Cost burden of cirrhosis and liver disease progression in metabolic dysfunction-associated steatohepatitis: A US cohort study.

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH), formerly nonalcoholic steatohepatitis, is characterized by fat accumulation and inflammation of the liver and may result in progression to cirrhosis and liver-related events. OBJECTIVE: To characterize the impact of cirrhosis and progression to liver-related events on costs and health care resource use (HCRU) among MASH patients in the United States. METHODS: The study cohort included patients with diagnosed nonalcoholic steatohepatitis (International Classification of Diseases, Tenth Revision, Clinical Modification code K75.81) in Optum's deidentified Clinformatics Data Mart Database (October 2015 to December 2022) and were stratified by baseline cirrhosis status. Among those without cirrhosis at baseline, patients were further stratified by status of progression to cirrhosis during follow-up. Total HCRU and costs per-person per-year (PPPY) were estimated and compared descriptively between the cohorts. In addition, gamma generalized linear models were used to compare costs PPPY between those with vs without cirrhosis at baseline, as well as with vs without progression during follow-up, while adjusting for baseline patient and disease characteristics. Annual costs per person were also longitudinally modeled using gamma generalized linear mixed models to understand longitudinal changes in costs PPPY while accounting for time correlations within individual patients. Lastly, a series of sensitivity analyses were conducted to assess the impact of study design features and clinical variations of total costs PPPY. RESULTS: A total of 28,576 adults were included, and 9,157 (32.0%) had baseline cirrhosis; of the 19,419 without baseline cirrhosis, a total of 4,235 (21.8%) progressed over follow-up. Mean (SD) HCRU and costs PPPY were higher among patients with cirrhosis ($110,403 [$226,037]) than without ($28,340 [$61,472]; P < 0.01) and among those with progression ($58,128 [$102,626]) than without ($20,031 [$39,740]; P < 0.01). Costs remained significantly greater when adjusted for covariates, with a risk ratio (95% CI) of 1.99 (1.89-2.09) when comparing with vs without baseline cirrhosis and 2.28 (2.15-2.42) when comparing with vs without progression over follow-up. Costs increased with each subsequent year, to 21% by year 6 among those with cirrhosis at baseline and 49% among those without baseline cirrhosis who progressed. CONCLUSIONS: The financial burden of MASH is substantial and significantly greater among those with cirrhosis or disease progression. Although patients without cirrhosis incur lower burden, the increase over time is greater and associated with progression. Therapies that slow progression may help alleviate the financial burden, and strategies are needed to identify patients with MASH at risk of progressing to cirrhosis.

Observing the Clinical Course of Duchenne Muscular Dystrophy in Medicaid Real-World Healthcare Data.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is a rare, severe progressive neuromuscular disease. Health insurance claims allow characterization of population-level real-world outcomes, based on observed healthcare resource use. An analysis of data specific to those with Medicaid insurance is presently unavailable. The objective was to describe the real-world clinical course of DMD based on claims data from Medicaid-insured individuals in the USA. METHODS: Individuals with DMD were identified from the MarketScan Multi-State Medicaid datasets (2013-2018). Diagnosis and procedure codes from healthcare claims were used to characterize the occurrence of DMD-relevant clinical observations; categories were scoliosis, cardiovascular-related, respiratory and severe respiratory-related, and neurologic/neuropsychiatric. Age-restricted analyses were conducted to focus on the ages at which DMD-relevant clinical observations were more likely to be captured, and to better understand the impact of both age and follow-up time. RESULTS: Of 2007 patients with DMD identified, median (interquartile range) age at index was 14 (9-20) years, and median follow-up was 3.1 (1.6-4.7) years. Neurologic and neuropsychiatric observations were most frequently identified, among 49.3% of the cohort; followed by cardiovascular (48.5%), respiratory (38.1%), scoliosis (36.3%), and severe respiratory (25.0%). Prevalence estimates for each category were higher when analyzed within age-restricted subgroups; and increased as follow-up time increased. CONCLUSIONS: This study is the first to use diagnosis and procedure codes from real-world Medicaid claims to document the clinical course in DMD. Findings were consistent with previously published estimates from commercially insured populations and clinical registries; and contribute to the expanding body of real-world evidence around clinical progression of patients with DMD.

