What Is the Potential Value of a Randomized Trial of Different Thresholds to Initiate Invasive Ventilation? A Health Economic Analysis.

OBJECTIVES: To estimate the expected value of undertaking a future randomized controlled trial of thresholds used to initiate invasive ventilation compared with usual care in hypoxemic respiratory failure. PERSPECTIVE: Publicly funded healthcare payer. SETTING: Critical care units capable of providing invasive ventilation and unconstrained by resource limitations during usual (nonpandemic) practice. METHODS: We performed a model-based cost-utility estimation with individual-level simulation and value-of-information analysis focused on adults, admitted to critical care, receiving noninvasive oxygen. In the primary scenario, we compared hypothetical threshold A to usual care, where threshold A resulted in increased use of invasive ventilation and improved survival compared with usual care. In the secondary scenario, we compared hypothetical threshold B to usual care, where threshold B resulted in decreased use of invasive ventilation and similar survival compared with usual care. We assumed a willingness-to-pay of 100,000 Canadian dollars (CADs) per quality-adjusted life year. RESULTS: In the primary scenario, threshold A was cost-effective compared with usual care due to improved hospital survival (78.1% vs. 75.1%), despite more use of invasive ventilation (62% vs. 30%) and higher lifetime costs (86,900 vs. 75,500 CAD). In the secondary scenario, threshold B was cost-effective compared with usual care due to similar survival (74.5% vs. 74.6%) with less use of invasive ventilation (20.2% vs. 27.6%) and lower lifetime costs (71,700 vs. 74,700 CAD). Value-of-information analysis showed that the expected value to Canadian society over 10 years of a 400-person randomized trial comparing a threshold for invasive ventilation to usual care in hypoxemic respiratory failure was 1.35 billion CAD or more in both scenarios. CONCLUSIONS: It would be highly valuable to society to identify thresholds that, in comparison to usual care, either increase survival or reduce invasive ventilation without reducing survival.

New Anticancer Drugs: Reliably Assessing "Value" While Addressing High Prices.

Countries face challenges in paying for new drugs. High prices are driven in part by exploding drug development costs, which, in turn, are driven by essential but excessive regulation. Burdensome regulation also delays drug development, and this can translate into thousands of life-years lost. We need system-wide reform that will enable less expensive, faster drug development. The speed with which COVID-19 vaccines and AIDS therapies were developed indicates this is possible if governments prioritize it. Countries also differ in how they value drugs, and generally, those willing to pay more have better, faster access. Canada is used as an example to illustrate how "incremental cost-effectiveness ratios" (ICERs) based on measures such as gains in "quality-adjusted life-years" (QALYs) may be used to determine a drug's value but are often problematic, imprecise assessments. Generally, ICER/QALY estimates inadequately consider the impact of patient crossover or long post-progression survival, therapy benefits in distinct subpopulations, positive impacts of the therapy on other healthcare or societal costs, how much governments willingly might pay for other things, etc. Furthermore, a QALY value should be higher for a lethal or uncommon disease than for a common, nonlethal disease. Compared to international comparators, Canada is particularly ineffective in initiating public funding for essential new medications. Addressing these disparities demands urgent reform.

Cashing in: cost-benefit analysis framework for digital hospitals.

BACKGROUND: For many countries, especially those outside the USA without incentive payments, implementing and maintaining electronic medical records (EMR) is expensive and can be controversial given the large amounts of investment. Evaluating the value of EMR implementation is necessary to understand whether or not, such investment, especially when it comes from the public source, is an efficient allocation of healthcare resources. Nonetheless, most countries have struggled to measure the return on EMR investment due to the lack of appropriate evaluation frameworks. METHODS: This paper outlines the development of an evidence-based digital health cost-benefit analysis (eHealth-CBA) framework to calculate the total economic value of the EMR implementation over time. A net positive benefit indicates such investment represents improved efficiency, and a net negative is considered a wasteful use of public resources. RESULTS: We developed a three-stage process that takes into account the complexity of the healthcare system and its stakeholders, the investment appraisal and evaluation practice, and the existing knowledge of EMR implementation. The three stages include (1) literature review, (2) stakeholder consultation, and (3) CBA framework development. The framework maps the impacts of the EMR to the quadruple aim of healthcare and clearly creates a method for value assessment. CONCLUSIONS: The proposed framework is the first step toward developing a comprehensive evaluation framework for EMRs to inform health decision-makers about the economic value of digital investments rather than just the financial value.

