Insurer costs of COVID-19 by disease severity and duration.

OBJECTIVES: To analyze US commercial insurance payments associated with COVID-19 as a function of severity and duration of disease. STUDY DESIGN: Retrospective database analysis. METHODS: Patients with COVID-19 between April 1, 2020, and June 30, 2021, in the Merative MarketScan Commercial database were identified and stratified as having asymptomatic, mild, moderate (with and without lower respiratory disease), or severe/critical (S/C) disease based on the severity of the acute COVID-19 infection. Duration of disease (DOD) was estimated for all patients. Patients with DOD longer than 12 weeks were defined as having post-COVID-19 condition (PCC). Outcomes were all-cause payments (ACP) and disease-specific payments (DSP) for the entire DOD. Variables included demographic and comorbidities at the time of acute disease. Adjusted payments by disease severity were estimated using generalized linear models (γ distribution with log link). RESULTS: A total of 738,339 patients were included (374,401 asymptomatic, 156,220 mild, 180,213 moderate, and 27,505 S/C cases). DSP increased from $217 (95% CI, $214-221) for asymptomatic cases to $2744 (95% CI, $2678-$2811) for moderate cases with lower respiratory disease and $28,250 (95% CI, $26,963-$29,538) for S/C cases. ACP increased from $505 (95% CI, $497-$512) for asymptomatic cases to $46,538 (95% CI, $44,096-$48,979) for S/C cases. The DSP and ACP further increased by $50,736 (95% CI, $45,337-$56,136) and $94,839 (95% CI, $88,029-$101,649), respectively, in S/C cases with PCC vs a DOD of fewer than 4 weeks. CONCLUSIONS: COVID-19 payments for S/C cases were more than 10-fold greater than those of moderate cases and further increased by nearly $95,000 in S/C cases with PCC vs a DOD of fewer than 4 weeks.

Health care costs of COVID-19 vs influenza and pneumonia.

OBJECTIVES: To estimate payments for the treatment of COVID-19 compared with that of influenza or viral pneumonia (IP), from the perspective of the US payer. STUDY DESIGN: Retrospective cohort analysis. METHODS: Patients with COVID-19 during the period from October 1, 2020, to February 1, 2021, or IP during the period from October 1, 2018, to February 1, 2019, in the IBM MarketScan databases were identified. The index was defined as the date of the first COVID-19 or IP diagnosis. Patients with COVID-19 were stratified by severity. Variables for all patients included demographics and comorbidities at the time of index and duration of disease. IP and COVID-19 cohorts were matched using propensity scores, and inflation-adjusted all-cause payments (ACP), and disease-specific payments (DSP) for IP vs COVID-19 were estimated using generalized linear models. RESULTS: Matched cohorts included 6332 Medicare (female, 58.5%; mean [SD] age, 75.3 [7.6] years), and 397,532 commercially insured patients (female, 57.6%; mean [SD] age, 34.7 [16.7] years). ACP and DSP were significantly higher in the COVID-19 cohort vs IP cohort. Payments for severe/critical COVID-19 were significantly greater than those for IP, with adjusted marginal incremental DSP and ACP of $24,852 (95% CI, $21,573-$28,132) and $50,325 (95% CI, $43,932-$56,718), respectively. IP was significantly less expensive than moderate COVID-19 for commercial payers but not Medicare. IP was more expensive than mild COVID-19 for all payers. CONCLUSIONS: Payments associated with severe/critical COVID-19 significantly exceeded those associated with IP. For Medicare, IP was more expensive than mild or moderate COVID-19. For commercial payers, IP was less expensive than moderate COVID-19 but more expensive than mild COVID-19.

Respiratory Syncytial Virus-Related Complications and Healthcare Costs Among a Medicare-Insured Population in the United States.

