How accurate should a precision medical test be to meet cost-effectiveness.

Comparative cost-effectiveness of SARS-CoV-2 testing strategies in the USA: a modelling study

We aimed to perform an early cost-effectiveness analysis of using a whole-genome sequencing-based tumor mutation burden (WGS-TMB), instead of programmed death-ligand 1 (PD-L1), for immunotherapy treatment selection in patients with non-squamous advanced/metastatic non-small cell lung cancer ineligible for targeted therapy, from a Dutch healthcare perspective. A decision-model simulating individual patients with metastatic non-small cell lung cancer was used to evaluate diagnostic strategies to select first-line immunotherapy only or the immunotherapy plus chemotherapy combination. Treatment was selected using PD-L1 [A, current practice], WGS-TMB [B], and both PD-L1 and WGS-TMB [C]. Strategies D, E, and F take into account a patient's disease burden, in addition to PD-L1, WGS-TMB, andboth PD-L1 andWGS-TMB, respectively. Disease burden was defined as a fast-growing tumor, a high number of metastases, and/or weight loss. A threshold of 10 mutations per mega-base was used to classify patients into TMB-high and TMB-low groups. Outcomes were discounted quality-adjusted life-years (QALYs) and healthcare costs measured from the start of first-line treatment to death. Healthcare costs includes drug acquisition, follow-up costs, and molecular diagnostic tests (i.e., standard diagnostic techniques and/or WGS for strategies involving TMB). Results were reported using the net monetary benefit at a willingness-to-pay threshold of €80,000/QALY. Additional scenario and threshold analyses were performed. Strategy B had the lowest QALYs (1.84) and lowest healthcare costs (€120,800). The highest QALYs and healthcare costs were 2.00 and €140,400 in strategy F. In the base-case analysis, strategy A was cost effective with the highest net monetary benefit (€27,300), followed by strategy B (€26,700). Strategy B was cost effective when the cost of WGS testing was decreased by at least 24% or when immunotherapy results in an additional 0.5 year of life gained or more for TMB high compared with TMB low. Strategies C and F, which combined TMB and PD-L1 had the highest net monetary benefit (≥ €76,900) when the cost of WGS testing, immunotherapy, and chemotherapy acquisition were simultaneously reduced by at least 47%, 39%, and 43%, respectively. Furthermore, strategy C resulted in the highest net monetary benefit (≥ €39,900) in a scenario where patients with both PD-L1 low and TMB low were treated with chemotherapy instead of immunotherapy plus chemotherapy. The use of WGS-TMB is not cost effective compared to PD-L1 for immunotherapy treatment selection in non-squamous metastatic non-small cell lung cancer in the Netherlands. WGS-TMB could become cost effective provided there is a reduction in the cost of WGS testing or there is an increase in the predictive value of WGS-TMB for immunotherapy effectiveness. Alternatively, a combination strategy of PD-L1 testing with WGS-TMB would be cost effective if used to support the choice to withhold immunotherapy in patients with a low expected benefit of immunotherapy.

Profit in a pig herd from performance testing and selection of breeding stock. The effect of variation in the accuracy and cost of testing

Organisational impact of information technology on the banking and insurance sector in Nigeria

The cost-effectiveness of diagnostic testing strategies for Helicobacter pylori

Current Stool DNA Tests More Costly and Less Effective for Colorectal Cancer Screening

This paper describes an approach to testing DDR echo clock outputs and transfer data specifications. Tester accuracy issues create difficulty in guaranteeing the 200 ps spec timing between these two groups of outputs. This approach will find the balance between accurate testing and test costs.

