Association of Hospitals' Experience with Bundled Payment for Care Improvement Model with the Diffusion of Acute Hospital Care at Home.

OBJECTIVE: To examine whether hospitals' experience in a prior payment model incentivizing care coordination is associated with their decision to adopt a new payment program for a care delivery innovation. DATA SOURCES: Data were sourced from Medicare fee-for-service claims in 2017, the list of participants in Bundled Payment for Care Improvement initiatives (BPCI and BPCI-Advanced), the list of hospitals approved for Acute Hospital Care at Home (AHCaH) between November 2020 and August 2022, and the American Hospital Association Survey. STUDY DESIGN: Retrospective cohort study. Hospitals' adoption of AHCaH was measured as a function of hospitals' BPCI experiences. Hospitals' BPCI experiences were categorized into five mutually exclusive groups: (1) direct BPCI participation, (2) indirect participation through physician group practices (PGPs) after dropout, (3) indirect participation through PGPs only, (4) dropout only, and (5) no BPCI exposure. DATA COLLECTION/EXTRACTION METHODS: All data are derived from pre-existing sources. General acute hospitals eligible for both BPCI initiatives and AHCaH are included. PRINCIPAL FINDINGS: Of 3248 hospitals included in the sample, 7% adopted AHCaH as of August 2022. Hospitals with direct BPCI experience had the highest adoption rate (17.7%), followed by those with indirect participation through BPCI physicians after dropout (11.8%), while those with no exposure to BPCI were least likely to participate (3.2%). Hospitals that adopted AHCaH were more likely to be located in communities where more peer hospitals participated in the program (median 10.8% vs. 0%). After controlling for covariates, the association of the adoption of AHCaH with indirect participation through physicians after dropout was as strong as with early BPCI adopter hospitals (average marginal effect: 5.9 vs. 6.2 pp, p < 0.05), but the other categories were not. CONCLUSIONS: Hospitals that participated in the bundled payment model either directly or indirectly PGPs were more likely to adopt a care delivery innovation requiring similar competence in the next period.

Hospital and Physician Group Practice Participation in Prior and Next-Generation Value-Based Payment Programs.

This cohort study examines whether prior direct or indirect participation in the Centers for Medicare & Medicaid Innovation Bundled Payments for Care Improvement (BCPI) Initiative was associated with their participation in the next generation of the program.

Characteristics of Prescription Drug Fills Using Pharmacy-Pharmacy Benefit Manager Discount Programs: The "GoodRx" Model.

OBJECTIVES: This study aimed to characterize products using pharmacy-pharmacy benefit manager (PBM) discounts and to estimate the association among such discounts, prescription utilization, and out-of-pocket costs. METHODS: This is a retrospective cohort study using IQVIA's Formulary Impact Analyzer, which contains anonymized, individual-level pharmacy claims representing US retail pharmacy transactions. We focused on 20 products with the greatest number of transactions using a pharmacy-PBM discount. Our unit of analysis was a treatment episode, defined as the length of time from an incident fill to no continuous use for 60 consecutive days after allowing for indefinite stockpiling. Outcome measures included products with greatest pharmacy-PBM discount use, characteristics of treatment episodes, and out-of-pocket costs with and without pharmacy-PBM discount. RESULTS: Across all products, 3.82% of transactions and 7.69% of treatment episodes were accompanied by a pharmacy-PBM discount. Commonly discounted products included generic treatments for chronic disease (lisinopril, levothyroxine, metformin) and neuropsychiatric conditions (alprazolam, amphetamine, buprenorphine, hydrocodone). The median postdiscount out-of-pocket cost was >2.5-fold higher during treatment episodes with a discount than those without ($15.15, interquartile range [IQR] $8.53-32.00, vs $5.88, IQR $1.40-15.00). Median treatment episode duration was 249 days (IQR 132-418) with discount use compared with 236 days (IQR 121-396) without discount use, although treatment episodes that began with a discount had fewer transactions per treatment episode and were shorter (median 212 days, IQR 114-360) than those that did not (313 days, IQR 178-500). CONCLUSIONS: Pharmacy-PBM discounts may foster market competition and improve access for under- and uninsured individuals; however, these programs may not generate savings for many insured individuals.

