The prognostic value of peak oxygen uptake in obstructive hypertrophic cardiomyopathy: a literature review to inform economic model development.

AIMS: Patients with obstructive hypertrophic cardiomyopathy (oHCM) experience significant clinical burden which is associated with a high economic burden. Peak oxygen uptake (pVO2), measured by cardiopulmonary exercise testing, is used to quantify functional capacity, and has been studied as a primary endpoint in recent clinical trials. This study aimed to gather evidence to consolidate the prognostic value of pVO2 in oHCM and to assess whether it is feasible to predict health outcomes in an economic model based on changes in pVO2. METHODS: A targeted literature review was conducted in MEDLINE (via PubMed) and Embase databases to identify evidence on the prognostic value of pVO2 as a surrogate health outcome to support future oHCM economic model development. Following screening, study characteristics, population characteristics, and pVO2 prognostic association data were extracted. RESULTS: A total of 4,687 studies were identified. In total, 3,531 and 538 studies underwent title/abstract and full-text screening, respectively, of which 151 were included and nine of these were in hypertrophic cardiomyopathy (HCM); only three studies focused on oHCM. The nine HCM studies consisted of one systematic literature review and eight primary studies reporting on 27 potentially predictive relationships from a pVO2-based metric with clinical outcomes including all-cause mortality, cardiovascular mortality, sudden cardiac death, transplant, paroxysmal, and permanent atrial fibrillation. pVO2 was described as a predictor of single and composite endpoints, in three and six studies, respectively, with one study reporting on both. LIMITATIONS: This study primarily uses systemic literature review methods but does not qualify as one due to not entailing parallel reviewers during title-abstract and full-text stages of review. CONCLUSION: The findings of this study suggest pVO2 is predictive of multiple health outcomes, providing a rationale to use pVO2 in the development of an economic model.

Obstructive hypertrophy cardiomyopathy (oHCM) is a condition where the heart muscle thickens, obstructing blood flow and potentially impacting health. Peak oxygen uptake (pVO2) measures the highest amount of oxygen consumption during peak exercise and serves as an indicator of fitness. pVO2 can be used to assess heart health and predict severe conditions and death, acting as a surrogate endpoint. Surrogate endpoints are valuable in drug investigations since they allow earlier decisions on drug approval and funding before longer-term patient follow-up is available.This study reviewed evidence on the relationship between pVO2 values in patients with heart disease and the risk of becoming sicker or dying. Our goal was to assess if these relationships had been established and whether it is feasible to use them to predict future treatment benefits and support economic evaluations of new treatments. Our review found that most studies reported on patients with heart failure, with only nine focusing on HCM. Evidence indicates that low pVO2 values in patients with heart disease are linked to an increased risk of developing other heart conditions, needing a heart transplant, or dying.

Cost-Effectiveness Analysis of a Prescription Digital Therapeutic in Type 2 Diabetes.

INTRODUCTION: BT-001 (AspyreRx™) prescription digital therapy, a form of personalized cognitive behavioral therapy, has demonstrated clinically meaningful and durable hemoglobin A1c reductions in patients with type 2 diabetes (T2D). The current study examined the cost-effectiveness of BT-001 plus standard of care (SoC) versus SoC alone in T2D over a lifetime horizon from a healthcare payer perspective. METHODS: We modeled the T2D pathway using an individual patient-level simulation; clinical data were sourced from the intention-to-treat subset of the BT-001 randomized clinical trial (RCT). SoC across both arms included the composition of oral and injectable treatments for T2D. Events were simulated using the United Kingdom Prospective Diabetes Study Outcomes Model 2 risk equation. A 3-month model cycle length was used in the first year, then annual model cycles were used in line with the original risk engine specifications. Patient characteristics informed event equations and Monte Carlo random sampling was used to assess the occurrence of events within each model cycle. Incidence of hypoglycemic events, drug discontinuation, costs, and health utilities and disutility values were sourced from the literature. RESULTS: From a payer perspective, BT-001 plus SoC versus SoC alone was dominant with a gain in quality-adjusted life years (QALYs) of 0.101 and cost savings of $7343 per patient over the lifetime horizon (i.e., more effective and less costly). BT-001 plus SoC was cost-effective at a willingness-to-pay of $100,000 per QALY (incremental net monetary benefit was $17,443). Savings with BT-001 were primarily driven by a reduction in drug acquisition costs. The reduction in hemoglobin A1c with BT-001 was associated with fewer T2D complications. CONCLUSIONS: BT-001 plus SoC was estimated to dominate SoC alone over the lifetime horizon from a payer perspective, suggesting that using BT-001 can empower patients to better manage their diabetes with the potential for lifelong advantages.