6638 Background: NGS testing for genomic alterations has been found to expedite time to appropriate targeted therapy initiation compared to PCR testing in mNSCLC. This study assessed US payers’ costs of testing, delayed care, and suboptimal treatment initiation for PCR versus NGS testing in patients with mNSCLC. Methods: A decision tree model evaluated testing for guideline-recommended alterations (EGFR, ALK, ROS1, BRAF, KRAS, MET, HER2, RET, NTRK1/2/3) in patients with newly-diagnosed mNSCLC from first test until appropriate therapy initiation using 1) liquid or tissue NGS (60% [90% tissue, 10% liquid] of patients), 2) exclusionary KRAS test followed by sequential PCR tests (5%), 3) sequential PCR tests (5%), or 4) hotspot panel (30%) PCR tests. The proportion of patients testing positive for a targetable alteration and time to appropriate therapy initiation were evaluated. Cost components included genetic testing, testing-related medical services, delayed care (i.e., costs for medical services while waiting for test results), immunotherapy [IO]/chemotherapy [CTX] initiation prior to test results, and suboptimal treatment initiation after test results (i.e., costs of first-line IO/CTX in patients falsely testing negative for an actionable mutation). Results: In a modeled cohort of 1 million members (75% commercial, 25% Medicare), an estimated 1,119 patients had mNSCLC and were tested. The proportion of patients testing positive for a targetable alteration was 45.9% for NGS and 39.4% for PCR testing (Table). Total mean per patient costs were lower for NGS ($8,866) than for PCR ($18,252), driven by more rapid treatment with appropriate therapy (2.1 versus 5.2 weeks), resulting in lower delayed care costs and IO/CTX costs prior to test results. Conclusions: Results suggest that NGS testing may lead to better patient care and reduced costs to the health system relative to PCR testing. Costs of inappropriate IO/CTX initiation are an important component of increased costs of PCR-based approaches. [Table: see text]

Aims Influenza-like illnesses (ILI) affect millions each year in the United States (US). Determining definitively the cause of symptoms is important for patient management. Xpert Xpress CoV-2/Flu/RSV plus (Xpert Xpress) is a rapid, point-of-care (POC), multiplex real-time polymerase chain reaction (RT-PCR) test intended for the simultaneous qualitative detection and differentiation of SARS-CoV-2, influenza A/B, and respiratory syncytial virus (RSV). The objective of our analysis was to develop a cost-consequence model (CCM) demonstrating the clinico-economic impacts of implementing PCR testing with Xpert Xpress compared to current testing strategies. Methods A decision tree model, with a 1-year time horizon, was used to compare testing with Xpert Xpress alone to antigen POC testing and send-out PCR strategies in the US outpatient setting from a payer perspective. A hypothetical cohort of 1,000,000 members was modeled, a portion of whom develop symptomatic ILIs and present to an outpatient care facility. Our main outcome measure is cost per correct treatment course. Results The total cost per correct treatment course was $1,131 for the Xpert Xpress strategy compared with a range of $3,560 to $5,449 in comparators. POC antigen testing strategies cost more, on average, than PCR strategies. Limitations Simplifying model assumptions were used to allow for modeling ease. In clinical practice, treatment options, costs, and diagnostic test sensitivity and specificity may differ from what is included in the model. Additionally, the most recent incidence and prevalence data was used within the model, which is not reflective of historical averages due to the SARS-CoV-2 pandemic. Conclusion The Xpert Xpress CoV-2/Flu/RSV plus test allows for rapid and accurate diagnostic results, leading to reductions in testing costs and downstream healthcare resource utilization compared to other testing strategies. Compared to POC antigen testing strategies, PCR strategies were more efficient due to improved diagnostic accuracy and reduced use of confirmatory testing.

Several noninvasive methods are now available for diagnosing Helicobacter pylori infection. Because the prevalence of H. pylori infection is variable in patients requiring testing, the optimal testing strategies may vary under different conditions. The aim of this study was to evaluate the cost-effectiveness of competing diagnostic strategies for H. pylori in patients with varying H. pylori prevalence. A decision analysis was performed comparing the costs per number of correct diagnoses achieved by alternative sequential testing strategies. Estimates of H. pylori prevalence and test characteristics were derived from a systematic review of the MEDLINE bibliographic database. Cost estimates were derived from the 2000 Medicare Fee Schedule. The enzyme-linked immunosorbent assay (ELISA) test had the lowest cost per correct diagnosis at low (30%), intermediate (60%), and high (90%) prevalence ($90-$95/correct diagnosis), but its diagnostic accuracy was low (80-84%). At low and intermediate prevalence the stool test was more accurate (93%), with an average cost of $126-$127 per correct diagnosis. Additional confirmatory testing of positive or negative tests increased the diagnostic accuracy of the stool test, but had high incremental costs. ELISA testing was preferable when prevalence rates were very high (90%), and using a confirmatory urea breath test for negative ELISA tests increased the diagnostic accuracy to 96%, with modest incremental costs. If the cost of the breath test was <$50 or if the cost of the stool test is >$82, breath testing became preferable to stool testing. If the cost of the stool test fell to <$20, it became preferable to ELISA. Similarly, if the cost of the ELISA serology was >$39 then stool testing became preferable at all prevalence rates. Fingerstick whole blood tests were not cost-effective. The choice of an initial test for H. pylori detection depends on the prevalence of H. pylori infection and the value placed on increased diagnostic accuracy. Although ELISA results in the lowest cost-effectiveness ratios, in patients at low-intermediate pretest probability of infection, the stool test provides increased accuracy, with modest incremental costs.