Asthma-related emergency admissions and associated healthcare resource use in Alberta, Canada.

BACKGROUND: There is a lack of real-world research assessing asthma management following asthma-related emergency department (ED) discharges. The objective of this study was to characterise follow-up care, healthcare resource use (HCRU) and medical costs following ED admissions in Alberta, Canada. METHODS: A retrospective cohort study was conducted on adults with asthma using longitudinal population-based administrative data from Alberta Health Services. Adult patients with asthma and ≥1 ED admission from 1 April 2015 to 31 March 2020 were included. ED admissions, outpatient visits, hospitalisations and asthma-specific medication use were measured in the 30 days before and up to 90 days after each asthma-related ED admission. Mean medical costs attributable to each type of HCRU were summarised. All outcomes were stratified by patient baseline disease severity. RESULTS: Among 128 063 patients incurring a total of 20 142 asthma-related ED visits, a substantial rate of ED readmission was observed, with 10% resulting in readmissions within 7 days and 35% within 90 days. Rates increased with baseline asthma severity. Despite recommendations for patients to be followed up with an outpatient visit within 2-7 days of ED discharge, only 6% were followed up within 7 days. The mean total medical cost per patient was $C8143 in the 30 days prior to and $C5407 in the 30 days after an ED admission. CONCLUSIONS: Despite recommendations regarding follow-up care for patients after asthma-related ED admissions, there are still low rates of outpatient follow-up visits and high ED readmission rates. New or improved multidimensional approaches must be integrated into follow-up care to optimise asthma control and prevent readmissions.

Characterizing the Occurrence of Key Clinical Milestones in Duchenne Muscular Dystrophy in the United States Using Real-World Data.

BACKGROUND: Data on the clinical course of Duchenne muscular dystrophy (DMD) exist from well-characterized clinical cohorts but estimates from real-world populations are fewer. OBJECTIVE: The objective was to estimate the prevalence of key clinical milestones by age, among real-world commercially-insured DMD patients in the United States. METHODS: MarketScan claims (2013-2018) were used to identify males with DMD. The percentages with wheelchair use or experiencing scoliosis, neurologic/neuropsychiatric involvement, cardiomyopathy, and respiratory involvement were tabulated; as were the median (interquartile range [IQR]) ages at first observed occurrence within the claims data. RESULTS: Among DMD patients (n = 1,964), the median (IQR) baseline age was 15 (9-21) years, and median follow-up was 1.7 years. Wheelchair use was observed in 55% of those aged 8 to 13 years at cohort entry; scoliosis, among 38% of those 8 to 10 and 52% of those 11 to 13 years; neurologic/neuropsychiatric involvement, among 41-43% of those 8 to 13 years; respiratory involvement, among 45% of those 14 to 19 years; and cardiomyopathy, among 68% of those 14 to 16 and 58% of those 17 to 19 years. CONCLUSIONS: The prevalence of key clinical milestones across ages was broadly consistent with published findings. Variability in estimates reflect clinical heterogeneity; these contemporary estimates from real-world data help characterize clinical outcomes in DMD.

SABA use as an indicator for asthma exacerbation risk: an observational cohort study (SABINA Canada).

