Monte Carlo Microsimulation Research Articles

Multiple myeloma: What is the most cost-effective imaging strategy for initial detection of bone lesions?

To determine the cost-effectiveness of different imaging modalities for initial detection of multiple myeloma (MM)-defining bone lesions. A Markov model from the health care system perspective for patients with MGUS was used to evaluate the incremental cost-effectiveness of five imaging techniques: skeletal survey (SS), low-dose computed tomography (LDCT), positron emission computed tomography (PETCT), and whole-body magnetic resonance imaging (WBMRI) with and without diffusion (DIFF). Model inputs, including probabilities, utilities, and costs were obtained from comprehensive literature review. Costs were estimated in 2024 U.S. dollars, effectiveness was measured in quality adjusted life years (QALYs), willingness-to-pay (WTP) threshold was set to $100,000/QALY, and timeframe of the simulation was 20years. Model analyses included Monte Carlo microsimulation and probabilistic sensitivity analysis (PSA). The most cost-effective imaging strategy was dependent on the number of patient risk factors for progression from MGUS to myeloma. At a WTP threshold of $100,000, for patients with no risk factors for progression, LDCT amassed the greatest net monetary benefit (NMB) ($1,030,913.57) while incurring the second lowest costs ($44,870.73). For patients with 1 or 2 risk factors for progression, WBMRI + DIFF amassed the greatest NMB (1 risk factor: $802,637.30, 2 risk factors: $664,430.36). WBMRI and PETCT were absolutely dominated in all cases. PSA also found that the most cost-effective strategy was dependent on the WTP threshold. Our model suggests that LDCT and WBMRI + DIFF can be the most cost-effective imaging strategies for the initial diagnosis of MM in patients, depending on the number of risk factors for progression.

Cemented Hemiarthroplasty Results in Substantial Cost Savings Over Uncemented Hemiarthroplasty for the Treatment of Femoral Neck Fractures in Patients Over 60 Years Old: A Markov Analysis

BackgroundWhile there is growing scientific evidence supporting superior outcomes following cemented versus uncemented hip hemiarthroplasty (HHA) in elderly femoral neck fractures (FNFs), the relative cost-effectiveness of this in the United States is unknown. Thus, the purpose of this study was to compare the cost-effectiveness of cemented versus uncemented HHA for the treatment of FNFs in patients > 60 years old in the United States, accounting for postoperative outcomes including periprosthetic fractures. MethodsA Markov model utilizing Monte Carlo microsimulation was developed to evaluate the outcomes and costs of patients at least 60 years of age (mean ± standard deviation, 84 ± 8 years) undergoing cemented versus uncemented HHA for the treatment of FNFs. Health utility values, transition probabilities, and upfront costs were derived from the published literature. Outcome measures included average total costs associated with each treatment (including those from patients who sustained a periprosthetic fracture), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). ResultsMean total costs resulting from cemented and uncemented HHA were $19,462 ± 3,581 and $21,997 ± 3,574, respectively (upfront costs from the published literature were $18,267 for cemented HHA and $16,803 for uncemented HHA). Average QALYs resulting from cemented and uncemented HHA were 4.0 ± 0.7 and 3.1 ± 0.6. The resulting ICER was -$2,688.9/QALY. Cemented HHA was found to be the most cost-effective treatment strategy in 89% of the patients in the Monte Carlo microsimulation model. ConclusionDespite documented higher upfront costs for cemented HHA, the averaged total costs over a 10-year time horizon were $2,534 less for cemented HHA than for uncemented HHA. In addition, cemented HHA resulted in an additional 0.9 QALYs relative to uncemented HHA. The findings of this United States-based study replicate the financial and quality-of-life benefits of cemented HHA for elderly FNFs seen in other health systems.

Unlocking the power of tobacco taxation to mitigate the social costs of smoking in Mexico: a microsimulation model.