Protocol for the development of joint attention-based subclassification of autism spectrum disorder and validation using multi-modal data.

BACKGROUND: Heterogeneity in clinical manifestation and underlying neuro-biological mechanisms are major obstacles to providing personalized interventions for individuals with autism spectrum disorder (ASD). Despite various efforts to unify disparate data modalities and machine learning techniques for subclassification, replicable ASD clusters remain elusive. Our study aims to introduce a novel method, utilizing the objective behavioral biomarker of gaze patterns during joint attention, to subclassify ASD. We will assess whether behavior-based subgrouping yields clinically, genetically, and neurologically distinct ASD groups. METHODS: We propose a study involving 60 individuals with ASD recruited from a specialized psychiatric clinic to perform joint attention tasks. Through the examination of gaze patterns in social contexts, we will conduct a semi-supervised clustering analysis, yielding two primary clusters: good gaze response group and poor gaze response group. Subsequent comparison will occur across these clusters, scrutinizing neuroanatomical structure and connectivity using structural as well as functional brain imaging studies, genetic predisposition through single nucleotide polymorphism data, and assorted socio-demographic and clinical information. CONCLUSIONS: The aim of the study is to investigate the discriminative properties and the validity of the joint attention-based subclassification of ASD using multi-modality data. TRIAL REGISTRATION: Clinical trial, KCT0008530, Registered 16 June 2023, https://cris.nih.go.kr/cris/index/index.do .

Comparison of Out-of-Pocket Spending on Ultra-Expensive Drugs in Medicare Part D vs Commercial Insurance.

Importance: Little is known about how out-of-pocket burden differs between Medicare and commercial insurance for ultra-expensive drugs. Objective: To investigate out-of-pocket spending for ultra-expensive drugs in the Medicare Part D program vs commercial insurance. Design, Setting, and Participants: This was a retrospective, population-based cohort study of individuals using ultra-expensive drugs included in a 20% nationally random sample of prescription drug claims from Medicare Part D and individuals aged 45 to 64 years using ultra-expensive drugs included in a large national convenience sample of outpatient pharmaceutical claims from commercial insurance plans. Claims data from 2013 through 2019 were used, and data were analyzed in February 2023. Main Outcomes and Measures: Claims-weighted mean out-of-pocket spending per beneficiary per drug by insurance type, plan, and age. Results: In 2019, 37 324 and 24 159 individuals using ultra-expensive drugs were identified in the 20% Part D and commercial samples, respectively (mean [SD] age, 66.2 [11.7] years; 54.9% female). A statistically significant higher share of commercial enrollees vs Part D beneficiaries were female (61.0% vs 51.0%; P < .001), and a statistically significantly lower share were using 3 or more branded medications (28.7% vs 42.6%; P < .001). Mean out-of-pocket spending per beneficiary per drug in 2019 was $4478 in Part D (median [IQR], $4169 [$3369-$5947]) compared with $1821 for commercial (median [IQR], $1272 [$703-$1924]); these differences were statistically significant every year. Differences in out-of-pocket spending comparing commercial enrollees aged 60 to 64 years and Part D beneficiaries aged 65 to 69 years exhibited similar magnitudes and trends. By plan, mean out-of-pocket spending per beneficiary per drug in 2019 was $4301 (median [IQR], $4131 [$3000-$6048]) in Medicare Advantage prescription drug (MAPD) plans, $4575 (median [IQR], $4190 [$3305-$5799]) in stand-alone prescription drug plans (PDPs), $1208 (median [IQR], $752 [$317-$1240]) in health maintenance organization plans, $1569 (median [IQR], $838 [$481-$1472]) in preferred provider organization plans, and $4077 (median [IQR], $2882 [$1075-$4226]) in high-deductible health plans. There were no statistically significant differences between MAPD plans and stand-alone PDPs in any study year. Mean out-of-pocket spending was statistically significantly higher in MAPD plans compared with health maintenance organization plans and in stand-alone PDPs compared with preferred provider organization plans in each study year. Conclusions and Relevance: This cohort study demonstrated that the $2000 out-of-pocket cap included in the Inflation Reduction Act may substantially moderate the potential increase in spending faced by individuals who use ultra-expensive drugs when moving from commercial insurance to Part D coverage.