Background: Patients with asthma use short-acting ß-agonists (SABA) to relieve symptoms but SABA alone does not treat underlying inflammation. Thus, over-reliance on SABA may result in poor asthma control and negative health outcomes. Objective: To describe use of SABA and characterise the relationship with severe exacerbations in the Canadian provinces of Nova Scotia (NS) and Alberta (AB). Methods: In this longitudinal Canadian SABA In Asthma (SABINA) study, patients with an asthma diagnosis were identified between 2016 and 2020 within two provincial administrative datasets (Health Data Nova Scotia and Alberta Health Services). All patients were followed for ≥24 months, with the first 12 months used to measure baseline asthma severity. Medication use and the relationship of SABA overuse (three or more canisters per year) with severe asthma exacerbations were characterised descriptively and via regression analysis. Results: A total of 115 478 patients were identified (NS: n=8034; AB: n=107 444). SABA overuse was substantial across both provinces (NS: 39.4%; AB: 28.0%) and across all baseline disease severity categories. Patients in NS with SABA overuse had a mean±sd annual rate of 0.46±1.11 exacerbations, compared to 0.30±1.36 for those using fewer than three canisters of SABA. Patients in AB had mean±sd exacerbation rates of 0.31±0.86 and 0.17±0.62, respectively. The adjusted risk of severe exacerbation was associated with SABA overuse (NS: incidence ratio rate 1.36, 95% CI 1.18-1.56; AB: incidence ratio rate 1.32, 95% CI 1.27-1.38). Conclusion: This study supports recent updates to Canadian Thoracic Society and Global Initiative for Asthma guidelines for asthma care. SABA overuse is associated with increased risk of severe exacerbations and can be used to identify patients at a higher risk for severe exacerbations.

Characterizing demographics, comorbidities, and costs of care among populations with Duchenne muscular dystrophy with Medicaid and commercial coverage.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neurodegenerative disease characterized by loss of ambulation, cardiomyopathy, respiratory insufficiency, and early mortality. Few data are available that describe the direct medical costs among patients with DMD in the United States. OBJECTIVE: To characterize the demographics, comorbidity burden, and direct monthly costs of care among patients with DMD with Medicaid and with commercial insurance coverage. METHODS: IBM MarketScan Commercial and Multi-State Medicaid claims (2013-2018) were used to identify males aged 30 years or under with diagnostic codes for muscular dystrophy or DMD; additional exclusion criteria were applied to identify those with probable DMD. Baseline characteristics and comorbidities were tabulated. The frequency of health care resource use and median (interquartile range [IQR]) monthly costs (in 2018 USD) were estimated from those with at least 12 months of continuous follow-up. RESULTS: Median (IQR) baseline ages were similar between the Medicaid (14 [9-20] years; n = 2,007) and commercial (15 [9-21] years; n = 1,964) DMD cohorts. The frequency of comorbidities over the period was slightly higher with those on Medicaid. The median duration of follow-up was 3.1 years among members of the Medicaid DMD cohort and 1.7 years among the commercial DMD cohort. Median monthly resource use was generally higher among the Medicaid DMD cohort; nonetheless, median (IQR) monthly costs were similar at $1,735 ($367-$5,281) for the Medicaid DMD cohort vs $1,883 ($657-$6,796) for the commercial DMD cohort. CONCLUSIONS: The demographic characteristics and median direct medical costs were similar between patients with commercial vs Medicaid coverage, even though patients with Medicaid coverage had higher resource use. Despite challenges in definitively identifying DMD patients using claims data, these findings help characterize contemporary DMD populations in the United States and the related direct economic burden to the payer. DISCLOSURES: This study was funded by Sarepta Therapeutics, Inc. Klimchak and Gooch are employees of Sarepta Therapeutics Inc. Szabo, Qian, and Popoff are employees of Broadstreet HEOR, which received funds from Sarepta Therapeutics, Inc., for work on this study. Iannaccone has received research funding or consulting fees from Avexis, Biogen, Fibrogen, Mallinkrodt, Regeneron, Sarepta Therapeutics, Inc., Scholar Rock, PTC Therapeutics, Pfizer, MDA, CureSMA, NIH, Genentech-Roche, and BCBS. Publication of the study results was not contingent on the sponsor's approval or censorship of the manuscript. Information from this study was presented, in part, at the AMCP Virtual Annual Meeting, April 21-24, 2020.

