher incidence of OAC and consequent reduction in lifetime ischemic strokes, with 53 fewer strokes projected per 1,000 patients. Total lifetime per-patient costs were $65,989 and $59,703 in the ICM and SoC arms, respectively. The incremental cost-effectiveness ratio was $37,760 per QALY gained compared to SoC (under the $50,000/QALY threshold considered highly cost-effective in the U.S.). Cost-effectiveness improved further in the subset with CHA 2 DS 2 -VASc≥6. In the patients at highest risk of AF detection (left atrial enlargement, heart failure, obesity, or prolonged QRS), the cost/QALY was $22,016. Conclusions: ICMs are likely to be cost-effective in the U.S. for the diagnosis of AF in the population with stroke attributed to LVD or SVD. This strategy was most cost-effective in patients with high CHA 2 DS 2 -VASc scores and those at greatest risk of AF.

Cost-utility analysis of molnupiravir plus usual care versus usual care alone as early treatment for community-based adults with COVID-19 and increased risk of adverse outcomes in the UK PANORAMIC trial.

The cost-effectiveness of molnupiravir, an oral antiviral for early treatment of SARS-CoV-2, has not been established in vaccinated populations. To evaluate the cost-effectiveness of molnupiravir relative to usual care alone among mainly vaccinated community-based people at higher risk of severe outcomes from COVID-19 over six months. Economic evaluation of the PANORAMIC trial in the UK. A cost-utility analysis that adopted a UK National Health Service and personal social services perspective and a six-month time horizon was performed using PANORAMIC trial data. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity and subgroup analyses assessed the impacts of uncertainty and heterogeneity. Threshold analysis explored the price for molnupiravir consistent with likely reimbursement. In the base case analysis, molnupiravir had higher mean costs of £449 (95% confidence interval [CI] 445 to 453) and higher mean QALYs of 0.0055 (95% CI 0.004 to 0.007) than usual care (mean incremental cost per QALY of £81190). Sensitivity and subgroup analyses showed similar results, except those aged ≥75 years with a 55% probability of being cost-effective at a £30000 per QALY threshold. Molnupiravir would have to be priced around £147 per course to be cost-effective at a £15000 per QALY threshold. Molnupiravir at the current cost of £513 per course is unlikely to be cost-effective relative to usual care over a six-month time horizon among mainly vaccinated COVID-19 patients at increased risk of adverse outcomes, except those aged ≥75 years.

Effectiveness and cost-effectiveness of online recorded recovery narratives in improving quality of life for people with non-psychotic mental health problems: a pragmatic randomized controlled trial.

Narratives describing first-hand experiences of recovery from mental health problems are widely available. Emerging evidence suggests that engaging with mental health recovery narratives can benefit people experiencing mental health problems, but no randomized controlled trial has been conducted as yet. We developed the Narrative Experiences Online (NEON) Intervention, a web application providing self-guided and recommender systems access to a collection of recorded mental health recovery narratives (n=659). We investigated whether NEON Intervention access benefited adults experiencing non-psychotic mental health problems by conducting a pragmatic parallel-group randomized trial, with usual care as control condition. The primary endpoint was quality of life at week 52 assessed by the Manchester Short Assessment (MANSA). Secondary outcomes were psychological distress, hope, self-efficacy, and meaning in life at week 52. Between March 9, 2020 and March 26, 2021, we recruited 1,023 participants from across England (the target based on power analysis was 994), of whom 827 (80.8%) identified as White British, 811 (79.3%) were female, 586 (57.3%) were employed, and 272 (26.6%) were unemployed. Their mean age was 38.4±13.6 years. Mood and/or anxiety disorders (N=626, 61.2%) and stress-related disorders (N=152, 14.9%) were the most common mental health problems. At week 52, our intention-to-treat analysis found a significant baseline-adjusted difference of 0.13 (95% CI: 0.01-0.26, p=0.041) in the MANSA score between the intervention and control groups, corresponding to a mean change of 1.56 scale points per participant, which indicates that the intervention increased quality of life. We also detected a significant baseline-adjusted difference of 0.22 (95% CI: 0.05-0.40, p=0.014) between the groups in the score on the "presence of meaning" subscale of the Meaning in Life Questionnaire, corresponding to a mean change of 1.1 scale points per participant. We found an incremental gain of 0.0142 quality-adjusted life years (QALYs) (95% credible interval: 0.0059 to 0.0226) and a £178 incremental increase in cost (95% credible interval: -£154 to £455) per participant, generating an incremental cost-effectiveness ratio of £12,526 per QALY compared with usual care. This was lower than the £20,000 per QALY threshold used by the National Health Service in England, indicating that the intervention would be a cost-effective use of health service resources. In the subgroup analysis including participants who had used specialist mental health services at baseline, the intervention both reduced cost (-£98, 95% credible interval: -£606 to £309) and improved QALYs (0.0165, 95% credible interval: 0.0057 to 0.0273) per participant as compared to usual care. We conclude that the NEON Intervention is an effective and cost-effective new intervention for people experiencing non-psychotic mental health problems.

