Cost-effectiveness of volume computed tomography in lung cancer screening: a cohort simulation based on Nelson study outcomes.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of lung cancer screening (LCS) with volume-based low-dose computed tomography (CT) versus no screening for an asymptomatic high-risk population in the United Kingdom (UK), utilising the long-term insights provided by the NELSON study, the largest European randomized control trial investigating LCS. METHODS: A cost-effectiveness analysis was conducted using a decision tree and a state-transition Markov model to simulate the identification, diagnosis, and treatments for a lung cancer high-risk population, from a UK National Health Service (NHS) perspective. Eligible participants underwent annual volume CT screening and were compared to a cohort without the option of screening. Screen-detected lung cancers, costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were predicted. RESULTS: Annual volume CT screening of 1.3 million eligible participants resulted in 96,474 more lung cancer cases detected in early stage, and 73,825 fewer cases in late stage, leading to 53,732 premature lung cancer deaths averted and 421,647 QALYs gained, compared to no screening. The ICER was £5,455 per QALY. These estimates were robust in sensitivity analyses. LIMITATIONS: Lack of long-term survival data for lung cancer patients; deficiency in rigorous micro-costing studies to establish detailed treatment costs inputs for lung cancer patients. CONCLUSIONS: Annual LCS with volume-based low-dose CT for a high-risk asymptomatic population is cost-effective in the UK, at a threshold of £20,000 per QALY, representing an efficient use of NHS resources with substantially improved outcomes for lung cancer patients, as well as additional societal and economic benefits for society as a whole. These findings advocate evidence-based decisions for the potential implementation of a nationwide LCS in the UK.

Factors associated with health status and exacerbations in COPD maintenance therapy with dry powder inhalers.

The study aimed to determine the associations of Peak Inspiratory Flow (PIF), inhalation technique and adherence with health status and exacerbations in participants with COPD using DPI maintenance therapy. This cross-sectional multi-country observational real-world study included COPD participants aged ≥40 years using a DPI for maintenance therapy. PIF was measured three times with the In-Check DIAL G16: (1) typical PIF at resistance of participant's inhaler, (2) maximal PIF at resistance of participant's inhaler, (3) maximal PIF at low resistance. Suboptimal PIF (sPIF) was defined as PIF lower than required for the device. Participants completed questionnaires on health status (Clinical COPD Questionnaire (CCQ)), adherence (Test of Adherence to Inhalers (TAI)) and exacerbations. Inhalation technique was assessed by standardised evaluation of video recordings. Complete data were available from 1434 participants (50.1% female, mean age 69.2 years). GOLD stage was available for 801 participants: GOLD stage I (23.6%), II (54.9%), III (17.4%) and IV (4.1%)). Of all participants, 29% had a sPIF, and 16% were shown able to generate an optimal PIF but failed to do so. sPIF was significantly associated with worse health status (0.226 (95% CI 0.107-0.346), worse units on CCQ; p = 0.001). The errors 'teeth and lips sealed around mouthpiece', 'breathe in', and 'breathe out calmly after inhalation' were related to health status. Adherence was not associated with health status. After correcting for multiple testing, no significant association was found with moderate or severe exacerbations in the last 12 months. To conclude, sPIF is associated with poorer health status. This study demonstrates the importance of PIF assessment in DPI inhalation therapy. Healthcare professionals should consider selecting appropriate inhalers in cases of sPIF.

Rotavirus Vaccination of Infants Delayed and Limited within the National Immunization Programme in the Netherlands: An Opportunity Lost.

In this study, we estimated the benefits of rotavirus vaccination for infants had the rotavirus vaccine been introduced in the Netherlands as of its market authorization in 2006. An age-structured, deterministic cohort model was developed to simulate different birth cohorts over a period of 15 years from 2006 until 2021, comparing both universal and targeted high-risk group vaccination to no vaccination. Different scenarios for the duration of protection (5 or 7 years) and herd immunity (only for universal vaccination) were analyzed. All birth cohorts together included 2.6 million infants, of which 7.9% were high-risk individuals, and an additional 13.2 million children between 1-15 years born prior to the first cohort in 2006. The costs and health outcomes associated with rotavirus vaccination were calculated per model scenario and discounted at 4% and 1.5%, respectively. Our analysis reveals that, had rotavirus vaccination been implemented in 2006, it would have prevented 356,800 (51% decrease) and 32,200 (5% decrease) cases of rotavirus gastroenteritis after universal and targeted vaccination, respectively. Over the last 15 years, this would have led to significant avoided costs and quality-adjusted life year losses for either vaccination strategy with the most favorable outcomes for universal vaccination. Clearly, an opportunity has been lost.

Costs of clinical events in type 2 diabetes mellitus patients in the Netherlands: A systematic review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an established risk factor for cardiovascular and nephropathic events. In the Netherlands, prevalence of T2DM is expected to be as high as 8% by 2025. This will result in significant clinical and economic impact, highlighting the need for well-informed reimbursement decisions for new treatments. However, availability and consistent use of costing methodologies is limited. OBJECTIVE: We aimed to systematically review recent costing data for T2DM-related cardiovascular and nephropathic events in the Netherlands. METHODS: A systematic literature review in PubMed and Embase was conducted to identify available Dutch cost data for T2DM-related events, published in the last decade. Information extracted included costs, source, study population, and costing perspective. Finally, papers were evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). RESULTS: Out of initially 570 papers, 36 agreed with the inclusion criteria. From these studies, 150 cost estimates for T2DM-related clinical events were identified. In total, 29 cost estimates were reported for myocardial infarction (range: €196-€27,038), 61 for stroke (€495-€54,678), fifteen for heart failure (€325-€16,561), 24 for renal failure (€2,438-€91,503), and seventeen for revascularisation (€3,000-€37,071). Only four estimates for transient ischaemic attack were available, ranging from €587 to €2,470. Adherence to CHEERS was generally high. CONCLUSIONS: The most expensive clinical events were related to renal failure, while TIA was the least expensive event. Generally, there was substantial variation in reported cost estimates for T2DM-related events. Costing of clinical events should be improved and preferably standardised, as accurate and consistent results in economic models are desired.