Johne's disease is an insidious infectious disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Johne's disease can have important implications for animal welfare and risks causing economic losses in affected herds due to reduced productivity, premature culling and replacement, and veterinary costs. Despite the limited accuracy of diagnostic tools, testing and culling is the primary option for controlling Johne's disease in beef herds. However, evidence to inform specific test and cull strategies is lacking. In this study, a stochastic, continuous-time agent-based model was developed to investigate Johne's disease and potential control options in a typical western Canadian cow-calf herd. The objective of this study was to compare different testing and culling scenarios that included varying the testing method and frequency as well as the number and risk profile of animals targeted for testing using the model. The relative effectiveness of each testing scenario was determined by the simulated prevalence of cattle shedding MAP after a 10-year testing period. A second objective was to compare the direct testing costs of each scenario to identify least-cost options that are the most effective at reducing within-herd disease prevalence. Whole herd testing with individual PCR at frequencies of 6 or 12 months were the most effective options for reducing disease prevalence. Scenarios that were also effective at reducing prevalence but with the lowest total testing costs included testing the whole herd with individual PCR every 24 months and testing the whole herd with pooled PCR every 12 months. The most effective method with the lowest annual testing cost per unit of prevalence reduction was individual PCR on the whole herd every 24 months. Individual PCR testing only cows that had not already been tested 4 times also ranked well when considering both final estimated prevalence at 10 years and cost per unit of gain. A more in-depth economic analysis is needed to compare the cost of testing to the cost of disease, taking into account costs of culling, replacements and impacts on calf crops, and to determine if testing is an economically attractive option for commercial cow-calf operations.

Evaluation of testing strategies to identify infected animals at a single round of testing within dairy herds known to be infected with Mycobacterium avium ssp. paratuberculosis

The testing stage, creating great opportunities to verify and shape software reliability, significantly increases the cost of its production. The effectiveness of the work related to testing, expressed by the interdependence of the level of program product reliability and the cost of testing it, strongly depends on the adopted testing strategy, specifying the organization and scope of the work performed. In this situation, therefore, there is a need to define the conditions for a compromise in terms of reliability and cost requirements set for the software. The practical finding of this compromise can be greatly facilitated if there are possibilities to formally assess the level of software quality and the cost of testing it using appropriate indicators. The paper attempts to describe a method of determining a program testing strategy as a result of solving a two-criteria optimization problem, with the program reliability coefficient and the cost of testing as component criteria. The paper consists of description of the program testing process and mathematical model of this process, formulation of the problem of two-criteria optimization of the program testing strategy, remarks on method of solving the problem that has been formulated. proposed. To illustrate the method of finding an optimal testing strategy that has been proposed a numerical example is considered.