Exploring the Cost-Utility of a Biomarker Predicting Persistent Severe Acute Kidney Injury: The Case of C-C Motif Chemokine Ligand 14 (CCL14).

Approximately 24% of hospitalized stage 2-3 acute kidney injury (AKI) patients will develop persistent severe AKI (PS-AKI), defined as KDIGO stage 3 AKI lasting ≥3 days or with death in ≤3 days or stage 2 or 3 AKI with dialysis in ≤3 days, leading to worse outcomes and higher costs. There is currently no consensus on an intervention that effectively reverts the course of AKI and prevents PS-AKI in the population with stage 2-3 AKI. This study explores the cost-utility of biomarkers predicting PS-AKI, under the assumption that such intervention exists by comparing C-C motif chemokine ligand 14 (CCL14) to hospital standard of care (SOC) alone. The analysis combined a 90-day decision tree using CCL14 operating characteristics to predict PS-AKI and clinical outcomes in 66-year-old patients, and a Markov cohort estimating lifetime costs and quality-adjusted life years (QALYs). Cost and QALYs from admission, 30-day readmission, intensive care, dialysis, and death were compared. Clinical and cost inputs were informed by a large retrospective cohort of US hospitals in the PINC AI Healthcare Database. Inputs and assumptions were challenged in deterministic and probabilistic sensitivity analyses. Two-way analyses were used to explore the efficacy and costs of an intervention preventing PS-AKI. Depending on selected costs and early intervention efficacy, CCL14-directed care led to lower costs and more QALYs (dominating) or was cost-effective at the $50,000/QALY threshold. Assuming the intervention would avoid 10% of PS-AKI complications in AKI stage 2-3 patients identified as true positive resulted in 0.066 additional QALYs and $486 reduced costs. Results were robust to substantial parameter variation. The analysis suggests that in the presence of an efficacious intervention preventing PS-AKI, identifying people at risk using CCL14 in addition to SOC is likely to represent a cost-effective use of resources.

Cost-effectiveness of second-line lisocabtagene maraleucel in relapsed or refractory diffuse large B-cell lymphoma

AbstractLisocabtagene maraleucel (liso-cel), a chimeric antigen receptor (CAR) T-cell therapy, received the US Food and Drug Administration approval in 2022 for second-line treatment of diffuse large B-cell lymphoma (DLBCL) for patients with refractory disease or early relapse after first-line chemoimmunotherapy. This decision was based on the TRANSFORM study demonstrating improvements in event-free survival with liso-cel compared with standard care. Given the high costs of CAR T-cell therapies, particularly as they transition to second-line treatment, a cost-effectiveness analysis is essential to determine their economic viability. The study used a partitioned survival model with standard parametric functions to evaluate the cost-effectiveness of liso-cel aganist platinum-based chemotherapy followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation over a lifetime horizon The analysis relied on data from the TRANSFORM and TRANSCEND trials, established literature, and public data sets to calculate the incremental cost-effectiveness ratio (ICER). For a representative cohort of US adults aged 60 years, ICER of liso-cel was $99 669 per quality-adjusted life-year (QALY) from a health care sector perspective and $68 212 per QALY from a societal perspective, confirming its cost-effectiveness at the $100 000 per QALY threshold. Nonetheless, under certain scenarios, liso-cel surpasses this benchmark but remains within the US acceptable range of $150 000 per QALY. A key finding underlines the importance of incorporating productivity losses into such analyses to capture the broader societal values of novel therapies. Although these therapies offer substantial clinical benefits, their high acquisition costs and limited long-term data critically challenge their economic sustainability.

Cost-effectiveness for high dose quadrivalent versus the adjuvanted quadrivalent influenza vaccine in the Italian older adult population.