Patterns of Manufacturer Coupon Use for Prescription Drugs in the US, 2017-2019.

Importance: Although manufacturer-sponsored coupons are commonly used, little is known about how patients use them within a treatment episode. Objectives: To examine when and how frequently patients use manufacturer coupons during a treatment episode for a chronic condition, and to characterize factors associated with more frequent use. Design, Setting, and Participants: This is a retrospective cohort study of a 5% nationally representative sample of anonymized longitudinal retail pharmacy claims data from October 1, 2017, to September 30, 2019, obtained from IQVIA's Formulary Impact Analyzer. The data were analyzed from September to December 2022. Patients with new treatment episodes using at least 1 manufacturer coupon over a 12-month period were identified. This study focused on patients with 3 or more fills for a given drug and characterized the association of the outcomes of interest with patient, drug, and drug class characteristics. Main Outcomes and Measures: The primary outcomes were (1) the frequency of coupon use, measured as the proportion of prescription fills accompanied by manufacturer coupon within the treatment episode, and (2) the timing of first coupon use relative to the first prescription fill within the treatment episode. Results: A total of 36 951 treatment episodes accounted for 238 474 drug claims and 35 352 unique patients (mean [SD] age, 48.1 [18.2] years; 17 676 women [50.0%]). Among these episodes, nearly all instances (35 103 episodes [95.0%]) of first coupon use occurred within the first 4 prescription fills. Approximately two-thirds of treatment episodes (24 351 episodes [65.9%]) used a coupon for the incident fill. Coupons were used for a median (IQR) of 3 (2-6) fills. The median (IQR) proportion of fills with a coupon was 70.0% (33.3%-100.0%), and many patients discontinued the drug after the last coupon. After adjustment for covariates, there was no significant association between an individual's out-of-pocket costs or neighborhood-level income and the frequency of coupon use. The estimated proportion of fills with a coupon was greater for products in competitive (19.5% increase; 95% CI, 2.1%-36.9%) or oligopolistic (14.5% increase; 95% CI, 3.5%-25.6%) markets than monopoly markets when there is only 1 drug in the therapeutic class. Conclusions and Relevance: In this retrospective cohort analysis of individuals receiving pharmaceutical treatment for chronic diseases, the frequency of manufacturer-sponsored drug coupon use was associated with the degree of market competition, rather than patients' out-of-pocket costs.

Macrophages in juvenile pig testis: Link with increase in Sertoli cells induced by oestradiol suppression.

Macrophage presence and location were evaluated in juvenile boar testes at the end of the first wave of Sertoli cell proliferation. Macrophage presence was compared in littermate boars treated with letrozole, a treatment which extended this first wave of proliferation beyond the sampling timepoint. Macrophages were identified as the CD68 positive cells following immunohistochemical labelling of paraffin sections and parenchymal macrophages enumerated. Macrophages present in a layer beneath the tunica albuginea received a score based on density and thickness of this layer. Density within the testicular parenchyma was highly variable in vehicle-treated boars (>100-fold) and did not differ from that observed in the letrozole-treated littermates. However, the macrophage layer beneath the tunica albuginea was denser and thicker in the letrozole-treated animals than in their vehicle-treated littermates. This suggests that macrophages might be involved in the letrozole-induced prolongation of Sertoli cell proliferation.

Investigating the effects of physical properties of sulphur-based carriers on autotrophic denitrification.

In this study, four sulphur-based carriers (C1-C4) which have different mass ratio of sodium silicate to carrier from 30% to 50% (C1-C3) and the existence of water (C4) were prepared in order to evaluate the effect of the different physical properties on denitrification in sulphur-based autotrophic processes. While the apparent density and the compressive strength decreased as the proportion of sodium silicate increased and water was added in the carriers, the average pore size and the porosity increased from 0.43 to 3.13 µm and from 38% to 67%, respectively. The treatment system using the carrier C4 with the highest surface area was stabilized most rapidly and achieved the highest nitrogen removal efficiency of 85.6 ± 5.0% during a relatively short HRT of 3 h. The efficiency of nitrate removal was enhanced by 36.9% due to the increase of the ratio of sodium silicate in the carriers from C1 to C3, and more 4.8% point of removal rate increased in the carrier C4 by adding water to the carrier C3. The sum of Thiobacillus and Sulfurimonas was obtained up to 65.90% among the microbial community in the carrier C4 which has the highest distribution (38.35%) of pore size above 20 µm considered to be favourable for retaining autotrophic denitrifiers. From the above results, it is obvious that the physical properties of the sulphur-based carrier and its ability of denitrification can be influenced significantly by the composition of the carrier.