Background: Literature describing respiratory syncytial virus (RSV)-related complications in older adults in the United States is scarce. This study described risk factors of RSV-related complications and healthcare costs of Medicare-insured patients aged ≥60 years with medically attended RSV. Methods: 100% Medicare Research Identifiable Files (1 January 2007-31 December 2019) were used to identify adults aged ≥60 years with RSV (index: first diagnosis date). Predictors of ≥1 RSV-related complication (ie, pneumonia, acute respiratory failure, congestive heart failure, hypoxia/dyspnea, non-RSV lower/upper respiratory tract infections, or chronic respiratory disease) during the up to 6-month post-RSV diagnosis period were identified. Patients with all aforementioned diagnoses during the 6 months pre-index could not be evaluated for a complication and were therefore ineligible for analyses. Differences between 6-month pre- and post-index total all-cause and respiratory/infection-related healthcare costs were assessed. Results: Overall, 175 392 patients with RSV were identified. Post-RSV diagnosis, 47.9% had ≥1 RSV-related complication, with mean time-to-event of 1.0 month. The most common complications were pneumonia (24.0%), chronic respiratory disease (23.6%), and hypoxia or dyspnea (22.0%). Baseline predictors of ≥1 RSV-related complication included having previous diagnoses for complication/comorbidity listed in the Methods, hypoxemia, chemotherapy, chest radiograph, stem cell transplant, and anti-asthmatic and bronchodilator use. Total all-cause and respiratory/infection-related healthcare costs were $7797 and $8863 higher, respectively, post-index versus pre-index (both P < .001). Conclusions: In this real-world study, almost half of patients with medically attended RSV experienced an RSV-related complication within 1 month post-RSV diagnosis, and costs significantly increased post-diagnosis. Having a complication/comorbidity pre-RSV predicted a higher risk of developing a different complication post-RSV infection.

Assessing barriers to access and equity for COVID-19 vaccination in the US.

BACKGROUND: Historical vaccination coverage in economically disadvantaged, ethnic minority, non-affluent white and agricultural populations in the US has lagged coverage in more affluent urban and suburban white populations due to a variety of social and economic factors. In the current COVID-19 pandemic, sociocultural and economic challenges continue to present significant obstacles to achieving equitable uptake of COVID-19 vaccines. The goal of this study was to qualitatively assess perceptions of key US healthcare stakeholders of the most significant barriers to COVID-19 vaccine access and equity to better characterize their expected impact on US communities. METHODS: After conducting a targeted literature review (TLR), we hypothesized 20 high-impact barriers which included structural and logistical barriers, capturing systemic challenges to vaccine accessibility, and attitudinal and informational barriers, affecting patient willingness to pursue vaccination. We developed a qualitative discussion guide, which included both open-ended and closed-ended questions, and interview stimulus material to conduct one-on-one in-depth interviews to assess the expected prevalence, severity, and persistence of these 20 high-impact barriers, which were hypothesized based on TLR. As a part of this qualitative study, we conducted one-on-one in-depth interviews with a diverse set of 15 US healthcare stakeholders who were involved in the COVID-19 vaccine rollout in states with relatively disparate vaccination rates by ethnicity. These stakeholders were selected to reflect an array of roles in the COVID-19 vaccine rollout, including infectious disease specialists, pharmacists, community advocacy representatives, and partners of local governments involved in the COVID-19 vaccine rollout and community education. RESULTS: Respondents identified limited vaccination sites in rural settings and technology-related barriers as the most prevalent and severe structural and logistical barriers in US communities. Respondents assessed COVID-19 vaccine safety concerns and politically motivated skepticism to be the most prevalent and severe attitudinal and informational barriers. Respondents cited proliferation of mobile vaccination clinics and local community messaging to endorse vaccines as the most effective solutions to these top structural and attitudinal barriers. Respondents expected politically motivated skepticism to be the most significant and persistent barrier to broader vaccine uptake in the US. CONCLUSIONS: Our study suggests that attitudinal barriers, particularly politically motivated skepticism, are likely to remain the most persistent challenges to widespread vaccination against COVID-19 in the US.

Global Implications for COVID-19 Vaccine Series Completion: Insights from Real-World Data from the United States.

