Latent Class Analysis of Prescribing Behavior of Primary Care Physicians in the Veterans Health Administration.

BACKGROUND: Benzodiazepines, opioids, proton-pump inhibitors (PPIs), and antibiotics are frequently prescribed inappropriately by primary care physicians (PCPs), without sufficient consideration of alternative options or adverse effects. We hypothesized that distinct groups of PCPs could be identified based on their propensity to prescribe these medications. OBJECTIVE: To identify PCP groups based on their propensity to prescribe benzodiazepines, opioids, PPIs, and antibiotics, and patient and PCP characteristics associated with identified prescribing patterns. DESIGN: Retrospective cohort study using VA data and latent class regression analyses to identify prescribing patterns among PCPs and examine the association of patient and PCP characteristics with class membership. PARTICIPANTS: A total of 2524 full-time PCPs and their patient panels (n = 2,939,636 patients), from January 1, 2017, to December 31, 2018. MAIN MEASURES: We categorized PCPs based on prescribing volume quartiles for the four drug classes, based on total days' supply dispensed of each medication by the PCP to their patients (expressed as days' supply per 1000 panel patient-days). We used latent class analysis to group PCPs based on prescribing and used multinomial logistic regression to examine patient and PCP characteristics associated with latent class membership. KEY RESULTS: PCPs were categorized into four groups (latent classes): low intensity (23% of cohort), medium-intensity overall/high-intensity PPI (36%), medium-intensity overall/high-intensity opioid (20%), and high intensity (21%). PCPs in the high-intensity group were predominantly in the highest quartile of prescribers for all four drugs (68% in the highest quartile for benzodiazepine, 86% opioids, 64% PPIs, 62% antibiotics). High-intensity PCPs (vs. low intensity) were substantially less likely to be female (OR: 0.30, 95% CI: 0.21-0.42) or practice in the northeast versus other census regions (OR: 0.10, 95% CI: 0.06-0.17). CONCLUSIONS: VA PCPs can be classified into four clearly differentiated groups based on their prescribing of benzodiazepines, opioids, PPIs, and antibiotics, suggesting an underlying typology of prescribing. High-intensity PCPs were more likely to be male.

Defining and Managing High-Priced Cures: Healthcare Payers' Opinions.

OBJECTIVES: Recent regulatory approvals of potentially curative but high-cost treatments have made these therapies a focus of health policy discussions. Cures present new challenges to healthcare payers because they have high upfront costs but have life-long health benefits. The objectives of this study are to understand how healthcare payers define and manage cures. We investigated payers' views on key features of curative treatments and the affordability and value challenges they present. METHODS: We conducted semistructured interviews in 2016 with key informants in US payer organizations. Interviewees were directly involved in coverage determination for highly effective and curative therapies. RESULTS: We contacted 24 individuals and 18 participated. When asked what aspects of cures were important for coverage determination, an equal percentage of respondents (61% each) mentioned clinical and economic factors. In defining a cure, half of respondents included an economic element such as no downstream costs associated with the disease. When asked about challenges, 72% of respondents mentioned uncertainty regarding long-term outcomes and 56% mentioned membership churn and competition. CONCLUSIONS: Payers expressed a novel definition of a cure-which we call a "healthcare cost cure"-that captures both the clinical and economic consequences of treatment. This definition may be more pertinent in fragmentary financing systems that unevenly distribute cure costs and benefits across payers. Overall findings indicate that decision makers desire evidence to ensure that the long-term real-world consequences of covering cures match the expected benefits. Future policies need to balance upfront acquisition costs with downstream financial benefits.

Association of Opioid and Concurrent Benzodiazepine, Skeletal Muscle Relaxant, and Gabapentinoid Usage on Healthcare Expenditure and Resource Utilization: A Serial Cross-Sectional Study, 2009 to 2019.