Association of hormone therapy and changes of objective sleep quality in women of late menopausal transition with sleep disorder: a preliminary study.

OBJECTIVE: The aim of this study was to investigate changes in objective sleep quality with hormone therapy (HT) in women with late menopausal transition. METHODS: Healthy midlife women with sleep difficulty who received HT were included. Those undergoing late menopausal transition were screened. Sleep patterns and self-reported questionnaires were collected before and 10 weeks after starting HT. RESULTS: Ten women who met the criteria (age, 50.1 ± 2.8 years) showed higher sleep efficiency and shorter wakefulness after sleep onset (WASO) 10 weeks after starting HT. However, no significant change was found in objective sleep quality after adjustment for multiple comparisons: sleep efficiency, 84.2 ± 7.7 versus 88.2% ± 4.7%, P = 0.037, adjusted P = 0.259; WASO, 59.0 ± 27.2 minutes versus 41.4 ± 17.4 minutes, P = 0.020, adjusted P = 0.140; average duration per awakening, 2.9 ± 1.0 minutes versus 2.2 ± 0.5 minutes, P = 0.033, adjusted P = 0.231. A better score of subjective sleep quality in the Pittsburgh Sleep Quality Index was observed 10 weeks after starting HT (2.0 ± 0.0 vs 1.2 ± 0.4, P = 0.006, adjusted P = 0.042), but sensitivity analysis did not show consistent results after adjustment for multiple comparisons (2.0 ± 0.0 vs 1.1 ± 0.4, P = 0.020, adjusted P = 0.140). Total scores of the Insomnia Severity Index and Menopause Rating Scale were better 10 weeks after starting HT (Insomnia Severity Index, 14.7 ± 3.0 vs 9.1 ± 3.8, P = 0.010; Menopause Rating Scale, 29.0 ± 5.2 vs 21.6 ± 3.0, P = 0.009) with consistent results in sensitivity analyses. There was no difference in the Epworth Sleepiness Scale before and after HT (7.2 ± 1.7 vs 8.6 ± 4.5, P = 0.309). The change in each objective sleep quality variable before and after HT showed strong positive or negative correlations with the change in only a few items in subjective sleep quality. CONCLUSION: Women in the late menopausal transition period showed higher sleep efficiency and shorter WASO after HT; however, multiple comparisons showed no statistically significant difference in objective sleep quality between before and after HT.

Panax notoginseng Saponins Protect Brain Microvascular Endothelial Cells against Oxygen-Glucose Deprivation/Resupply-Induced Necroptosis via Suppression of RIP1-RIP3-MLKL Signaling Pathway.

Recently, necroptosis has emerged as one of the important mechanisms of ischemia stroke. Necroptosis can be rapidly activated in endothelial cells to cause vascular damage and neuroinflammation. Panax notoginseng saponins (PNS), an ingredient extracted from the root of Panax notoginseng (Burk.) F.H. Chen, was commonly used for ischemic stroke, while its molecular mechanism and targets have not been fully clarified. Our study aimed to clarify the anti-necroptosis effect of PNS by regulating RIP1-RIP3-MLKL signaling pathway in brain microvascular endothelial cells (BMECs) subjected to transient oxygen-glucose deprivation (OGD/resupply [R]). In vitro, the necroptosis model of rat BMECs was established by testing the effect of OGD/R in the presence of the pan-caspase inhibitor z-VAD-FMK. After administration of PNS and Nec-1, cell viability, cell death modality, the expression of RIP1-RIP3-MLKL pathway and mitochondrial membrane potential (Δψm) level were investigated in BMECs upon OGD/R injury. The results showed that PNS significantly enhanced cell viability of BMECs determined by CCK-8 analysis, and protected BMECs from necroptosis by Flow cytometry and TEM. In addition, PNS inhibited the phosphorylation of RIP1, RIP3, MLKL and the downstream expression of PGAM5 and Drp1, while similar results were observed in Nec-1 intervention. We further investigated whether PNS prevented the Δψm depolarization. Our current findings showed that PNS effectively reduced the occurrence of necroptosis in BMECs exposed to OGD/R by inhibition of the RIP1-RIP3-MLK signaling pathway and mitigation of mitochondrial damage. This study provided a novel insight of PNS application in clinics.