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

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

The Short-Term Cost-Effectiveness of a Fixed-Ratio Combination of Insulin Degludec and Aspart: A Cost of Control Analysis in Australia and India.

OBJECTIVES: The real-world ARISE study demonstrated initiation of fixed-ratio combination insulin degludec and aspart (IDegAsp) led to improvements in people achieving key glycemic control targets compared with prior therapies in Australia and India. This study evaluated the short-term cost-effectiveness of IDegAsp in these countries, in terms of the cost per patient achieving these targets. METHODS: A model was developed to evaluate the cost of control (treatment costs divided by the proportion of patients achieving each target) of IDegAsp versus prior therapies received in ARISE for 2 endpoints: glycated hemoglobin (HbA1c) <7.0%, and HbA1c less than a predefined individual treatment target. Costs, expressed from a healthcare payer perspective, were captured in 2022 Australian dollars (AUD) and 2022 Indian rupees (INR). RESULTS: The number of patients needed to treat to bring one to endpoints of HbA1c <7.0% and less than an individualized target with IDegAsp was 51% and 87% lower, respectively, than with prior therapies in Australia, and 52% and 66% lower, respectively, versus prior therapies in India. Cost of control was AUD 2449 higher and AUD 64 863 lower with IDegAsp versus prior therapies for endpoints of HbA1c <7.0% and less than an individualized target, respectively, in Australia and INR 211 142 and INR 537 490 lower with IDegAsp compared with prior therapies in India. CONCLUSIONS: IDegAsp was estimated to be cost-effective versus prior therapies when considering an individualized HbA1c target in Australia, and when considering an individualized HbA1c target and HbA1c <7.0% in India.

Peripherally Inserted Central Catheter Versus Centrally Inserted Central Catheter for In-Hospital Infusion Therapy: A Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate the comparative effectiveness and cost-effectiveness of peripherally inserted central catheters (PICCs) compared with centrally inserted central catheters (CICCs). METHODS: Prospective cohort study was followed by an economic analysis over a 30-day time horizon. Propensity score matching was used to select hospitalized adults with similar indications for PICC or CICC. The composite outcome was device removal or replacement because of complications before the end of treatment. The economic evaluation was based on a decision tree model for cost-effectiveness analysis, with calculation of the incremental cost-effectiveness ratio (ICER) per catheter removal avoided. All costs are presented in Brazilian reais (BRL) (1 BRL = 0.1870 US dollar). RESULTS: A total of 217 patients were followed in each group; 172 (79.3%) of those receiving a PICC and 135 (62.2%) of those receiving a CICC had no device-related complication, respectively. When comparing the events leading to device removal, the risk of composite endpoint was significantly higher in the CICC group (hazard ratio 0.20; 95% CI 0.11-0.35). The cost of PICC placement was BRL 1290.98 versus BRL 467.16 for a CICC. In the base case, the ICER for placing a PICC instead of a CICC was BRL 3349.91 per removal or replacement avoided. On univariate sensitivity analyses, the model proved to be robust within an ICER range of 2500.00 to 4800.00 BRL. CONCLUSIONS: PICC placement was associated with a lower risk of complications than CICC placement. Although the cost of a PICC is higher, its use avoided complications and need for catheter replacement before the end of treatment.

Cost-Effectiveness Analysis Comparing QuantiFERON-TB Gold Plus Test and Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Immunocompetent Subjects in Colombia.