Despite being the most cost-effective tobacco control policy, tobacco taxation is the least implemented component of the World Health Organization MPOWER package to reduce smoking worldwide. In Mexico, both smoking prevalence and taxation have remained stable for more than a decade. This study aims to provide evidence about the potential effects of taxation to reduce the burden of tobacco-related diseases and the main attributable social costs in Mexico, including informal (unpaid) care costs, which are frequently ignored. We employ a first-order Monte Carlo microsimulation model that follows hypothetical population cohorts considering the risks of an adverse health event and death. First, we estimate tobacco-attributable morbidity and mortality, direct medical costs and indirect costs, such as labour productivity losses and informal care costs. Then, we assess the potential effects of a 50% cigarette price increase through taxation and two alternative scenarios of 25% and 75%. The inputs come from several sources, including national surveys and vital statistics. Each year, 63 000 premature deaths and 427 000 disease events are attributable to tobacco in Mexico, while social costs amount to MX$194.6 billion (US$8.5)-MX$116.2 (US$5.1) direct medical costs and MX$78.5 (US$3.4) indirect costs-representing 0.8% of gross domestic product. Current tobacco tax revenue barely covers 23.3% of these costs. Increasing cigarette prices through taxation by 50% could reduce premature deaths by 49 000 over the next decade, while direct and indirect costs averted would amount to MX$87.9 billion (US$3.8) and MX$67.6 billion (US$2.9), respectively. The benefits would far outweigh any potential loss even in a pessimistic scenario of increased illicit trade. Tobacco use imposes high social costs on the Mexican population, but tobacco taxation is a win-win policy for both gaining population health and reducing tobacco societal costs.

Comparing Recurrence Rates and the Cost-Effectiveness of Arthroscopic Labral Repair and Nonoperative Management for Primary Anterior Shoulder Dislocations in Young Patients: A Decision-Analytic Markov Model-Based Analysis

Background: Value-based decision-making regarding nonoperative management versus early surgical stabilization for first-time anterior shoulder instability (ASI) events remains understudied. Purpose: To perform (1) a systematic review of the current literature and (2) a Markov model–based cost-effectiveness analysis comparing an initial trial of nonoperative management to arthroscopic Bankart repair (ABR) for first-time ASI. Study Design: Economic and decision analysis; Level of evidence, 3. Methods: A Markov chain Monte Carlo probabilistic model was developed to evaluate the outcomes and costs of 1000 simulated patients (mean age, 20 years; range, 12-26 years) with first-time ASI undergoing nonoperative management versus ABR. Utility values, recurrence rates, and transition probabilities were derived from the published literature. Costs were determined based on the typical patient undergoing each treatment strategy at the authors’ institution. Outcome measures included costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). Results: The Markov model with Monte Carlo microsimulation demonstrated mean (± standard deviation) 10-year costs for nonoperative management and ABR of $38,649 ± $10,521 and $43,052 ± $9352, respectively. Total QALYs acquired over the 10-year time horizon were 7.67 ± 0.43 and 8.44 ± 0.46 for nonoperative management and ABR, respectively. The ICER comparing ABR with nonoperative management was found to be just $5725/QALY, which falls substantially below the $50,000 willingness-to-pay (WTP) threshold. The mean numbers of recurrences were 2.55 ± 0.31 and 1.17 ± 0.18 for patients initially assigned to the nonoperative and ABR treatment groups, respectively. Of 1000 samples run over 1000 trials, ABR was the optimal strategy in 98.7% of cases, with nonoperative management the optimal strategy in 1.3% of cases. Conclusion: ABR reduces the risk for recurrent dislocations and is more cost-effective despite higher upfront costs when compared with nonoperative management for first-time ASI in the young patient. While all these factors are important to consider in surgical decision-making, ultimate treatment decisions should be made on an individual basis and occur through a shared decision-making process.

Cost-effectiveness of expanding national health insurance coverage for composite resin restorations in cancer patients in South Korea

ObjectivesCancer patients often have compromised oral health, making them vulnerable to severe dental caries and restoration failures. Due to the nature of cervical or anterior caries in cancer patients, the use of adequate restorative materials is important. However, public dental insurance coverage for composite treatments varies among countries and only glass ionomer cements (GICs) are covered in all age groups in South Korea. This study examined the cost-effectiveness of expanding national health insurance coverage to include resin composite (RC) restorations as compared with GIC in cancer patients. MethodsData from cancer patients who received direct restoration using GIC were identified from the National Health Screening Cohort. The relative effect of RC compared to GIC was determined through a meta-analysis, which was then utilized in calculating corresponding transition probabilities within a multi-state model. A Markov-chain Monte Carlo microsimulation was performed to estimate useful life-years and total treatment costs at the tooth level. The incremental cost-effectiveness ratio (ICER) of RC versus GIC was calculated, considering scenarios with and without expanded national health insurance coverage. The robustness of the results was confirmed through various sensitivity analyses. ResultsBetween the two materials, RC resulted in a 0.4-year longer useful life. From a limited societal perspective, it cost $9.6 less with expanded coverage but $24.3 more without expansion, resulting in an ICER of -$25.2 and $63.9 per tooth-year, respectively. From a patient's perspective, the ICER values were -$72.7 versus $138.8 per tooth-year, respectively, translating into $200 more in savings with the expansion. Various sensitivity analyses consistently demonstrated a smaller ICER when insurance coverage was expanded. ConclusionsThe expansion of national health insurance coverage to include RC restorations for cancer patients appears to be clearly cost-effective. This emphasizes the need for further policy considerations to ensure access to dental care for cancer patients. Clinical SignificanceTimely management of dental caries is crucial for cancer patients, as untreated caries can escalate into severe oral conditions, negatively impacting treatment outcomes and increasing care costs. Expanding a national health insurance coverage for cancer patients in the treatment of early dental lesions is necessary to prevent advanced dental diseases.

