Economics of hematopoietic stem cell transplant in immune-mediated neurologic autoimmune diseases.

Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic procedure for autoimmune diseases which suppresses inflammation and resets the immune system, thereby halting disease activity and disability progression in treatment-resistant patients. This chapter reviews existing guidelines and health economic evaluations of AHSCT for multiple sclerosis (MS) and presents a cost-utility analysis from the UK NHS and personal social services perspective comparing AHSCT with disease-modifying therapies (DMTs) in patients with highly active relapsing-remitting MS (RRMS) based on the only published randomized controlled trial, "MIST," in this population. Over a 5-year time horizon, AHSCT was dominant (more effective and less costly) over the DMTs in MIST. At a threshold of £20,000 per QALY, there was a 100% probability that AHSCT was cost-effective. This result is explained by the high ongoing costs of DMTs compared with the up-front cost of AHSCT, combined with the high effectiveness of AHSCT. When compared with natalizumab, the result did not change; AHSCT remained dominant. These results support current guideline recommendations regarding AHSCT for highly active RRMS. The cost-effectiveness of AHSCT in progressive and aggressive MS and other immune-mediated neurologic diseases remains uncertain due to a lack of health economic analyses, reflecting the limited clinical evidence base.

Management training programs in healthcare: effectiveness factors, challenges and outcomes.

BACKGROUND: Different professionals working in healthcare organizations (e.g., physicians, veterinarians, pharmacists, biologists, engineers, etc.) must be able to properly manage scarce resources to meet increasingly complex needs and demands. Due to the lack of specific courses in curricular university education, particularly in the field of medicine, management training programs have become an essential element in preparing health professionals to cope with global challenges. This study aims to examine factors influencing the effectiveness of management training programs and their outcomes in healthcare settings, at middle-management level, in general and by different groups of participants: physicians and non-physicians, participants with or without management positions. METHODS: A survey was used for gathering information from a purposive sample of professionals in the healthcare field attending management training programs in Italy. Factor analysis, a set of ordinal logistic regressions and an unpaired two-sample t-test were used for data elaboration. RESULTS: The findings show the importance of diversity of pedagogical approaches and tools and debate, and class homogeneity, as effectiveness factors. Lower competencies held before the training programs and problems of dialogue and discussion during the course are conducive to innovative practice introduction. Interpersonal and career outcomes are greater for those holding management positions. CONCLUSIONS: The study reveals four profiles of participants with different gaps and needs. Training programs should be tailored based on participants' profiles, in terms of pedagogical approaches and tools, and preserve class homogeneity in terms of professional backgrounds and management levels to facilitate constructive dialogue and solution finding approach.

Oral aripiprazole in the treatment of tic disorders in China: a cost-effectiveness analysis based on a mapping algorithm derived from a Chinese children and adolescents population.

BACKGROUND: Oral aripiprazole exhibits favorable clinical efficacy and safety in the suppression of tics in children and adolescents with tic disorders. This study aims to evaluate and compare the cost-effectiveness of high-dose and low-dose aripiprazole in children and adolescents with tic disorders from the perspective of the Chinese healthcare system. METHODS: A questionnaire survey was conducted on 146 patients with tic disorders, of whom 144 completed EQ-5D-Y and YGTSS. Four models were built to convert YGTSS onto EQ-5D-Y utility using two mapping algorithms. We constructed a decision tree model containing efficacy and safety to compare the cost-effectiveness of high-dose and low-dose aripiprazole based on our mapping function. RESULTS: The GLM with model 1 (YGTSS total tic scores) was selected as the preferred function in our decision tree model. The base case cost-effectiveness analysis showed that compared to low-dose aripiprazole, high-dose aripiprazole improves effectiveness by 0.001QALYs and increases the overall cost by $197.99, resulting in an ICER of $174339.22 per QALY, which exceeds three times the gross domestic product per capita. Hence, high-dose aripiprazole is not likely to be a cost-effective option for child patients with tic disorders. One-way sensitivity analysis and probabilistic sensitivity analysis showed that these results is robust. CONCLUSION: On the basis of currently available data, low-dose aripiprazole may be a safe, effective, and economical dosage for children and adolescents with tic disorders. LIMITATIONS: The main limitation of our study is the lack of utility directly used for cost-effectiveness analysis. We obtained the utility of patients with tic disorders indirectly by the mapping function. This may introduce some bias and uncertainty. And it is a limitation to use the direct medical costs of Germany in our model. Although we converted it to the equivalent value of China using purchasing power parities, caution should be exercised when interpreting the results of this study.

