Improved implementation of medical tests - barriers and opportunities.

Applying the concept of a value proposition to medical testing is just one of the many ways to identify and monitor the value of tests. A key part of this concept focusses on processes that should take place after a test is introduced into routine local practice, namely test implementation. This process requires identification of the clinical pathway, the stakeholders and the benefits or disbenefits that accrue to those stakeholders. There are various barriers and challenges to test implementation. Implementation requires the process of clinical audit which involves measurement of outcomes external to the laboratory but this is not widely performed in laboratory medicine. A second key challenge is that implementation requires liaison with stakeholders outside of the laboratory including clinicians and other healthcare professional such as finance managers. Many laboratories are remote from clinical care and other stakeholders making such liaison difficult. The implementation process is based on data which again will be primarily on processes outside of the laboratory. However the recent enthusiasm for so-called real world data and new data mining techniques may represent opportunities that will facilitate better test implementation. A final barrier is that a range of new tools not currently in the education curriculum of the laboratory professional is required for implementation such as those of preparing a business case to support the introduction of a test and health economic analysis. The professional bodies in laboratory medicine could assist with education in these areas.

HCV core antigen comes of age: a new opportunity for the diagnosis of hepatitis C virus infection.

The diagnosis of hepatitis C virus (HCV) infection has been traditionally based on the detection of the host antibody response. Although antibody assays are available in different formats and are fairly accurate, they cannot distinguish between an ongoing infection with HCV replicative activity and a past infection where HCV has been cleared, spontaneously or after a successful therapy. As a chronic infection is mostly asymptomatic until the late clinical stages, there is a compelling need to detect active HCV infection by simple and reproducible methods. On this purpose, the clinical guidelines have suggested to search for the HCV ribonucleic acid (HCV-RNA) after anti-HCV has been detected, but this second step carries several limitations especially for population screening. The availability of fast and automated serological assays for the hepatitis C core antigen (HCVAg) has prompted an update of the guidelines that now encompass the use of HCVAg as a practical alternative to HCV-RNA, both for screening and monitoring purposes. In this paper, we summarize the features, benefits and limitations of HCVAg testing and provide an updated compendium of the evidences on its clinical utility and on the indications for use.

A cost-effectiveness evaluation of a high-sensitivity troponin I guided voluntary cardiovascular risk assessment program for asymptomatic women in Croatia.

Background: To estimate the effectiveness and cost-effectiveness of a high-sensitivity troponin I (hsTnI) guided cardiovascular risk assessment program in women in Croatia. Methods: An observational study of a voluntary program for cardiovascular disease (CVD) risk assessment in women aged above 45 years with no specific symptoms, no confirmed or known coronary artery disease was conducted (WHP). Participants were stratified into three categories according to their hsTnI level. Subjects in the moderate or high-risk class were referred to cardiac work-up and invasive cardiovascular investigation as appropriate. Study information were applied to a discrete-event simulation model to estimate the cost-effectiveness of WHP against current practice. The number of CVD events and deaths, costs, and quality-adjusted life years (QALY) were assessed over 10 years from a societal perspective. Results: Of 1034 women who participated in the program, 921 (89.1%), 100 (9.7%), and 13 (1.3%) subjects fall into the low, moderate, and high-risk class. Of 26 women referred for angiography, significant coronary artery disease (CAD) was diagnosed in 12 women (46.1%). WHP gained 15.8 (95%CI 12.8; 17.2) QALYs per 1000 subjects, increased costs by 490€ (95%CI 487; 500), decreased CVD-related mortality by 40%. At a willingness-to-pay threshold of 45,000 €/QALY, WHP was cost-effective with a probability of 90%. Model results were most sensitive to utility weights and cost of medical prevention. Conclusions: Assessing the cardiovascular risk in asymptomatic women with hsTnI and guiding those at higher risk to further cardiac testing, identified individuals with CAD, could reduce CVD related burden, and would be cost-effective.

Cost-effectiveness of applying high-sensitivity troponin I to a score for cardiovascular risk prediction in asymptomatic population.