Genetic counseling and subsequent cascade genetic testing for women with a family history of pathogenic BRCA1 mutation: A cost-effectiveness model.

10621 Background: BRCA1 pathogenic mutations significantly increase the lifetime risk for breast and ovarian cancer, but risk reducing interventions such as bilateral salpingo-oophorectomy (RRBSO) and mastectomy (RRM) can improve outcomes. For women with a known family history of pathogenetic mutation, genetic counseling and testing is recommended. We sought to determine the cost-effectiveness (CE) of referral to genetic counseling with subsequent cascade testing. Methods: A decision analytic model was created using TreeAgePro 2023 software to evaluate the strategies of routine genetics consultation with Ambry panel testing versus no referral. It was assumed that known BRCA1 carriers would undergo annual breast cancer screening with mammogram and MRI at 25yo, RRBSO at 35yo, and RRM at 40yo. Non-carriers underwent routine annual mammogram at 40yo. Additionally, women who did not undergo genetic testing initially do so at the time of diagnosis of first cancer (breast of ovary) and subsequently underwent all recommended risk reducing strategies if found to have a pathogenic BRCA1 mutation. Outcomes included cost, quality adjusted life years (QALYs), ovarian and breast cancer cases and deaths. Univariate and multi-variate analyses were used to investigate the impact of the strategies. Results: In a Monte Carlo Microsimulation cohort of 10,000 women with a first degree relative with a pathogenic BRCA1 mutation, referral to genetic counseling with testing was the dominate strategy. This strategy resulted in a similar mean cost ($185,543 vs $185,171), but with 2,322 additional QALYs and incremental CE ratio (ICER) of 1,605 per QALY. This dominant strategy also resulted in 73 fewer ovarian cancer cases and 545 fewer breast cancer cases. Sensitivity analysis for the age of RRM was remarkable for an annual reduction in breast cancer cases by 97 cases and an annual cost savings of 375,658 for year prior to age 40 that mastectomy was performed. Conclusions: Routine genetic counseling and screening for all patients with a known family history of pathogenic BRCA1 mutation reduces breast and ovarian cancer diagnoses by prompting risk-reducing procedures without significant increase in cost when compared to diagnosis-based testing. Routine access to genetic counseling in a high-risk population would help inform earlier counseling and further decrease cancer risk, particularly as earlier RRM may improve outcomes. This is further supported by the low cost to implement. Improvement in identification and early referral could be targeted. [Table: see text]

Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2.

Our aim was to compare the costs and efficacy of ambroxol in combination with imiglucerase with the costs and efficacy of imiglucerase only in the treatment of Gaucher disease type 2 (GD2) in the socio-economic settings of the Republic of Serbia, an upper-middle-income European economy. The perspective of the Serbian Republic Health Insurance Fund was chosen for this study, and the time horizon was 6 years. The main outcomes of the study were quality-adjusted life years gained with ambroxol + imiglucerase and comparator, and direct costs of treatment. The study was conducted through the generation and simulation of the Markov chain model. The model results were obtained after Monte Carlo microsimulation of a sample with 1,000 virtual patients. Treatment with ambroxol in combination with imiglucerase was cost-effective when compared with imiglucerase only and was associated with positive values of net monetary benefit regardless of the onset of the disease. Such beneficial result for ambroxol and imiglucerase combination is primarily driven by the low cost of ambroxol and its considerable clinical effectiveness in slowing the progression of neural complications of GD2. If ambroxol and imiglucerase are used in combination for the treatment of GD2, it is more cost-effective than using imiglucerase alone.