To assess the cost-effectiveness of switching from adjuvanted quadrivalent vaccine (aQIV) to high-dose quadrivalent influenza vaccine (HD-QIV) in those aged ≥65 years from the Italian National Health Service perspective. We developed a decision tree model over a 1-year time-horizon to assess influenza-related costs and health outcomes. Two hospitalization approaches were considered: "hospitalization conditional on developing influenza" and "hospitalization possibly related to Influenza." The first approach considered only hospitalizations with influenza ICD-9-CM diagnosis codes. The second included hospitalizations for cardiorespiratory events possibly related to influenza to better capture the "hidden burden". Since comparative efficacy of high-dose quadrivalent influenza vaccine versus adjuvanted quadrivalent vaccine was lacking, we assumed relative efficacy versus a common comparator, standard-dose influenza quadrivalent vaccines (SD-QIV). We assumed the relative efficacy of HD-QIV vs. SD-QIV was 24.2 and 18.2% for the first and second hospitalization approaches, respectively, based on published information. Due to lack of comparative efficacy data for aQIV vs. SD-QIV, we assumed three different scenarios: 0, 6, and 12% relative efficacy in scenarios 1, 2, and 3, respectively. For the first hospitalization approach, HD-QIV was a cost-effective alternative to aQIV in all scenarios at a willingness-to-pay threshold of €30,000 per Quality Adjusted Life Years. The incremental cost-effectiveness ratios across the scenarios were €7,301, €9,805, and €14,733, respectively, much lower than the willingness-to-pay per Quality Adjusted Life Years threshold. For the second hospitalization approach, HD-QIV was a dominant alternative to aQIV across all scenarios. The robustness of the results was confirmed in one-way and probabilistic sensitivity analyses. Switching to HD-QIV from aQIV for the older adult in Italy would improve health-related outcomes, and would be cost-effective or cost saving.

Cost-Effectiveness Analysis of Pembrolizumab as an Adjuvant Treatment of Renal Cell Carcinoma Post-nephrectomy in the United States.

Pembrolizumab was recently approved as an adjuvant treatment of renal cell carcinoma (RCC), based on prolonged disease-free survival compared to placebo in the phase III KEYNOTE-564 trial. The objective of this study was to evaluate the cost-effectiveness of pembrolizumab as monotherapy in the adjuvant treatment of RCC post-nephrectomy, from a US health sector perspective. A Markov model with 4 health states (disease-free, locoregional recurrence, distant metastases, and death) was developed to compare the cost and effectiveness of pembrolizumab versus routine surveillance or sunitinib. Transition probabilities were estimated using patient-level KEYNOTE-564 data (cutoff: June 14, 2021), a retrospective study, and published literature. Costs of adjuvant and subsequent treatments, adverse events, disease management, and terminal care were estimated in 2022 US$. Utilities were based on EQ-5D-5L data collected in KEYNOTE-564. Outcomes included costs, life-years (LYs), and quality-adjusted LYs (QALYs). Robustness was assessed through one-way and probabilistic sensitivity analyses. Total cost per patient was $549,353 for pembrolizumab, $505,094 for routine surveillance, and $602,065 for sunitinib. Over a lifetime, pembrolizumab provided gains of 0.96 QALYs (1.00 LYs) compared to routine surveillance, yielding an incremental cost-effectiveness ratio of $46,327/QALY. Pembrolizumab dominated sunitinib with 0.89 QALYs (0.91 LYs) gained while saving costs. At a $150,000/QALY threshold, pembrolizumab was cost-effective versus both routine surveillance and sunitinib in 84.2% of probabilistic simulations. Pembrolizumab is projected to be cost-effective as an adjuvant RCC treatment versus routine surveillance or sunitinib based on a typical willingness-to-pay threshold.

Cost-effectiveness analysis of dinutuximab β for the treatment of high-risk neuroblastoma in China.

Dinutuximab β can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab β is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab β in children with high-risk NB is of high importance. The health utilities and economic outcomes in children with high-risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add-on treatment with dinutuximab β (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event-related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality-adjusted life-years (QALYs) were measured over a 10-year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted. Compared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost-effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab β was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost-effective in the PSA at the $37,920/QALY threshold. Results found that dinutuximab β is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced.

Cost-Effectiveness of a Hypothetical Gene Therapy for Alzheimer's Disease: A Markov Simulation Analysis.