Cost-effectiveness of neuropsychological rehabilitation for acquired brain injuries: Update of Stolwyk et al.'s (2019) review.

Acquired brain injuries (ABI), resulting from stroke or traumatic brain injury, cause a range of neuropsychological impairments and many patients continue to experience neuropsychological deficits years after onset. The increasing average age of the population highlights the importance of effective management strategies for the consequences of ABI. Despite the well-documented impact of rehabilitation interventions, the cost-effectiveness of neuropsychological rehabilitation remains largely unknown. This study conducted a scoping review to update the findings of Stolwyk et al. (Neuropsychological Rehabilitation, 2021, 31, 316), focusing on the economic evaluations of neuropsychological rehabilitation for individuals with ABI. Following the PIO framework, PRISMA ScR guidelines, and systematic review reporting checklist, the review screened 1027 articles and included eight studies published between 2019 and 2024. The studies encompassed either language rehabilitation or general neuropsychological programs, including neuropsychological interventions. The economic analyses, including two cost-effectiveness, five cost-utility, and one cost-benefit study, mostly adhered to CHEERS guidelines, enhancing the transparency and methodological rigour of their reporting. These studies demonstrated varying degrees of cost-effectiveness for interventions targeting post-stroke language disorders and neuropsychological rehabilitation for ABI, with significant cost savings and health benefits observed, particularly for home-based rehabilitation interventions. The included studies suffered from a short time horizon, limiting the ability to capture the long-term economic impacts and effectiveness of the interventions. Future research should focus on longer-term follow-up data and include broader search strategies to enhance understanding and optimise health care interventions. A comprehensive implementation of these economic analyses is crucial for informing policymakers, enabling them to introduce rehabilitative interventions based on solid evidence.

Analyzing quality of life among people with opioid use disorder from the National Institute on Drug Abuse Data Share initiative: implications for decision making.

PURPOSE: We aimed to estimate health state utility values (HSUVs) for the key health states found in opioid use disorder (OUD) cost-effectiveness models in the published literature. METHODS: Data obtained from six trials representing 1,777 individuals with OUD. We implemented mapping algorithms to harmonize data from different measures of quality of life (the SF-12 Versions 1 and 2 and the EQ-5D-3 L). We performed a regression analysis to quantify the relationship between HSUVs and the following variables: days of extra-medical opioid use in the past 30 days, injecting behaviors, treatment with medications for OUD, HIV status, and age. A secondary analysis explored the impact of opioid withdrawal symptoms. RESULTS: There were statistically significant reductions in HSUVs associated with extra-medical opioid use (-0.002 (95% CI [-0.003,-0.0001]) to -0.003 (95% CI [-0.005,-0.002]) per additional day of heroin or other opiate use, respectively), drug injecting compared to not injecting (-0.043 (95% CI [-0.079,-0.006])), HIV-positive diagnosis compared to no diagnosis (-0.074 (95% CI [-0.143,-0.005])), and age (-0.001 per year (95% CI [-0.003,-0.0002])). Parameters associated with medications for OUD treatment were not statistically significant after controlling for extra-medical opioid use (0.0131 (95% CI [-0.0479,0.0769])), in line with prior studies. The secondary analysis revealed that withdrawal symptoms are a fundamental driver of HSUVs, with predictions of 0.817 (95% CI [0.768, 0.858]), 0.705 (95% CI [0.607, 0.786]), and 0.367 (95% CI [0.180, 0.575]) for moderate, severe, and worst level of symptoms, respectively. CONCLUSION: We observed HSUVs for OUD that were higher than those from previous studies that had been conducted without input from people living with the condition.