To evaluate DNA testing for detecting hereditary haemochromatosis (HHC) in subgroups of patients suspected of having the disorder and in family members of those diagnosed with HHC. Major electronic databases, searched from inception to April 2007. A systematic review was undertaken using a priori methods and a de novo model developed to assess costs and consequences of DNA testing. Eleven studies were identified for estimating the clinical validity of genotyping for the C282Y mutation for the diagnosis of HHC. No clinical effectiveness studies meeting the inclusion criteria were identified. Two North American cost-effectiveness studies of reasonable quality were identified but their generalisability to the UK is not clear. Three cohort studies met the inclusion criteria for the review of psychosocial aspects. All had methodological limitations and their generalisability is difficult to determine. The clinical sensitivity of C282Y homozygosity for HHC ranged from 28.4% to 100%, or from 91.3% to 92.4% when considering only the most relevant studies. Clinical specificity ranged from 98.8% to 100%. One study found that gene testing was a cost-effective method of screening relatives of patients with haemochromatosis, whereas the other found that genotyping the spouse of a homozygote was the most cost-efficient strategy. Genetic testing for haemochromatosis appears to be well accepted, is accompanied by few negative psychosocial outcomes and may lead to reduced anxiety. The de novo economic model showed that, in people suspected of having haemochromatosis, the DNA strategy is cost saving compared with the baseline strategy using liver biopsy (cost saved per case detected 123 pounds), largely because of the reduction in liver biopsies. For family testing of siblings the DNA strategy is not cost saving because of the costs of the DNA test (additional cost per case detected 200 pounds). If the cost of the test were to reduce from 100 pounds to 60 pounds, the DNA strategy would be the cheaper one. For family testing of offspring the DNA test strategy is cheaper than the baseline biochemical testing strategy (cost saved per case detected 7982 pounds). Sensitivity analyses showed that the conclusions in each case are robust across all reasonable parameter values. The preferred strategy in practice is DNA testing in conjunction with testing iron parameters when there is clear clinical indication of risk for haemochromatosis because of biochemical criteria or when there is familial risk for HHC. Access to genetic testing and centralisation of test provision in expert laboratories would lower the cost of testing, improve the cost-effectiveness of the strategy and improve the quality of information provided to clinicians and patients.

To determine whether less invasive imaging tests [ultrasound (US), magnetic resonance angiography (MRA), computed tomographic angiography (CTA) and contrast-enhanced MRA (CEMRA)], alone or combined, could replace intra-arterial angiography (IAA), what effect this would have on strokes and deaths, endarterectomies performed and costs, and whether less invasive tests were cost-effective. Electronic databases covering the years 1980-2003 inclusive, updated to April 2004. Key journals from 1990 to the end of 2002. The authors constituted a panel of experts in stroke, imaging, vascular surgery, statistics and health economic modelling. The accuracy of less invasive carotid imaging was systematically reviewed using Standards for Reporting of Diagnostic Accuracy (STARD) methodology, supplemented by individual patient data from UK primary research and audit studies. A systematic review of the costs of less invasive tests, outpatient clinics, endarterectomy and stroke was performed, along with a microcosting exercise. A model of the process of care following a transient ischaemic attack (TIA)/minor stroke was developed, populated with data from stroke epidemiology studies in the UK, effects of medical and surgical interventions, outcomes, quality of life and costs. A survey of UK stroke prevention clinics provided typical timings. Twenty-two different carotid imaging strategies were evaluated for short- and long-term outcomes, quality-adjusted life-years (QALYs) and net benefit. In 41 included studies (2404 patients, median age 60-65 years), most data were available on 70-99% stenosis. CEMRA was the most accurate [sensitivity 0.94, 95% confidence interval (CI) 0.88 to 0.97; specificity 0.93, 95% CI 0.89 to 0.96], compared with US, MRA and CTA, which were all similar (e.g. for US: sensitivity 0.89, 95% CI 0.85 to 0.92; specificity 0.84, 95% CI 0.77 to 0.89). Data for 50-69% stenoses and on combinations of tests were too sparse to be reliable. There was heterogeneity between studies for all imaging modalities except for CTA. The individual patient data (2416 patients) showed that the literature overestimated test accuracy in routine practice and that, in general, tests perform with higher sensitivity and specificity in asymptomatic than in symptomatic arteries. In the cost-effectiveness model, on current UK timings, strategies allowed more patients to reach endarterectomy very quickly, and where those with 50-69% stenosis would be offered surgery in addition to those with 70-99%, prevented most strokes and produced greatest net benefit. This included most strategies with US as first or repeat test, and not those with IAA. However, the model was sensitive to less invasive test accuracy, cost and timing of endarterectomy. In patients investigated late after TIA, test accuracy is crucial and CEMRA should be used before surgery. In the UK, less invasive tests can be used in place of IAA if radiologists trained in carotid imaging are available. Imaging should be carefully audited. Stroke prevention clinics should reduce waiting times at all stages to improve speed of access to endarterectomy. In patients presenting late after TIA, test accuracy is very important and US results should be confirmed by CEMRA, as patients with 50-69% stenosis are less likely to benefit. More data are required to define the accuracy of the less invasive tests, with improvements made in the data collection methods used and how data are presented. Consideration should also be given to the use of new technologies and randomised trials.