OBJECTIVES: To determine the cost-effectiveness of the QuantiFERON-TB Gold Plus (QFT-Plus) test versus the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent subjects in the context of the Colombian healthcare system. METHODS: A hypothetical cohort of 2000 immunocompetent adults vaccinated with Bacillus Calmette-Guérin at birth who are asymptomatic for tuberculosis disease was simulated and included in a decision tree over a horizon of <1 year. The direct healthcare costs related to tests, antituberculosis treatment, and medical care were considered, and diagnostic performance was used as a measure of effectiveness. The incremental cost-effectiveness ratio (ICER) was estimated, and univariate deterministic and probabilistic sensitivity analyses were carried out using 5000 simulations. The currency was the US dollar for the year 2022, with a cost-effectiveness threshold of $6666 USD (1 gross domestic product per capita for 2022). RESULTS: QFT-Plus was cost-effective with an ICER of $5687 USD for each correctly diagnosed case relative to a threshold of $6666 USD. In the deterministic analysis, QFT-Plus was cost-effective in half of the proposed scenarios. The variable that most affected the ICER was the prevalence of latent tuberculosis and test sensitivities. In the probabilistic analysis, QFT-Plus was cost-effective in 54.74% of the simulated scenarios, and tuberculin skin test was dominant in 13.84%. CONCLUSIONS: The study provides evidence of the cost-effectiveness of QFT-Plus compared with the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent adults in the Colombian context.

Assessment of Extent and Quality of Pharmacoeconomic Studies in India Using Quality of Health Economic Studies Score: A Targeted Literature Review.

OBJECTIVES: We assessed the quality of pharmacoeconomic studies conducted in India to report key areas of focus on the findings from the reviewed studies. METHODS: A targeted literature review was conducted using well-defined search strategy in PubMed to identify economic studies conducted in India from May 2017 to April 2022. Only economic evaluation studies were included, whereas trial-based cost analyses were excluded. The quality of included studies was assessed using the Quality of Health Economic Studies tool, which comprised 16 evaluation criteria related to objectives, source, funding, perspective, subgroup analysis, scales, and economic modeling related parameters. Based on scores (100 points), studies were rated as good (≥75), fair (50-74), and poor (≤49) quality. RESULTS: Search strategy provided 888 studies; 95 of these were economic studies, and 74 were included in the analysis. These 74 studies included budget impact analysis (n = 4), burden of illness (n = 8), cost-benefit analysis (n = 5), cost-consequences analysis (n = 1), cost-effectiveness analysis (n = 55), and cost-utility analysis (n = 1). The average quality score of studies was 64.08. Of the studies, 15 studies were rated as "good," 51 "fair," and 8 "poor." It was observed that primary outcome measures, stating negative outcomes, reporting bias, and implementing statistical and sensitivity analysis significantly affected the quality score. CONCLUSIONS: Most of the health economic studies conducted in India are of fair quality, and there is a need for standardization of guidelines and increase in number of Indian peer-reviewed health economics journals. A collaborative effort from pharma companies, policy makers, education experts, curriculum planners, and medical faculty is needed to promote quality economic studies.

Economic Evaluation of Neoadjuvant Versus Adjuvant Chemotherapy in Cancer Treatment: A Systematic Review and Meta-Analysis.

OBJECTIVES: In the absence of evidence on whether neoadjuvant (NAC) or adjuvant chemotherapy (AC) is more beneficial for various tumor treatments, economic evaluation (EE) can assist medical decision making. There is limited evidence on their cost-effectiveness and their prospective evaluation is less likely in the future. Therefore, a systematic review and meta-analysis about EE for NAC versus AC in solid tumor help compare these therapies from various perspectives. METHODS: Various databases were searched for studies published from inception to 2021. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and economic-specific guidelines. The data were pooled using a random effects model when possible. RESULTS: The retrieval identified 15 EE studies of NAC versus AC in 8 types of cancer. NAC is the dominant strategy for pancreatic, head and neck, rectal, prostate cancers and colorectal liver metastases. For ovarian cancer, NAC is cost-effective with a lower cost and higher or similar quality-adjusted life-year. There were no significant differences in cost and outcomes for lung cancer. For stage IV or high-risk patients with ovarian or prostate cancer, NAC was cost-effective but not for patients who were not high risk. CONCLUSIONS: The EEs results for NAC versus AC were inconsistent because of their different model structures, assumptions, cost inclusions, and a shortage of studies. There are multiple sources of heterogeneity across EEs evidence synthesis. More high-quality EE studies on NAC versus AC in initial cancer treatment are necessary.

