The State of State Biomarker Testing Insurance Coverage Laws.

This Viewpoint discusses laws mandating insurance coverage of biomarker testing to broaden access to care for patients with cancer.

New Approaches to Assessment and Management of Tricuspid Regurgitation Before Intervention.

Severe tricuspid regurgitation (TR) is a progressive condition associated with substantial morbidity, poor quality of life, and increased mortality. Patients with TR commonly have coexisting conditions including congestive heart failure, pulmonary hypertension, chronic lung disease, atrial fibrillation, and cardiovascular implantable electronic devices, which can increase the complexity of medical and surgical TR management. As such, the optimal timing of referral for isolated tricuspid valve (TV) intervention is undefined, and TV surgery has been associated with elevated risk of morbidity and mortality. More recently, an unprecedented growth in TR treatment options, namely the development of a wide range of transcatheter TV interventions (TTVI) is stimulating increased interest and referral for TV intervention across the entire medical community. However, there are no stepwise algorithms for the optimal management of symptomatic severe TR before TTVI. This article reviews the contemporary assessment and management of TR with addition of a medical framework to optimize TR before referral for TTVI.

Oral and monoclonal antibody treatments for relapsing forms of multiple sclerosis: Effectiveness and value.

DISCLOSURES: Ms McKenna, Dr Lin, Dr Whittington, Mr Nikitin, Ms Herron-Smith, Dr Campbell, and Dr Peterson report grants from Arnold Ventures, grants from Blue Cross Blue Shield of MA, grants from California Healthcare Foundation, grants from The Commonwealth Fund, and grants from The Peterson Center on Healthcare, during the conduct of the study; other from America's Health Insurance Plans, other from Anthem, other from AbbVie, other from Alnylam, other from AstraZeneca, other from Biogen, other from Blue Shield of CA, other from CVS, other from Editas, other from Express Scripts, other from Genentech/Roche, other from GlaxoSmithKline, other from Harvard Pilgrim, other from Health Care Service Corporation, other from Kaiser Permanente, other from LEO Pharma, other from Mallinckrodt, other from Merck, other from Novartis, other from National Pharmaceutical Council, other from Premera, other from Prime Therapeutics, other from Regeneron, other from Sanofi, other from United Healthcare, other from HealthFirst, other from Pfizer, other from Boehringer-Ingelheim, other from uniQure, other from Envolve Pharmacy Solutions, other from Humana, and other from Sun Life, outside the submitted work.

Association of Device Industry Payments, Physician Supply, and Regional Utilization of Orthopedic and Cardiac Procedures.

BACKGROUND: Geographic variation in high-cost medical procedure utilization in the USA is not fully explained by patient factors but may be influenced by the supply of procedural physicians and marketing payments. OBJECTIVE: To examine the association between physician supply, medical device-related marketing payments to physicians, and utilization of knee arthroplasty (KA) and percutaneous coronary interventions (PCI) within hospital referral regions (HRRs). DESIGN: Cross-sectional analysis of data from the 2018 CMS Open Payments database and procedural utilization data from the CMS Provider Utilization and Payment database. PARTICIPANTS: Medicare-participating procedural cardiologists and orthopedic surgeons. MAIN MEASURES: Regional rates of PCIs and KAs per 100,000 Medicare fee-for-service (FFS) beneficiaries were estimated after adjustment for beneficiary demographics. KEY RESULTS: Across 306 HRRs, there were 109,301 payments (value $17,554,728) to cardiologists for cardiac stents and 68,132 payments (value $40,492,126) to orthopedic surgeons for prosthetic knees. Among HRRs, one additional interventional cardiologist was associated with an increase of 12.9 (CI, 9.3-16.5) PCIs per 100,000 beneficiaries, and one additional orthopedic surgeon was associated with an increase of 20.6 (CI, 16.9-24.4) KAs per 100,000 beneficiaries. A $10,000 increase in gift payments from stent manufacturers was associated with an increase of 26.0 (CI, 5.1-46.9) PCIs per 100,000 beneficiaries, while total and service payments were not associated with greater regional PCI utilization. A $10,000 increase in total payments from knee prosthetic manufacturers was associated with an increase of 2.9 (CI, 1.4-4.5) KAs per 100,000 beneficiaries, while a similar increase in gift and service payments was associated with an increase of 14.5 (CI, 5.0-24.1) and 3.4 (CI, 1.6-5.2) KAs, respectively. CONCLUSIONS: Among Medicare FFS beneficiaries, regional supply of physicians and receipt of industry payments were associated with greater use of PCIs and KAs. Relationships between payments and procedural utilization were more consistent for KAs, a largely elective procedure, compared to PCIs, which may be elective or emergent.