The long-term cost-effectiveness of once-weekly semaglutide versus sitagliptin for the treatment of type 2 diabetes in China

BackgroundTo estimate the long-term cost-effectiveness of once-weekly semaglutide versus sitagliptin as an add-on therapy for type 2 diabetes patients inadequately controlled on metformin in China, to better inform healthcare decision making.MethodsThe Cardiff diabetes model which is a Monte Carlo micro-simulation model was used to project short-term effects of once-weekly semaglutide versus sitagliptin into long-term outcomes. Short-term data of patient profiles and treatment effects were derived from the 30-week SUSTAIN China trial, in which 868 type 2 diabetes patients with a mean age of 53.1 years inadequately controlled on metformin were randomized to receive once-weekly semaglutide 0.5 mg, once-weekly semaglutide 1 mg, or sitagliptin 100 mg. Costs and quality-adjusted life years (QALYs) were estimated from a healthcare system perspective at a discount rate of 5%. Univariate sensitivity analysis, scenario analysis, and probabilistic sensitivity analysis were conducted to test the uncertainty.ResultsOver patients’ lifetime projections, patients in both once-weekly semaglutide 0.5 mg and 1 mg arms predicted less incidences of most vascular complications, mortality, and hypoglycemia, and lower total costs compared with those in sitagliptin arm. For an individual patient, compared with sitagliptin, once-weekly semaglutide 0.5 mg conferred a small QALY improvement of 0.08 and a lower cost of $5173, while once-weekly semaglutide 1 mg generated an incremental QALY benefit of 0.12 and a lower cost of $7142, as an add-on to metformin. Therefore, both doses of once-weekly semaglutide were considered dominant versus sitagliptin with more QALY benefits at lower costs.ConclusionOnce-weekly semaglutide may represent a cost-effective add-on therapy alternative to sitagliptin for type 2 diabetes patients inadequately controlled on metformin in China.

Early Arthroscopic Debridement May Be More Cost-Effective Than Nonoperative Management for Symptomatic Osteochondritis Dissecans Lesions of the Capitellum

To compare the cost-effectiveness of an initial trial of nonoperative treatment to that of early arthroscopic debridement for stable osteochondritis dissecans (OCD) lesions of the capitellum. A Markov Chain Monte Carlo probabilistic model was developed to evaluate the outcomes and costs of 1,000 simulated patients undergoing nonoperative management versus early arthroscopic debridement for stable OCD lesions of the capitellum. Health utility values, treatment success rates, and transition probabilities were derived from the published literature. Costs were determined on the basis of the typical patient undergoing each treatment strategy at our institution. Outcome measures included costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). Mean total costs resulting from nonoperative management and early arthroscopic debridement were $5,330 and $21,672, respectively. On average, early arthroscopic debridement produced an additional 0.64 QALYS, resulting in an ICER of $25,245/QALY, which falls well below the widely accepted $50,000 willingness-to-pay (WTP) threshold. Overall, early arthroscopic debridement was determined to be the preferred cost-effective strategy in 69% of patients included in the microsimulation model. Results of the Monte Carlo microsimulation and probabilistic sensitivity analysis demonstrated early arthroscopic debridement to be a cost-effective treatment strategy for the majority of stable OCD lesions of the capitellum. Although early arthroscopic debridement was associated with higher total costs, the increase in QALYS that resulted from early surgery was enough to justify the cost difference based on an ICER substantially below the $50,000 WTP threshold. Level III, economic computer simulation model.

Cost-Effectiveness of Annual Prostate MRI and Potential MRI-Guided Biopsy After Prostate-Specific Antigen Test Results

Magnetic resonance imaging (MRI) and potential MRI-guided biopsy enable enhanced identification of clinically significant prostate cancer. Despite proven efficacy, MRI and potential MRI-guided biopsy remain costly, and there is limited evidence regarding the cost-effectiveness of this approach in general and for different prostate-specific antigen (PSA) strata. To examine the cost-effectiveness of integrating annual MRI and potential MRI-guided biopsy as part of clinical decision-making for men after being screened for prostate cancer compared with standard biopsy. Using a decision analytic Markov cohort model, an economic evaluation was conducted projecting outcomes over 10 years for a hypothetical cohort of 65-year-old men in the US with 4 different PSA strata (<2.5 ng/mL, 2.5-4.0 ng/mL, 4.1-10.0 ng/mL, >10 ng/mL) identified by screening through Monte Carlo microsimulation with 10 000 trials. Model inputs for probabilities, costs in 2020 US dollars, and quality-adjusted life-years (QALYs) were from the literature and expert consultation. The model was specifically designed to reflect the US health care system, adopting a federal payer perspective (ie, Medicare). Magnetic resonance imaging with potential MRI-guided biopsy and standard biopsy. Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold of $100 000 per QALY was estimated. One-way and probabilistic sensitivity analyses were performed. For the 3 PSA strata of 2.5 ng/mL or greater, the MRI and potential MRI-guided biopsy strategy was cost-effective compared with standard biopsy (PSA 2.5-4.0 ng/mL: base-case ICER, $21 131/QALY; PSA 4.1-10.0 ng/mL: base-case ICER, $12 336/QALY; PSA >10.0 ng/mL: base-case ICER, $6000/QALY). Results varied depending on the diagnostic accuracy of MRI and potential MRI-guided biopsy. Results of probabilistic sensitivity analyses showed that the MRI and potential MRI-guided biopsy strategy was cost-effective at the willingness-to-pay threshold of $100 000 per QALY in a range between 76% and 81% of simulations for each of the 3 PSA strata of 2.5 ng/mL or more. This economic evaluation of a hypothetical cohort suggests that an annual MRI and potential MRI-guided biopsy was a cost-effective option from a US federal payer perspective compared with standard biopsy for newly eligible male Medicare beneficiaries with a serum PSA level of 2.5 ng/mL or more.