Thus far, health-related quality of life estimates for patients with opioid use disorder in the United States are limited, and importantly, they were not generated from studies among people living with the condition. This study extracted data from six clinical trials providing data among 1,777 people with opioid use disorder, made publicly available by the National Institutes of Health, to produce estimates of health-related quality of life. Our study found higher health-related quality of life estimates as compared to previous studies, modest impact of medications for opioid use disorder and strong impact of withdrawal symptoms on this outcome. These higher values among people with opioid use disorder might reflect the very negative perception of this condition among members of the general population (among whom these estimates have been generated previously). However, these relatively high estimates could also reflect an adaptation to the condition or a lack of awareness of associated-health damage in the context of dependence. The low number of observations providing data on medications for opioid use disorder led to high uncertainty around related estimates of health-related quality of life, but our findings could also reflect real experiences by patients in the absence of the positive effects of non-medication opioids, which deserve more attention in clinical practice. Our study suggests that systematically measuring withdrawal symptoms and representing these in health economic models might provide a more accurate representation of health-related quality of life among people with opioid use disorder and therefore of the impact and cost-effectiveness of interventions.

Real-World Pharmacokinetics, Effectiveness, and Safety of Atezolizumab in Patients With Unresectable Advanced or Recurrent NSCLC: An Exploratory Study of J-TAIL.

Introduction: This study validated real-world pharmacokinetic (PK) data using an established population PK (PopPK) model for atezolizumab in Japanese patients with NSCLC and explored the relationship between PK parameters, effectiveness, and adverse events (AEs) for the 1200 mg once every three weeks regimen. Methods: A subgroup of 262 of 1039 patients from J-TAIL consented to this exploratory research for PK evaluation of atezolizumab monotherapy for unresectable advanced/recurrent NSCLC (August 2018 to October 2019; 197 institutions). We evaluated plasma concentrations before the start of the third cycle of atezolizumab infusion classified into quartiles 1 to 4, their association with effectiveness, and the association between atezolizumab maximum plasma concentrations (Cmax) calculated using the existing PopPK model and AEs of special interest (AESIs). Results: Overall, 175 of 262 patients were included; baseline characteristics were similar to those of patients enrolled in J-TAIL (Eastern Cooperative Oncology Group performance status ≥ 2, 12.0%; age ≥ 75 y, 28.9%; atezolizumab as more than or equal to third-line treatment, 57.5%). Atezolizumab plasma concentrations were similar to previously reported data among Japanese/non-Japanese patients. The overall survival was significantly shorter in patients with lower atezolizumab plasma concentrations in Q1 versus Q2 to Q4, although progression-free survival remained the same. The PK data adequately fit the PopPK model, with the frequency of AESIs increasing as the calculated Cmax at cycle 1 increased. Conclusions: In real-world Japanese patients with unresectable advanced/recurrent NSCLC, PKs were similar to previous reports. Certain patient populations had shorter overall survival, and atezolizumab plasma concentrations in cycle 3 were lower in this population. Elevated Cmax at cycle 1 may be associated with an increased frequency of AESIs.

Cost-effectiveness analysis of 11 pharmacotherapies for recurrent glioblastoma in the USA and China.

Background: Several studies have systematically assessed the efficacy and safety of progressive or recurrent glioblastoma multiforme (GBM). However, the discernible limitations of efficacy and the elevated costs of interventions instigate an investigation into the cost-effectiveness of these treatments. Objectives: This study aimed to evaluate cost-effectivenesses of 11 pharmacotherapeutic interventions for recurrent GBM from the perspective of healthcare payers in the United States (US) and China. Design: A model-based pharmacoeconomic evaluation. Methods: A partitioned survival model was employed to evaluate the cost-effectiveness of 11 distinct drug-based treatments. The clinical efficacy and safety data were obtained from a network meta-analysis, while the medical expenditure and health utility were primarily derived from published literature. One-way sensitivity analyses, scenario analyses, and probabilistic sensitivity analyses (PSA) were performed to scrutinize the impact of potential uncertainties to ensure the robustness of the model. The primary endpoint was the incremental cost-effectiveness ratio. Results: Among the therapeutic interventions evaluated, lomustine emerged as the cheapest option, with costs amounting to $78,998 in the United States and $30,231 in China, respectively. Regorafenib displayed the highest quality-adjusted life years at 0.475 in the United States and 0.465 in China. The one-way sensitivity analyses underscored that drug price was a key factor influencing cost-effectiveness. Both scenario and PSA consistently demonstrated that, considering the willingness-to-pay thresholds, lomustine was a cost-effective treatment with probability of more than 94%. Conclusion: In comparison to the alternative antitumor agents, lomustine was likely to be a cost-effective option for relapsed GBM patients from the perspective of healthcare payers in both the United States and China.