Treatment patterns and costs among patients with OAB treated with combination oral therapy, sacral nerve stimulation, percutaneous tibial nerve stimulation, or onabotulinumtoxinA in the United States.

INTRODUCTION: Treatment patterns and costs were characterized among patients with overactive bladder (OAB) receiving later-line target therapies (combination mirabegron/antimuscarinic, sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], or onabotulinumtoxinA). METHODS: In a retrospective cohort study using 2013 to 2017 MarketScan databases, two partially overlapping cohorts of adults with OAB ("IPT cohort": patients with incident OAB pharmacotherapy use; "ITT cohort," incident target therapy) with continuous enrollment were identified; first use was index. Demographic characteristics, treatment patterns and costs over the 24-month follow-up period were summarized. Crude mean (standard deviation [SD]) OAB-specific (assessed by OAB diagnostic code or pharmaceutical dispensation record) costs were estimated according to target therapy. RESULTS: The IPT cohort comprised 54 066 individuals (mean [SD] age 58.5 [15.0] years; 76% female), the ITT cohort, 1662 individuals (mean [SD] age 62.8 [14.9] years; 83% female). Seventeen percent of the IPT cohort were treated with subsequent line(s) of therapy after index therapy; among those, 73% received antimuscarinics, 23% mirabegron, and 1.4% a target therapy. For the ITT cohort, 32% were initially treated with SNS, 27% with onabotulinumtoxinA, 26% with combination mirabegron/antimuscarinic, and 15% with PTNS. Subsequently, one-third of this cohort received additional therapies. Mean (SD) costs were lowest among patients receiving index therapy PTNS ($6959 [$7533]) and highest for SNS ($29 702 [$26 802]). CONCLUSIONS: Costs for SNS over 24 months are substantially higher than other treatments. A treatment patterns analysis indicates that oral therapies predominate; first-line combination therapy is common in the ITT cohort and uptake of oral therapy after procedural options is substantial.

Costs of in-house genomic profiling and implications for economic evaluation: a case example of non-small cell lung cancer (NSCLC).

OBJECTIVES: Genomic profiling in oncology is vital for determining eligible patients for mutation-specific targeted therapies. Use of commercial genomic testing has the potential to improve patient outcomes. Economic evaluations of in-house genomic profiling typically only include material costs while external commercial services include many other factors. Using non-small cell lung cancer (NSCLC) as an example, this study sought to characterize the unique challenges of costing testing services and their impact on results of economic evaluations. METHODS: Structured interviews with Canadian oncologists, pathologists, and laboratory directors were conducted to identify material and non-material costs associated with genomic-testing laboratories to allow estimation of a more complete cost of in-house testing, with NSCLC cost-per-test calculated using annual operational costs and NSCLC-specific testing volume. A health and budget impact model of in-house versus external commercial profiling services was used to compare the impact of non-material costs on results. RESULTS: In-house testing costs, limited to materials, was $133/single-gene test and $1,400/panel. For a laboratory running 1,300 in-house tests/year, total annual non-material costs included equipment maintenance ($6,842), labor ($502,313; technicians, administrative, and medical staff), shipping/reporting and software updates ($146,050), for an additional $519/test. The combined cost of $652/single-gene and $1,919/panel was compared to a cost of $6,194 for a commercial external test. Based on current Canadian testing patterns and anticipated utilization of external testing, inclusion of in-house non-material costs reduced the estimated 3-year budget impact by 12%. CONCLUSION: When conducting economic evaluation to assess the value of introducing external tests, it is critical that non-material costs of standard testing strategies be measured and incorporated.

Assessment of potential bias in research grant peer review in Canada.