INTRODUCTION: Risk stratification scores such as the European Systematic COronary Risk Evaluation (SCORE) are used to guide individuals on cardiovascular disease (CVD) prevention. Adding high-sensitivity troponin I (hsTnI) to such risk scores has the potential to improve accuracy of CVD prediction. We investigated how applying hsTnI in addition to SCORE may impact management, outcome, and cost-effectiveness. METHODS: Characteristics of 72,190 apparently healthy individuals from the Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project were included into a discrete-event simulation comparing two strategies for assessing CVD risk. The standard strategy reflecting current practice employed SCORE (SCORE); the alternative strategy involved adding hsTnI information for further stratifying SCORE risk categories (S-SCORE). Individuals were followed over ten years from baseline examination to CVD event, death or end of follow-up. The model tracked the occurrence of events and calculated direct costs of screening, prevention, and treatment from a European health system perspective. Cost-effectiveness was expressed as incremental cost-effectiveness ratio (ICER) in € per quality-adjusted life year (QALYs) gained during 10 years of follow-up. Outputs were validated against observed rates, and results were tested in deterministic and probabilistic sensitivity analyses. RESULTS: S-SCORE yielded a change in management for 10.0% of individuals, and a reduction in CVD events (4.85% vs. 5.38%, p<0.001) and mortality (6.80% vs. 7.04%, p<0.001). S-SCORE led to 23 (95%CI: 20-26) additional event-free years and 7 (95%CI: 5-9) additional QALYs per 1,000 subjects screened, and resulted in a relative risk reduction for CVD of 9.9% (95%CI: 7.3-13.5%) with a number needed to screen to prevent one event of 183 (95%CI: 172 to 203). S-SCORE increased costs per subject by 187€ (95%CI: 177 € to 196 €), leading to an ICER of 27,440€/QALY gained. Sensitivity analysis was performed with eligibility for treatment being the most sensitive. CONCLUSION: Adding a person's hsTnI value to SCORE can impact clinical decision making and eventually improves QALYs and is cost-effective compared to CVD prevention strategies using SCORE alone. Stratifying SCORE risk classes for hsTnI would likely offer cost-effective alternatives, particularly when targeting higher risk groups.

Estimating the cost-effectiveness of screening a general population for cardiovascular risk with high-sensitivity troponin-I.

AIMS: To estimate the cost-effectiveness of using the cardiac specific marker high-sensitivity troponin-I (hsTnI) for assessing cardiovascular disease (CVD) risk in a general population. METHODS AND RESULTS: A discrete-event simulation model was developed from a societal perspective of a low-risk (Germany) and a high-risk (Kazakhstan) country. The model compared a Screen&Prevent strategy guided by hsTnI against a do-nothing strategy. Risk functions were derived from published data of a prospective cohort study [Nord-Trøndelag Health (HUNT) Study]. The model assessed the number of CVD events and deaths, healthy life years, direct and indirect costs in PPP 2018 Dollar, and quality-adjusted life years (QALY) over a time horizon of 10 years. Screen&Prevent reduced the number of CVD events per 1000 subjects by 5.1 and 5.0, equal to a number-needed-to-screen of 195 and 191 in Kazakhstan and Germany. Screen&Prevent was cost saving in Kazakhstan and cost-effective in Germany with an incremental-cost-effectiveness ratio of $6755 ($2294; $24 054) per QALY gained at an opportunity-cost based willingness-to-pay threshold of $27 373. Varying input variables in univariate and probabilistic sensitivity analyses confirmed the robustness of the analysis. CONCLUSION: Assessing the cardiovascular risk with hsTnI in a general population and subsequently referring those at high risk to preventive means would very likely be cost-effective or cost-saving by avoiding CVD events and associated direct and indirect costs. This conclusion is retained even if only the direct costs or only the costs for screening and prevention are considered. Future studies should evaluate the incremental cost-effectiveness of hsTnI-guided assessment strategies against established risk algorithms.

Health economic evaluations of medical tests: Translating laboratory information into value - A case study example.