BACKGROUND: Healthcare providers may be utilizing central nervous system (CNS) depressants to reduce opioid use due to recent changes in public policy. Combination use of these agents with opioids increases the risk of respiratory depression and death. Healthcare expenditures by individuals using these drug combinations have not been previously quantified. We sought to characterize healthcare costs and expenditures associated with a population reporting concurrent CNS depressants and opioid use compared with nonopioid analgesics in the United States from 2009 to 2019. METHODS: A serial cross-sectional design was used to compare the healthcare expenditures of adult Medical Expenditure Panel Survey respondents who were prescribed nonopioid analgesics, opioids only, opioids/benzodiazepines (BZD), opioids/BZD/skeletal muscle relaxants (SMR), or opioids/gabapentin (gaba) using pooled data from 2009 to 2019. Expenditure (cost and resource utilization) categories included inpatient, outpatient, office-based, and prescription medicine. Average marginal effects were used to compare survey-weighted annual costs and resource utilizations across the groups as compared to nonopioid analgesic respondents, adjusted for covariates. RESULTS: A weighted total of 34 241 838 individuals were identified. Most were opioid-only respondents (46.5%), followed by nonopioid analgesic (43.4%), opioid/BZD (5.3%), opioid-gaba (3.5%), and opioid/BZD/SMR respondents (1.3%). In comparison to the study groups with nonopioid analgesics, opioid-gaba users had the highest significant incremental cost difference among the different pairings (+$11 684, P < .001). Opioid-gaba, opioid/BZD, and opioid/BZD/SMR respondents had significantly higher inpatient, emergency department, and prescription drug costs and use compared to nonopioid analgesic respondents. Opioid-only respondents had higher outpatient and office-based costs and visits compared to nonopioid analgesic respondents. CONCLUSIONS: As healthcare providers seek to utilize fewer opioids for pain management, attention must be paid to ensuring safe and effective use of concurrent CNS depressants to mitigate high healthcare costs and burden.

Projecting long-term clinical outcomes with larotrectinib compared with immune checkpoint inhibitors in metastatic nonsmall cell lung cancer and differentiated thyroid cancer.

BACKGROUND: Larotrectinib is approved for patients with advanced NTRK gene fusion-positive solid tumors. Prior studies demonstrated promising results with larotrectinib compared with other systemic therapy. However, comparisons to checkpoint inhibitors, such as nivolumab or pembrolizumab, have not been done. OBJECTIVE: To estimate and compare expected life-years (LYs) and quality-adjusted LYs (QALYs) for patients with nonsmall cell lung cancer (NSCLC) eligible for larotrectinib vs patients with unknown NTRK gene fusion status on nivolumab or pembrolizumab. We also assessed patients with metastatic differentiated thyroid cancer (DTC), as pembrolizumab may be considered in certain circumstances. METHODS: We developed partitioned survival models to project long-term comparative effectiveness of larotrectinib vs nivolumab or pembrolizumab. Larotrectinib survival data were derived from an updated July 2021 analysis of 21 adult patients (≥18 years of age) with metastatic NTRK gene fusion-positive NSCLC and 21 with DTC. Survival inputs for nivolumab and pembrolizumab were obtained from published articles. Progression-free and overall survival were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Log-normal). Exponential fits were chosen based on goodness-of-fit and clinical plausibility. RESULTS: In NSCLC, larotrectinib resulted in gains of 5.87 and 5.91 LYs compared to nivolumab and pembrolizumab, respectively, which translated to gains of 3.53 and 3.56 QALYs. In DTC, larotrectinib resulted in a gain of 5.23 LYs and 4.24 QALYs compared to pembrolizumab. CONCLUSIONS: In metastatic NSCLC and DTC, larotrectinib may produce substantial life expectancy and QALY gains compared to immune checkpoint inhibitors. Additional data with longer follow-up will further inform this comparison.

The effectiveness and value of AMX0035 and oral edaravone for amyotrophic lateral sclerosis: A summary from the Institute for Clinical and Economic Review's Midwest Comparative Effectiveness Public Advisory Council.

DISCLOSURES: Funding for this summary was contributed by Blue Cross Blue Shield of MA, California Healthcare Foundation, The Patrick and Catherine Weldon Donaghue Medical Research Foundation, Arnold Ventures, and Kaiser Foundation Health Plan Inc., 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, AbbVie, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy Solutions, Express Scripts, Genentech/ Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health First, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer. Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, Sun Life Financial, uniQure, and United Healthcare. Mr Nikitin, Ms McKenna, Ms Richardson, and Drs Rind and Pearson are employed by ICER. Through their affiliated institutions, Drs Makam, Carlson, and Suh received funding from ICER for the work described in this summary.

Community-Based Service Use After Clozapine Treatment: A Mirror-Image Analysis of Public Claims Data.

Although clozapine demonstrates unique efficacy for treatment-resistant schizophrenia, its impact on community-based services remains largely underexplored. The authors examined changes in use of community-based services after clozapine treatment among a sample of 163 patients with schizophrenia by using public claims data in Allegheny County, Pennsylvania. Mirror-image analyses of service utilization were used to compare the 180-day period before treatment initiation with the 180-day period that began after 6 months of adherent treatment, accounting for age, race, and gender. Across demographic variables, clozapine treatment was associated with increased use of community-based services and decreased use of psychiatric inpatient services (p<0.05, Bonferroni corrected), suggesting that clozapine treatment shifts service needs from emergency care to community-based care and recovery.