Background: Alzheimer's disease is a prevalent neurodegenerative condition causing significant health and economic burden. With limited therapeutic options, clinical trials have been investigating Alzheimer's disease treatment using more novel approaches, including gene therapy. However, there is limited evidence on the cost-effectiveness of such treatments. Objectives: This research aims to explore the cost-effectiveness of a hypothetical gene therapy for patients with Alzheimer's disease at varying degrees of severity. Methods: A Markov model with a 20-year time horizon was constructed for simulated cohorts with mild cognitive impairment due to Alzheimer's disease, assigned to receive either standard of care or a one-time gene therapy administration. Varying costs of care due to disease severity and treatment efficacy were utilized to determine the effect of those variables at different willingness-to-pay thresholds. Results: Under the initial assumption that the hypothetical gene therapy grants a 30% risk reduction in disease progression and entry into institutional care, the maximum cost-effective price for gene therapy is $141,126 per treatment using the threshold of $150,000 per quality-adjusted life year (QALY). By increasing the treatment effectiveness to 50%, cost-effective price nearly doubled at each willingness-to-pay threshold (e.g.,$260,902 at the $150,000/QALY threshold). Conclusion: Despite being cost-effective at a very high price, the hypothetical gene therapy for AD would still need to be priced considerably lower than other approved gene therapies on the market. Thus, a comprehensive pharmacoeconomic assessment remains critical in pricing innovative therapy and determining coverage for patients in need.

Public Health Impact and Cost-Effectiveness of Empagliflozin (JARDIANCE®) in the Treatment of Patients with Heart Failure with Preserved Ejection Fraction in France, Based on the EMPEROR-Preserved Clinical Trial.

The efficacy and safety of empagliflozin in the treatment of heart failure with preserved ejection fraction (HFpEF) were demonstrated in the EMPEROR-Preserved trial, which showed a 21% reduction in combined risks of cardiovascular death or HF hospitalization [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69-0.90, p<0.001] and a 27% reduction in the total number of HF hospitalizations (HR 0.73; 95% CI 0.61-0.88, p<0.001) compared with placebo. On the basis of these results, the present study aimed to assess the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone in the treatment of HFpEF. A published Markov model was adapted to compare the health and economic outcomes in France, considering a collective perspective, in patients treated with empagliflozin in addition to SoC versus patients treated by SoC alone. The model simulated the intention-to-treat (ITT) population of the trial, transitioning between four mutually exclusive health states representing the quartiles of the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). For each arm, the model estimated (over a lifetime time horizon) the economics and the health outcomes (HF hospitalizations avoided, and life years and quality-adjusted life years (QALYs) gained) to calculate the incremental cost-effectiveness ratios (ICERs). The resources used were derived by pairing the FREnch Survey on HF (FRESH) cohort data to French health insurance claims data, and the utilities were derived on the basis of the EQ-5D-5L questionnaire valued on the French tariff. Both economic and health outcomes were discounted at a 2.5% annual rate. The model predicted that treatment of HFpEF patients with empagliflozin would prevent, for 1000 patients treated, 74 HF hospitalizations and 15 deaths attributable to cardiovascular events, resulting on average in a gain of 1 month in overall survival (7.24 versus 7.16years with placebo) and 0.11 QALYs (6.14 versus 6.03 with placebo). Empagliflozin costs were partially offset by the cost savings from avoided hospitalizations. The ICERs were €18,597 per life year gained and €13,980 per QALY gained. The sensitivity analyses conducted showed that empagliflozin has a 65% probability to be cost-effective under the €25,000/QALY threshold. The base-case results showed that empagliflozin is a cost-effective strategy for management of HFpEF, in addition to the impact on public health by preventing HF-hospitalizations and deaths in France. Sensitivity analyses suggest that 65% of simulations are under the €25,000/QALY threshold.

Better post-operative prediction and management of chronic pain in adults after total knee replacement: the multidisciplinary STAR research programme including RCT