Community paramedic hospital reduction and mitigation program: study protocol for a randomized pragmatic clinical trial.

BACKGROUND: New patient-centered models of care are needed to individualize care and reduce high-cost care, including emergency department (ED) visits and hospitalizations for low- and intermediate-acuity conditions that could be managed outside the hospital setting. Community paramedics (CPs) have advanced training in low- and high-acuity care and are equipped to manage a wide range of health conditions, deliver patient education, and address social determinants of health in the home setting. The objective of this trial is to evaluate the effectiveness and implementation of the Care Anywhere with Community Paramedics (CACP) program with respect to shortening and preventing acute care utilization. METHODS: This is a pragmatic, hybrid type 1, two-group, parallel-arm, 1:1 randomized clinical trial of CACP versus usual care that includes formative evaluation methods and assessment of implementation outcomes. It is being conducted in two sites in the US Midwest, which include small metropolitan areas and rural areas. Eligible patients are ≥ 18 years old; referred from an outpatient, ED, or hospital setting; clinically appropriate for ambulatory care with CP support; and residing within CP service areas of the referral sites. Aim 1 uses formative data collection with key clinical stakeholders and rapid qualitative analysis to identify potential facilitators/barriers to implementation and refine workflows in the 3-month period before trial enrollment commences (i.e., pre-implementation). Aim 2 uses mixed methods to evaluate CACP effectiveness, compared to usual care, by the number of days spent alive outside of the ED or hospital during the first 30 days following randomization (primary outcome), as well as self-reported quality of life and treatment burden, emergency medical services use, ED visits, hospitalizations, skilled nursing facility utilization, and adverse events (secondary outcomes). Implementation outcomes will be measured using the RE-AIM framework and include an assessment of perceived sustainability and metrics on equity in implementation. Aim 3 uses qualitative methods to understand patient, CP, and health care team perceptions of the intervention and recommendations for further refinement. In an effort to conduct a rigorous evaluation but also speed translation to practice, the planned duration of the trial is 15 months from the study launch to the end of enrollment. DISCUSSION: This study will provide robust and timely evidence for the effectiveness of the CACP program, which may pave the way for large-scale implementation. Implementation outcomes will inform any needed refinements and best practices for scale-up and sustainability. TRIAL REGISTRATION: ClinicalTrials.gov NCT05232799. Registered on 10 February 2022.

Unsupervised Machine Learning for Assessment of Left Ventricular Diastolic Function and Risk Stratification.

BACKGROUND: The 2016 American Society of Echocardiography guidelines have been widely used to assess left ventricular diastolic function. However, limitations are present in the current classification system. The aim of this study was to develop a data-driven, unsupervised machine learning approach for diastolic function classification and risk stratification using the left ventricular diastolic function parameters recommended in the 2016 American Society of Echocardiography guidelines; the guideline grading was used as the reference standard. METHODS: Baseline demographics, heart failure hospitalization, and all-cause mortality data were obtained for all adult patients who underwent transthoracic echocardiography at Mayo Clinic Rochester in 2015. Patients with prior mitral valve intervention, congenital heart disease, cardiac transplantation, or cardiac assist device implantation were excluded. Nine left ventricular diastolic function variables (mitral E- and A-wave peak velocities, E/A ratio, deceleration time, medial and lateral annular e' velocities and E/e' ratio, and tricuspid regurgitation peak velocity) were used for an unsupervised machine learning algorithm to identify different phenotype clusters. The cohort average of each variable was used for imputation. Patients were grouped according to the algorithm-determined clusters for Kaplan-Meier survival analysis. RESULTS: Among 24,414 patients (mean age, 63.6 ± 16.2 years), all-cause mortality occurred in 4,612 patients (18.9%) during a median follow-up period of 3.1 years. The algorithm determined three clusters with echocardiographic measurement characteristics corresponding to normal diastolic function (n = 8,312), impaired relaxation (n = 11,779), and increased filling pressure (n = 4,323), with 3-year cumulative mortality of 11.8%, 19.9%, and 33.4%, respectively (P < .0001). All 10,694 patients (43.8%) classified as indeterminate were reclassified into the three clusters (n = 3,324, n = 5,353, and n = 2,017, respectively), with 3-year mortality of 16.6%, 22.9%, and 34.4%, respectively. The clusters also outperformed guideline-based grade for prognostication (C index = 0.607 vs 0.582, P = .013). CONCLUSIONS: Unsupervised machine learning identified physiologically and prognostically distinct clusters on the basis of nine diastolic function Doppler variables. The clusters can be potentially applied in echocardiography laboratory practice and future clinical trials for simple, replicable diastolic function-related risk stratification.