This retrospective cohort analysis leveraged vaccination data for BNT162b2, mRNA-1273, and Ad26.COV2.S in the United States from the Komodo Healthcare Map database, the TriNetX Dataworks USA Network, and Cerner Real-World EHR (electronic health record) Data to evaluate rates of adherence to and completion of COVID-19 vaccination series (November 2020 through June 2021). Individuals were indexed on the date they received the first dose of a COVID-19 vaccine, with an adherence follow-up window of 42 days. Adherence/completion rates were calculated in the overall cohort of each database and by month of initiation and stratified by age, race/ethnicity, and urban/rural status. Overall adherence and completion to 2-dose COVID-19 mRNA vaccine schedules ranged from 79.4% to 87.4% and 81.0% to 89.2%, respectively. In TriNetX and Cerner, mRNA-1273 recipients were generally less adherent compared with BNT162b2 across sociodemographic groups. In Komodo, rates of adherence/completion between mRNA-1273 and BNT162b2 were similar. Adherence/completion were generally lower in younger (<65 years) versus older recipients (≥65 years), particularly for mRNA-1273. No other sociodemographic-based gaps in vaccine adherence/completion were identified. These data demonstrate high but incomplete adherence to/completion of multidose COVID-19 vaccines during initial vaccine rollout in the United States. Multidose schedules may contribute to challenges associated with successful global vaccination.

Direct health care costs associated with COVID-19 in the United States.

BACKGROUND: Data on the real-world health care burden of COVID-19 in the United States are limited. OBJECTIVE: To compare health care resource use (HRU), direct health care costs, and long-term COVID-19-related complications between patients with vs patients without COVID-19 diagnoses. METHODS: Using IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits administrative claims databases (January 1, 2018, to March 1, 2021), this retrospective, matched cohort study compared patients with a recorded COVID-19 diagnosis to control subjects with no recorded diagnosis for COVID-19, personal history of COVID-19, or pneumonia due to COVID-19. To capture typical health care utilization, the control group was analyzed in 2019 (prepandemic); their index date was assigned as 1 year before the index date (first observed COVID-19 diagnosis) of their matched COVID-19 patient. All patients had continuous health plan coverage for at least 6 months pre-index (baseline) and at least 6 months post-index (allowing censoring during month 6). Separately for commercial and Medicare cohorts, COVID-19 and control patients were matched 1:1 using propensity scores, number of followup months, and indicator of age 18 years or older. During each month of the 6-month follow-up, all-cause HRU, health care costs, and COVID-19-related complications were compared between patients with COVID-19 and controls. RESULTS: After matching COVID-19 and control patients 1:1, a total of 150,731 commercial matched pairs and 1,862 Medicare matched pairs were retained; baseline characteristics were similar between patients with COVID-19 and controls. Patients with COVID-19 and controls had mean ages of 38.9 and 39.7 years in the commercial cohort and 74.3 and 75.3 years in the Medicare cohort, respectively. In month 1 of follow-up, patients with COVID-19 relative to controls were significantly more likely to have at least 1 inpatient admission (commercial: 6.9% vs 0.5%; Medicare: 29.1% vs 1.3%; both P < 0.001) and at least 1 emergency department visit (commercial: 37.3% vs 3.4%; Medicare: 26.2% vs 4.1%; both P < 0.001). Total health care costs in month 1 were significantly higher among patients with COVID-19 than controls (mean differences: $3,706 for commercial; $10,595 for Medicare; both P < 0.001), driven by inpatient costs. Though the incremental HRU and cost burden of COVID-19 decreased over time, patients with COVID-19 continued to have significantly higher total costs through month 5 (all P < 0.001 for both commercial and Medicare). During follow-up, patients with COVID-19 had significantly higher rates of complications than controls (commercial: 52.8% vs 29.0% with any; Medicare: 74.5% vs 47.9% with any; both P < 0.001), most commonly cough, dyspnea, and fatigue. CONCLUSIONS: COVID-19 was associated with significant economic and clinical burden, both in the short-term and over 6 months following diagnosis. DISCLOSURES: Jessica K DeMartino is an employee of Janssen Scientific Affairs, LLC. Elyse Swallow, Debbie Goldschmidt, Karen Yang, Marta Viola, Tyler Radtke, and Noam Kirson are employees of Analysis Group, Inc., which has received consulting fees from Janssen Scientific Affairs, LLC. This study was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design, interpretation of the results, manuscript review, and the decision to publish the article.

Burden of opioid use for pain management among adult herpes zoster patients in the US and the potential impact of vaccination.