Ross procedure or mechanical aortic valve, which is the best lifetime option for an 18-year-old? A decision analysis

Objective(s)Identifying the optimal solution for young adults requiring aortic valve replacement (AVR) is challenging, given the variety of options and their lifetime complication risks, impacts on quality of life, and costs. Decision analytic techniques make comparisons incorporating these measures. We evaluated lifetime valve-related outcomes of mechanical aortic valve replacement (mAVR) versus the Ross procedure (Ross) using decision tree microsimulations modeling. MethodsTransition probabilities, utilities, and costs derived from published reports were entered into a Markov model decision tree to explore progression between health states for hypothetical 18-year-old patients. In total, 20,000 Monte Carlo microsimulations were performed to model mortality, quality-adjusted-life-years (QALYs), and health care costs. The incremental cost-effectiveness ratio (ICER) was calculated. Sensitivity analyses was performed to identify transition probabilities at which the preferred strategy switched from baseline. ResultsFrom modeling, average 20-year mortality was 16.3% and 23.2% for Ross and mAVR, respectively. Average 20-year freedom from stroke and major bleeding was 98.6% and 94.6% for Ross, and 90.0% and 82.2% for mAVR, respectively. Average individual lifetime (60 postoperative years) utility (28.3 vs 23.5 QALYs) and cost ($54,233 vs $507,240) favored Ross over mAVR. The average ICER demonstrated that each QALY would cost $95,345 more for mAVR. Sensitivity analysis revealed late annual probabilities of autograft/left ventricular outflow tract disease and homograft/right ventricular outflow tract disease after Ross, and late death after mAVR, to be important ICER determinants. ConclusionsOur modeling suggests that Ross is preferred to mAVR, with superior freedom from valve-related morbidity and mortality, and improved cost-utility for young adults requiring aortic valve surgery.

Cost-effectiveness analysis of full versus selective root canal retreatment.

Selective root-canal retreatment has been proposed as an alternative to full retreatment in multirooted, root-canal-filled teeth with evidence of apical pathology, where only the affected root(s) is retreated. Whilst this option may save costs initially, failures and retreatments may compensate for these initial savings. We assessed the cost-effectiveness of full versus selective root-canal retreatment using data from a recent clinical pilot study, employing a modelling approach. A Markov model was constructed to follow up a previously root-canal treated maxillary molar with apical pathology on a single root (mesio-buccal), receiving either selective or full root-canal retreatment. A private-payer perspective in Dutch health care was adopted. Permanent molar teeth with apical lesions on the mesial root were simulated over the lifetime of initially 50-year-old patients. Teeth could have endodontic complications and require interventions such as retreatment or tooth extraction and replacement. Costs were calculated based on the Dutch dental fee catalogues. Monte-Carlo microsimulations were performed to assess lifetime costs and effectiveness (measured as tooth retention time), and the resulting cost-effectiveness. Probabilistic joint uncertainty and sensitivity analyses were performed, and cost-effectiveness at different willingness-to-pay-thresholds was evaluated. In the base-case scenario, selective retreatment was less costly (2137; 2.5%-97.5% percentiles: 1944-2340 Euro) and more effective (19.6; 18.3-20.8 Years) than full retreatment (2495; 2305-2671 Euro; 16.5; 15.2-17.9 Years) in 100% of the simulations and regardless of the willingness-to-pay threshold. Only in a worst case scenario was selective retreatment more costly, but remained more effective. Selective retreatment, when clinically applicable, is likely to be more cost-effective than full retreatment in endodontically treated molars with persistent apical periodontitis. Our results should be interpreted with caution because the quality of the underlying data is limited.

