High Incremental Cost-effectiveness Ratio Research Articles

Comparative Cost-Effectiveness of Atezolizumab Versus Durvalumab as First-Line Combination Treatment with Chemotherapy for Patients with Extensive-Disease Small-Cell Lung Cancer in Japan.

IMpower 133 and CASPIAN data were used to create a partitioned survival model. Medical expenses and quality-adjusted life years (QALYs) were considered. The analysis period, discount rate, and threshold were set at 20 years, 2%, and 15 million Japanese yen (JPY) [114,068 US dollars (USD)] per QALY, respectively. The incremental cost-effectiveness ratio (ICER) was calculated by gathering reasonable parameters from published reports and combining the costs and effects using parametric models. Monte Carlo simulations, scenario analysis, and one-way sensitivity analyses were employed to quantify uncertainty. After comparing atezolizumab plus CE (ACE) and durvalumab plus CE (DCE) with CE, it was found that the ICERs exceeded the threshold at 35,048,299 JPY (266,527 USD) and 36,665,583 JPY (278,826 USD) per QALY, respectively. For one-way sensitivity and scenario assessments, the ICERs exceeded the threshold, even with considerably adjusted parameters. For the probabilistic sensitivity analyses, there was no probability that the ICER of the ICI combination treatment with chemotherapy would fall below the threshold. ACE and DCE were not cost-effective compared with CE as first-line therapy for ED-SCLC in Japan. Both these therapies exhibited high ICERs.

Cost-effectiveness of liquid biopsy for molecular profiling of newly diagnosed advanced non-squamous NSCLC in an Asian population.

178 Background: Liquid biopsy is complementary to tissue biopsy for lung cancer profiling, yet evidence of the cost-effectiveness is limited. This could retard implementation and reimbursement in clinical practice. The aim of this study is to estimate the cost-effectiveness of profiling strategies that include liquid biopsy and to identify the optimal profiling approach for newly diagnosed advanced non-squamous non-small cell lung cancer (NSCLC) in an Asian population using Singapore as an example. Methods: A decision tree and partitioned-survival model was developed from the Singapore healthcare system’s perspective to evaluate the cost-effectiveness of five molecular profiling strategies: either tissue or plasma next-generation sequencing (NGS) alone, a concurrent, and two sequential approaches. Model inputs were informed by local data or published literature. Sensitivity analyses and scenario analyses were undertaken to understand the robustness of the conclusions for decision making. The optimal strategy at different willingness-to-pay (WTP) thresholds was presented by cost-effectiveness acceptability frontier and the expected loss curve. Results: The sequential tissue-plasma NGS approach revealed an additional 0.0981 quality adjusted life years (QALYs) for an extra cost of S$3,074 over a 20-year time horizon compared to tissue NGS alone, resulting in an incremental cost-effectiveness ratio (ICER) of S$31,318/QALY and an incremental net monetary benefit of S$1,343 per patient. The findings were sensitive to the costs of pembrolizumab and osimertinib and the probabilities of re-biopsy after tissue NGS. Sequential plasma-tissue NGS and plasma NGS alone were more costly and less effective than alternatives. Conclusions: The sequential tissue-plasma NGS approach generated the highest net monetary benefit and was the optimal testing strategy when WTP was S$45,000/QALY. It retained superiority but understandably with a higher ICER when expensive, non-first line treatments were included. Overall, its routine clinical practice should be proactively considered for newly diagnosed advanced non-squamous NSCLC in an Asian population.

The cost-effectiveness of including liquid biopsy into molecular profiling strategies for newly diagnosed advanced non-squamous non-small cell lung cancer in an Asian population