The Use of Cost-Effectiveness Thresholds for Evaluating Health Interventions in Low- and Middle-Income Countries From 2015 to 2020: A Review.

OBJECTIVES: Evidence-informed priority setting, in particular cost-effectiveness analysis (CEA), can help target resources better to achieve universal health coverage. Central to the application of CEA is the use of a cost-effectiveness threshold. We add to the literature by looking at what thresholds have been used in published CEA and the proportion of interventions found to be cost-effective, by type of threshold. METHODS: We identified CEA studies in low- and middle-income countries from the Global Health Cost-Effectiveness Analysis Registry that were published between January 1, 2015, and January 6, 2020. We extracted data on the country of focus, type of interventions under consideration, funder, threshold used, and recommendations. RESULTS: A total of 230 studies with a total 713 interventions were included in this review; 1 to 3× gross domestic product (GDP) per capita was the most common type of threshold used in judging cost-effectiveness (84.3%). Approximately a third of studies (34.2%) using 1 to 3× GDP per capita applied a threshold at 3× GDP per capita. We have found that no study used locally developed thresholds. We found that 79.3% of interventions received a recommendation as "cost-effective" and that 85.9% of studies had at least 1 intervention that was considered cost-effective. The use of 1 to 3× GDP per capita led to a higher proportion of study interventions being judged as cost-effective compared with other types of thresholds. CONCLUSIONS: Despite the wide concerns about the use of 1 to 3× GDP per capita, this threshold is still widely used in the literature. Using this threshold leads to more interventions being recommended as "cost-effective." This study further explore alternatives to the 1 to 3× GDP as a decision rule.

Key Considerations in the Health Technology Assessment of Advanced Therapy Medicinal Products in Scotland, The Netherlands, and England.

OBJECTIVES: Advanced therapy medicinal products (ATMPs) are highly innovative therapies. Their costs and uncertain value claims have raised concerns among health technology assessment (HTA) bodies and payers. Little is known about how underlying considerations in HTA of ATMPs shape assessment and reimbursement recommendations. We aim to identify and assess key considerations that played a role in HTA of ATMPs underlying reimbursement recommendations. METHODS: A review of HTA reports was conducted of all authorized ATMPs in Scotland, The Netherlands, and England. Considerations were extracted and categorized into EUnetHTA Core Model domains. Per jurisdiction, considerations were aggregated and key considerations identified (defined as occurring in >1/assessment per jurisdiction). A narrative analysis was conducted comparing key considerations between jurisdictions and different reimbursement recommendations. RESULTS: We identified 15 ATMPs and 18 HTA reports. In The Netherlands and England most key considerations were identified in clinical effectiveness (EFF) and cost- and economic effectiveness (ECO) domains. In Scotland, the social aspects domain yielded most key considerations, followed by ECO and EFF. More uncertainty in evidence and assessment outcomes was accepted when orphan or end-of-life criteria were applied. A higher percentage of considerations supporting recommendations were identified for products with positive recommendations compared with restricted and negative recommendations. CONCLUSIONS: This is the first empirical review of HTA's using the EUnetHTA Core Model to identify and structure key considerations retrospectively. It provides insights in supporting and opposing considerations for reimbursement of individual products and differences between jurisdictions. Besides the EFF and ECO domain, the social, ethical, and legal domains seem to bear considerable weight in assessment of ATMPs.

Assessing Payers' Preferences for Real-World Evidence in the United States: A Discrete Choice Experiment.