PLAIN LANGUAGE SUMMARYWhat is the context? Herpes zoster or shingles and its complications such as postherpetic neuralgia - a painful condition that affects the nerve fibers and skin - may lead to complex pain that can be addressed using opioids in some patients.The recombinant zoster vaccine (RZV) vaccine prevents shingles and, therefore, may reduce the use of opioids and the negative health outcomes and costs associated with it.What is new? In this retrospective medical claims study, including patients between 2012 and 2017, we evaluated the receipt of pain medication including opioids in herpes zoster patients, and assessed factors associated with opioid prescription.estimated health care resource utilization and costs associated with opioid use among patients with herpes zoster.assessed the impact of vaccination on opioid prescriptions.Among subjects receiving opioids, 78.5% started with a weak opioid dose. Dose escalation was uncommon.Postherpetic neuralgia, immunocompromised status, and comorbidities are the main risk factors associated with opioid prescription.Health care costs are almost double in patients with herpes zoster receiving opioids compared with patients without an opioid prescription.In a population of 1 million adults aged 50 years or older, vaccination with the recombinant zoster vaccine could prevent over 19,000 patients from receiving opioids.What is the impact? Prevention of herpes zoster through vaccination may be a highly effective strategy to reduce opioid prescriptions and costs related to pain management in a susceptible population.Increasing RZV vaccination coverage in adults aged ≥50 years may further reduce potential opioid prescriptions through a decrease in shingles incidence.

Cost-benefit analysis of vaccination against four preventable diseases in older adults: Impact of an aging population.

OBJECTIVE: This exploratory study estimates the economic value of the current vaccination program and increased coverage against four preventable diseases in older adults in the United States (US). METHODS: A population-based, age-structured economic model was used to conduct a cost-benefit analysis of vaccination against influenza, pertussis, herpes zoster, and pneumococcal disease among US adults aged 50 years and older, accounting for aging of the population. The model used separate decision trees for each disease to project the discounted number of vaccinated individuals, number of disease cases, and direct medical and indirect costs (2018 US$) over a 30-year period. Benefit-cost ratios (BCRs) and net present values were calculated for two primary analyses comparing current vaccination coverage versus no vaccination and comparing increased coverage versus current coverage. Key parameter values were varied in deterministic sensitivity analyses. RESULTS: Current adult vaccination coverage (vs. no vaccination) is estimated to result in nearly 65 million averted disease cases, $185 billion averted costs of cases, and $136 billion in incremental vaccination costs over a 30-year period from a societal perspective (BCR = 1.4). Increased vaccination coverage (vs. current coverage) is associated with over 33 million additional averted disease cases, $96 billion additional averted costs of cases, and nearly $83 billion in incremental vaccination costs, resulting in a societal BCR of 1.2 over 30 years. Deterministic sensitivity analyses demonstrated that results were most sensitive to disease incidence, vaccine efficacy, and productivity costs for time required for vaccination. CONCLUSIONS: Study results highlight the economic value of vaccination programs for older adults in the US and indicate that efforts to further increase vaccination coverage may be warranted and economically justifiable.

Impact of population aging on the burden of vaccine-preventable diseases among older adults in the United States.

Despite vaccination recommendations, the burden of vaccine-preventable diseases remains high in older adults in the United States (US), contributing to substantial morbidity, mortality, and health care resource use and costs. To adequately plan for health care resource needs and to help inform vaccination policies, burden of disease projections that account for population aging over the coming decades are needed. As a first step, this exploratory study projects the burden of influenza, pertussis, herpes zoster, and pneumococcal disease in adults aged 50 y and older in the US, using a population-based modeling framework with separate decision trees for each vaccine-preventable disease. The model uses projected population estimates from the US Census Bureau to account for changes in the US population over time and then calculates expected numbers of cases and associated costs for each disease, keeping current estimates of age-specific disease incidence, vaccine coverage, and efficacy constant over time. This approach was used to focus the exploratory analysis on the burden of disease that may be expected due to population changes alone, assuming that all else remains unchanged. Due to population growth and the shifting age distribution over the next 30 y, the annual societal economic burden for the four vaccine-preventable diseases is projected to increase from approximately $35 billion to $49 billion, resulting in cumulative costs of approximately $1.3 trillion, as well as more than 1 million disease-related deaths. Given such notable burden, further efforts to increase vaccination coverage and effectiveness in older adults are needed.

NCCN Work Group Report: Emerging Issues in Tissue Allocation.