Health-care providers and funders are focused on identifying value in all their services and that includes laboratories. This means that in order to gain a share of scarce resources, laboratory professionals must also understand and assess the value of tests and that includes their economic impact. This can be assessed using health economic modelling tools which, when used in conjunction with a detailed value proposition for the test, can translate laboratory information into value. While a variety of health economic assessment tools are available, this review will focus on the use of decision analytic models which essentially compare the outcomes from pathways with and without the new test, the value of which is being assessed. A step-by-step framework is provided to guide laboratory professionals through the essential steps of conducting the evaluation. Initial steps include mapping the clinical pathway, understanding the goal of the evaluation, identifying the key stakeholders and their needs and determining a suitable analytical model. Following collection of the actual data, the validity of the model must be checked, and the robustness of the outcomes tested through sensitivity analysis. The last step is to translate the findings into measures of value which can then inform appropriate decisions by the stakeholders. This review of basic health economic modelling should enable laboratory professionals to have an understanding of how modelling can be applied to tests in their own environment and help deliver their potential value.

Implementation of medical tests in a Value-Based healthcare environment: A framework for delivering value.

Significant variation in the utilisation of medical tests is known to have an adverse impact on health outcomes and analysis of this variation is an important tool for quality assurance in healthcare. The introduction of a new medical test into a care pathway requires two distinct processes, termed adoption and implementation. One cause of the unwarranted variation in the use of medical tests is poor adoption and implementation. Adoption is the decision to acquire a technology and make it available to the users and is supported with evidence of clinical and cost effectiveness. Implementation is delivering the benefits promised in the business case, based on evidence of the impact of a test on each stakeholder involved in delivering the care pathway. The business case will have identified the benefits delivered to all stakeholders, as set out in a value proposition, and according to the quality domains typically addressed in quality improvement, namely clinical, process and structure (resource utilisation) outcomes. The outcome measures extend beyond those of clinical and cost effectiveness required for adoption. We describe an implementation framework which is designed to document the changes to the care pathway, the resource inputs and the expected outcomes with associated quality metrics.

Who Conducts Health Economic Evaluations of Laboratory Tests? A Scoping Review.

BACKGROUND: Health economic evaluations (HEEs) are effectively used to inform decision making in healthcare. We sought to assess the level of involvement of laboratory professionals (LPs) in HEEs of laboratory tests. METHODS: A systematic literature search was conducted in Medline (2013 to November 28, 2018) for original articles reporting HEEs of medical laboratory tests. Eligible studies were characterized by indication, utilization, region, setting, study design, primary outcome measures, and sponsorship. Authors were classified based on stated affiliation as clinician, scientist, public health expert, or LP. RESULTS: In total, 140 HEEs were included in the study, of which 24 (17.1%) had contributions from LPs. Studies were primarily focused on infectious disease (n = 68), oncology (n = 23), and cardiovascular disease (n = 16). Cost-utility or cost-effectiveness analyses (n = 117) were the most frequent study types, with effectiveness measured mainly in terms of quality-adjusted life-years (n = 57) and detected cases (n = 41). Overall, 76% of HEEs followed a social or health system perspective, whereas 15% took a hospital viewpoint. Partial or full funding was received from public health organizations or industry in 39% and 16% of studies, respectively. The involvement of LPs was associated with test utilization, secondary care, analytic perspective, and an immediate time horizon (all P < 0.05). Quality of studies was found to be lower in HEEs coauthored by LPs. CONCLUSION: Multidisciplinary collaboration is essential to understanding the complexity of clinical pathways. HEEs are used effectively to inform healthcare decision making. The involvement of LPs in HEEs is low. This implies that laboratory expertise is frequently not considered in decision processes.

A value proposition for natriuretic peptide measurement in the assessment of patients with suspected acute heart failure.

There is robust clinical trial evidence supporting the role of natriuretic peptides [NPs] in the assessment of patients presenting with suspected acute heart failure [AHF]. Despite the fact that clinical guidelines have for some time advocated NP measurement, the availability and uptake of NP testing in acute care services remains patchy and incomplete. The reasons for this are multifactorial but are underpinned by compartmentalised management and budget structures within complex healthcare delivery organisations. This paper outlines a value proposition for NP testing in the acute care setting which crosses the continuum of services and budgets. It articulates the expected benefits to each stakeholder in terms of efficiency of processes, clinical outcomes and cost effectiveness. It describes a pathway to implementation and suggests metrics that may be used to measure the effectiveness of introduction of NP testing. It is hoped that the value proposition will facilitate the uptake of NT testing fostering collaboration between laboratory, clinical, management and finance teams and by informing the development of business cases.