Framework for determining the optimal course of action when efficiency and affordability measures differ by perspective in cost-effectiveness analysis—with an illustrative case of HIV treatment in Mozambique

BackgroundCost-effectiveness analysis (CEA) is a standard tool for evaluating health programs and informing decisions about resource allocation and prioritization. Most CEAs evaluating health interventions in low- and middle-income countries adopt a health sector perspective, accounting for resources funded by international donors and country governments, while often excluding out-of-pocket expenditures and time costs borne by program beneficiaries. Even when patients’ costs are included, a companion analysis focused on the patient perspective is rarely performed. We view this as a missed opportunity.MethodsWe developed methods for assessing intervention affordability and evaluating whether optimal interventions from the health sector perspective also represent efficient and affordable options for patients. We mapped the five different patterns that a comparison of the perspective results can yield into a practical framework, and we provided guidance for researchers and decision-makers on how to use results from multiple perspectives. To illustrate the methodology, we conducted a CEA of six HIV treatment delivery models in Mozambique. We conducted a Monte Carlo microsimulation with probabilistic sensitivity analysis from both patient and health sector perspectives, generating incremental cost-effectiveness ratios for the treatment approaches. We also calculated annualized patient costs for the treatment approaches, comparing the costs with an affordability threshold. We then compared the cost-effectiveness and affordability results from the two perspectives using the framework we developed.ResultsIn this case, the two perspectives did not produce a shared optimal approach for HIV treatment at the willingness-to-pay threshold of 0.3 × Mozambique’s annual GDP per capita per DALY averted. However, the clinical 6-month antiretroviral drug distribution strategy, which is optimal from the health sector perspective, is efficient and affordable from the patient perspective. All treatment approaches, except clinical 1-month distributions of antiretroviral drugs which were standard before Covid-19, had an annual cost to patients less than the country’s annual average for out-of-pocket health expenditures.ConclusionIncluding a patient perspective in CEAs and explicitly considering affordability offers decision-makers additional insights either by confirming that the optimal strategy from the health sector perspective is also efficient and affordable from the patient perspective or by identifying incongruencies in value or affordability that could affect patient participation.

Cost-Effectiveness Analysis of Regenerative Endodontics versus MTA Apexification.

With the introduction of stem cell engineering in dentistry, regenerative endodontics has emerged as a potential alternative to mineral trioxide aggregate (MTA) apexification in the management of necrotic immature permanent teeth. However, the utility of this modality in terms of cost-effectiveness has not yet been established. Therefore, we performed cost-effectiveness analysis to determine the dominant treatment modality that would influence decision making from the private payer perspective. A Markov model was constructed with a necrotic immature permanent tooth in a 7-y-old patient, followed over the lifetime using TreeAge Pro Healthcare 2022. Transition probabilities were estimated based on the existing literature. Costs were estimated based on United States health care, and cost-effectiveness was determined using Monte Carlo microsimulations. The model was validated internally by sensitivity analyses, and face validation was performed by an experienced endodontist and health economist. In the base-case scenario, regenerative endodontics did not turn out to be a dominant treatment option as it was associated with an additional cost of USD$1,012 and fewer retained tooth-years (15.48 y). Likewise, in the probabilistic sensitivity analysis, regenerative endodontics was again dominated by apexification against different willingness-to-pay values. Based on current evidence, regenerative endodontic treatment was not cost-effective compared with apexification in the management of necrotic immature permanent teeth over an individual's lifetime. The study provides valuable insight regarding the cost valuation and cost-efficacy of regenerative endodontic treatment versus apexification in the management of necrotic immature permanent teeth, as this would aid in effective clinical decision making, allowing for the functional allocation of resources.

Early surgery compared to nonoperative management for mild degenerative cervical myelopathy: a cost-utility analysis