Use of Disease-Modifying Treatments in Patients With Sickle Cell Disease.

Importance: Despite hydroxyurea being an established treatment for sickle cell disease (SCD), it remains underused. The recent approval of the disease-modifying treatments (DMTs) l-glutamine, crizanlizumab, and voxelotor underscores the need to understand the uptake of DMTs in the current treatment landscape. Objective: To explore characteristics that may be associated with DMT use and to describe observed patterns of yearly DMT use from 2014 to 2021. Design, Setting, and Participants: This cross-sectional study used administrative claims data from Optum's deidentified Clinformatics Data Mart Database from January 1, 2014, to September 30, 2021, to identify adults and children with SCD. Data were analyzed from August 1, 2022, to August 28, 2023. Exposure: Use of DMTs. Main Outcomes and Measures: Patient characteristics across groups with varying patterns of DMT use and yearly patterns of prescription fills for hydroxyurea, crizanlizumab, voxelotor, and l-glutamine. Results: A total of 5022 beneficiaries with SCD (2081 [41.4%] aged 18-45 years; 2929 [58.3%] female) were included in sample A (144 [2.9%] inconsistent users, 274 [5.5%] incident users, 892 [17.8%] consistent users, and 3712 [73.9%] non-DMT users). Inconsistent users had a higher prevalence of vaso-occlusive crises (mean [SD], 3.7 [4.7]), splenic complications (6 of 144 [4.2%]), pulmonary complications (36 of 144 [25.0%]), kidney disease (21 of 144 [14.6%]), acute chest syndrome (18 of 144 [12.5%]), and health care visits (eg, mean [SD] inpatient visits, 7.0 [10.7]) compared with the other use groups. Non-DMT users had the lowest prevalence of vaso-occlusive crises (mean [SD], 0.8 [2.4]), acute chest syndrome (109 of 3712 [2.9%]), and inpatient (mean [SD], 2.0 [6.6]) and emergency department (mean [SD], 0.7 [3.1]) visits and the highest proportion of adults 65 years and older (593 of 3712 [16.0%]). In sample B (6387 beneficiaries with SCD), hydroxyurea use modestly increased from 428 of 2188 participants (19.6%) in 2014 to 701 of 2880 (24.3%) in 2021. Use of l-glutamine increased briefly but gradually decreased throughout the study period. In 2021, out of 2880 participants, 102 (3.5%) had at least 1 fill for crizanlizumab and 131 (4.6%) had at least 1 fill for voxelotor. Overall, total DMT use increased from 428 of 2188 participants (19.6%) in 2014 to 815 of 2880 patients (28.3%) in 2021. Conclusions and Relevance: In this cross-sectional analysis of adults and children with SCD, uptake of DMTs remained low from 2014 to 2021, despite the approval of newer therapies. Notable differences in patient characteristics across varied DMT exposure types necessitate further exploration into factors that facilitate DMT use and the creation of strategies to enhance DMT uptake.

Cost Effectiveness of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Patients with Knee Osteoarthritis.

OBJECTIVES: The aim of this study was to assess the cost effectiveness of allogeneic umbilical cord blood-derived mesenchymal stem cells with sodium hyaluronate (hUCB-MSC) compared with microfracture in patients with knee cartilage defects caused by osteoarthritis (OA) in South Korea. METHODS: A partitioned survival model approach was taken consisting of five mutually exclusive health states: excellent, good, fair, poor, and death over a 20-year time horizon. Utility values were obtained from a randomized clinical trial. Cost data were extracted from a database provided by the Health Insurance Review & Assessment Service, and the utilization of healthcare services was estimated from an expert panel of orthopedic surgeons using a structured questionnaire. The incremental cost-effectiveness ratio (ICER) in terms of quality-adjusted life-years (QALY) was calculated. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the base case, the incremental costs of US$14,410 for hUCB-MSC therapy along with its associated QALY gain of 0.857 resulted in an ICER of US$16,812 (₩18,790,773) per QALY (95% confidence interval [CI] US$13,408-US$20,828) when compared with microfracture treatment from a healthcare payer perspective. From a societal perspective, the ICER was US$268 (₩299,255) per QALY (95% CI -US$2915 to US$3784). When using a willingness-to-pay threshold of US$22,367/QALY, the probability of hUCB being cost effectiveness compared with microfracture was 99% from the healthcare payer perspective and 100% from the societal perspective. CONCLUSIONS: The study demonstrated that hUCB-MSC therapy was cost effective compared with microfracture when treating patients with knee OA. These findings should inform health policy decision makers about considerations for cost-effective therapy for treating knee OA to ultimately enhance population health.