Reproductive Life Span and Severe Hypoglycemia Risk in Postmenopausal Women with Type 2 Diabetes Mellitus.

BACKGROUND: Estrogen promotes glucose homeostasis, enhances insulin sensitivity, and maintains counterregulatory responses in recurrent hypoglycemia in women of reproductive age. Postmenopausal women with type 2 diabetes mellitus (T2DM) might be more vulnerable to severe hypoglycemia (SH) events. However, the relationship between reproductive factors and SH occurrence in T2DM remains unelucidated. METHODS: This study included data on 181,263 women with postmenopausal T2DM who participated in a national health screening program from January 1 to December 31, 2009, obtained using the Korean National Health Insurance System database. Outcome data were obtained until December 31, 2018. Associations between reproductive factors and SH incidence were assessed using Cox proportional hazards models. RESULTS: During the mean follow-up of 7.9 years, 11,279 (6.22%) postmenopausal women with T2DM experienced SH episodes. A longer reproductive life span (RLS) (≥40 years) was associated with a lower SH risk compared to a shorter RLS (<30 years) (adjusted hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.69 to 0.80; P for trend <0.001) after multivariable adjustment. SH risk decreased with every 5-year increment of RLS (with <30 years as a reference [adjusted HR, 0.91; 95% CI, 0.86 to 0.95; P=0.0001 for 30-34 years], [adjusted HR, 0.80; 95% CI, 0.76 to 0.84; P<0.001 for 35-39 years], [adjusted HR, 0.74; 95% CI, 0.68 to 0.81; P<0.001 for ≥40 years]). The use of hormone replacement therapy (HRT) was associated with a lower SH risk than HRT nonuse. CONCLUSION: Extended exposure to endogenous ovarian hormone during lifetime may decrease the number of SH events in women with T2DM after menopause.

Association between Serum Uric Acid Levels and Bone Mineral Density in Postmenopausal Women: A Cross-Sectional and Longitudinal Study.

BACKGROUND: Uric acid is one of natural antioxidants in human body. There have been several studies on the correlation between uric acid with oxidative stress and osteoporosis. However, the data are insufficient and results are controversial. In this regard, we determined the association between uric acid levels and bone mineral density (BMD) during the postmenopausal period. METHODS: We analyzed data from 328 postmenopausal women (mean age, 57.3 ± 6.5 years; mean serum uric acid level, 4.6 ± 1.0 mg/dL). The participants were divided into three groups based on tertiles of the serum uric acid level. The participants receiving hormone replacement therapy (HRT), bisphosphonates, or lipid-lowering agents were included. RESULTS: Blood urea nitrogen, serum creatinine, and serum triglyceride levels were significantly higher in the upper tertiles of uric acid levels. No significant difference was found in the mean uric acid levels between medication users and non-users. Each HRT regimen had a different mean serum uric acid level. A cross-sectional analysis showed no significant correlation between the serum uric acid levels and BMD in the spine and femoral neck (spine BMD: 1.050 ± 0.131, 1.060 ± 0.160, 1.084 ± 0.140, p = 0.22; femoral neck BMD: 0.837 ± 0.110, 0.849 ± 0.096, 0.863 ± 0.115, p = 0.28 for each tertile of uric acid). Longitudinal analysis of data from 186 women with follow-up examinations at a mean interval of 14.6 months also revealed no difference in reduction in both spine and femoral neck BMD between tertile groups of serum uric acid (the median BMD reduction for spine: -0.02, 0.01, -0.04, p = 0.95; the median BMD reduction for femoral neck: 0.008, 0.005, -0.003, p = 0.34). CONCLUSIONS: Serum uric acid level is not associated with BMD in postmenopausal women.