ObjectivesLiquid biopsy is complementary to tissue biopsy for lung cancer profiling, yet evidence of the cost-effectiveness is limited. This could retard implementation and reimbursement in clinical practice. The aim of this study is to estimate the cost-effectiveness of profiling strategies that include liquid biopsy and to identify the optimal profiling approach for newly diagnosed advanced non-squamous non-small cell lung cancer (NSCLC) in an Asian population using Singapore as an example. Materials and methodsA decision tree and partitioned-survival model was developed from the Singapore healthcare system’s perspective to evaluate the cost-effectiveness of five molecular profiling strategies: either tissue or plasma next-generation sequencing (NGS) alone, a concurrent, and two sequential approaches. Model inputs were informed by local data or published literature. Sensitivity analyses and scenario analyses were undertaken to understand the robustness of the conclusions for decision making. The optimal strategy at different willingness-to-pay (WTP) thresholds was presented by cost-effectiveness acceptability frontier and the expected loss curve. ResultsThe sequential tissue-plasma NGS approach revealed an additional 0.0981 quality adjusted life years (QALYs) for an extra cost of S$3,074 over a 20-year time horizon compared to tissue NGS alone, resulting in an incremental cost-effectiveness ratio (ICER) of S$31,318/QALY and an incremental net monetary benefit of S$1,343 per patient. The findings were sensitive to the costs of pembrolizumab and osimertinib and the probabilities of re-biopsy after tissue NGS. Sequential plasma-tissue NGS and plasma NGS alone were more costly and less effective than alternatives. ConclusionThe sequential tissue-plasma NGS approach generated the highest net monetary benefit and was the optimal testing strategy when WTP was S$45,000/QALY. It retained superiority but understandably with a higher ICER when expensive, non-first line treatments were included. Overall, its routine clinical practice should be proactively considered for newly diagnosed advanced non-squamous NSCLC in an Asian population.

Exploring Structural Uncertainty in Cost-Effectiveness Modeling of Gestational Diabetes Screening: An Application Example from Norway.

Screening pregnant women for gestational diabetes mellitus (GDM) has recently been expanded in Norway, although screening eligibility criteria continue to be debated. We aimed to compare the cost-effectiveness of alternative GDM screening strategies and explored structural uncertainty and the value of future research in determining the most cost-effective eligibility criteria for GDM screening in Norway. We developed a probabilistic decision tree to estimate the total costs and health benefits (i.e., quality-adjusted life-years; QALYs) associated with 4 GDM screening strategies (universal, current guidelines, high-risk, and no screening). We identified the most cost-effective strategy as the strategy with the highest incremental cost-effectiveness ratio below a Norwegian benchmark for cost-effectiveness ($28,400/QALY). We excluded inconclusive evidence on the effects of screening on later maternal type 2 diabetes mellitus (T2DM) in the primary analysis but included this outcome in a secondary analysis using 2 different sources of evidence (i.e., Cochrane or US Preventive Services Task Force). To quantify decision uncertainty, we conducted scenario analysis and value-of-information analyses. Current screening recommendations were considered inefficient in all analyses, while universal screening was most cost-effective in our primary analysis ($26,014/QALY gained) and remained most cost-effective when we assumed a preventive effect of GDM treatment on T2DM. When we assumed no preventive effect, high-risk screening was preferred ($19,115/QALY gained). When we assumed GDM screening does not prevent perinatal death in scenario analysis, all strategies except no screening exceeded the cost-effectiveness benchmark. In most analyses, decision uncertainty was high. The most cost-effective screening strategy, ranging from no screening to universal screening, depended on the source and inclusion of GDM treatment effects on perinatal death and T2DM. Further research on these long-term outcomes could reduce decision uncertainty. This article analyses the cost-effectiveness of 4 alternative gestational diabetes mellitus (GDM) screening strategies in Norway: universal screening, current (broad) screening, high-risk screening, and no screening.The current Norwegian screening recommendations were considered inefficient under all analyses.The most cost-effective screening strategy ranged from no screening to universal screening depending on the source and inclusion of GDM treatment effects on later maternal diabetes and perinatal death.The parameters related to later maternal diabetes and perinatal death accounted for most of the decision uncertainty.

Inter-facility transfers for emergency obstetrical and neonatal care in rural Madagascar: a cost-effectiveness analysis

ContextThere is a substantial lack of inter-facility referral systems for emergency obstetrical and neonatal care in rural areas of sub-Saharan Africa. Data on the costs and cost-effectiveness of such systems...

Genotypic study of Chlamydia trachomatis for lymphogranuloma venereum diagnosis in rectal specimens from men who have sex with men: a cost-effectiveness analysis