OBJECTIVES: To rank the US payers' preferences for attributes of real-world evidence (RWE) studies in the context of chronic disease and to quantify trade-offs among them. METHODS: We conducted a discrete choice experiment in which 180 employees from payer organizations were tasked to choose between 2 RWE studies assuming they were assessing evidence to inform formulary decisions for chronic disease treatment. Each RWE study was characterized by 7 attributes with 3 levels each: very informative, moderately informative, and not measured. We used a D-optimal main-effects design. Survey data were fitted to a conditional logit model to obtain a relative measure of the ranking of importance for each attribute. RESULTS: Clinical outcomes were the most preferred attribute. It was 4.68 times as important as productivity outcomes-the least preferred attribute. It was followed by health-related quality of life (2.78), methodologic rigor (2.09), resource utilization (1.71), and external validity (1.56). CONCLUSIONS: This study provides a quantification of the value payers place on key RWE attributes. Across attributes, payers have higher preferences for clinical and health-related quality of life outcomes than the other attributes. Between attributes' levels, payers prefer high levels of information in clinical outcomes and methodologic rigor but are indifferent in other attributes. Our results bridge the gap between the information that payers seek and the attributes that RWE studies prioritize and effectively guide future research design.

Investigating 5-Level EQ-5D (EQ-5D-5L) Values Based on Preferences of Patients With Heart Disease.

OBJECTIVES: Several studies have shown that patients with heart disease value hypothetical health states differently from the general population. We aimed to investigate the health preferences of patients with heart disease and develop a value set for the 5-level EQ-5D (EQ-5D-5L) based on these patient preferences. METHODS: Patients with confirmed heart disease were recruited from 2 hospitals in Singapore. A total of 86 EQ-5D-5L health states (10 per patient) were valued using a composite time trade-off method according to the international valuation protocol for EQ-5D-5L; 20-parameter linear models and 8-parameter cross-attribute level effects models with and without an N45 term (indicating whether any health state dimension at level 4 or 5 existed) were estimated. Each model included patient-specific random intercepts. Model performance was evaluated for out-of-sample and in-sample predictive accuracy in terms of root mean square error. The discriminative ability of the utility values was assessed using heart disease-related functional classes. RESULTS: A total of 576 patients were included in the analysis. The preferred model, with the lowest out-of-sample root mean square error, was a 20-parameter linear model including N45. Predicted utility values ranged from -0.727 for the worst state to 1 for full health; the value for the second-best state was 0.981. Utility values demonstrated good discriminative ability in differentiating among patients of varied functional classes. CONCLUSIONS: An EQ-5D-5L value set representing the preferences of patients with heart disease was developed. The value set could be used for patient-centric economic evaluation and health-related quality of life assessment for patients with heart disease.

Methodologic and Reporting Quality of Economic Evaluations in Hand and Wrist Surgery: A Systematic Review.

BACKGROUND: Economic evaluations can inform decision-making; however, previous publications have identified poor quality of economic evaluations in surgical specialties. METHODS: Study periods were from January 1, 2006, to April 20, 2020 (methodologic quality) and January 1, 2014, to April 20, 2020 (reporting quality). Primary outcomes were methodologic quality [Guidelines for Authors and Peer Reviewers of Economic Submissions to The BMJ (Drummond's checklist), 33 points; Quality of Health Economic Studies (QHES), 100 points; Consensus on Health Economic Criteria (CHEC), 19 points] and reporting quality (Consolidated Health Economic Evaluation Standards (CHEERS) statement, 24 points). RESULTS: Forty-seven hand economic evaluations were included. Partial economic analyses (i.e., cost analysis) were the most common (n = 34; 72 percent). Average scores of full economic evaluations (i.e., cost-utility analysis and cost-effectiveness analysis) were: Drummond's checklist, 27.08 of 33 (82.05 percent); QHES, 79.76 of 100 (79.76 percent); CHEC, 15.54 of 19 (81.78 percent); and CHEERS, 20.25 of 24 (84.38 percent). Cost utility analyses had the highest methodologic and reporting quality scores: Drummond's checklist, 28.89 of 35 (82.54 percent); QHES, 86.56 of 100 (86.56 percent); CHEC, 16.78 of 19 (88.30 percent); and CHEERS, 20.8 of 24 (86.67 percent). The association (multiple R) between CHEC and CHEERS was strongest: CHEC, 0.953; Drummond's checklist, 0.907; and QHES, 0.909. CONCLUSIONS: Partial economic evaluations in hand surgery are prevalent but not very useful. The Consensus on Health Economic Criteria and Consolidated Health Economic Evaluation Standards should be used in tandem when undertaking and evaluating economic evaluation in hand surgery.