Expanding research interests in molecular profiling over the past several years have led researchers in academia and pharmaceutical and biotechnology companies to significantly increase their need for access to tissue specimens collected through clinical care and clinical trials. As a result, tissue allocation has become a growing issue for many clinical and translational investigators. High-quality biospecimens are needed by all stakeholders in order to have scientifically accurate studies and results. At the center of the process are the patients, who have increasingly become active partners in the clinical research enterprise as individuals and through highly sophisticated patient advocacy organizations. All stakeholders must recognize that human specimens, including tissue, represent a valuable and unique resource that must have proper acquisition, handling, custodianship, and consent for use in accordance with best practices for biospecimen resources.

Measuring quality in oncology: challenges and opportunities.

Variations in the quality of cancer care are well documented. A key element of quality monitoring is standardized measures of care. Quality measures may include both process measures and outcome measures. Process measurement is only one aspect of assessing the quality of cancer care; measuring outcomes and providing the appropriate structure for care are also important. A variety of stakeholders, including professional oncology organizations and public and private payors, have developed programs and quality measures to address variations in the delivery of cancer care. To fulfill the current need to explore and discuss how quality is measured in oncology care, NCCN convened the NCCN Oncology Policy Summit: Measuring Quality in Oncology - Challenges and Opportunities. The summit was a forum to discuss current efforts to use quality measures, the value of quality measures, and patient and caretaker perspectives on quality.

Biological and structural evaluation of 10R- and 10S-methylthio-DDACTHF reveals a new role for sulfur in inhibition of glycinamide ribonucleotide transformylase.

Glycinamide ribonucleotide transformylase (GAR Tfase) is a folate-dependent enzyme in the de novo purine biosynthesis pathway, which has long been considered a potential target for development of anti-neoplastic therapeutics. Here we report the biological and X-ray crystallographic evaluations of both independent C10 diastereomers, 10S- and 10R-methylthio-DDACTHF, bound to human GAR Tfase, including the highest-resolution apo GAR Tfase structure to date (1.52 Å). Both diastereomers are potent inhibitors (Ki = 210 nM for 10R, and Ki = 180 nM for 10S) of GAR Tfase and exhibit effective inhibition of human leukemia cell growth (IC50 = 80 and 50 nM, respectively). Their inhibitory activity was surprisingly high, and these lipophilic C10-substituted analogues show distinct advantages over their hydrophilic counterparts, most strikingly in retaining potency in mutant human leukemia cell lines that lack reduced folate carrier protein activity (IC50 = 70 and 60 nM, respectively). Structural characterization reveals a new binding mode for these diastereoisomers, in which the lipophilic thiomethyl groups penetrate deeper into a hydrophobic pocket within the folate-binding site. In silico docking simulations of three other sulfur-containing folate analogues also indicate that this hydrophobic cleft represents a favorable region for binding lipophilic substituents. Overall, these results suggest sulfur and its substitutions play an important role in not only the binding of anti-folates to GAR Tfase but also the selectivity and cellular activity (growth inhibition), thereby presenting new possibilities for the future design of potent and selective anti-folate drugs that target GAR Tfase.

Equity in cancer care: pathways, protocols, and guidelines.

The quality of patient care varies based on numerous factors, such as health care setting, geographic location, access to medications, insurance coverage, and treatment protocols. Recently, the issue of whether use of clinical pathways can reduce costs and inappropriate variability in care has been the subject of much debate. As clinical treatment guidelines and pathways are increasingly deployed in oncology practice, they have a growing impact on the quality of treatment and how it is delivered. To fulfill the current need to discuss the use of pathways and clinical treatment guidelines in oncology and to address how patient care is impacted by their use, the National Comprehensive Cancer Network convened the NCCN Oncology Policy Summit: Equity in Cancer Care-Pathways, Protocols, and Guidelines. The summit was a forum to discuss the use and implementation of pathways, including how much flexibility pathways should allow in care, pathways' impact on public and private health insurance benefit design, what data is used to select pathway regimens and protocols, and ultimately what impact pathways may have on variation in care. The use and implementation of clinical treatment guidelines in practice was also explored from a variety of perspectives.

Binding and inactivation mechanism of a humanized fatty acid amide hydrolase by alpha-ketoheterocycle inhibitors revealed from cocrystal structures.