PurposeThe significant proportion of asymptomatic patients and the scarcity of genotypic analysis of lymphogranuloma venereum (LGV), mainly among men who have sex with men (MSM), triggers a high incidence of underdiagnosed patients, highlighting the importance of determining the most appropriate strategy for LGV diagnosis, at both clinical and economical levels.Materials and methodsWe conducted L1-L3 serovar detection by molecular biology in stored Chlamydia trachomatis-positive samples from MSM patients with HIV, another STI or belonging to a Pre-exposure prophylaxis program, to make a cost effectiveness study of four diagnostic strategies with a clinical, molecular, or mixed approach.ResultsA total of 85 exudates were analyzed: 35urethral (31 symptomatic/4 positive) and 50 rectal (22 symptomatic/25 positive), 70/85 belonging to MSM with associated risk factors. The average cost per patient was €77.09 and €159.55 for clinical (Strategy I) and molecular (Strategy IV) strategies respectively. For molecular diagnosis by genotyping of all rectal exudate samples previously positive for CT (Strategy II), the cost was €123.84. For molecular diagnosis by genotyping of rectal and/or urethral exudate samples from all symptomatic patients (proctitis or urethritis) with a previous positive result for CT (Strategy III), the cost was €129.39. The effectiveness ratios were 0.80, 0.95, 0.91, and 1.00 for each strategy respectively. The smallest ICER was €311.67 for Strategy II compared to Strategy I.ConclusionsWith 30% asymptomatic patients, the most cost-effective strategy was based on genotyping all rectal exudates. With less restrictive selection criteria, thus increasing the number of patients with negative results, the most sensitive strategies tend to be the most cost-effective, but with a high incremental cost-effectiveness ratio.

Cost-effectiveness of dapagliflozin for patients with heart failure across the spectrum of ejection fraction: A pooled analysis of DAPA-HF and DELIVER data.

To assess the cost-effectiveness of dapagliflozin in addition to usual care, compared with usual care alone, in a large population of patients with heart failure (HF), spanning the full range of left ventricular ejection fraction (LVEF). Patient-level data were pooled from HF trials (DAPA-HF, DELIVER) to generate a population including HF with reduced, mildly reduced and preserved LVEF, to increase statistical power and enable exploration of interactions among LVEF, renal function and N-terminal pro-B-type natriuretic peptide levels, as they are relevant determinants of health status in this population. Survival and HF recurrent event risk equations were derived and applied to a lifetime horizon Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire total symptom score quartiles; costs and utilities were in the UK setting. The base case incremental cost-effectiveness ratio (ICER) was £6470 per quality-adjusted life year (QALY) gained, well below the UK willingness-to-pay (WTP) threshold of £20 000/QALY gained. In interaction sensitivity analyses, the highest ICER was observed for elderly patients with preserved LVEF (£16 624/QALY gained), and ranged to a region of dominance (increased QALYs, decreased costs) for patients with poorer renal function and reduced/mildly reduced LVEF. Results across the patient characteristic interaction plane were mostly between £5000 and £10 000/QALY gained. Dapagliflozin plus usual care, versus usual care alone, yielded results well below the WTP threshold for the UK across a heterogeneous population of patients with HF including the full spectrum of LVEF, and is likely a cost-effective intervention.

Cost-effectiveness and budget impact analysis of enzalutamide in comparison to abiraterone in treatment of metastatic prostate cancer resistant to castration in Iran

IntroductionIn recent years, enzalutamide and abiraterone have been widely used as treatments for metastatic castration-resistant prostate cancer (mCRPC). However, the cost-effectiveness of these drugs in Iran is unknown. This study evaluated the cost-effectiveness of enzalutamide for the treatment of metastatic prostate cancer resistant to castration in Iran.MethodsA 3-state Markov model was developed to evaluate the cost-effectiveness of enzalutamide and abiraterone from a social perspective over 10 years. The clinical inputs were obtained from the meta-analysis studies. The direct medical costs were obtained from the tariffs of the healthcare system, while the direct non-medical and indirect costs were collected from the patients. The data of utilities were derived from the literature. In addition, sensitivity analyses were conducted to assess the uncertainties.ResultsCompared with Abiraterone, enzalutamide was associated with a high incremental cost-effectiveness ratio (ICER) of $6,260 per QALY gained. According to the one-way sensitivity analysis, ICER was most heavily influenced by the prices of enzalutamide and Abiraterone, non-medical costs, and indirect costs. Regardless of the variation, enzalutamide remained cost-effective. The budget impact analysis of enzalutamide in the health system during 5 years was estimated at $6,362,127.ConclusionsAt current prices, adding enzalutamide to pharmaceutical lists represents the cost-effective use of the healthcare resources in Iran for the treatment of metastatic castration-resistant prostate cancer.

Cost-effectiveness study of therapeutic approaches for mucosal leishmaniasis.