Cost-effectiveness analysis design for interventions to prevent children's oral disease.

Introduction: In 2015, the National Institute of Dental and Craniofacial Research (NIDCR) launched the Multidisciplinary Collaborative Research Consortium to Reduce Oral Health Disparities in Children, supporting four randomized trials testing strategies to improve preventive care. A Coordinating Center provides scientific expertise, data acquisition and quality assurance services, safety monitoring, and final analysis-ready datasets. This paper describes the trials' economic analysis strategies, placing these strategies within the broader context of contemporary economic analysis methods. Methods: The Coordinating Center established a Cost Collaborative Working Group to share information from the four trials about the components of their economic analyses. Study teams indicated data sources for their economic analysis using a set of structured tables. The Group meets regularly to share progress, discuss challenges, and coordinate analytic approaches. Results: All four trials will calculate incremental cost-effectiveness ratios; two will also conduct cost-utility analyses using proxy diseases to estimate health state utilities. Each trial will consider at least two perspectives. Key process measures include dental services provided to child participants. The non-preference-weighted Early Childhood Oral Health Impact Scale (ECOHIS) will measure oral health-related quality of life. All trials are measuring training, implementation, personnel and supervision, service, supplies, and equipment costs. Conclusions: Consistent with best practices, all four trials have integrated economic analysis during their planning stages. This effort is critical since poor quality or absence of essential data can limit retrospective analysis. Integrating economic analysis into oral health preventive intervention research can provide guidance to clinicians and practices, payers, and policymakers.

The Cost-Utility analysis of adding ocrelizumab to the treatment plan for primary progressive multiple sclerosis in Iran.

BACKGROUND: To evaluate the cost-effectiveness of adding ocrelizumab to supportive care in the management of primary progressive multiple sclerosis (PPMS) in Iran. RESEARCH DESIGN AND METHODS: This study, conducted from the payer's perspective in Iran, employed a lifetime horizon. An economic evaluation model was designed based on considering various Expanded Disability Status Scales (EDSS) as different Markov health states while taking transition probabilities and treatment effects into account. Data originated from clinical trials, alongside other available scientific sources. The target population was PPMS patients who either receive supportive care or ocrelizumab. The evaluation relied on total costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) to assess comparative cost-effectiveness. Due to uncertainties in study parameters, the deterministic and probabilistic sensitivity analyses were conducted as well. RESULTS: The addition of ocrelizumab brings about an incremental 0.89 QALYs besides an incremental cost of US$76,771.34. Ocrelizumab also had an ICER of US$ 86220.35, which is 5.2 times Iran's GDP per capita ($16,557). Therefore, considering the cost-effectiveness threshold in Iran (one times GDP per capita) ocrelizumab, compared to supportive care, does not align with cost-effectiveness optimization. Nevertheless, the findings from the cost Effectiveness acceptability plane demonstrate that the probability of cost-effectiveness for ocrelizumab increases at higher thresholds. Furthermore, overall sensitivity analyses showed that the base case results were robust. CONCLUSION: While adding ocrelizumab is not a cost-effective strategy at the threshold of one-time GDP per capita, its substantial clinical benefits should not be overlooked. Therefore, the importance of formulating healthcare policies regarding the use of high-cost medications like ocrelizumab, including budget allocation, resource distribution, and potential shifts in healthcare priorities, has become more crucial than ever.

Evaluating the cost-effectiveness of Cy-Tb for LTBI in India: a comprehensive economic modelling analysis.