Evaluating the cost-effectiveness of a pre-exposure prophylaxis program for HIV prevention for men who have sex with men in Japan.

Men who have sex with men (MSM) have been disproportionally affected by the HIV epidemic in many countries, including Japan. Although pre-exposure prophylaxis (PrEP) is a strong prevention tool, it is not yet approved in Japan. A Markov model was developed to describe HIV infection and disease progression in an MSM cohort (N = 1000) in Japan receiving a PrEP program. The model was used to evaluate the cost-effectiveness of a PrEP program. HIV/AIDS treatment, screening, hospitalization due to AIDS, and PrEP were considered as costs and quality-adjusted life-years (QALYs) gained as utilities. Cost-effectiveness was assessed by comparing the incremental cost-effectiveness ratio (ICER) over a 30-year period against the willingness to pay (WTP) threshold. One-way sensitivity and probabilistic sensitivity analyses were performed. With 50% PrEP coverage, the PrEP program became dominant against the program without PrEP, using a threshold of 5.0 million JPY/QALY (45,455 USD). The probabilistic sensitivity analysis revealed that the PrEP program was dominant or at least cost-effective in most cases of 10,000 simulations. Therefore, preparing cheaper PrEP pills, which results in PrEP being dominant or ICER being lower than the WTP threshold, is important to make the program cost-effective. Introduction of PrEP to an MSM cohort in Japan would be cost-effective over a 30-year time horizon.

Several explorations on how to construct an early warning system for local government debt risk in China.

This paper aims to explore several ways to construct a scientific and comprehensive early warning system (EWS) for local government debt risk in China. In order to achieve this goal, this paper studies the local government debt risk from multiple perspectives, i.e., individual risk, contagion risk, static risk and dynamic risk. Firstly, taking China's 30 provinces over the period of 2010~ 2018 as a sample, this paper establishes early warning indicators for individual risk of local government debt, and uses the network model to establish early warning indicators for contagion risk of local government debt. Then, this paper applies the criteria importance though intercrieria correlation (CRITIC) method and coefficient of variation method to obtain the proxy variable Ⅰ, which combines the above two risks. Secondly, based on the proxy variable Ⅰ, both the Markov-switching autoregressive (MS-AR) model and coefficient of variation method are used to obtain the proxy variable Ⅱ, which comprehensively considers the individual risk, contagion risk, static risk and dynamic risk of local government debt. Finally, machine learning algorithms are adopted to generalize the EWS designed in this paper. The results show that: (1) From different perspectives of local government debt risk, the list of provinces that require early warning is different; (2) The support vector machines can well generalize our EWS.

Proportional-assist ventilation with load-adjustable gain factors for mechanical ventilation: a cost-utility analysis.