This study aimed to estimate the cost-effectiveness of four therapeutic approaches available for mucosal leishmaniasis in Brazil: miltefosine, meglumine antimoniate, combined with and without pentoxifylline, and liposomal amphotericin B. The perspective adopted was that of the Brazilian Unified National Health System (SUS). The outcome of interest was "cured patient", which was analyzed using a decision tree model. Estimates of direct costs and effectiveness were obtained from the scientific literature. Meglumine antimoniate alone was the base comparator strategy; liposomal amphotericin B showed an incremental cost-effectiveness ratio (ICER) of USD 7,409.13 per cured patient, and the combination of meglumine antimoniate with pentoxifylline presented an ICER of USD 85.13. Miltefosine was absolutely dominated, with higher cost and similar effectiveness when compared to meglumine antimoniate. Sensitivity analyses, varying the cost by ±25%, did not change the results. However, when the cost of miltefosine was estimated at less than USD 171.23, this strategy was dominant over meglumine antimoniate alone. The results confirm that treatment with liposomal amphotericin B remains the option with the highest ICER among the approaches analyzed. Miltefosine may be cost-effective based on the variation in the acquisition price, which deserves attention because it is the only available oral option. The non-accounting of other aspects prevent the use of these results immediately to support decision-making, but they point out the need to negotiate the prices of drugs available for mucosal leishmaniasis and indicates the need of encouraging technology transfer or other actions aimed at expanding the performance of the Brazilian national industrial complex.

PP93 Health Technology Assessments For Rare Diseases In Australia: A Case Study On Cystic Fibrosis

IntroductionCurrently, no cure exists for the 1 in 2,500 Australian babies born with potentially fatal cystic fibrosis (CF). The authors conducted a health technology assessment (HTA) case study analysis of all regulatory approved CF treatments in Australia from January 1994 to July 2022. Submissions were also made under the Therapeutics Goods Administration and Pharmaceutical Benefits Advisory Committee (TGA-PBAC) parallel process.MethodsPublic summary and source materials were researched to understand relevant clinical and health economic evidence requirements, and access decisions from Australia’s lead HTA body, PBAC.ResultsThe review found that there are more than seven approved products in Australia. Of those, all four novel CF transmembrane conductance regulator (CFTR) modulating medications, which treat the underlying disease, received an orphan drug designation and were eventually listed. However, initial HTA decisions were mixed, with one recommended (25%), one not recommended (25%), and two deferred (50%). Clinical efficacy, cost-effectiveness, clinical need, as well as patient/carer-centric perspectives were most influential in HTA recommendations. Like other rare disease treatments, price, high incremental cost-effectiveness ratios (ICERs), uncertainty around cost-effectiveness and/or efficacy were key barriers to positive decisions. Notably, Australian stakeholders did not recommend CF medicines when their ICERs significantly exceeded a threshold of AUD200,000 (USD134,700) per quality-adjusted life year (QALY) gained. Administratively, Australia addresses risks associated with poor cost-effectiveness and high costs through managed access programs, risk-sharing agreements (RSA) and special pricing arrangements.Recently approved elexacaftor-tezacaftor-ivacaftor would be inaccessible to many Australian patients without inclusion in the Pharmaceutical Benefits Scheme (PBS); this placement increases access by limiting patients’ payments to AUD42.50 (USD28.62) maximum per prescription. Alternatively, manufacturers of therapies for other chronic or rare life-threatening conditions can participate in Australia’s Highly Specialised Drugs Program and/or Life Saving Drugs Program to facilitate access.ConclusionsCompanies can accelerate and optimize market access by using the TGA-PBAC parallel process. Other Asia-Pacific countries can model components of Australia’s approach to advancing access to innovative, live-saving therapies.

PP61 Cost-Effectiveness Analysis Of Trastuzumab Deruxtecan Versus Chemotherapy For Previously Treated HER2-Positive Gastric Cancer In Singapore

IntroductionThe phase two DESTINY-Gastric-01 trial demonstrated that trastuzumab deruxtecan (T-DXd) improved overall survival in Asian patients with human epidermal growth factor receptor 2 (HER2)-positive, advanced gastric or gastroesophageal adenocarcinoma that had progressed following two or more treatments, compared with chemotherapy (irinotecan or paclitaxel monotherapy). Considering the high cost of T-DXd, we assessed the cost-effectiveness of T-DXd versus chemotherapy from the Singapore healthcare system’s perspective.MethodsA partitioned survival model with three health states (progression-free, progressed disease and death) was developed, with a five-year time horizon. Survival curves from DESTINY-Gastric-01 were extrapolated beyond the trial duration using parametric functions. Health state utilities were obtained from published literature and direct costs were sourced from public healthcare institutions in Singapore. Utility decrements for adverse events such as interstitial lung disease was incorporated into the model for the differences in safety profiles. A discount rate of three percent was applied to costs and outcomes. One-way deterministic sensitivity analyses (OWSA) and scenario analyses were conducted to assess parameter and model uncertainties.ResultsTreatment with T-Dxd, compared to chemotherapy, had a high base case incremental cost-effectiveness ratio (ICER) of over SGD450,000 (USD334,900) per quality-adjusted life-year gained. The cost of T-DXd greatly influenced the results according to OWSA. Seventy-three percent of the total costs accrued in the T-DXd arm was due to the cost of the drug, compared to seven percent in the chemotherapy arm. The ICER was also sensitive to the assumptions around extrapolation of the survival curves, but when tested across all scenario analyses, the results remained unfavorable.ConclusionsAt the current cost, T-DXd does not represent good value compared to chemotherapy for previously treated HER2-positive gastric cancer in Singapore. The findings from our cost-effectiveness analysis, alongside other considerations, will be useful to inform policy makers on funding decisions.