Performance of Echocardiographic Algorithms for Assessment of High Aortic Bioprosthetic Valve Gradients.

BACKGROUND: Bioprosthetic aortic valve dysfunction (BAVD) is a challenging diagnosis. Commonly used algorithms to classify high-gradient BAVD are the 2009 American Society of Echocardiography, 2014 Blauwet-Miller, and 2016 European Association of Cardiovascular Imaging algorithms. We sought (1) to evaluate the accuracy of existing algorithms against objectively proven BAVD and (2) to propose an improved algorithm. METHODS: This was a retrospective study of 266 patients with objectively proven BAVD (pathology of explanted valves, four-dimensional computed tomography prior to transcatheter valve-in-valve replacement, or therapeutically confirmed bioprosthetic thrombosis) who were treated. Of those, 191 had obstruction, 48 had regurgitation, 15 had mixed stenosis and regurgitation, and 12 had patient-prosthesis mismatch (PPM). Normal controls were matched 1:1 (age, prosthesis size, and type), of which 43 had high gradients (PPM in 30, high flow in nine, and normal prosthesis in nine). Algorithm assignment was based on the echocardiogram leading to BAVD diagnosis and the predischarge "fingerprint" echocardiogram after surgical or transcatheter aortic valve replacement. A novel algorithm (Mayo Clinic algorithm) incorporating valve appearance in addition to Doppler parameters was developed to improve observed deficiencies. RESULTS: The accuracy of existing algorithms was suboptimal (2009 American Society of Echocardiography, 62%; 2014 Blauwet-Miller, 62%; 2016 European Association of Cardiovascular Imaging, 57%). The most common overdiagnosis was PPM (22%-29% of patients and controls with high gradients). The novel Mayo Clinic algorithm correctly identified the mechanism in 256 of 307 patients and controls (83%). Recognition of regurgitation was substantially improved (42 of 47 patients, 89%), and the number of PPM misdiagnoses was significantly reduced (five patients). CONCLUSION: Currently recommended algorithms misclassify a significant number of BAVD patients. The accuracy was improved by a newly proposed algorithm.

Cost-Effectiveness and Value-Based Pricing of Aducanumab for Patients With Early Alzheimer Disease.

BACKGROUND AND OBJECTIVES: Aducanumab was granted accelerated approval with a conflicting evidence base, near-unanimous Food and Drug Administration Advisory Committee vote to reject approval, and a widely criticized launch price of $56,000 per year. The objective of this analysis was to estimate its cost-effectiveness. METHODS: We developed a Markov model to compare aducanumab in addition to supportive care to supportive care alone over a lifetime horizon. Results were presented from both the health system and modified societal perspective. The model tracked the severity of disease and the care setting. Incremental cost-effectiveness ratios were calculated and a threshold analysis was conducted to estimate at what price aducanumab would meet commonly used cost-effectiveness thresholds. RESULTS: Using estimates of effectiveness based on pooling of data from both pivotal trials, patients treated with aducanumab spent 4 more months in earlier stages of Alzheimer disease. Over the lifetime time horizon, treating a patient with aducanumab results in 0.154 more quality-adjusted life-years (QALYs) gained per patient and 0.201 equal value of life-years gained (evLYG) per patient from the health care system perspective, with additional costs of approximately $204,000 per patient. The incremental outcomes were similar for the modified societal perspective. At the launch price of $56,000 per year, the cost-effectiveness ranged from $1.02 million per evLYG to $1.33 million per QALY gained from the health care system perspective and from $938,000 per evLYG to $1.27 million per QALY gained in the modified societal perspective. The annual price to meet commonly used cost-effectiveness thresholds ranged from $2,950 to $8,360, which represents a discount of 85%-95% off from the annual launch price set by the manufacturer. Using estimates of effectiveness based only on the trial that suggested a benefit, the mean incremental cost was greater than $400,000 per QALY gained. CONCLUSION: Patients treated with aducanumab received minimal improvements in health outcomes at considerable cost. This resulted in incremental cost-effectiveness ratios that far exceeded commonly used value thresholds, even under optimistic treatment effectiveness assumptions. These findings are subject to the substantial uncertainty regarding whether aducanumab provides any true net health benefit, but evidence available currently suggests that an annual price of aducanumab of $56,000 is not in reasonable alignment with its clinical benefits.