BACKGROUND: Peer review is used to determine what research is funded and published, yet little is known about its effectiveness, and it is suspected that there may be biases. We investigated the variability of peer review and factors influencing ratings of grant applications. METHODS: We evaluated all grant applications submitted to the Canadian Institutes of Health Research between 2012 and 2014. The contribution of application, principal applicant and reviewer characteristics to overall application score was assessed after adjusting for the applicant's scientific productivity. RESULTS: Among 11 624 applications, 66.2% of principal applicants were male and 64.1% were in a basic science domain. We found a significant nonlinear association between scientific productivity and final application score that differed by applicant gender and scientific domain, with higher scores associated with past funding success and h-index and lower scores associated with female applicants and those in the applied sciences. Significantly lower application scores were also associated with applicants who were older, evaluated by female reviewers only (v. male reviewers only, -0.05 points, 95% confidence interval [CI] -0.08 to -0.02) or reviewers in scientific domains different from the applicant's (-0.07 points, 95% CI -0.11 to -0.03). Significantly higher application scores were also associated with reviewer agreement in application score (0.23 points, 95% CI 0.20 to 0.26), the existence of reviewer conflicts (0.09 points, 95% CI 0.07 to 0.11), larger budget requests (0.01 points per $100 000, 95% CI 0.007 to 0.02), and resubmissions (0.15 points, 95% CI 0.14 to 0.17). In addition, reviewers with high expertise were more likely than those with less expertise to provide higher scores to applicants with higher past success rates (0.18 points, 95% CI 0.08 to 0.28). INTERPRETATION: There is evidence of bias in peer review of operating grants that is of sufficient magnitude to change application scores from fundable to nonfundable. This should be addressed by training and policy changes in research funding.

What is in your wallet? A cluster randomized trial of the effects of showing comparative patient out-of-pocket costs on primary care prescribing for uncomplicated hypertension.

BACKGROUND: Drug expenditures are responsible for an increasing proportion of health costs, accounting for $1.1 trillion in annual expenditure worldwide. As hundreds of billions of dollars are being spent each year on overtreatment with prescribed medications that are either unnecessary or are in excess of lowest cost-effective therapy, programs are needed that optimize fiscally appropriate use. We evaluated whether providing physicians with information on the patient out-of-pocket payment consequences of prescribing decisions that were in excess of lowest cost-effective therapy would alter prescribing decisions using the treatment of uncomplicated hypertension as an exemplar. METHODS: A single-blind cluster randomized trial was conducted over a 60-month follow-up period in 76 primary care physicians in Quebec, Canada, and their patients with uncomplicated hypertension who were using the MOXXI integrated electronic health record for drug and health problem management. Physicians were randomized to an out-of-pocket expenditure module that provided alerts for comparative out-of-payment costs, thiazide diuretics as recommended first-line therapy, and tools to monitor blood pressure targets and medication compliance, or alternatively the basic MOXXI system. System software and prescription claims were used to analyze the impact of the intervention on treatment choice, adherence, and overall and out-of-pocket payment costs using generalized estimating equations. RESULTS: Three thousand five-hundred ninety-two eligible patients with uncomplicated hypertension were enrolled, of whom 1261 (35.1%) were newly started (incident patient) on treatment during follow-up. There was a statistically significant increase in the prescription of diuretics in the newly treated intervention (26.6%) compared to control patients (19.8%) (RR 1.65, 95% CI 1.17 to 2.33). For patients already treated (prevalent patient), there was a statistically significant interaction between the intervention and patient age, with older patients being less likely to be switched to a diuretic. Among the incident patients, physicians with less than 15 years of experience were much more likely to prescribe a diuretic (OR 10.69; 95% CI 1.49 to 76.64) than physicians with 15 to 25 years (OR 0.67; 95%CI 0.25 to 1.78), or more than 25 years of experience (OR 1.80; 95% CI 1.23 to 2.65). There was no statistically significant effect of the intervention on adherence or out-of-pocket payment cost. CONCLUSIONS: The provision of comparative information on patient out-of-pocket payments for treatment of uncomplicated hypertension had a statistically significant impact on increasing the initiation of diuretics in incident patients and switching to diuretics in younger prevalent patients. The impact of interventions to improve the cost-effectiveness of prescribing may be enhanced by also targeting patients with tools to participate in treatment decision-making and by providing physicians with comparative out-of-pocket information on all evidence-based alternatives that would enhance clinical decision-making. TRIAL REGISTRATION: ISRCTN96253624.