BACKGROUND: Latent tuberculosis infection (LTBI) remains a significant challenge, as there is no gold standard diagnostic test. Current methods used for identifying LTBI are the interferon-γ release assay (IGRA), which is based on a blood test, and the tuberculin skin test (TST), which has low sensitivity. Both these tests are inadequate, primarily because they have limitations with the low bacterial burden characteristic of LTBI. This highlights the need for the development and adoption of more specific and accurate diagnostic tests to effectively identify LTBI. Herein we estimate the cost-effectiveness of the Cy-Tb test as compared with the TST for LTBI diagnosis. METHODS: An economic modelling study was conducted from a health system perspective using decision tree analysis, which is most widely used for cost-effectiveness analysis using transition probabilities. Our goal was to estimate the incremental cost and number of TB cases prevented from LTBI using the Cy-Tb diagnostic test along with TB preventive therapy (TPT). Secondary data such as demographic characteristics, treatment outcome, diagnostic test results and cost data for the TST and Cy-Tb tests were collected from the published literature. The incremental cost-effectiveness ratio was calculated for the Cy-Tb test as compared with the TST. The uncertainty in the model was evaluated using one-way sensitivity analysis and probability sensitivity analysis. RESULTS: The study findings indicate that for diagnosing an additional LTBI case with the Cy-Tb test and to prevent a TB case by providing TPT prophylaxis, an additional cost of 18 658 Indian rupees (US${\$}$223.5) is required. The probabilistic sensitivity analysis indicated that using the Cy-Tb test for diagnosing LTBI was cost-effective as compared with TST testing. If the cost of the Cy-Tb test is reduced, it becomes a cost-saving strategy. CONCLUSIONS: The Cy-Tb test for diagnosing LTBI is cost-effective at the current price, and price negotiations could further change it into a cost-saving strategy. This finding emphasizes the need for healthcare providers and policymakers to consider implementing the Cy-Tb test to maximize economic benefits. Bulk procurements can also be considered to further reduce costs and increase savings.

Telehealth-Supported Exercise or Physical Activity Programs for Knee Osteoarthritis: Systematic Review and Meta-Analysis.

BACKGROUND: The integration of telehealth-supported programs in chronic disease management has become increasingly common. However, its effectiveness for individuals with knee osteoarthritis (KOA) remains unclear. OBJECTIVE: This study aimed to assess the effectiveness of telehealth-supported exercise or physical activity programs for individuals with KOA. METHODS: A comprehensive literature search encompassing Embase, MEDLINE, CENTRAL, Web of Science, PubMed, Scopus, PEDro, GreyNet, and medRxiv from inception to September 2023 was conducted to identify randomized controlled trials comparing telehealth-supported exercise or physical activity programs to a control condition for KOA. Data were extracted and qualitatively synthesized across eligible studies, and a meta-analysis was performed to evaluate the effects. The study was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. RESULTS: In total, 23 studies met eligibility criteria, with 20 included in the meta-analysis. Results showed that telehealth-supported exercise or physical activity programs reduced pain (g=-0.39; 95% CI -0.67 to -0.11; P<.001), improved physical activity (g=0.13; 95% CI 0.03-0.23; P=.01), and enhanced physical function (g=-0.51; 95% CI -0.98 to -0.05; P=.03). Moreover, significant improvements in quality of life (g=0.25; 95% CI 0.14-0.36; P<.001), self-efficacy for pain (g=0.72; 95% CI 0.53-0.91; P<.001), and global improvement (odds ratio 2.69, 95% CI 1.41-5.15; P<.001) were observed. However, self-efficacy for physical function (g=0.14; 95% CI -0.26 to 0.53; P=.50) showed insignificant improvements. Subgroup analyses based on the World Health Organization classification of digital health (pain: χ22=6.5; P=.04 and physical function: χ22=6.4; P=.04), the type of teletechnology in the intervention group (pain: χ24=4.8; P=.31 and function: χ24=13.0; P=.01), and active or inactive controls (pain: χ21=5.3; P=.02 and physical function: χ21=3.4; P=.07) showed significant subgroup differences. CONCLUSIONS: Telehealth-supported exercise or physical activity programs might reduce knee pain and improve physical activity, physical function, quality of life, self-efficacy, and global improvement in individuals with KOA. Future research should consider longer implementation durations and assess the feasibility of incorporating wearables and standardized components into large-scale interventions to evaluate the effects. TRIAL REGISTRATION: PROSPERO CRD42022359658; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=359658.