Background The treatment of osteoarthritis with knee replacement aims to reduce pain and disability. However, some people experience chronic pain. Objectives To improve outcomes for people with chronic pain after knee replacement by identifying post-surgical predictors and effective interventions, characterising patient pathways and resource use, developing and evaluating a new care pathway, and exploring non-use of services. Design The programme comprised systematic reviews, national database analyses, a cohort study, intervention development, a randomised controlled trial, health economic analyses, qualitative studies and stakeholder engagement. Extensive and meaningful patient and public involvement underpinned all studies. Setting NHS, secondary care, primary care. Participants People with, or at risk of, chronic pain after knee replacement and health-care professionals involved in the care of people with pain. Interventions A care pathway for the management of people with pain at 3 months after knee replacement. Main outcome measures Patient-reported outcomes and cost-effectiveness over 12 months. Data sources Literature databases, the National Joint Registry, Hospital Episode Statistics, patient-reported outcomes, the Clinical Practice Research Datalink, the Clinical Outcomes in Arthroplasty Study, the Support and Treatment After joint Replacement randomised trial, interviews with 90 patients and 14 health-care professionals, and stakeholder events. Review methods Systematic reviews of cohort studies or randomised trials, using meta-analysis or narrative synthesis. Results In the Clinical Outcomes in Arthroplasty Study cohort, 14% of people experienced chronic pain 1 year after knee replacement. By 5 years, 65% reported no pain, 31% fluctuated and 4% remained in chronic pain. People with chronic pain had a worse quality of life, higher primary care costs, and more frequent analgesia prescriptions, particularly for opioids, than those not in chronic pain. People with chronic pain after knee replacement who made little or no use of services often felt nothing more could be done, or that further treatments may have no benefit or cause harm. People described a feeling of disconnection from their replaced knee. Analysis of UK databases identified risk factors for chronic pain after knee replacement. Pre-operative predictors were mild knee pain, smoking, deprivation, body mass index between 35 and 40 kg/m2 and knee arthroscopy. Peri- and post-operative predictors were mechanical complications, infection, readmission, revision, extended hospital stay, manipulation under anaesthetic and use of opioids or antidepressants. In systematic reviews, pre-operative exercise and education showed no benefit in relation to chronic pain. Peri-operative interventions that merit further research were identified. Common peri-operative treatments were not associated with chronic pain. There was no strong evidence favouring specific post-operative physiotherapy content. We evaluated the Support and Treatment After joint Replacement care pathway in a multicentre randomised controlled trial. We randomised 363 people with pain at 3 months after knee replacement from eight NHS Trusts in England and Wales. At 12 months’ follow-up, the intervention group had lower mean pain severity (adjusted difference –0.65, 95% confidence interval –1.17 to -0.13; p = 0.014) and pain interference (adjusted difference –0.68, 95% confidence interval –1.29 to -0.08; p = 0.026), as measured on the Brief Pain Inventory subscales (scale 0–10). People receiving the Support and Treatment After joint Replacement pathway had lower NHS and Personal Social Services costs (–£724, 95% confidence interval –£150 to £51) and higher quality-adjusted life-years (0.03, 95% confidence interval –0.008 to 0.06) than those with usual care. The Support and Treatment After joint Replacement pathway was cost-effective with an incremental net monetary benefit at the £20,000 per quality-adjusted life-year threshold of £1256 (95% confidence interval £164 to £2348), indicating a 98.79% probability that the intervention is the cost-effective option. Participants found the Support and Treatment After joint Replacement pathway acceptable, with opportunities to receive information and discuss concerns while ensuring further treatment and support. In systematic reviews considering treatments for chronic pain after surgery we identified some unifactorial interventions that merit further research after knee replacement. Health-care professionals delivering and implementing the Support and Treatment After joint Replacement pathway valued its focus on neuropathic pain and psychosocial issues, enhanced patient care, formalised referrals, and improved pain management. Stakeholders supported pathway implementation. Limitations Database analyses were limited to factors recorded in data sets. Pain was only measured 6 months after surgery. However, analyses including large numbers of centres and patients should be generalisable across the NHS. In many studies found in systematic reviews, long-term pain was not a key outcome. Conclusions The Support and Treatment After joint Replacement pathway is a clinically effective and cost-effective, acceptable intervention for the management of chronic pain after knee replacement. Unifactorial interventions merit further study before inclusion in patient care. People with pain should be empowered to seek health care, with the support of health-care professionals. Future work Future work should include research relating to the implementation of the Support and Treatment After joint Replacement pathway into the NHS, an assessment of its long-term clinical effectiveness and cost-effectiveness and wider application, and an evaluation of new interventions for incorporation in the pathway. It will also be important to design and conduct research to improve communication between patients and health-care professionals before surgery; explore whether or not education and support can enable earlier recognition of chronic pain; consider research that may identify how to support people’s feelings of disconnectedness from their new knee; and design and evaluate a pre-surgical intervention based on risk factors. Study registration All systematic reviews were registered on PROSPERO (CRD42015015957, CRD42016041374 and CRD42017041382). The Support and Treatment After joint Replacement randomised trial was registered as ISRCTN92545361. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 11, No. 3. See the NIHR Journals Library website for further project information.