Hereditary cancer panel testing challenges and solutions for the latinx community: costs, access, and variants.

Hereditary breast and ovarian cancers (HBOCs) are common among the Latinx population, and risk testing is recommended using multi-gene hereditary cancer panels (HCPs). However, little is known about how payer reimbursement and out-of-pocket expenses impact provider ordering of HCP in the Latinx population. Our objective is to describe key challenges and possible solutions for HCP testing in the Latinx population. As part of a larger study, we conducted semi-structured interviews with key provider informants (genetic counselors, oncologist, nurse practitioner) from safety-net institutions in the San Francisco Bay Area. We used a deductive thematic analysis approach to summarize themes around challenges and possible solutions to facilitating HCP testing in Latinx patients. We found few financial barriers for HCP testing for the Latinx population due to laboratory patient assistance programs that cover testing at low or no cost to patients. However, we found potential challenges related to the sustainability of low-cost testing and out-of-pocket expenses for patients, access to cascade testing for family members, and pathogenic variants specific to Latinx. Providers questioned whether current laboratory payment programs that decrease barriers to testing are sustainable and suggested solutions for accessing cascade testing and ensuring variants specific to the Latinx population were included in testing. The use of laboratories with payment assistance programs reduces barriers to HCP testing among the US population; however, other barriers are present that may impact testing use in the Latinx population and must be addressed to ensure equitable access to HCP testing for this population.

Influence of payer coverage and out-of-pocket costs on ordering of NGS panel tests for hereditary cancer in diverse settings.

The landscape of payment for genetic testing has been changing, with an increase in the number of laboratories offering testing, larger panel offerings, and lower prices. To determine the influence of payer coverage and out-of-pocket costs on the ordering of NGS panel tests for hereditary cancer in diverse settings, we conducted semi-structured interviews with providers who conduct genetic counseling and order next-generation sequencing (NGS) panels purposefully recruited from 11 safety-net clinics and academic medical centers (AMCs) in California and North Carolina, states with diverse populations and divergent Medicaid expansion policies. Thematic analysis was done to identify themes related to the impact of reimbursement and out-of-pocket expenses on test ordering. Specific focus was put on differences between settings. Respondents from both safety-net clinics and AMCs reported that they are increasingly ordering panels instead of single-gene tests, and tests were ordered primarily from a few commercial laboratories. Surprisingly, safety-net clinics reported few barriers to testing related to cost, largely due to laboratory assistance with prior authorization requests and patient payment assistance programs that result in little to no patient out-of-pocket expenses. AMCs reported greater challenges navigating insurance issues, particularly prior authorization. Both groups cited non-coverage of genetic counseling as a major barrier to testing. Difficulty of access to cascade testing, particularly for family members that do not live in the United States, was also of concern. Long-term sustainability of laboratory payment assistance programs was a major concern; safety-net clinics were particularly concerned about access to testing without such programs. There were few differences between states. In conclusion, the use of laboratories with payment assistance programs reduces barriers to NGS panel testing among diverse populations. Such programs represent a major change to the financing and affordability of genetic testing. However, access to genetic counseling is a barrier and must be addressed to ensure equity in testing.

The effectiveness and value of aducanumab for Alzheimer's disease.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Sun Life Financial, uniQure, and United Healthcare. Whittington, Rind, and Pearson are employed by ICER. Through their affiliated institutions, Synnott and Lin received funding from ICER for the work described in this summary. In addition, Synnott reports support from Biogen for the Tufts Medical Center Cost-Effectiveness Analysis Registry, which is maintained by the Center for the Evaluation of Value and Risk in Health.

The effectiveness and value of bempedoic acid and inclisiran for heterozygous familial hypercholesterolemia and secondary prevention of ASCVD.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Agboola, McKenna, and Pearson are employed by ICER. Lin and Kazi received funding from ICER for work on this report.

Exploring the terminology and descriptions of services that connect children with neurodisability and their families to needed support in the community: a scoping review protocol.