Streamlining the screening cascade for active Hepatitis C in Russia: A cost-effectiveness analysis.

OBJECTIVE: Screening for hepatitis C in Russia is a complex process that involves several visits and stepwise testing, limiting adherence and substantially reducing the yield in the identification of active infections. We aimed to evaluate the cost-effectiveness of different screening algorithms from a health system perspective. METHODS: A decision analytic model was applied to a hypothetical adult population eligible to participate in a general screening program for hepatitis C in Russia. The standard pathway (I: Screen for anti-HCV antibodies followed by a nucleic acid test for HCV RNA on antibody positives) was compared to three alternatives (II: Screen for antibodies, a reflexed test for HCV antigen on antibody positives, and RNA on antigen negatives; III: Screen for antibodies, a reflexed test for HCV antigen on antibody positives; IV: Screen for antigen). Each strategy considered a cascade of events (referral, adherence, testing, diagnosis) that must occur for screening to be effective. The primary measure of effectiveness was the number of diagnosed active infections. Calculations followed a health system perspective with costs derived from 2017 reimbursement rates and a willingness-to-pay of 2,000RUB ($82) per diagnosed active infection. Model was tested with deterministic and probabilistic sensitivity analyses. RESULTS: Non-adherence to screening stages reduced the capture rate of active infections in Strategy I from 79.0% to 40.6%. Strategies II, III, and IV were less affected and identified 69%, 67%, and 104% more infections. Average costs per diagnosed infection were decreased by 41% from 89,599RUB ($3,681) for I to 53,072RUB ($2,180), 53,004RUB ($2,177), and 59,633RUB ($2,450) for II, III, and IV, respectively. With a probability of 97%, Strategy III was most cost-effective with an incremental cost-effectiveness ratio vs. I of -1,373RUB (CI: -5,011RUB to -2,033RUB; $-56; CI: -$206 to -$84). Below a willingness-to-pay of 91,000RUB ($3,738), Strategy IV was not cost-effective. Sensitivity analyses confirmed the robustness of results. CONCLUSIONS: Testing strategies for hepatitis C with HCV antigen on HCV antibody positive cases offer a streamlining opportunity for population screening programs. Those shall increase the chances for detecting active infections and are cost-effective over current practice in Russia.

Identifying cost-effective screening algorithms for active hepatitis C virus infections in a high prevalence setting.

OBJECTIVE: To evaluate the cost-effectiveness of different screening patterns for active chronic hepatitis C virus (HCV) infections utilizing the hepatitis C core antigen test compared to standard care in the context of a general screening program in a high-prevalence country. METHODS: This study developed a decision analytic model to estimate the cost-effectiveness of four screening algorithms for the detection of active HCV infections among asymptomatic individuals with an unknown HCV status in a context of high (>5%) HCV prevalence. Three algorithms started with a serological test for antibodies (AB) followed by a nucleic acid test for HCV-RNA (RNA), the HCVAg (AG) assay, or both. An additional single marker screening strategy with AG was added to the analysis. By the example of the Republic of Georgia, strategies were compared in terms of total costs for screening and diagnosis of an active infection from a health system perspective. RESULTS: Replacing RNA with AG for confirmation of positive AB identified fewer active infections (-110 per 100,000 screened subjects) at significantly reduced total costs (-$2.74 per screened) and costs per diagnosed infection (-$44). Adding a subsequent RNA confirmatory test on AG negative results captured at least the same rate compared to the standard (AB followed by RNA) at still reduced costs (-$1.16 per subject screened, -$22 per case detected). Utilizing AG as the frontline test revealed the highest detection rate (97.9%) at the highest costs (+$3.80 per subject, +$323 per case detected vs standard). CONCLUSION: A combined pattern of HCV AB screening followed by sequential confirmation with AG and RNA on AG negatives would provide equal or better diagnostic performance at lower cost over a broad range of scenarios. Potential long-term consequences of screening strategies to patients and society have to be considered, since the latency period for HCV to develop into severe liver disease is long.

Developing a value proposition for high-sensitivity troponin testing.