Safety Assessment of Endocrine Disruption by Menopausal Health Functional Ingredients.

During menopause, women experience various symptoms including hot flashes, mood changes, insomnia, and sweating. Hormone replacement therapy (HRT) has been used as the main treatment for menopausal symptoms; however, other options are required for women with medical contraindications or without preference for HRT. Functional health foods are easily available options for relieving menopausal symptoms. There are growing concerns regarding menopausal functional health foods because the majority of them include phytoestrogens which have the effect of endocrine disruption. Phytoestrogens may cause not only hormonal imbalance or disruption of the normal biological function of the organ systems, but also uterine cancer or breast cancer if absorbed and accumulated in the body for a long period of time, depending on the estrogen receptor binding capacity. Therefore, we aimed to determine the effects and safety of menopausal functional health ingredients and medicines on the human body as endocrine disruptors under review in the literature and the OECD guidelines.

The RIG-I Signal Pathway Mediated Panax notoginseng Saponin Anti-Inflammatory Effect in Ischemia Stroke.

Panax notoginseng saponins (PNS), the main bioactive constituents of a traditional Chinese herb Panax notoginseng, were commonly used for ischemic stroke in China. However, the associated cellular and molecular mechanisms of PNS have not been well examined. This study aimed to decipher the underlying molecular target of PNS in the treatment of cerebral ischemia. The oxygen-glucose-deprived (OGD) model of rat brain microvascular endothelial cells (BMECs) was used in this study. The alteration of gene expression in rat BMECs after PNS treatment was measured by microarray and indicated that there were 38 signaling pathways regulated by PNS. Among them, RIG-I receptor and related signaling molecules TNF receptor-associated factor 2 (Traf2) and nuclear factor-kappa B (NF-κB) were significantly suppressed by PNS, which was verified again in OGD-induced BMECs measured by FQ-PCR and western blotting and in middle cerebral artery occlusion (MCAO) rats measured by immunohistochemistry. The levels of TNF-α, IL-8, and the downstream cytokines regulated by RIG-I receptor pathway were also decreased by PNS. Meanwhile, the neurological evaluation, hematoxylin and eosin (HE) staining, and Evans blue staining were conducted to evaluate the effect of PNS in MCAO rats. Results showed PNS significantly improved functional outcome and cerebral vascular leakage. Flow cytometry showed the number of the inflammatory cells infiltrated in brain tissue was decreased in PNS treatment. Our results identified that RIG-I signaling pathway mediated anti-inflammatory properties of PNS in cerebral ischemia, which provided the novel insights of PNS application in clinics.

Ultra-Expensive Drugs And Medicare Part D: Spending And Beneficiary Use Up Sharply.

The proliferation of "ultra-expensive" drugs has sparked debate on their sustainability and affordability. Medicare Part D's share of annual spending on these drugs increased by 1,170 percent between 2012 and 2018, largely because the number of beneficiaries receiving them increased during this period.

Variables that prolong total operative time for robotic-assisted laparoscopic myomectomy: A 10-year tertiary hospital study in Korea.

STUDY OBJECTIVE: To identify factors that prolong total operative time (TOT) in robotic-assisted laparoscopic myomectomy (RALM). DESIGN: Retrospective cohort study. SETTING: Tertiary university hospital. PATIENTS: Women who underwent RALM between April 2009 and May 2019 conducted by a single high-volume gynecologic surgeon. INTERVENTIONS: Patients' demographic data and intraoperative records were obtained. The association between the perioperative characteristics and TOT was analyzed. MEASUREMENTS AND MAIN RESULTS: A total of 584 cases met the inclusion criteria, with a mean TOT of 231.6 ± 86.7 min. The mean patient age was 36.3 ± 5.5 years, and the patients had a mean of 4.2 ± 4.0 myomas. The dominant myoma had a mean diameter of 7.6 ± 2.6 cm. The mean total weight of the extracted myomas removed was 202.2 ± 152.6 g. From multiple regression analysis, the following perioperative factors were intimately associated with the TOT: ① body mass index, ② the number of myomas, ③ weight of total myomas, ④ location of dominant myoma, ⑤ type of da Vinci robot system, ⑥ endometrial cavity opening during the operation, ⑦ intraoperative blood loss, and ⑧ patient hospitalization period. The number of myoma was most closely related to the TOT, with an R2 value of 0.330. All of the above factors with the exception of the type of robot system and location of dominant myoma were related to the console time. Age, parity, history of previous abdominal surgery, surgical indication, diameter, and FIGO classification were not associated with the TOT. CONCLUSION: With an accurate identification of the perioperative parameters above, we can improve the quality of RALM by counselling, selecting an appropriate patient selection, and preoperative planning.