The cocrystal X-ray structures of two isomeric alpha-ketooxazole inhibitors (1 (OL-135) and 2) bound to fatty acid amide hydrolase (FAAH), a key enzymatic regulator of endocannabinoid signaling, are disclosed. The active site catalytic Ser241 is covalently bound to the inhibitors' electrophilic carbonyl groups, providing the first structures of FAAH bound to an inhibitor as a deprotonated hemiketal mimicking the enzymatic tetrahedral intermediate. The work also offers a detailed view of the oxyanion hole and an exceptional "in-action" depiction of the unusual Ser-Ser-Lys catalytic triad. These structures capture the first picture of inhibitors that span the active site into the cytosolic port providing new insights that help to explain FAAH's interaction with substrate leaving groups and their role in modulating inhibitor potency and selectivity. The role for the activating central heterocycle is clearly defined and distinguished from that observed in prior applications with serine proteases, reconciling the large electronic effect of attached substituents found unique to this class of inhibitors with FAAH. Additional striking active site flexibility is seen upon binding of the inhibitors, providing insights into the existence of a now well-defined membrane access channel with the disappearance of a spatially independent portion of the acyl chain-binding pocket. Finally, comparison of the structures of OL-135 (1) and its isomer 2 indicates that they bind identically to FAAH, albeit with reversed orientations of the central activating heterocycle, revealing that the terminal 2-pyridyl substituent and the acyl chain phenyl group provide key anchoring interactions and confirming the distinguishing role of the activating oxazole.

Asymmetric synthesis of inhibitors of glycinamide ribonucleotide transformylase.

Glycinamide ribonucleotide transformylase (GAR Tfase) catalyzes the first of two formyl transfer steps in the de novo purine biosynthetic pathway that require folate cofactors and has emerged as a productive target for antineoplastic therapeutic intervention. The asymmetric synthesis and evaluation of the two diastereomers of 10-methylthio-DDACTHF (10R-3 and 10S-3) and related analogues as potential inhibitors of GAR Tfase are reported. This work, which defines the importance of the C10 stereochemistry for this class of inhibitors of GAR Tfase, revealed that both diastereomers are potent inhibitors of rhGAR Tfase (10R-3 Ki = 210 nM, 10S-3 Ki = 180 nM) that exhibit effective cell growth inhibition (CCRF-CEM IC50 = 80 and 50 nM, respectively), which is dependent on intracellular polyglutamation by folylpolyglutamate synthetase (FPGS) but not intracellular transport by the reduced folate carrier.

Exploration of a fundamental substituent effect of alpha-ketoheterocycle enzyme inhibitors: Potent and selective inhibitors of fatty acid amide hydrolase.

A series of C4 substituted alpha-ketooxazoles were examined as inhibitors of the serine hydrolase fatty acid amide hydrolase in efforts that further define and generalize a fundamental substituent effect on enzyme inhibitory potency. Thus, a plot of the Hammett sigma(m) versus -logK(i) provided a linear correlation (R(2)=0.90) with a slope of 3.37 (rho=3.37), that is of a magnitude that indicates that of the electron-withdrawing character of the substituent dominates its effects (a one unit change in sigma(m) provides a >1000-fold change in K(i)).

Discovery of a potent, nonpolyglutamatable inhibitor of glycinamide ribonucleotide transformylase.

Glycinamide ribonucleotide transformylase (GAR Tfase) catalyzes the first of two formyl transfer steps in the de novo purine biosynthetic pathway that require folate cofactors. Herein we report the discovery of a potent, nonpolyglutamatable, and selective inhibitor of GAR Tfase. Compound 12, which possesses a tetrazole in place of the gamma-carboxylic acid in the l-glutamate subunit of the potent GAR Tfase inhibitor 1, was active in cellular-based functional assays exhibiting purine-sensitive cytotoxic activity (IC(50) = 40 nM, CCRF-CEM) and was selective for inhibition of rhGAR Tfase (K(i) = 130 nM). Notably, 12 was only 2.5-fold less potent than 1 in cellular assays and 4-fold less potent against rhGAR Tfase. Like 1, this functional activity of 12 in the cell-based assay benefits from and requires transport into the cell by the reduced folate carrier but, unlike 1, is independent of folyl polyglutamate synthase (FPGS) expression levels and polyglutamation.