Economic Consequences and Potentially Preventable Costs Related to Osteoporosis in the Netherlands.

BACKGROUND: Osteoporosis often does not involve symptoms, and so the actual number of patients with osteoporosis is higher than the number of diagnosed individuals. This underdiagnosis results in a treatment gap. OBJECTIVES: To estimate the total health care resource use and costs related to osteoporosis in the Netherlands, explicitly including fractures, and to estimate the proportion of fracture costs that are linked to the treatment gap and might therefore be potentially preventable; to also formulate, on the basis of these findings, strategies to optimize osteoporosis care and treatment and reduce its related costs. METHODS: In this retrospective study, data of the Achmea Health Database representing 4.2 million Dutch inhabitants were used to investigate the economic consequence of osteoporosis in the Netherlands in 2010. Specific cohorts were created to identify osteoporosis-related fractures and their costs. Besides, costs of pharmaceutical treatment regarding osteoporosis were included. Using data from the literature, the treatment gap was estimated. Sensitivity analysis was performed on the base-case results. RESULTS: A total of 108,013 individuals with a history of fractures were included in this study. In this population, 59,193 patients were using anti-osteoporotic medication and 86,776 patients were using preventive supplements. A total number of 3,039 osteoporosis-related fractures occurred. The estimated total costs were €465 million. On the basis of data presented in the literature, the treatment gap in our study population was estimated to vary from 60% to 72%. CONCLUSIONS: The estimated total costs corrected for treatment gap were €1.15 to €1.64 billion. These results indicate room for improvement in the health care policy against osteoporosis.

Cost-effectiveness Analysis for Apixaban in the Acute Treatment and Prevention of Venous Thromboembolism in the Netherlands.

PURPOSE: Low-molecular weight heparin (LMWH) followed by vitamin K antagonists (VKAs) are the current standard treatment of acute venous thromboembolism (VTE) and prevention of recurrent VTE. The direct oral anticoagulant apixaban was recently found noninferior in efficacy and superior in preventing major bleeding compared with LMWH/VKAs in the AMPLIFY (Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy) trial. The objective of this study was to calculate the cost-effectiveness of apixaban compared with LMWH/VKA in the treatment of acute VTE and prevention of recurrent VTE in the Netherlands. METHODS: A Markov model was designed to simulate a cohort of 1,000 VTE patients receiving either apixaban or LMWH/VKA. Transition probabilities, costs, and utilities were obtained from the AMPLIFY trial and other literature. The incremental cost-effectiveness ratio (ICER) was calculated from the societal perspective; therefore, the model included both direct (inside and outside the health care sector) and indirect costs. In the univariate and probabilistic sensitivity analyses (PSAs) the robustness of the results was tested, and various additional scenario analyses were conducted. FINDINGS: In the base-case analysis, apixaban saved €236 and 0.044 quality-adjusted life years (QALYs) and 0.039 LYs were gained compared with LMWH/VKA. In the univariate sensitivity analysis the model appeared to be robust. The results of 2,000 iterations in the PSA found that the probability of apixaban being cost-effective at a willingness-to-pay threshold of €20,000/QALY was 100% and cost-saving was 94%. The scenario of 18-month treatment duration was the only scenario not indicating cost-savings with an ICER of €425/QALY. IMPLICATIONS: In acute anticoagulation use apixaban was found to be cost-saving. A longer anticoagulation period (18 months) resulted in a higher difference in drug costs, indicating a higher ICER. The cost-effectiveness of long-term or life-long use should be examined in future research.

Comparative Cost-Effectiveness of Drugs in Early versus Late Stages of Cancer; Review of the Literature and a Case Study in Breast Cancer.

BACKGROUND: Many oncological drugs that are being used in the adjuvant setting were first submitted for reimbursement in the metastatic stage, with differences in incremental cost-effectiveness ratios (ICERs) in both settings having potential implications for reimbursement and pricing. The aim of this study is to identify a possible trend in the cost-effectiveness for the early/adjuvant and late/metastatic stages of oncological drugs through review and case study. METHODS: We reviewed pairs of cost-effectiveness analyses of the same oncological drug in different stages for Scotland and the Netherlands. The case study in this report was directed at trastuzumab in the Dutch situation. Using a simplified Markov model, the cost-effectiveness in early and late stage of breast cancer was calculated and compared to the findings from the review. RESULTS: Comparable studies were found for cetuximab, bortezomib and bosutinib. Treatments in the late stage were found to be more expensive per QALY by a factor ranging from 1.5 to 12. The case study provided a similar result; late stage treatment was more expensive by a factor 10. Using, for example, a threshold of € 80,000/QALY, the early stage of cetuximab, bosutinib and trastuzumab are deemed cost-effective, while their compared late stage is lifted over the threshold and potentially considered not cost-effective. CONCLUSION: ICERs of oncological drugs used in different stages are more unfavourable in the late stage than in the early stage. Applying a reasonable threshold may result in early stage treatment being deemed cost-effective while late stage potentially not. Authorities should be aware of this when assessing oncological drugs and interpreting the corresponding ICERs, in the situation where oncological drugs are generally most submitted for reimbursement in the late stage initially.