R and Shiny for Cost-Effectiveness Analyses: Why and When? A Hypothetical Case Study.

INTRODUCTION: Health economics models are typically built in Microsoft Excel® owing to its wide familiarity, accessibility and perceived transparency. However, given the increasingly rapid and analytically complex decision-making needs of both the pharmaceutical industry and the field of health economics and outcomes research (HEOR), the demands of cost-effectiveness analyses may be better met by the programming language R. OBJECTIVE: This case study provides an explicit comparison between Excel and R for contemporary cost-effectiveness analysis. METHODS: We constructed duplicate cost-effectiveness models using Excel and R (with a user interface built using the Shiny package) to address a hypothetical case study typical of contemporary health technology assessment. RESULTS: We compared R and Excel versions of the same model design to determine the advantages and limitations of the modelling platforms in terms of (i) analytical capability, (ii) data safety, (iii) building considerations, (iv) usability for technical and non-technical users and (v) model adaptability. CONCLUSIONS: The findings of this explicit comparison are used to produce recommendations for when R might be more suitable than Excel in contemporary cost-effectiveness analyses. We conclude that selection of appropriate modelling software needs to consider case-by-case modelling requirements, particularly (i) intended audience, (ii) complexity of analysis, (iii) nature and frequency of updates and (iv) anticipated model run time.

A Picture is Worth a Thousand Words: The Role of Survey Training Materials in Stated-Preference Studies.

BACKGROUND: Online survey-based methods are increasingly used to elicit preferences for healthcare. This digitization creates an opportunity for interactive survey elements, potentially improving respondents' understanding and/or engagement. OBJECTIVE: Our objective was to understand whether, and how, training materials in a survey influenced stated preferences. METHODS: An online discrete-choice experiment (DCE) was designed to elicit public preferences for a new targeted approach to prescribing biologics ("biologic calculator") for rheumatoid arthritis (RA) compared with conventional prescribing. The DCE presented three alternatives, two biologic calculators and a conventional approach (opt out), described by five attributes: delay to treatment, positive predictive value, negative predictive value, infection risk, and cost saving to the national health service. Respondents were randomized to receive training materials as plain text or an animated storyline. Training materials contained information about RA and approaches to treatment and described the biologic calculator. Background questions included sociodemographics and self-reported measures of task difficulty and attribute non-attendance. DCE data were analyzed using conditional and heteroskedastic conditional logit (HCL) models. RESULTS: In total, 300 respondents completed the DCE, receiving either plain text (n = 158) or the animated storyline (n = 142). The HCL showed the estimated coefficients for all attributes aligned with a priori expectations and were statistically significant. The scale term was statistically significant, indicating that respondents who received plain-text materials had more random choices. Further tests suggested preference homogeneity after accounting for differences in scale. CONCLUSIONS: Using animated training materials did not change the preferences of respondents, but they appeared to improve choice consistency, potentially allowing researchers to include more complex designs with increased numbers of attributes, levels, alternatives or choice sets.

A Micro-Costing Study of Screening for Lynch Syndrome-Associated Pathogenic Variants in an Unselected Endometrial Cancer Population: Cheap as NGS Chips?

Background: Lynch syndrome is the most common inherited cause of endometrial cancer. Identifying individuals affected by Lynch syndrome enables risk-reducing interventions including colorectal surveillance, and cascade testing of relatives. Methods: We conducted a micro-costing study of screening all women with endometrial cancer for Lynch syndrome using one of four diagnostic strategies combining tumor microsatellite instability testing (MSI), immunohistochemistry (IHC), and/or MLH1 methylation testing, and germline next generation sequencing (NGS). Resource use (consumables, capital equipment, and staff) was identified through direct observation and laboratory protocols. Published sources were used to identify unit costs to calculate a per-patient cost (£; 2017) of each testing strategy, assuming a National Health Service (NHS) perspective. Results: Tumor triage with MSI and reflex MLH1 methylation testing followed by germline NGS of women with likely Lynch syndrome was the cheapest strategy at £42.01 per case. Tumor triage with IHC and reflex MLH1 methylation testing of MLH1 protein-deficient cancers followed by NGS of women with likely Lynch syndrome cost £45.68. Tumor triage with MSI followed by NGS of all women found to have tumor microsatellite instability cost £78.95. Immediate germline NGS of all women with endometrial cancer cost £176.24. The cost of NGS was affected by the skills and time needed to interpret results (£44.55/patient). Conclusion: This study identified the cost of reflex screening all women with endometrial cancer for Lynch syndrome, which can be used in a model-based cost-effectiveness analysis to understand the added value of introducing reflex screening into clinical practice.