Improving patient safety and efficiency of medication reconciliation through the development and adoption of a computer-assisted tool with automated electronic integration of population-based community drug data: the RightRx project.

Background and Objective: Many countries require hospitals to implement medication reconciliation for accreditation, but the process is resource-intensive, thus adherence is poor. We report on the impact of prepopulating and aligning community and hospital drug lists with data from population-based and hospital-based drug information systems to reduce workload and enhance adoption and use of an e-medication reconciliation application, RightRx. Methods: The prototype e-medical reconciliation web-based software was developed for a cluster-randomized trial at the McGill University Health Centre. User-centered design and agile development processes were used to develop features intended to enhance adoption, safety, and efficiency. RightRx was implemented in medical and surgical wards, with support and training provided by unit champions and field staff. The time spent per professional using RightRx was measured, as well as the medication reconciliation completion rates in the intervention and control units during the first 20 months of the trial. Results: Users identified required modifications to the application, including the need for dose-based prescribing, the role of the discharge physician in prescribing community-based medication, and access to the rationale for medication decisions made during hospitalization. In the intervention units, both physicians and pharmacists were involved in discharge reconciliation, for 96.1% and 71.9% of patients, respectively. Medication reconciliation was completed for 80.7% (surgery) to 96.0% (medicine) of patients in the intervention units, and 0.7% (surgery) to 82.7% of patients in the control units. The odds of completing medication reconciliation were 9 times greater in the intervention compared to control units (odds ratio: 9.0, 95% confidence interval, 7.4-10.9, P < .0001) after adjusting for differences in patient characteristics. Conclusion: High rates of medication reconciliation completion were achieved with automated prepopulation and alignment of community and hospital medication lists.

Pneumonia risk in asthma patients using inhaled corticosteroids: a quasi-cohort study.

AIM: Studies have linked the use of inhaled corticosteroids (ICSs) to excess pneumonia risk in chronic obstructive pulmonary disease patients. The risk in asthma patients remains unclear. The objective of the present study was to examine the risk of pneumonia with ICSs in asthma patients aged 12-35 years. METHODS: We formed a cohort of asthma patients treated from 1990 to 2007 using Quebec health insurance databases. Subjects were considered currently exposed if they had had an ICS dispensed within the 60 days prior to their pneumonia index event or matched person-moment. Secondary analyses investigated the risk of pneumonia according to ICS dose and type. Rate ratios (RRs) and rate differences (RDs) were both estimated through a quasi-cohort approach. RESULTS: The cohort included 152 412 subjects, of whom 1928 had a pneumonia event during follow-up. There was an increased risk of pneumonia associated with current use of ICSs [RR 1.83; 95% confidence interval (CI) 1.57, 2.14] or an excess risk of 1.44 cases per 1000 person-years (RD 1.44; 95% CI 1.03, 1.85). There was an excess pneumonia risk with low doses (RR 1.60; 95% CI 1.06, 2.45), moderate doses (RR 1.53; 95% CI 1.12, 2.08) and high doses (RR 1.96; 95% CI 1.64, 2.34) of ICSs, and with budesonide (RR 2.67; 95% CI 2.05, 3.49) and fluticasone (RR 1.93; 95% CI 1.58, 2.36), specifically relative to no use. When accounting for potential protopathic bias, the risk with current use of ICSs was attenuated (RR 1.48; 95% CI 1.22, 1.78). CONCLUSION: ICS use in asthma patients appears to be associated with an increased risk of pneumonia and is present for both budesonide and fluticasone.