Economic evaluations of radioembolization with yttrium-90 microspheres in liver metastases of colorectal cancer: a systematic review

BackgroundTransarterial radioembolization with yttrium-90 (Y-90 TARE) microspheres therapy has demonstrated positive clinical benefits for the treatment of liver metastases from colorectal cancer (lmCRC). This study aims to conduct a systematic review of the available economic evaluations of Y-90 TARE for lmCRC.MethodsEnglish and Spanish publications were identified from PubMed, Embase, Cochrane, MEDES health technology assessment agencies, and scientific congress databases published up to May 2021. The inclusion criteria considered only economic evaluations; thus, other types of studies were excluded. Purchasing-power-parity exchange rates for the year 2020 ($US PPP) were applied for cost harmonisation.ResultsFrom 423 records screened, seven economic evaluations (2 cost-analyses [CA] and 5 cost-utility-analyses [CUA]) were included (6 European and 1 USA). All included studies (n = 7) were evaluated from a payer and the social perspective (n = 1). Included studies evaluated patients with unresectable liver-predominant metastases of CRC, refractory to chemotherapy (n = 6), or chemotherapy-naïve (n = 1). Y-90 TARE was compared to best supportive care (BSC) (n = 4), an association of folinic acid, fluorouracil and oxaliplatin (FOLFOX) (n = 1), and hepatic artery infusion (HAI) (n = 2). Y-90 TARE increased life-years gained (LYG) versus BSC (1.12 and 1.35 LYG) and versus HAI (0.37 LYG). Y-90 TARE increased the quality-adjusted-life-year (QALY) versus BSC (0.81 and 0.83 QALY) and versus HAI (0.35 QALY). When considering a lifetime horizon, Y-90 TARE reported incremental cost compared to BSC (range 19,225 to 25,320 $US PPP) and versus HAI (14,307 $US PPP). Y-90 TARE reported incremental cost-utility ratios (ICURs) between 23,875 $US PPP/QALY to 31,185 $US PPP/QALY. The probability of Y-90 TARE being cost-effective at £ 30,000/QALY threshold was between 56% and 57%.ConclusionsOur review highlights that Y-90 TARE could be a cost-effective therapy either as a monotherapy or when combined with systemic therapy for treating ImCRC. However, despite the current clinical evidence on Y-90 TARE in the treatment of ImCRC, the global economic evaluation reported for Y-90 TARE in ImCRC is limited (n = 7), therefore, we recommend future economic evaluations on Y-90 TARE versus alternative options in treating ImCRC from the societal perspective.

Cost-Effectiveness Analysis of Pembrolizumab as an Adjuvant Treatment of Resected Stage IIB or IIC Melanoma in the United States.

Pembrolizumab was approved in the US as adjuvant treatment of patients with stage IIB or IIC melanoma post-complete resection, based on prolonged recurrence-free survival vs. placebo in the Phase 3 KEYNOTE-716 trial. This study aimed to evaluate the cost-effectiveness of pembrolizumab vs. observation as adjuvant treatment of stage IIB or IIC melanoma from a US health sector perspective. A Markov cohort model was constructed to simulate patient transitions among recurrence-free, locoregional recurrence, distant metastasis, and death. Transition probabilities from recurrence-free and locoregional recurrence were estimated via multistate parametric modeling based on patient-level data from an interim analysis (data cutoff date: 04-Jan-2022). Transition probabilities from distant metastasis were based on KEYNOTE-006 data and network meta-analysis. Costs were estimated in 2022 US dollars. Utilities were based on applying US value set to EQ-5D-5L data collected in trial and literature. Compared to observation, pembrolizumab increased total costs by $80,423 and provided gains of 1.17 quality-adjusted life years (QALYs) and 1.24 life years (LYs) over lifetime, resulting in incremental cost-effectiveness ratios of $68,736/QALY and $65,059/LY. The higher upfront costs of adjuvant treatment were largely offset by reductions in costs of subsequent treatment, downstream disease management, and terminal care, reflecting the lower risk of recurrence with pembrolizumab. Results were robust in one-way sensitivity and scenario analyses. At a $150,000/QALY threshold, pembrolizumab was cost-effective vs. observation in 73.9% of probabilistic simulations that considered parameter uncertainty. As an adjuvant treatment of stage IIB or IIC melanoma, pembrolizumab was estimated to reduce recurrence, extend patients' life and QALYs, and be cost-effective versus observation at a US willingness-to-pay threshold.