BACKGROUND: Mechanical ventilation is an important component of patient critical care, but it adds expense to an already high-cost setting. This study evaluates the cost-utility of 2 modes of ventilation: proportional-assist ventilation with load-adjustable gain factors (PAV+ mode) versus pressure-support ventilation (PSV). METHODS: We adapted a published Markov model to the Canadian hospital-payer perspective with a 1-year time horizon. The patient population modelled includes all patients receiving invasive mechanical ventilation who have completed the acute phase of ventilatory support and have entered the recovery phase. Clinical and cost inputs were informed by a structured literature review, with the comparative effectiveness of PAV+ mode estimated via pragmatic meta-analysis. Primary outcomes of interest were costs, quality-adjusted life years (QALYs) and the (incremental) cost per QALY for patients receiving mechanical ventilation. Results were reported in 2017 Canadian dollars. We conducted probabilistic and scenario analyses to assess model uncertainty. RESULTS: Over 1 year, PSV had costs of $50 951 and accrued 0.25 QALYs. Use of PAV+ mode was associated with care costs of $43 309 and 0.29 QALYs. Compared to PSV, PAV+ mode was considered likely to be cost-effective, having lower costs (-$7642) and increased QALYs (+0.04) after 1 year. In cost-effectiveness acceptability analysis, 100% of simulations would be cost-effective at a willingness-to-pay threshold of $50 000 per QALY gained. INTERPRETATION: Use of PAV+ mode is expected to benefit patient care in the intensive care unit (ICU) and be a cost-effective alternative to PSV in the Canadian setting. Canadian hospital payers may therefore consider how best to optimally deliver mechanical ventilation in the ICU as they expand ICU capacity.

Comparing Modeling Approaches for Discrete Event Simulations With Competing Risks Based on Censored Individual Patient Data: A Simulation Study and Illustration in Colorectal Cancer.

OBJECTIVES: This study aimed to provide detailed guidance on modeling approaches for implementing competing events in discrete event simulations based on censored individual patient data (IPD). METHODS: The event-specific distributions (ESDs) approach sampled times from event-specific time-to-event distributions and simulated the first event to occur. The unimodal distribution and regression approach sampled a time from a combined unimodal time-to-event distribution, representing all events, and used a (multinomial) logistic regression model to select the event to be simulated. A simulation study assessed performance in terms of relative absolute event incidence difference and relative entropy of time-to-event distributions for different types and levels of right censoring, numbers of events, distribution overlap, and sample sizes. Differences in cost-effectiveness estimates were illustrated in a colorectal cancer case study. RESULTS: Increased levels of censoring negatively affected the modeling approaches' performance. A lower number of competing events and higher overlap of distributions improved performance. When IPD were censored at random times, ESD performed best. When censoring occurred owing to a maximum follow-up time for 2 events, ESD performed better for a low level of censoring (ie, 10%). For 3 or 4 competing events, ESD better represented the probabilities of events, whereas unimodal distribution and regression better represented the time to events. Differences in cost-effectiveness estimates, both compared with no censoring and between approaches, increased with increasing censoring levels. CONCLUSIONS: Modelers should be aware of the different modeling approaches available and that selection between approaches may be informed by data characteristics. Performing and reporting extensive validation efforts remains essential to ensure IPD are appropriately represented.

The ICEpop Capability Measure for Adults Instrument for Capabilities: Development of a Tariff for the Dutch General Population.

OBJECTIVES: The ICEpop Capability Measure for Adults (ICECAP-A) assesses 5 capabilities (stability, attachment, autonomy, achievement, and enjoyment) that are important to one's quality of life and might be an important addition to generic health questionnaires currently used in economic evaluations. This study aimed to develop a Dutch tariff of the Dutch translation of the ICECAP-A. METHODS: The methods used are similar to those used in the development of the UK tariff. A profile case best-worst scaling task was presented to 1002 participants from the general Dutch population. A scale-adjusted latent class analysis was performed to test for preferences of ICECAP-A capabilities and scale heterogeneity. RESULTS: A 3-preference class 2-scale class model with worst choice as scale predictor was considered optimal and was used to calculate the resulting tariff. Results indicated that the capabilities stability, attachment, and enjoyment were considered more important aspects of quality of life than autonomy and achievement. Additionally, improving capabilities from low to moderate levels had a larger effect on quality of life than improving capabilities that were already at a higher level. CONCLUSIONS: The ICECAP-A tariffs found in this study could be used in economic evaluations of healthcare interventions in The Netherlands.