BACKGROUND CONTEXTDegenerative cervical myelopathy (DCM) is a form of acquired spinal cord compression and contributes to reduced quality of life secondary to neurological dysfunction and pain. There remains uncertainty regarding optimal management for individuals with mild myelopathy. Specifically, owing to lacking long-term natural history studies in this population, we do not know whether these individuals should be treated with initial surgery or observation. PURPOSEWe sought to perform a cost-utility analysis to examine early surgery for mild degenerative cervical myelopathy from the healthcare payer perspective. STUDY DESIGN/SETTINGWe utilized data from the prospective observational cohorts included in the Cervical Spondylotic Myelopathy AO Spine International and North America studies to determine health related quality of life estimates and clinical myelopathy outcomes. PATIENT SAMPLEWe recruited all patients that underwent surgery for DCM enrolled in the Cervical Spondylotic Myelopathy AO Spine International and North America studies between December 2005 and January 2011. OUTCOME MEASURESClinical assessment measures were obtained using the Modified Japanese Orthopedic Association scale and health-related quality of life measures were obtained using the Short Form-6D utility score at baseline (preoperative), 6 months, 12 months and 24 months postsurgery. Cost measures inflated to January 2015 values were obtained using pooled estimates from the hospital payer perspective for surgical patients. METHODSWe employed a Markov state transition model with Monte Carlo microsimulation using a lifetime horizon to obtain an incremental cost utility ratio associated with early surgery for mild myelopathy. Parameter uncertainty was assessed through deterministic means using one-way and two-way sensitivity analyses and probabilistically using parameter estimate distributions with microsimulation (10,000 trials). Costs and utilities were discounted at 3% per annum. RESULTSInitial surgery for mild degenerative cervical myelopathy was associated with an incremental lifetime increase of 1.26 quality-adjusted life years (QALY) compared to observation. The associated cost incurred to the healthcare payer over a lifetime horizon was $12,894.56, resulting in a lifetime incremental cost-utility ratio of $10,250.71/QALY. Utilizing a willingness to pay threshold in keeping with the World Health Organization definition of "very cost-effective" ($54,000 CDN), the probabilistic sensitivity analysis demonstrated that 100% of cases were cost-effective. CONCLUSIONSSurgery compared to initial observation for mild degenerative cervical myelopathy was cost-effective from the Canadian healthcare payer perspective and was associated with lifetime gains in health-related quality of life.

Economic analysis of cerliponase alfa for treatment of late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2)

ABSTRACT Background Cerliponase alfa is an orphan drug approved for the treatment of late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2). Aim Our goal was to assess the cost-effectiveness of cerliponase alfa in patients with CLN2 in the socioeconomic context of the Republic of Serbia in contrast to symptomatic therapy. Method For this study, a forty-year horizon and the perspective of the Serbian Republic Health Insurance Fund were used. Quality-adjusted life years gained with cerliponase alfa and comparator, as well as direct treatment costs, were the study’s key outcomes. The creation and simulation of a discrete-event simulation model served as the basis for the investigation. Monte Carlo microsimulation was performed on a sample of 1000 virtual patients. Results When compared to symptomatic therapy, cerliponase alfa treatment was not cost-effective and was linked to negative net monetary benefit regardless of when the illness signs started. Conclusion Cerliponase alfa is not more economical than symptomatic therapy for the treatment of CLN2 when using typical pharmacoeconomic analysis. Cerliponase alfa has been shown to be effective but more has to be done to make it accessible to all CLN2 patients.

Cost-Effectiveness Analysis of Open Versus Endovascular Revascularization for Chronic Mesenteric Ischemia

Recent studies have shown a trend supporting endovascular revascularization (ER) in the treatment of chronic mesenteric ischemia (CMI). However, few studies have compared the cost effectiveness of ER and open revascularization (OR) for this indication. The purpose of this study is to conduct a cost-effectiveness analysis comparing open versus ER for CMI. We built a Markov model with Monte Carlo microsimulation using transition probabilities and utilities from existing literature for CMI patients undergoing OR versus ER. Costs were derived from the hospital perspective using the 2020 Medicare Physician Fee Schedule. The model randomized 20,000 patients to either OR or ER and allowed for 1 subsequent reintervention with 3 other intervening health states: alive, alive with complications, and dead. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) were analyzed over a 5-year period. One-way sensitivity and probabilistic sensitivity analyses were conducted to study the impact of parameter variability on cost effectiveness. OR cost $4,532 for 1.03 QALYs while ER cost $5,092 for 1.21 QALYs, leading to an ICER of $3,037 per QALY gained in the ER arm. This ICER was less than our willingness to pay threshold of $100,000. Sensitivity analysis demonstrated that our model was most sensitive to costs, mortality, and patency rates after OR and ER. Probabilistic sensitivity analysis demonstrated ER would be considered cost effective 99% of iterations. This study found that while 5-year costs for ER were greater than OR, ER afforded greater QALYs than OR. Although ER is associated with lower long-term patency and higher rates of reintervention, it appears to be more cost effective than OR for the treatment of CMI.

Cost-effectiveness of miglustat versus symptomatic therapy of Niemann-Pick disease type C.