Assessing surveillance utilization and value in commercially insured patients with colorectal cancer.

OBJECTIVES: Real-world patterns of surveillance testing in colorectal cancer (CRC) and the effects on health and cost outcomes are largely unknown. Our objectives were to (1) assess trends in carcinoembryonic antigen (CEA) testing, CT scans, and colonoscopy utilization and (2) examine the value of CEA testing intensity by characterizing receipt of curative treatment for recurrence and measuring direct medical costs. STUDY DESIGN: Prospective cohort study. METHODS: We used an IBM MarketScan database to identify patients with a diagnosis of and treatment for CRC between 2008 and 2015. We used a negative binomial model to assess utilization of CEA testing and logistic models to assess utilization of CT scans and colonoscopies. We used a Cox proportional hazards model to assess surveillance intensity and time to curative treatment. We estimated direct medical costs using the Kaplan-Meier sample average estimator to account for censored costs. RESULTS: We identified 3197 eligible patients. The mean numbers of CEA tests, CT scans, and colonoscopies remained relatively constant in the study period, but adherence to guidelines varied by surveillance. When categorizing individuals by their CEA utilization adherence to guidelines (perfect utilizers and overutilizers), overutilizers had an HR for curative treatment of 2.11 (95% CI, 1.46-3.05) relative to perfect utilizers. Although overutilizers underwent potentially curative procedures for recurrence at higher rates compared with perfect utilizers, direct medical costs were much higher in the overutilizer group. CONCLUSIONS: Higher intensity of surveillance, beyond what is recommended by guidelines, may lead to earlier recurrence detection and subsequent treatment, but this is associated with significantly higher direct medical costs.

Trends in endpoint use in pivotal trials and efficacy for US Food and Drug Administration-approved solid tumor therapies, 1995-2021.

BACKGROUND: Many cancer therapies are now approved based on surrogate endpoints such as progression-free survival (PFS) to ensure that patients have speedy access to life-saving cancer medicines. However, the link between surrogate endpoints and overall survival (OS) is not well established in many cancers. OBJECTIVE: To characterize trends in endpoints used in pivotal trials leading to approval for US Food and Drug Administration (FDA)-approved solid tumor therapies and their efficacy from 1995 to 2021. METHODS: We reviewed the FDA Oncology (Cancer)/Hematologic Malignancies Approval Notifications webpage to extract data on median OS and PFS among solid tumor therapy approvals from 1995 to 2021. We summarized trends in percentage of trials reporting OS vs PFS, median OS and PFS, and trial designs. We conducted subgroup analyses for lung and breast cancer therapies. RESULTS: Median OS was reported more frequently until 2010 to 2012, when median PFS and OS were reported in 65.2% and 60.9% of trials, respectively. Between 1995 and 2021, there were no observable trends in median OS over time for solid tumor therapy approvals. Median PFS increased by 3.0 months over time. For lung cancer therapies, median OS increased by 6.8 months between the time periods of 1998-2000 and 2019-2021, whereas median PFS increased by 5.0 months between the time periods of 2007-2009 and 2019-2021. For breast cancer therapy, median OS slightly decreased over time, whereas median PFS has increased by 3.4 months since 1995. There has been a recent shift in use of single-arm trials leading to oncology drug approvals. CONCLUSIONS: There has been a transition from reporting OS to PFS, and median PFS has increased by 3 months while median OS has remained stable. The different trends in overall and progression-free survival highlights the challenge and importance of measuring the value of oncology drugs. DISCLOSURES: Dr Suh reports personal fees from Bayer US LLC.

A Computational Framework to Characterize the Cancer Drug Induced Effect on Aging Using Transcriptomic Data.

Cancer treatments such as chemotherapies may change or accelerate aging trajectories in cancer patients. Emerging evidence has shown that "omics" data can be used to study molecular changes of the aging process. Here, we integrated the drug-induced and normal aging transcriptomic data to computationally characterize the potential cancer drug-induced aging process in patients. Our analyses demonstrated that the aging-associated gene expression in the GTEx dataset can recapitulate the well-established aging hallmarks. We next characterized the drug-induced transcriptomic changes of 28 FDA approved cancer drugs in brain, kidney, muscle, and adipose tissues. Further drug-aging interaction analysis identified 34 potential drug regulated aging events. Those events include aging accelerating effects of vandetanib (Caprelsa®) and dasatinib (Sprycel®) in brain and muscle, respectively. Our result also demonstrated aging protective effect of vorinostat (Zolinza®), everolimus (Afinitor®), and bosutinib (Bosulif®) in brain.