OP129 A Cost-Utility Analysis Of Denosumab (Prolia®) For Treating Osteoporosis In Postmenopausal Women: A Swiss Healthcare Payer Perspective

IntroductionOsteoporosis is characterized by decreased bone mass and density, increasing skeletal fragility, and the risk of fragility fracture. Fragility fractures are associated with a high economic burden. Denosumab (Prolia®) is a pharmacological therapy used to treat osteoporosis and reduce the risk of fragility fracture. This study aimed to assess the cost effectiveness of denosumab, compared with other pharmacological therapies (oral bisphosphonates, intravenous [IV] ibandronate, zoledronate, raloxifene, and bazedoxifene) and no treatment, for treating postmenopausal women with osteoporosis.MethodsA discrete event simulation model was developed using a lifetime time horizon. A Swiss healthcare payer perspective was adopted. Time-to-fracture distributions were derived from Swiss-specific Fracture Risk Assessment Tool (FRAX®) probabilities. Reductions in the risk of vertebral and nonvertebral fractures due to treatment were informed by a Bayesian network meta-analysis. Cost-effectiveness frontier analysis was utilized. Pairwise incremental cost-effectiveness ratios (ICERs) between denosumab and each comparator were also estimated. Sensitivity analyses were conducted to identify key drivers and explore the overall certainty of findings.ResultsAt a hypothetical willingness-to-pay (WTP) threshold of CHF100,000 (EUR101,630), IV ibandronate was the most cost-effective therapy in women aged 60 years who had a very high risk of fracture, and in women aged 70 or 80 years of any risk level. In women aged 60 years with a lower risk level, zoledronate was the most cost-effective option. Nevertheless, ICERs from pairwise comparisons between denosumab and some comparators (no treatment, bazedoxifene, raloxifene, and/or zoledronate depending on the cohort’s age and risk profile) were below the hypothetical WTP threshold. Higher intervention costs, smaller reductions in the risk of hip fracture, and shorter duration of residual benefit associated with denosumab contributed to the high ICER values seen in pairwise comparisons with oral bisphosphonates (as a class) and IV ibandronate.ConclusionsThe present evaluation supported the cost effectiveness of denosumab against some, but not all, comparators. Nevertheless, these results should be interpreted cautiously in light of uncertainty in the true effect of treatments on fracture risk.

OP71 Road To Public Funding Of Cancer Codependent Technologies In Australia In The Last Ten Years

IntroductionIn Australia, cancer codependent technologies (cCDTs) mostly comprise a biomarker targeting medicine and a companion diagnostic test (CDx). Health technology assessment (HTA) of cCDTs is carried out to inform funding deliberations on CDxs by the Medical Services Advisory Committee (MSAC) and on personalized medicine by the Pharmaceutical Benefits Advisory Committee (PBAC). To understand the strengths and weaknesses of this dual assessment mechanism, we studied the journey of cCDTs in getting funding support from the two committees since the introduction of the codependent technology evaluation framework.MethodsPublic summary documents summarizing deliberations by each committee were reviewed from 2012 to 2022. Information was retrieved on the patient indication, date, biomarkers related to the tests, and PBAC or MSAC funding outcomes. The alignment of HTA decisions, time taken until dual funding approval (if approved), and the reasons for discrepant and negative decision-making were determined.ResultsFrom 2012 to 2022, a total of 26 cCDT applications were submitted to PBAC and MSAC, corresponding with 43 paired PBAC/MSAC considerations and 11 single committee considerations. Non-small cell lung cancer and programmed cell death ligand 1 were the most frequently nominated cancer and biomarker test, respectively. When a cCDT was submitted in the same decision round to both committees, 60 percent of funding decisions were aligned, reaching 73 percent when the considerations were made separately (resubmissions). Only 9 percent of considerations received polarized, where one committee supported and the other committee rejected funding. After multiple resubmissions, 73 percent of cCDTs obtained dual funding support after an average of 34.8 weeks, with considerations by PBAC and MSAC occurring an average of 2.3 and 1.9 times, respectively.ConclusionsMost cCDTs obtain funding support, but only after multiple resubmissions to PBAC and MSAC. Polarized decisions are rare. Reasons for rejection primarily relate to uncertain clinical benefit and an unacceptably high incremental cost-effectiveness ratio.