Laboratories are looking for ways that they can identify and deliver value through their service rather than just provide high quality test results. One way to demonstrate value has been described in the form of a value proposition where the application of a laboratory test is described explicitly in terms of the process of care and the patient outcomes. We have applied this concept to the use of high sensitivity troponin assays for the assessment of patients with suspected acute coronary syndrome. From a previously described framework we use a checklist to describe the various steps in the complete intervention or clinical pathway, demonstrating how the test should be used, highlighting key evidence in the literature that supports the intervention and list some of the measures which can be used to assess how well the intervention is being adopted and implemented. While the value proposition concept is based on the foundations of evidence based medicine it also requires collaboration between the laboratory and other stakeholders including clinicians to ensure that appropriate resources are applied across the complete clinical pathway in order to ensure its effectiveness.

The organisational value of diagnostic strategies using high-sensitivity troponin for patients with possible acute coronary syndromes: a trial-based cost-effectiveness analysis.

OBJECTIVES: To evaluate hospital-specific health economic implications of different protocols using high-sensitivity troponin I for the assessment of patients with chest pain. DESIGN: A cost prediction model and an economic microsimulation were developed using a cohort from a single centre recruited as part of the (ADAPT) trial, a prospective observational trial conducted from 2008 to 2011. The model was populated with 40 000 bootstrapped samples in five high-sensitivity troponin I-enabled algorithms versus standard care. SETTING: Adult emergency department (ED) of a tertiary referral hospital. PARTICIPANTS: Data were available for 938 patients who presented to the ED with at least 5 min of symptoms suggestive of acute coronary syndrome. The analyses included 719 patients with complete data. MAIN OUTCOMES/MEASURES: This study examined direct hospital costs, number of false-negative and false-positive cases in the assessment of acute coronary syndrome. RESULTS: High-sensitivity troponin I-supported algorithms increased diagnostic accuracy from 90.0% to 94.0% with an average cost reduction per patient compared with standard care of $490. The inclusion of additional criteria for accelerated rule-out (limit of detection and the modified 2-hour ADAPT trial rules) avoided 7.5% of short-stay unit admissions or 25% of admissions to a cardiac ward. Protocols using high-sensitivity troponin I alone or high-sensitivity troponin I within accelerated diagnostic algorithms reduced length of stay by 6.2 and 13.6 hours, respectively. Overnight stays decreased up to 43%. Results were seen for patients with non-acute coronary syndrome; no difference was found for patients with acute coronary syndrome. CONCLUSIONS: High-sensitivity troponin I algorithms are likely to be cost-effective on a hospital level compared with sensitive troponin protocols. The positive effect is conferred by patients not diagnosed with acute coronary syndrome. Implementation could improve referral accuracy or facilitate safe discharge. It would decrease costs and provide significant hospital benefits. TRIAL REGISTRATION: The original ADAPT trial was registered with the Australia-New Zealand Clinical trials Registry, ACTRN12611001069943.

Assessing the value of cardiac biomarkers: going beyond diagnostic accuracy?

In this era of scrutinized resource utilization, providers and payers are focused on the value of healthcare interventions more than ever. Cost-effectiveness evaluations are required by some health authorities and requested by others in order to guide budget allocation decisions. In the past, these evaluations did not methodologically consider laboratory diagnostics. We set out to explore the current requirements of health technology agencies that include laboratory diagnostics and describe, through a review of the literature, alternative methods for establishing the value of a biomarker or labroatory diagnostic beyond assay specifications and performance. The aim of this study was to evaluate the current use of a linked evidence approach in cost-effectiveness studies for cardiac laboratory tests in the last 5 years.

The Range of Uncertainty: a Tool for Efficiently Addressing Result Variability Around Clinical Decision Points for Hepatitis C Response-guided Therapy.

Despite efforts to standardize molecular diagnostic tests, performance differences are not rare. Laboratories are challenged in situations where treatment rules have been established using a reference assay that is different from the assays being used in daily practice. Assessing the viral load status of patients with chronic hepatitis C under modern triple therapy is a recognized example. We demonstrate the use of the range of uncertainty as an easy and efficient tool that can provide information on the certainty of a test result's interpretation in the context of making hepatitis C virus treatment decisions.