Patterns of Utilization and Expenditure Across Multiple Sclerosis Disease-Modifying Therapies: A Retrospective Cohort Study Using Claims Data from a Commercially Insured Population in the United States, 2010-2019.

INTRODUCTION: Comparisons of healthcare utilization and expenditure among multiple sclerosis (MS) disease-modifying therapies (DMTs) are limited. METHODS: In this retrospective cohort study using commercial insurance claims data of a US population (2010-2019), we compared healthcare utilization and costs in MS across different DMTs. We assigned patients to different treatment arms: no DMT (ND), high-efficacy (HE) DMT (alemtuzumab, B cell depletion, cladribine, and natalizumab), and standard-efficacy (SE) DMT (dimethyl fumarate, glatiramer acetate, interferon beta, sphingosine-1-phosphate receptor modulator, and teriflunomide). We obtained healthcare costs and occurrences of healthcare services: outpatient visits, emergency room visits, hospitalizations, MS-related magnetic resonance imaging (MRI). We quantified relapses (based on MS-related hospitalizations, as well as outpatient visits with prescription of high-dose steroids) and medical complexity (based on unique drug classes of prescriptions). We calculated covariate-adjusted incidence rate ratio of healthcare services using negative binomial regression with ND as reference and covariate-adjusted mean cumulative healthcare costs using a generalized linear model with log-link function and gamma distribution. RESULTS: Among the 25,932 patients with MS (mean age 52.8 years, 75.2% women), both HE (mean age 54.0 years, 76.2% women) and SE (mean age 43.9 years, 75.6% women) groups had more non-pharmacy healthcare utilization than ND (mean age 57.6 years, 75.4% women), including overall outpatient doctor visits, neurology visits, and MS-related MRIs as well as relapses and medical complexities. Relative to ND, both HE and SE groups had higher pharmacy costs and overall healthcare costs 12 months after treatment initiation, despite having lower or equivalent non-pharmacy medical costs. In patients on DMT, pharmacy costs accounted for up to 65% of overall healthcare costs with over 85% of pharmacy costs attributable to DMT costs. CONCLUSION: DMT cost is a key driver of the overall healthcare expenditure in MS. Future comparative and cost-effectiveness studies integrating claims and electronic health records data with better balancing of patient characteristics are warranted.

The potential long-term comparative effectiveness of larotrectinib vs standard of care for treatment of metastatic TRK fusion thyroid cancer, colorectal cancer, and soft tissue sarcoma.

BACKGROUND: Larotrectinib is approved for patients with metastatic TRK fusion cancers, including differentiated thyroid (DTC), colorectal cancer (CRC), and soft tissue sarcoma (STS). Given the basket clinical trial design of larotrectinib, direct comparisons against standard of care in each of the mentioned cancers have not been assessed. Also, owing to the limited duration of follow-up in clinical trials, long-term outcomes for treatments are generally not known or estimated. OBJECTIVE: To compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for patients with metastatic DTC, CRC, and STS who are eligible to receive larotrectinib against patients with unknown NTRK gene fusion status receiving standard-of-care therapy. METHODS: We developed a partitioned survival model to estimate the long-term comparative effectiveness of larotrectinib and standard of care for 3 tumor types. Larotrectinib survival data, assessed by independent review committee, were derived from an updated July 2020 analysis of 19, 8, and 23 adult patients (aged ≥ 18 years) with metastatic TRK fusion DTC, CRC, and STS, respectively. The DTC survival data also included 2 patients aged less than 18 years for a total of 21 patients. Survival estimates for standard of care were derived from published clinical trials. Progressionfree and overall survival for all treatments were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Lognormal) fit to the available data. The final exponential form was selected based on goodness-of-fit and clinical plausibility. QALYs were estimated by adjusting the time spent in the preprogression and postprogression health states by utility weights derived from publicly available literature. RESULTS: Patients receiving larotrectinib experienced more LYs and QALYs compared with those receiving standard-of-care treatments across all 3 assessed cancer types. In DTC, patients receiving larotrectinib had 7.15-8.26 additional LYs (5.87-6.12 QALYs); in CRC, patients receiving larotrectinib had 1.26-1.27 additional LYs (1.00 QALYs); and in STS, patients receiving larotrectinib had 5.56 additional LYs (1.99 QALYs). CONCLUSIONS: Compared with standard of care in metastatic TRK wild-type cancers, larotrectinib is estimated to result in improved LY and QALY outcomes based on parametric extrapolations of intrial survival data. Because patient-level data were unavailable for adjusted analyses, a cross-trial comparison was performed. Given the limitations of this analytic approach and the small sample size for larotrectinib in trials, future studies should reassess the comparative effectiveness of larotrectinib vs standard of care as treated patients accrue and long-term survival data mature. DISCLOSURES: K. Suh, J. Carlson, and S. Sullivan report consulting fees from Bayer US LLC. F. Xia and T. Williamson are employees of Bayer US LLC. This study was funded by Bayer US LLC. The sponsor had no role in the design of the study and did not have any role in the execution, analyses, interpretation of the data, or decision to submit results.