Use of Health Technology Assessment for the Continued Funding of Health Technologies: The Case of Immunoglobulins for the Management of Multifocal Motor Neuropathy.

Funding decisions for many health technologies occur without undergoing health technology assessment (HTA), in particular, without assessment of cost effectiveness (CE). Immunoglobulins in Australia are an interesting case study because they have been used for a long time for various rare disorders and their price is publicly available. Undertaking an HTA enables us to assess CE for an intervention for which there is limited clinical and economic evidence. This study presents a post-market review to assess the CE of immunoglobulins for the treatment of multifocal motor neuropathy (MMN) compared with best supportive care. A Markov model was used to estimate costs and quality-adjusted life-years (QALYs). Input sources included randomised controlled trials, single-arm studies, the Australian clinical criteria for MMN, clinical guidelines, previous Medical Services Advisory Committee (MSAC) reports and inputs from clinical experts. Sensitivity analyses were conducted to assess the uncertainty and robustness of the CE results. The cost per patient of treating MMN with immunoglobulin was AU$275,853 versus AU$26,191when no treatment was provided, with accrued QALYs of 6.83 versus 6.04, respectively. The latter translated into a high incremental cost-effectiveness ratio (ICER) of AU$317,552/QALY. The ICER was most sensitive to the utility weights and the price of immunoglobulins. MSAC advised to continue funding of immunoglobulins on the grounds of efficacy, despite the high and uncertain ICER. Beyond the ICER framework, other factors were acknowledged, including the high clinical need in a patient population for which there are no other active treatments available. This case study highlights the challenges of conducting HTA for already funded interventions, and the efficiency trade-offs required to fund effective high-cost therapies in rare conditions.

Adoption of colonoscopy surveillance intervals in subjects who received polypectomy in southern China: A cost-effectiveness analysis.

We aimed to evaluate the cost-effectiveness of different colonoscopy intervals among average-risk (5 vs 10years) and high-risk (1 vs 3years) southern Chinese populations. We constructed a Markov model with a hypothetical population of 100000 individuals aged 50-85years. Average risk was defined as 1-2 non-advanced adenomas (tubular adenoma sized <10mm without high-grade dysplasia). High risk was defined as ≥3 non-advanced adenomas or any advanced adenoma (adenoma sized ≥10mm, with high-grade dysplasia, or with villous/tubulovillous histology). Three strategies were compared: a 5/1 strategy (average-risk subjects: 5-year interval; high-risk subjects: 1-year interval), a 10/3 strategy, and a control strategy (a 10/10 strategy). Costs (US dollar), quality-adjusted-life-years, incremental cost-effectiveness ratio, and net health benefit were calculated. If the incremental cost-effectiveness ratio of one strategy against another was less than willingness-to-pay ($24302 US/quality-adjusted-life-years), the strategy was more cost-effective than another. Compared with the 10/3 strategy, the 5/1 strategy involved more costs and effects (incremental cost-effectiveness ratio=$40044 US/quality-adjusted life-years). When the 10/10 strategy was regarded as the control, the 5/1 strategy had a higher incremental cost-effectiveness ratio than the 10/3 strategy ($26056 vs $10344 US/quality-adjusted life-years). Furthermore, the 10/3 strategy had the highest net health benefit. A 10/3 interval was more cost-effective than a 5/1 interval. From an economic perspective, our findings supported a 10-year interval for average-risk individuals and a 3-year interval for high-risk subjects. The findings could help form the optimal colonoscopy interval for average-risk and high-risk patients.