The health benefits, costs, and cost-effectiveness of ultra-orphan drugs.

OBJECTIVE: To examine ultra-orphan drugs in terms of incremental health, costs, and cost-effectiveness compared to more prevalent disease drugs. METHODS: We identified FDA drug approvals from 1999-2019. For drugs approved for multiple indications, we considered each drug-indication pair separately. Utilizing FDA's orphan drug designation and US disease prevalence, we categorized drug-indication pairs as: ultra-orphan (<10,000 patients), 'other' orphan (≥10,000 and <200,000), and non-orphan (≥200,000). We searched the PubMed database for cost-effectiveness and cost-utility studies. We excluded manufacturer-funded studies. We extracted estimates of incremental health gains in terms of quality-adjusted life-years (QALYs) and incremental costs associated with drug-indication pairs compared to the standard of care at the time of their approval. We compared QALY gains, added costs, and incremental cost-effectiveness ratios (ICERs) using the Kruskal-Wallis (KW), Mann-Whitney U (MWU), and Kolmogorov-Smirnov (KS) tests. RESULTS: Median incremental QALYs, costs, and ICERs differed across non-orphan, 'other' orphan, and ultra-orphan categories (KW p<0.01). Compared to non-orphan drugs, ultra-orphan drugs had larger QALY gains (0.700 vs. 0.050, MWU p<0.01, KS p<0.01), larger costs ($172,231 vs. $3,360, MWU p<0.01, KS p<0.01), and larger ICERs ($1,216,184/QALY vs. $114,061/QALY, MWU p<0.01, KS p<0.01). Compared to 'other' orphan drugs, ultra-orphan drugs had larger QALY gains (0.700 vs. 0.310, MWU p=0.65, KS p=0.32), larger costs ($172,231 vs. $69,308, MWU p=0.03, KS p=0.03), and larger ICERs ($1,216,184/QALY vs. $223,472/QALY, MWU p<0.01, KS p<0.01). CONCLUSIONS: Novel ultra-orphan drugs typically offer larger incremental health gains than drugs for more prevalent diseases, but due to their substantial added costs, are typically less cost-effective.

Informing the US Medicare drug price negotiation for apixaban and rivaroxaban: Methodological considerations for value assessments many years after launch.

OBJECTIVES: To demonstrate how health technology assessment (HTA) methods can be used to support Medicare's price negotiations for apixaban and rivaroxaban. METHODS: Following the statutory outline of evidence that will be considered by Medicare, we conducted a systematic literature review, network meta-analyses (NMAs), and decision analyses to evaluate the health outcomes and costs associated with apixaban and rivaroxaban compared to warfarin and dabigatran for patients with non-valvular atrial fibrillation. Our methods inform discussions about the therapeutic impact of apixaban and rivaroxaban and suggest price premiums above their therapeutic alternatives over a range of cost-effectiveness thresholds. RESULTS: NMAs found apixaban resulted in a lower risk of major bleeding compared to warfarin and dabigatran, and a lower risk of stroke/systemic embolism compared to warfarin, but not compared to dabigatran. Rivaroxaban resulted in a lower risk of stroke/systemic embolism versus warfarin but not dabigatran, and there was no difference in major bleeding. Decision-analytic modeling of apixaban suggested annual price premiums up to $4,350 above the price of warfarin and up to $530 above the price for dabigatran at cost-effectiveness thresholds up to $200,000 per equal value of life years gained. Analyses of rivaroxaban showed an annual price premium of up to $3,920 above warfarin, and no premium above that paid for dabigatran. CONCLUSIONS: Although HTA is typically performed near the time of regulatory approval, with modifications, we produced comparative clinical and relative cost-effectiveness findings to help guide negotiations on a "fair" price for drugs on the market for over a decade.