Comparative effectiveness of larotrectinib versus entrectinib for the treatment of metastatic NTRK gene fusion cancers.

Aim: To extrapolate clinical trial results to estimate and compare expected progression-free and overall life years (LYs) and quality-adjusted LYs (QALYs) for larotrectinib and entrectinib in patients with colorectal cancer (CRC), soft tissue sarcoma (STS) and brain metastases prior to treatment with larotrectinib or entrectinib. Methods: A naive direct comparison of larotrectinib versus entrectinib was made using partitioned survival modeling methods from clinical trial data. Results: Larotrectinib resulted in an additional 1.58 LYs (1.17 QALYs), 5.81 LYs (2.02 QALYs) and 1.01 LYs in CRC, STS and baseline brain metastases, respectively, compared with entrectinib. Conclusion: Larotrectinib provided life expectancy and QALY gains compared with entrectinib. Additional studies will be beneficial as more patients are treated and survival data develop to better inform comparative effectiveness results.

Consensus Obtained for the Nephrotoxic Potential of 167 Drugs in Adult Critically Ill Patients Using a Modified Delphi Method.

INTRODUCTION: The approach to evaluating nephrotoxins in studies of drug-associated acute kidney injury varies. Some studies use a list of under ten drugs for evaluation whereas others include over 100 drugs. Drugs are typically assigned a binary classification, nephrotoxic or not nephrotoxic. This oversimplifies the nephrotoxic potential of the drugs under investigation. OBJECTIVE: This study aimed to assign a nephrotoxin potential for 167 drugs used in the adult critical care setting. METHODS: A three-round, international, interdisciplinary, web-based modified-Delphi study was used to evaluate nephrotoxins used in adult critically ill patients. Twenty-four international experienced clinicians were identified through the Acute Disease Quality Initiative group and professional affiliations. Included individuals represented the fields of intensive care, nephrology, and pharmacy. One hundred and fifty-nine medications were identified from the literature, with eight additional medications added after the first round, for a total of 167 medications. The primary outcome was consensus achieved for nephrotoxicity ratings. Scores were evaluated each round to determine if a consensus was met. RESULTS: Our nephrotoxin potential index rating indicated that 20 drugs were nephrotoxicity probable or probable/definite per consensus. Nephrotoxic potential was assessed based on the standard use of medications in intensive care and the following consensus scores: 0 = no nephrotoxic potential, 1 = possible nephrotoxic potential, 2 = probable nephrotoxic potential, 3 = definite nephrotoxic potential. CONCLUSIONS: The nephrotoxin potential index rating allows for prioritization of targeted drugs with greater nephrotoxic potential for institutional nephrotoxin stewardship programs. Furthermore, the nephrotoxin potential index rating provides homogeneity for research and guidance on detailed assessments by severity for each drug.

Exploring Medication Adherence with P2Y12 Inhibitors Using Conditional and Unconditional Quantile Regression Approaches.