Niemann-Pick disease type C (NP-C) is a progressive neurodegenerative disorder with early infantile (< 2years), late infantile (2-6years), juvenile (7-15years) and adolescent (> 15years) onset. The mainstay of therapy for NP-C patients with neurological symptoms is miglustat, a drug that may modify the course of the disease. Our aim was to evaluate the cost-effectiveness of miglustat in comparison to symptomatic therapy in patients with NP-C in the socio-economic settings of the Republic of Serbia, an upper-middle-income European economy. The perspective of the Serbian Republic Health Insurance Fund was chosen for this study, and the time horizon was eighty years. The main outcomes of the study were quality-adjusted life years gained with miglustat and comparator, and direct costs of treatment. The study was conducted through the generation and simulation of the Discrete-Event Simulation model. The model results were obtained after Monte Carlo microsimulation of a sample with 1000 virtual patients. Treatment with miglustat was not cost-effective when compared with symptomatic therapy and was associated with negative values of net monetary benefit regardless of the onset of neurological manifestations (- 110,447,627.00 ± 701,614.00 RSD, - 343,871,695.00 ± 2,577,441.00 RSD, - 1,397,908,502.00 ± 23,084,235.00 RSD and - 2,953,680,879.00 ± 33,297,412.00 RSD) for early infantile, late infantile, juvenile and adolescent cohorts, respectively). When traditional pharmacoeconomic evaluation is employed, miglustat is not a cost-effective option in comparison to symptomatic therapy for the treatment of NP-C. However, given the proven efficacy of miglustat, there is a need to find ways to make this drug available to all patients with NP-C.

Cost-effectiveness of direct surgery versus preoperative octreotide therapy for growth-hormone secreting pituitary adenomas

PurposeThe objective of this study was to compare the cost-effectiveness of preoperative octreotide therapy followed by surgery versus the standard treatment modality for growth-hormone secreting pituitary adenomas, direct surgery (that is, surgery without preoperative treatment) from a public third-party payer perspective.MethodsWe developed an individual-level state-transition microsimulation model to simulate costs and outcomes associated with preoperative octreotide therapy followed by surgery and direct surgery for patients with growth-hormone secreting pituitary adenomas. Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs [2020 United States (US) Dollars], quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).ResultsUnder base case assumptions, direct surgery was found to be the dominant strategy as it yielded lower costs and greater health effects (QALYs) compared to preoperative octreotide strategy in the second-order Monte Carlo microsimulation. The ICER was most sensitive to probability of remission following primary therapy and duration of preoperative octreotide therapy. Accounting for joint parameter uncertainty, direct surgery had a higher probability of demonstrating a cost-effective profile compared to preoperative octreotide treatment at 77% compared to 23%, respectively.ConclusionsUsing standard benchmarks for cost-effectiveness in the US ($100,000/QALY), preoperative octreotide therapy followed by surgery may not be cost-effective compared to direct surgery for patients with growth-hormone secreting pituitary adenomas but the result is highly sensitive to initial treatment failure and duration of preoperative treatment.

Artificial Intelligence for Caries Detection: Value of Data and Information

If increasing practitioners’ diagnostic accuracy, medical artificial intelligence (AI) may lead to better treatment decisions at lower costs, while uncertainty remains around the resulting cost-effectiveness. In the present study, we assessed how enlarging the data set used for training an AI for caries detection on bitewings affects cost-effectiveness and also determined the value of information by reducing the uncertainty around other input parameters (namely, the costs of AI and the population’s caries risk profile). We employed a convolutional neural network and trained it on 10%, 25%, 50%, or 100% of a labeled data set containing 29,011 teeth without and 19,760 teeth with caries lesions stemming from bitewing radiographs. We employed an established health economic modeling and analytical framework to quantify cost-effectiveness and value of information. We adopted a mixed public–private payer perspective in German health care; the health outcome was tooth retention years. A Markov model, allowing to follow posterior teeth over the lifetime of an initially 12-y-old individual, and Monte Carlo microsimulations were employed. With an increasing amount of data used to train the AI sensitivity and specificity increased nonlinearly, increasing the data set from 10% to 25% had the largest impact on accuracy and, consequently, cost-effectiveness. In the base-case scenario, AI was more effective (tooth retention for a mean [2.5%–97.5%] 62.8 [59.2–65.5] y) and less costly (378 [284–499] euros) than dentists without AI (60.4 [55.8–64.4] y; 419 [270–593] euros), with considerable uncertainty. The economic value of reducing the uncertainty around AI’s accuracy or costs was limited, while information on the population’s risk profile was more relevant. When developing dental AI, informed choices about the data set size may be recommended, and research toward individualized application of AI for caries detection seems warranted to optimize cost-effectiveness.