Generating EQ-5D-3L Utility Scores from the Dermatology Life Quality Index: A Mapping Study in Patients with Psoriasis.

OBJECTIVES: To develop an algorithm to predict the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) utility scores from the Dermatology Life Quality Index (DLQI) in psoriasis. METHODS: This mapping study used data from the British Association of Dermatologists Biologic Interventions Register-a pharmacovigilance register comprising patients with moderate to severe psoriasis on systemic therapies. Conceptual overlap between the EQ-5D-3L and DLQI was assessed using Spearman rank correlation coefficients and exploratory factor analysis. Six regression methods to predict the EQ-5D-3L index (direct mapping) and two regression methods to predict EQ-5D-3L domain responses (response mapping) were tested. Random effects models were explored to account for repeated observations from the same individual. Estimated and actual EQ-5D-3L utility scores were compared using 10-fold cross-validation (in-sample) to evaluate predictive performance. Final models were selected using root mean squared error, mean absolute error, and mean error. RESULTS: The data set comprised 22,085 observations for which DLQI and EQ-5D-3L were recorded on the same day. A moderate correlation was found between the measures (r = -0.47). Exploratory factor analysis showed that two EQ-5D-3L domains (pain/discomfort and depression/anxiety) were associated with all six DLQI domains. The best-performing model used ordinary least squares with DLQI items, age, and sex as explanatory variables (with squared, cubic, and interaction terms). A tool was produced to allow users to map their data to the EQ-5D-3L, and includes algorithms that require fewer variables (e.g., total DLQI scores). CONCLUSIONS: This study produced mapping algorithms that can generate EQ-5D-3L utility scores from DLQI data for economic evaluations of health interventions for patients with psoriasis.

Exploring the feasibility of delivering standardized genomic care using ophthalmology as an example.

PURPOSE: Broadening access to genomic testing and counseling will be necessary to realize the benefits of personalized health care. This study aimed to assess the feasibility of delivering a standardized genomic care model for inherited retinal dystrophy (IRD) and of using selected measures to quantify its impact on patients. METHODS: A pre-/post- prospective cohort study recruited 98 patients affected by IRD to receive standardized multidisciplinary care. A checklist was used to assess the fidelity of the care process. Three patient-reported outcome measures-the Genetic Counselling Outcome Scale (GCOS-24), the ICEpop CAPability measure for Adults (ICECAP-A), and the EuroQol 5-dimension questionnaire (EQ-5D)-and a resource-use questionnaire were administered to investigate rates of missingness, ceiling effects, and changes over time. RESULTS: The care model was delivered consistently. Higher rates of missingness were found for the genetic-specific measure (GCOS-24). Considerable ceiling effects were observed for the generic measure (EQ-5D). The ICECAP-A yielded less missing data without significant ceiling effects. It was feasible to use telephone interviews for follow-up data collection. CONCLUSION: The study highlighted challenges and solutions associated with efforts to standardize genomic care for IRD. The study identified appropriate methods for a future definitive study to assess the clinical effectiveness and cost-effectiveness of the care model.Genet Med advance online publication 02 March 2017.

Toward health technology assessment of whole-genome sequencing diagnostic tests: challenges and solutions.

Whole-genome sequencing (WGS) is being applied within research settings across Europe to develop genomic WGS-based diagnostic tests. The focus of this perspective paper is to describe if, and how, current approaches of health technology assessment could be applied to WGS-based diagnostic tests. This perspective draws on the collective view from a trans-European multidisciplinary consortium of methodologists, clinicians and scientists. Specific challenges can be described by using the PICO (population, intervention, comparator, outcome) framework to inform health technology assessment. Practical solutions are suggested which require joined-up, multidisciplinary working across healthcare systems using existing expert networks so that emergent issues for the health technology assessment of WGS can be met in a timely fashion.