BACKGROUND: Previous research assessing medication adherence with P2Y12 inhibitors has shown good adherence rates, ranging from 78% to 92%. Studies that used administrative claims data defined adherence using an arbitrary cut point of ≥ 80% medication possession ratio (MPR) or proportion of days covered (PDC). While this method is used frequently, it does not allow the researcher to observe how each factor impacts adherence along the entire distribution. The objective of the study was to use conditional quantile regression (CQR) and unconditional quantile regression (UQR) to assess heterogenous effects of adherence to P2Y12 inhibitors and covariates of interest and compare these results to those from a traditional logistic regression framework. METHODS AND RESULTS: This study used the commercial claims and encounters databases from IBM® MarketScan® from 2010 to 2017. We included patients who had an incident percutaneous coronary intervention, used a drug-eluting stent, and filled an incident prescription for a P2Y12 inhibitor. Adherence was measured for 185 days using PDC. Adherence to branded clopidogrel, generic clopidogrel, branded prasugrel, and branded ticagrelor was assessed, along with factors that could impact adherence, using logistic regression, CQR, and UQR. We found that while adherence to the antiplatelets was generally high, prasugrel and ticagrelor had significantly lower PDC compared to branded clopidogrel, especially around the 30th percentile. Across all quantiles in both the CRQ and UQR frameworks, comorbidities such as diabetes and depression and living in the southern region had significant negative effects on adherence, although the relative impact differed across quantiles. CONCLUSIONS: Using CQR and UQR allowed for heterogenous assessment of covariates along the adherence distribution, which is not possible with the traditional logistic regression method. The UQR framework revealed patients who initiate prasugrel or ticagrelor generally have lower adherence compared to those treated with branded clopidogrel, especially around the 30th quantile. Using these methods in other types of data sets, such as electronic health records, could help strengthen our results to develop policies to improve antiplatelet adherence in a targeted population.

A systematic review of cost-effectiveness analyses across the acute kidney injury landscape.

Introduction: Acute kidney injury (AKI) is a complex and common condition associated with increased morbidity, mortality, and costs. Evidence from cost-effectiveness analysis (CEA) have targeted various aspects of AKI including detection with biomarkers, treatment with renal replacement therapy, and prevention when using contrast media. However, there has not been a systematic review of these studies across the entirety of AKI.Areas covered: PubMed, Embase, and Cochrane library were used to identify CEA studies that involved AKI from 2004 onwards. These studies compared AKI treatment through renal replacement therapies (n = 6), prevention of contrast-induced-AKI (CI-AKI) using different media (n = 3), and diagnosis with novel biomarkers (n = 2). Treatment strategies for AKI focused on continuous versus intermittent renal replacement therapy. While there was no consensus, the majority of studies favored the continuous form. For contrast media, both studies found iodixanol to be cost-effective compared to iohexol for preventing CI-AKI. Additionally, novel biomarkers showed potential to be cost-effective in risk assessment and detection of AKI.Expert opinion: Consistent criteria such as a lifetime time horizon would allow for better model comparisons. Further research on clinical parameters to capture transition probabilities between stages within AKI and progression to downstream kidney disease is needed.

Trends in healthcare expenditures and resource utilization among a nationally representative population with opioids in the United States: a serial cross-sectional study, 2008 to 2017.

BACKGROUND: Previous reports on healthcare costs and expenditures associated with populations prescribed an opioid primarily focused on populations who chronically use opioids or have opioid use disorder. However, studies that characterize the healthcare and expenditures costs among the wider number of people prescribed opioids in a nationally representative population are unavailable. We sought to characterize the healthcare costs and expenditures associated with a population prescribed an opioid in the U.S. from 2008 to 2017. METHODS: A serial cross-sectional design was used to compare the economic burden of adult household respondents who were prescribed and not prescribed an opioid using pooled data from the Medical Expenditure Panel Survey (MEPS) between 2008 and 2017. Respondents with an opioid prescription were matched to respondents without an opioid prescription using propensity score match methods with survey weights. Two-part generalized linear models were used to estimate the survey-weighted annual healthcare expenditures and resource utilization adjusting for multiple covariates. Additionally, 10-year trend comparisons between the groups were performed. Costs were adjusted to 2019 US dollars. RESULTS: There was a weighted total of 31,696,671 respondents with an opioid and 31,536,639 respondents without an opioid after propensity score matching. The sample had a mean (SD) age of 50.63 years (18.03), 58.9% females, and 81.6% Whites. Total annual economic burden among RPOs was $524 billion. Annual total expenditures per respondent with and without an opioid were $16,542 and $7067, respectively (P < 0.001). Similarly, adjusted prescription, outpatient, emergency department, and inpatient expenditures were significantly higher for respondents with an opioid compared to respondents without an opioid. Average annual increases in expenditures were significantly greater among respondents with an opioid compared to respondents without an opioid for total (+$185; 95% CI: $37-$334) and prescription (+$78; 95% CI: $28-$128) expenditures. There were no differences in the average annual trends for outpatient, emergency department, and inpatient expenditures between respondents with and without an opioid. CONCLUSIONS: Respondents with an opioid prescription had higher healthcare expenditures and resource utilization compared to respondents without an opioid prescription from 2008 to 2017. Specifically, significant annual increases were observed for total and prescription expenditures. Additionally, 10-year trends in total and prescription expenditures were higher among respondents with an opioid than respondents without an opioid.