Discriminatory properties of QALY-based CEA for patients with disabilities: A Duchenne muscular dystrophy case study.

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

Relative vaccine effectiveness of ChAdOx1/AZD1222 vaccines as booster dose via intradermal injection with a one-fifth dose compared with the intramuscular injection in the prevention of SAR-CoV-2 infections in Phuket - A Retrospective Cohort Study.

OBJECTIVES: This study assessed the real-world relative vaccine effectiveness of the ChAdOx1/AZD1222 vaccine given intradermally at one-fifth dose compared to the standard intramuscular injection, following the completion of two doses of CoronaVac, due to limited vaccine availability in Thailand during the Coronavirus disease 2019 (COVID-19) pandemic. METHOD: This retrospective cohort study used 138,264 records from Vachira Phuket Hospital, Phuket, Thailand. The records were divided into two groups: 49,387 recipients received one-fifth doses via intradermal injections, and 88,877 recipients received standard-dose intramuscular injections from September 14 to October 3, 2021, with follow-up until December 31, 2021. Relative vaccine effectiveness for the cohorts was estimated using Cox regression, adjusting for demographic and clinical risk factors. RESULTS: The adjusted hazard ratio between the intradermal and intramuscular groups was 0.88 (95% Confidence Interval 0.76-1.02, p = 0.09), indicating a non-significant protective factor for the intradermal group. Further stratified analysis revealed no significant difference between the two groups. The 21 and 28-day post-vaccination periods minimized the possibility of confounding due to differences in the cohorts' timeframes. CONCLUSION: A booster dose of ChAdOx1/AZD1222 given intradermally at one-fifth dose did not show a significant difference compared to the standard intramuscular injection.

A New Horizon for Understanding the Comparative Effectiveness for Cooling Prospectively Infants with Mild Encephalopathy.

The authors summarize the methodology for a new pragmatic comparative effectiveness research investigation, Cooling Prospectively Infants with Mild Encephalopathy (COOLPRIME), which uses sites' existing mild hypoxic-ischemic encephalopathy (HIE) treatment preference (hypothermia or normothermia) to assess hypothermia effectiveness and safety. COOLPRIME's primary aim is to determine the safety and effectiveness of hypothermia compared to normothermia in mild HIE. Engagement of Families and Community Affected by Hypoxic-Ischemic Encephalopathy strongly favored Effectiveness over Efficacy Trials leading to COOL PRIME design.

A health decision analytical model to evaluate the cost-effectiveness of female genital schistosomiasis screening strategies: The female genital schistosomiasis SCREEN framework.

Female genital schistosomiasis is a chronic gynaecological disease caused by the waterborne parasite Schistosoma (S.) haematobium. It affects an estimated 30-56 million girls and women globally, mostly in sub-Saharan Africa where it is endemic, and negatively impacts their sexual and reproductive life. Recent studies found evidence of an association between female genital schistosomiasis and increased prevalence of HIV and cervical precancer lesions. Despite the large population at risk, the burden and impact of female genital schistosomiasis are scarcely documented, resulting in neglect and insufficient resource allocation. There is currently no standardised method for individual or population-based female genital schistosomiasis screening and diagnosis which hinders accurate assessment of disease burden in endemic countries. To optimise financial allocations for female genital schistosomiasis screening, it is necessary to explore the cost-effectiveness of different strategies by combining cost and impact estimates. Yet, no economic evaluation has explored the value for money of alternative screening methods. This paper describes a novel application of health decision analytical modelling to evaluate the cost-effectiveness of different female genital schistosomiasis screening strategies across endemic settings. The model combines a decision tree for female genital schistosomiasis screening strategies, and a Markov model for the natural history of cervical cancer to estimate the cost per disability-adjusted life-years averted for different screening strategies, stratified by HIV status. It is a starting point for discussion and for supporting priority setting in a data-sparse environment.

Commentary: What young people want from psychotherapy.