Characteristics of Copayment Offsets for Prescription Drugs in the United States.

Importance: Despite ongoing debate regarding the high prices that patients pay for prescription drugs, to our knowledge, little is known regarding the use of coupons, vouchers, and other types of copayment "offsets" that reduce patients' out-of-pocket drug spending. Although offsets reduce patients' immediate cost burden, they may encourage the use of higher-cost products and diminish health insurers' ability to optimize pharmaceutical value. Objective: To examine the drugs most commonly covered by offsets, the percentage of out-of-pocket costs covered by offsets, and the characteristics of patients using offsets for retail pharmacy transactions in the United States in 2017 through 2019. Design, Setting, and Participants: A retrospective cohort analysis was conducted of a 5% nationally random sample of anonymized pharmacy claims from IQVIA's Formulary Impact Analyzer, which captures more than 60% of all US pharmacy transactions. This analysis focused on 631 249 individuals who used at least 1 offset between October 1, 2017, and September 30, 2019. Main Outcomes and Measures: Offset source, types of drugs covered by offsets, offset dollar value and percentage of out-of-pocket payment covered, and county characteristics of offset recipients. Results: The 631 249 individuals in the study (361 855 female participants [57.3%]; mean [SD] age, 45.7 [18.6] years) had approximately 33 million prescription fills, of which 12.8% had an offset used. Of these, 50.2% originated from a pharmaceutical manufacturer, 47.2% originated from a pharmacy or pharmacy benefit manager (PBM), and 2.6% originated from a state assistance program. A total of 80.0% of manufacturer-sponsored offsets were concentrated among 6.2% of unique products, and 79.9% of pharmacy-PBM offsets were concentrated among 4.9% of unique products. Most manufacturer offsets (88.2%) were for branded products, while most pharmacy-PBM offsets were for generic products (90.5%). The median manufacturer offset was $51.00, covering 87.1% of out-of-pocket costs; the median pharmacy-PBM offset was $16.30, covering 39.3% of out-of-pocket costs. There was no meaningful association between offset magnitude and county-level income, health insurance coverage, or race/ethnicity. Conclusions and Relevance: In this analysis of patient-level pharmacy claims from 2017 to 2019, approximately half of all offsets involved pharmacy-PBM contractual arrangements, and half were offered by manufacturers. All offsets were associated with a significant reduction in patients' out-of-pocket costs, were highly concentrated among a few drugs, and were generally not more generous among individuals in counties with lower income or larger Black or uninsured populations.

Assessing the Added Therapeutic Benefit of Ultra-Expensive Drugs.

OBJECTIVES: While the United States does not have a method for assessing the added therapeutic benefit of drugs, France, Canada, and Germany do. We examined the added therapeutic benefit of the most expensive drugs prescribed to Medicare Part D beneficiaries in the United States. METHODS: We identified ultra-expensive drugs with annual Medicare spending that exceeded $62 794 (United States GDP per capita in 2018) using Medicare Part D Prescription Drug Spending and Utilization Data. We used added therapeutic benefit ratings assessed by health technology assessment agencies in France, Canada, and Germany. RESULTS: We identified 122 ultra-expensive drugs in 2018. Sixty-five percent of these drugs (n = 79) were assessed by at least one of the countries. Based on these assessments, approximately 75% received a low added therapeutic benefit rating. CONCLUSIONS: Most ultra-expensive drugs prescribed in the United States and assessed by France, Canada, and Germany provide low added therapeutic benefit. Policy reforms in the United States could use added therapeutic benefit to inform coverage and pricing decisions for ultra-expensive drugs. Similar to Germany, one approach would be to allow the company to set a market price for a limited period of time before requiring a price reduction if the added therapeutic benefit is below a certain threshold. Another approach would be to identify when drug prices are substantially more expensive in the United States and conduct an added therapeutic benefit assessment and price review on these drugs.