Cost-effectiveness of opicapone and entacapone in reducing OFF-time in Parkinson's disease patients treated with levodopa/carbidopa.

AIMS: To assess from a US payer perspective the relative cost-effectiveness of the catechol-O-methyltransferase inhibitors opicapone and entacapone when used adjunctively to levodopa/carbidopa (LD/CD) in patients with Parkinson's disease (PD), based on the drugs' effects to reduce absolute OFF-time hours in PD patients. MATERIALS AND METHODS: A Markov model was created to estimate cost-effectiveness of adjunctive opicapone treatment compared with adjunctive entacapone treatment in a synthetic cohort of 1,000 patients with PD taking LD/CD. Clinical inputs were derived from clinical trials, published literature, and expert opinion. Cost data (in 2018 US dollars) were obtained from the Centers for Medicare & Medicaid Services, the Kaiser Family Foundation, and Analy$ource. Cost-effectiveness outcomes included incremental cost per OFF-time hours avoided, cost per life year gained, and cost per quality-adjusted life year (QALY) gained. Outcomes were projected over a 25-year lifetime horizon and discounted at 3% annually. RESULTS: Opicapone treatment was associated with an average of 1,187 fewer OFF-time hours per patient and an increase of 0.07 QALYs compared with entacapone. Total lifetime costs for opicapone were $3,100 higher than entacapone, resulting in an incremental cost-effectiveness ratio of $46,900 per QALY. One-way sensitivity analyses showed the model was most sensitive to mean OFF-time hours associated with opicapone and entacapone. Probabilistic sensitivity analysis suggested a 60-65% probability that opicapone was cost-effective relative to entacapone at any willingness-to-pay threshold ≥$5,000. LIMITATIONS: There exists a single head-to-head clinical trial comparing the effectiveness of opicapone with entacapone, thus the clinical inputs regarding relative treatment effect of the drugs to reduce OFF-time hours in PD patients receiving LD/CD were derived from that single non-inferiority trial. CONCLUSIONS: Add-on treatment with opicapone in PD patients receiving LD/CD appeared to be cost-effective compared with entacapone.

Effect of Treatment with the PD-1/PD-L1 Inhibitors on Key Health Outcomes of Cancer Patients.

BACKGROUND: Recent studies have shown that treatment with the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor class could significantly improve survival outcomes in several oncology indications. However, there is some clinical uncertainty. OBJECTIVE: This study aimed to obtain high-level estimates of the impact of treatment with PD-1/PD-L1 inhibitor class to oncology treatment on key health outcomes in real-world situations and to inform public health policy decisions about cancer care after reducing uncertainties around new immuno-oncology therapy options in South Korea. METHODS: A model was developed to estimate the impact of PD-1/PD-L1 inhibitors on outcomes in situations wherein both anti-PD-1/PD-L1s and standard of care (SOC) were available versus SOC only. A partitioned survival model was utilized to estimate the impact of introducing anti-PD-1/PD-L1s on outcomes, including life-years gained, quality-adjusted life-years gained, progression-free survival-years obtained, and grade 3 or higher adverse events avoided for six indications over 5 years. An exponential distribution was fitted to the survival function of the SOC based on visual inspection. Outcomes associated with anti-PD-1/PD-L1s were estimated using a piecewise modeling approach with Kaplan-Meier analysis followed by best-fitting survival analysis. The incident number of patients and market share of anti-PD-1/PD-L1s during 2020-2024 were projected using published literature and Korean market survey data. Sensitivity analyses were performed to test the uncertainty of input parameters. RESULTS: During the next 5-year period (2020-2024), introducing the anti-PD-1/PD-L1 class led to a gain of 22,001 life-years (+ 31%), 19,073 quality-adjusted life-years (+ 38%), and 22,893 progression-free survival-years (+ 82%); it also avoided 3610 adverse events (- 11%) compared with SOC alone. Most adverse events associated with anti-PD-1/PD-L1s were attributed to combination therapy with cytotoxic chemotherapy (91%). In a scenario wherein the time to reimbursement of the anti-PD-1/PD-L1s was accelerated by 1 year, the life-years gained increased by 14% compared with the base-case scenario. CONCLUSIONS: Anti-PD-1/PD-L1 therapy is expected to provide marked survival benefits for patients with cancer. This study demonstrated the potentially beneficial health impacts of utilizing the anti-PD-1/PD-L1 class at the population level. The findings could inform health policy decision makers about cancer care and ultimately enhance population health through rapid access to innovative cancer drugs.