OBJECTIVE: This scoping review aims to fill a gap in knowledge on terminology and descriptions of services that connect children with neurodisability and their families to needed support in the community. INTRODUCTION: Children with neurodisability represent a significant population with a demonstrated need for coordinated support. Patient navigation is a concept that was founded on the principle of coordinating care for patients based on individual needs. Despite the history of patient navigation, a definition for the concept itself is lacking. Moreover, children with neurodisability and their families are not often the target population of such initiatives. It is not known whether existing terminology and descriptions encompass the particular needs of children with neurodisability and their families. INCLUSION CRITERIA: This review will examine published, peer-reviewed articles related to navigation-type resources, support, and services within the community as intended for children under the age of 18 years with neurodisability, and their families. All eligible studies pertaining to this context will be examined. METHODS: A preliminary search was completed to find initial search terms, upon which a full search strategy was developed. Search results yielded from PubMed (NCBI), MEDLINE (Ovid), and CINAHL (EBSCO) were screened to ensure articles were peer-reviewed, published in English from 1990 onward, and relevant to both children with neurodisability/their families and navigation-related resources. A full-text review of relevant articles will be conducted and data extracted using the included extraction tool. Extracted terminology and concepts will be analyzed using a modified grounded theory approach, which will inform a working definition of navigational services and related terms. SCOPING REVIEW REGISTRATION: Open Science Framework: https://osf.io/cbvy9.

The Effectiveness and Value of Deflazacort and Exon-Skipping Therapies for the Management of Duchenne Muscular Dystrophy.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Agboola, Fluetsch, Rind, and Pearson are employed by ICER. Lin reports support from ICER during work on this economic model and grants from Mount Zion Health Fund, National Institutes of Health (National Cancer Institute and National Heart, Lung, and Blood Institute), and the Tobacco-Related Diseases Research Program, unrelated to this work. Walton reports support from ICER for work on this economic model and unrelated consulting fees from Baxter.

Association of Primary Language and Hospitalization for Ambulatory Care Sensitive Conditions.

BACKGROUND: Limited English proficiency is associated with decreased access to ambulatory care, however, it is unclear if this disparity leads to increased use of emergency departments (EDs) for low severity ambulatory care sensitive conditions (ACSCs). OBJECTIVE: We sought to determine the association between the patient's preferred language and hospital utilization for ACSCs. RESEARCH DESIGN: We conducted a retrospective cohort study of all ED visits in New Jersey in 2013 and 2014. The primary outcome was hospital admission for acute ACSCs, chronic ACSCs, and fractures (a nonambulatory care sensitive control condition). Secondary outcomes included intensive care unit (ICU) utilization and length of stay. Mixed-effect regression models estimated the association between preferred language (English vs. non-English) and study outcomes, controlling for demographics, comorbidities, and hospital characteristics. RESULTS: We examined 201,351 ED visits for acute ACSCs, 251,193 visits for chronic ACSCs, and 148,428 visits for fractures, of which 13.5%, 11.1%, and 9.9%, respectively, were by non-English speakers. In adjusted analyses, non-English speakers were less likely to be admitted for acute ACSCs [-3.1%; 95% confidence interval (CI), -3.6% to -2.5%] and chronic ACSCs (-2.3%; 95% CI, -2.8% to -1.7%) but not fractures (0.4%; 95% CI, -0.2% to 1.0%). Among hospitalized patients, non-English speakers were less likely to receive ICU services but had no difference in length of stay. CONCLUSIONS: These findings suggest non-English-speaking patients may seek ED care for lower acuity ACSCs than English-speaking patients. Efforts to decrease preventable ED and increase access to ambulatory care use should consider the needs of non-English-speaking patients.

The Effectiveness and Value of Lanadelumab and C1 Esterase Inhibitors for Prophylaxis of Hereditary Angioedema Attacks.

DISCLOSURES: Funding for this summary was contributed by the Laura and John Arnold Foundation, Blue Shield of California, and California Health Care Foundation to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, AHIP Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, Cambia Health Solutions, United Healthcare, Kaiser Permanente, Premera Blue Cross, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical Council, Prime Therapeutics, Sanofi, Spark Therapeutics, Health Care Service Corporation, Editas, Alnylam, Regeneron, Mallinkrodt, Biogen, HealthPartners, and Novartis. Agboola, Dreitlein, and Pearson are ICER employees. Lin reports personal fees from ICER, during the conduct of this study, and grants from the National Institutes of Health and the California Department of Insurance, outside the submitted work. Carlson and Lubinga report grants from ICER, during the conduct of this study.