Factors Associated With Manufacturer Drug Coupon Use at US Pharmacies.

Importance: Drug companies offer coupons to lower the out-of-pocket costs for prescription drugs, yet little is known about why they do so for some drugs but not for others. Objective: To examine whether the following factors are associated with manufacturer drug coupon use: (1) patient-cost characteristics (mean per-patient cost per drug, mean patient copay); (2) drug characteristics (generics availability or "later-in-class-entrant" drugs); (3) drug-class characteristics (in-class coupon use among competitors; in-class generic competition; in-class mean cost and copay). Design Setting and Participants: This was a retrospective cohort analysis of anonymized transactional pharmacy claims sourced from retail US pharmacies from October 2017 to September 2019, supplemented with information derived from Medi-Span, Red Book, and FDA.gov. Data were analyzed from September 2020 to February 2021. Main Outcomes and Measures: The primary outcome was availability of a manufacturer's coupon. The secondary outcome was the mean proportion of transactions in which a coupon was used for each product. Results: The sample of 2501 unique brand-name prescription drugs accounted for a total of 8 995 141 claims. Manufacturers offered a coupon for 1267 (50.7%) of these drugs. When the manufacturer offered a coupon, it was used in a mean (SD) 16.3% (20.3%) of the transactions. Within a drug class, higher mean total cost per patient was positively associated with the likelihood of coupon use (odds ratio [OR], 1.03 per 10% increase; 95% CI, 1.01-1.04), but higher mean patient copay was inversely associated (OR, 0.98; 95% CI, 0.97-0.99). For drug characteristics, single-source later-in-class-entrant products were associated with a greater likelihood of coupon use compared with first entrants and multisource brands (OR, 1.44; 95% CI, 1.09-1.89). The intensity of coupon use was associated with later-in-class-entrant products and the class mean per-patient cost (4.16-percentage-point increase; 95% CI, 1.20-7.13; 0.27 per 10% increase; 95% CI, 0.09-0.44). Drugs with a new in-class brand-name competitor had greater mean coupon use compared with drugs without a new competitor (10.2% of claims with a coupon vs 5.9%). Conclusions and Relevance: In this cohort study of transactional pharmacy claims, higher mean per-patient total cost within a class was significantly associated with the likelihood of coupon use, but not patient out-of-pocket cost. Manufacturers' coupons were more likely to be used for expensive later-in-class-entrant products facing within-class competition where coupon use was prevalent.

Critical Care Beds With Continuous Lateral Rotation Therapy to Prevent Ventilator-Associated Pneumonia and Hospital-Acquired Pressure Injury: A Cost-effectiveness Analysis.

OBJECTIVES: Mechanical ventilation increases the risk of hospital-acquired conditions (HACs) such as ventilator-associated pneumonia (VAP) and pressure injury (PrI). Beds with continuous lateral rotation therapy (CLRT) are shown to reduce HAC incidence, but the value of switching to CLRT beds is presently unknown. We compared the cost-effectiveness of CLRT beds with standard care in intensive care units. METHODS: A cost-effectiveness analysis from the healthcare sector and societal perspectives was conducted. A Markov model was constructed to predict health state transitions from time of ventilation through 28 days for the healthcare sector perspective and 1 year for the U.S. societal perspective. Value of information was calculated to determine whether parameter uncertainty warranted further research. RESULTS: Our analysis suggested that CLRT beds dominate standard care from both perspectives. From the healthcare sector perspective, expected cost for CLRT was U.S. $47,165/patient compared with a higher cost of U.S. $49,258/patient for standard care. The expected effectiveness of CLRT is 0.0418 quality-adjusted life years/patient compared with 0.0416 quality-adjusted life years/patient for standard care. Continuous lateral rotation therapy dominated standard care in approximately 93% of Monte Carlo simulations from both perspectives. Value of information analysis suggests that additional research is potentially cost-effective. CONCLUSIONS: Continuous lateral rotation therapy is highly cost-effective compared with standard care by preventing HACs that seriously harm patients in the intensive care unit.