Designing Guidelines for Those Who Do Not Follow Them: The Impact of Adherence Assumptions on Optimal Screening Guidelines

ObjectivesModel-based cost-effectiveness analyses can inform decisions about screening guidelines by quantifying consequences of alternative algorithms. Although actual screening adherence is imperfect, incorporating nonadherence into analyses that aim to determine optimal screening may affect the policy recommendations. We evaluated the impact of nonadherence assumptions on the optimal cervical cancer screening in Norway. MethodsWe used a microsimulation model of cervical carcinogenesis to project the long-term health and economic outcomes under alternative screening algorithms and adherence patterns. We compared 18 algorithms involving primary human papillomavirus testing (5-yearly) that varied follow-up management of different human papillomavirus results. We considered 12 adherence scenarios: perfect adherence, 8 high- and low-coverage “random-complier” scenarios, and 3 “systematic-complier” scenarios that reflect conditional screening behavior over a lifetime. We calculated incremental cost-effectiveness ratios and considered a strategy with the highest incremental cost-effectiveness ratio < 55 000 US dollars/quality-adjusted life-year as “optimal.” ResultsUnder perfect adherence, the least intensive screening strategy was optimal; in contrast, assuming any nonadherence resulted in a more intensive optimal strategy. Accounting for lower adherence resulted in both lower costs and health benefits, which allowed for a more intensive strategy to be considered optimal, but more harms for women who screen according to guidelines (ie, up to 41% more colposcopies when comparing the optimal strategy in the lowest-adherence scenario with the optimal strategy under perfect adherence). ConclusionsAssuming nonadherence in analyses designed to inform national guidelines may lead to a relatively more intensive recommendation. Designing guidelines for those who do not adhere to them may lead to over-screening of those who do.

Cost-Effectiveness of Abemaciclib in Early Breast Cancer Patients: One Size Fits All or Tailoring to Patients' Needs?

The addition of two years of abemaciclib treatment to standard adjuvant endocrine therapy in all patients with high risk ER+, HER2- early breast cancer (EBC) has been approved by the US Food and Drug Administration (FDA). Pre-selection of patients with an immediate risk of recurrence within the group of clinically high risk patients using detection of minimal residual disease (MRD) using patient-informed circulating tumor DNA assays during follow-up could enhance efficacy. Here, we investigate the cost-effectiveness of the addition of two years abemaciclib in all high risk HR+, HER2- patients and in MRD-guided high risk patients only. Two semi-Markov models were developed to evaluate the cost-effectiveness of adding two years of abemaciclib compared to "standard treatment": 1) "abemaciclib all" and 2) "MRD-guided abemaciclib" using MRD-guidance. Data of the MonarchE trial were used to model the invasive disease-free survival (iDFS). Since iDFS and overall survival (OS) data of abemaciclib were currently limited, abemaciclib effects were extrapolated using a favorable, intermediate and unfavorable effect scenario. The addition of abemaciclib in all high-risk EBC patients prolonged iDFS slightly (0.04 additional quality adjusted life years (QALYs)) and led to higher costs compared to standard ET, leading to a high incremental cost effectiveness ratio (ICER) of €1,551,876/QALY. Neither the favorable effect scenario (additional 1.09 QALYs) was cost-effective (ICER €62,935/QALY), using a willingness-to-pay threshold of €50,000/QALY. The "MRD-guided abemaciclib" strategy resulted in lower costs and an increase in QALYs (1.27) compared to "standard treatment" in the unfavorable effect scenario. The addition of abemaciclib to adjuvant endocrine therapy in all high-risk ER+, HER2- EBC patients is not cost-effective. However, using MRD detection to justify the addition of abemaciclib treatment dominates standard treatment in this cost-effectiveness analysis. Further evaluation of MRD detection in EBC by means of prospective clinical trials assessing clinical utility is recommended and promising in terms of cost-effectiveness.

Cost-utility analysis and net monetary benefit of Platelet Rich Plasma (PRP), intra-articular injections in compared to Plasma Rich in Growth Factors (PRGF), Hyaluronic Acid (HA) and ozone in knee osteoarthritis in Iran

PurposeTo evaluate the cost-effectiveness of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factors (PRGF), Hyaluronic Acid (HA) and ozone as effective treatment approaches in knee osteoarthritis management from Iran Health care perspective.MethodsA decision tree model was conducted to assess the cost-effectiveness of four common intra-articular treatment approaches in patients with mild and moderate knee osteoarthritis. The data on clinical effectiveness was obtained from a randomized controlled trial (RCT) conducted in Iran and used to estimate utility values. The direct medical costs were estimated according to tariffs for public medical centers and hospitals, approved by the Iran Ministry of Health and Medical Education in 2021. The incremental cost-effectiveness ratio (ICER) and the net monetary benefit (NMB) were used to evaluate the cost-utility analysis. Deterministic and probabilistic sensitivity analyses are performed to investigate the robustness of the results and account for the different sources of uncertainty.ResultsIn this study, HA intra-articular injection-related costs ($581.67/patient) were defined as the highest cost, followed by PRGF ($328.10/patient), PRP (318.58/patient), and Ozone (103.20/patient). According to the utility value, PRP and PRGF (0.68) have the same and the most utility among Intra-articular injections in knee osteoarthritis management. However, the PRP injection method was identified as the most cost-effective intervention due to its high NMB and ICER estimates. Based on the Monte Carlo Simulation, PR intervention, compared to other ones, was introduced as the dominant strategy regarding knee OA management, with a WTP of $10,000 for 100% of cases.ConclusionThe study result demonstrated that intra-articular injection of PRP, compare to other injections, is a cost-effective treatment option for patients with mild and moderate knee osteoarthritis. In addition, intra-articular injection of PRP was identified as the best injection, with the highest level of net monetary benefit, for knee OA management.