In recent times there has been increasing acknowledgement of the importance of attending to the agenda of people with lived experience in psychotherapy research. In particular, young people's voices have been recognised as central to the design and development of psychotherapies that work for them. It is important to recognise the limits of professional agendas and make sure that young people's own priorities are represented in the indicators against which we measure change in research evaluations of psychotherapy. This requires an extension of evaluation research indicators from psychiatric symptomatology, to include aspects of wellbeing that matter to young people themselves. This article joins others in calling for a shift from the focus on symptom change in the evaluation of psychotherapy with youth, to acknowledge subjective indicators identified through research conducted with young people. New indicators might, for example, be centred on the degree to which young people experience increased capacity for acceptance of their emotions, a comfortable sense of identity, improved relational trust, and a stronger sense of their own agency. If psychotherapy is to be meaningful to young people, it is vital that we tailor it to young people's own needs and priorities and evaluate it against the aspects of change that matter to them.

The cost-effectiveness of semaglutide in reducing cardiovascular risk among people with overweight and obesity and existing cardiovascular disease, but without diabetes.

BACKGROUND AND AIMS: The Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial demonstrated significant reductions in cardiovascular outcomes in people with cardiovascular disease (CVD) and overweight or obesity (but without diabetes). However, the cost of the medication has raised concerns about its financial viability and accessibility within healthcare systems. This study explored whether use of semaglutide for the secondary prevention of CVD in overweight or obesity is cost-effective from the Australian healthcare perspective. METHODS: A Markov model was developed based on the SELECT trial to model the clinical outcomes and costs of a hypothetical population treated with semaglutide versus placebo, in addition to standard care, and followed up over 20 years. With each annual cycle, subjects were at risk of having non-fatal CVD events or dying. Model inputs were derived from SELECT and published literature. Costs were obtained from Australian sources. All outcomes were discounted by 5% annually. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. RESULTS: With an annual estimated cost of semaglutide of A${\$}$4175, the model resulted in ICERs of A${\$}$99 853 (US${\$}$143 504; £40 873) per YoLS and A${\$}$96 055 (US${\$}$138 046; £39 318) per QALY gained. CONCLUSIONS: Assuming a willingness-to-pay threshold of A${\$}$50 000, semaglutide is not considered cost-effective at the current price. A price of ≤ A${\$}$2000 per year or more targeted use in high-risk patients would be needed for it to be considered cost-effective in the Australian setting.

Identifying Patients at Risk for Alcohol-Exposed Pregnancies: The Importance of Addressing Multiple Risk Factors.

BACKGROUND: The increasing prevalence of fetal alcohol spectrum disorders is a critical public health issue. Two behaviors, consuming alcohol and using less effective pregnancy prevention, may result in alcohol-exposed pregnancies (AEPs) in individuals who can become pregnant. In the context of alcohol screening and brief intervention (SBI) services, cutoff scores on widely used alcohol risk assessments (eg, Alcohol Use Disorders Identification Test, U.S. version [USAUDIT]) may fail to identify individuals whose relatively low alcohol consumption may still put them at risk for an AEP due to their pregnancy prevention method. METHODS: To identify this gap in alcohol SBI service delivery, we examined data from 2 reproductive healthcare systems implementing alcohol SBI, to explore the prevalence of individuals who met both of the following risk conditions: reported any alcohol use on the USAUDIT and a pregnancy prevention method less than 88% effective. Electronic health records for individuals aged 18 to 49 presenting for preventive care in 2021 were analyzed. RESULTS: Of 11 567 screened, 7638 reported some alcohol use, but screened at a lower-risk level and were not flagged to receive an alcohol-focused brief intervention (BI). Of these, 1477 were using a method of pregnancy prevention that was less than 88% effective. In addition, 118 of the 1676 who screened positive on the USAUDIT were using less effective contraception and did not receive a BI. In summary, the number of individuals at risk of an AEP who did not receive an alcohol BI was 1595 (13.8%) of the total patients screened for at-risk alcohol use. CONCLUSIONS: There is a need for system modifications to assess multiple behaviors simultaneously and alert providers when a combination of behaviors increases a specific health risk, such as an AEP. Tailored alcohol BIs that include the risks/benefits of various pregnancy prevention methods to reduce AEPs provide opportunities to enhance the reach of standard alcohol SBI services.