Tremelimumab and durvalumab with chemotherapy in first-line treatment for metastatic non-small cell lung cancer: a US-based cost-effectiveness analysis.

While the tremelimumab plus durvalumab combined with chemotherapy (T + D + CT) has shown promise in treating epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) wild-type metastatic non-small cell lung cancer (mNSCLC), particularly in patients with low or no programmed cell death ligand 1 (PD-L1) expression, the economic implications of its high cost remain poorly understood. This study fills a critical gap in knowledge by evaluating the cost-effectiveness of T + D + CT from a US health care perspective, offering valuable insights for clinical and policy decision-making. A 10-year Markov model was crafted to track the disease progression, survival, and treatment-related toxicities of a patient cohort with EGFR/ALK wild-type mNSCLC. Transition probabilities were derived from the POSEIDON trial, while health state utilities were obtained from the literature. Cost data, including drug acquisition and administration, subsequent anticancer therapies, and adverse event management were estimated using the Centers for Medicare and Medicaid Services and the Healthcare Cost and Utilization Project databases, with additional costs sourced from current literature. All cost and effectiveness measures were discounted at an annual rate of 3%. The model's robustness was assessed through deterministic sensitivity analysis (DSA), probabilistic sensitivity analysis (PSA), and scenario analysis. T + D + CT compared to chemotherapy alone yielded incremental cost-effectiveness ratios (ICERs) of $370,208 to $691,960 per quality-adjusted life-year (QALY) gained, exceeding the standard willingness-to-pay (WTP) threshold of $100,000 to $150,000 per QALY. Against durvalumab plus chemotherapy, T + D + CT was only cost-effective in all subgroups. DSA results for patients with PD-L1 expression <1% showed that the ICER for first-line T + D + CT remained above the WTP threshold range, even with substantial changes to model inputs. PSA revealed a higher likelihood of T + D + CT being cost-effective as WTP thresholds increased. Scenario analysis confirmed the study's primary findings, with the exception of a scenario where durvalumab was offered at no cost. The findings suggests that T + D + CT may not be a cost-effectiveness first-line treatment for EGFR/ALK wild-type mNSCLC in the US, given its high ICERs and limited cost-effectiveness in the majority of PD-L1 expression subgroups.

Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Systematic Review of Economic Evaluations

Several studies have evaluated the economic evaluation of a group of medications known as novel oral anticoagulant drugs (NOACs) in recent years. The aim of this study is to review and systematically analyze the cost-utility studies results of warfarin compared with other NOAC drugs in atrial fibrillation patients. A systematic review was performed to identify all studies evaluating the NOAC medications in comparison with warfarin. For this purpose, PubMed, Cochrane Library, ISI Web of Science, and Scopus were searched from 2013 to 2022. Articles were independently screened with inclusion criteria, and full texts were reviewed. First, the Consolidated Health Economic Evaluation Reporting Standards checklist was used to evaluate the quality of the articles. Then, the costs and outcomes of the studies were analyzed, and findings were appraised critically. A total of 84 costs-per-quality-adjusted life-year (QALY) cases were extracted from the studies in which the share of rivaroxaban, edoxaban, apixaban, and dabigatran were 31%, 13%, 29%, and 27%, respectively. The median cost per QALY of rivaroxaban, edoxaban, apixaban, and dabigatran was 21 910$/QALY, 22 096$/QALY, 17 765$/QALY, and 24 161$/QALY, respectively. Subgroup analysis based on perspective showed that dabigatran had the highest incremental cost-effectiveness ratio (ICER) and edoxaban had the lowest ICER value. Edoxaban and apixaban had the highest and the lowest cost per QALY from an insurance perspective, respectively. Despite the differences and variations in the economic evaluation studies of NOAC drugs, these drugs have shown acceptable cost-effectiveness in developed and developing countries. Among NOAC drugs, apixaban has the lowest ICER and the highest cost-effectiveness.