Drugs anticipated to be selected for the Medicare Drug Price Negotiation Program in 2025.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) recently announced the Maximum Fair Price for the first 10 Medicare Part D drugs selected for price negotiation. By February 2025, CMS should announce the list of Part D drugs to be negotiated with implementation of the negotiated prices in 2027. OBJECTIVE: To identify up to 15 Medicare Part D single-source drugs anticipated to be selected by CMS for price negotiation in 2025. METHODS: We followed selection criteria identified in the Inflation Reduction Act and CMS guidance to identify drugs. We projected 2023 Part D gross spending using 2020-2022 data reported by CMS and linear prediction models. We ranked products according to the projected spending figure and identified those not eligible for selection because of (1) number of years since approval, (2) availability of a biosimilar or generic version, (3) approval for a single orphan indication, (4) whole human blood or plasma-derived, or (5) eligibility for the small biotech exception. RESULTS: We identified 13 products likely subject to Medicare drug price negotiation, including 4 anticancer therapies, 3 noninsulin antidiabetic products, 2 inhalers, 1 antifibrotic therapy, 1 gastrointestinal agent, 1 enzyme replacement therapy, and 1 product indicated for dyskinesia. These 13 products each had projected annual gross Part D spending more than $1 billion. We identified 7 additional products with uncertainty to complete the list of 15, including an insulin, an antiviral, an antibiotic, an immunologic agent, an antidiabetic, and 2 cancer drugs. These products had projected gross Part D spending between $877 million and $1.399 billion. Twenty-two products with comparable levels of spending were deemed ineligible for selection because of availability of a generic or biosimilar version (10 products), insufficient years since approval (8 products), eligibility for the small biotech exception (3 products), and expected market discontinuation (1 product). CONCLUSIONS: Our identification of products anticipated to be selected for negotiation in 2025 (with implementation of negotiated prices in 2027) will help inform manufacturers, payers, patients, and policymakers of the products that will likely see a decrease in Medicare drug prices as result of negotiation. We identified 22 products with levels of spending that are comparable with those anticipated to be selected for negotiation but are not eligible, primarily because of generic or biosimilar availability or insufficient time on market.

COVID-19 Diagnosis, Oral Anticoagulation, and Stroke Risk in Patients with Atrial Fibrillation.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of stroke. It remains unclear whether the risk of stroke associated with a diagnosis of COVID-19 differed with oral anticoagulation (OAC) use. The aim of this study was to evaluate the association between COVID-19 infection, OAC use, and stroke in patients with atrial fibrillation (AF). METHODS: A retrospective cohort study was conducted in individuals with established AF using data from Optum's deidentified Clinformatics® Data Mart Database. Cox proportional hazard models with time-dependent variables were employed to assess the association between possession of OAC, COVID-19 diagnosis in both inpatient and outpatient setting, and time to ischemic stroke. RESULTS: A total of 561,758 individuals aged 77 ± 10 were included in the study, with a mean follow up time of 1.3 years. OAC use was associated with a reduced stroke risk [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.82-0.88]. COVID-19 infection was associated with an increased risk of stroke (HR 2.11, 95% CI 1.87-2.38); this increased risk was particularly pronounced for patients diagnosed with an inpatient diagnosis of COVID-19 (HR 3.95, 95% CI 3.33-4.68). There was no significant interaction between OAC use and COVID-19 diagnosis (p value = 0.96). As a result, the relative increase in stroke risk associated with COVID-19 did not differ between patients on OAC (HR 2.12; 95% CI 1.71-2.62) and those not on OAC (HR 2.11; 95% CI 1.83-2.43). CONCLUSION: In a nationwide sample of patients with established AF, we found the relative increase in stroke risk associated with COVID-19 was independent of OAC use.

Pharmacoepidemiology evaluation of bumetanide as a potential candidate for drug repurposing for Alzheimer's disease.

INTRODUCTION: Bumetanide, a loop diuretic, was identified as a candidate drug for repurposing for Alzheimer's disease (AD) based on its effects on transcriptomic apolipoprotein E signatures. Cross-sectional analyses of electronic health records suggest that bumetanide is associated with decreased prevalence of AD; however, temporality between bumetanide exposure and AD development has not been established. METHODS: We evaluated Medicare claims data using Cox proportional hazards regression to evaluate the association between time-dependent use of bumetanide and time to first AD diagnosis while controlling for patient characteristics. Multiple sensitivity analyses were conducted to test the robustness of the findings. RESULTS: We sampled 833,561 Medicare beneficiaries, 60.8% female, with mean (standard deviation) age of 70.4 (12). Bumetanide use was not significantly associated with AD risk (hazard ratio 1.05; 95% confidence interval, 0.99-1.10). DISCUSSION: Using a nationwide dataset and a retrospective cohort study design, we were not able to identify a time-dependent effect of bumetanide lowering AD risk. HIGHLIGHTS: Bumetanide was identified as a candidate for repurposing for Alzheimer's disease (AD). We evaluated the association between bumetanide use and risk of AD. We used Medicare data and accounted for duration of bumetanide use. Bumetanide use was not significantly associated with risk of AD.

Price benchmarks of drugs selected for Medicare price negotiation and their therapeutic alternatives.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) are currently negotiating prices with pharmaceutical manufacturers for the first 10 Part D drugs selected for Medicare drug price negotiation. Non-publicly available data, including the net prices of selected drugs and their therapeutic alternatives, will play a central role in the determination of the maximum fair prices (MFPs). OBJECTIVE: To estimate price benchmarks involved in the derivation of the starting point of the CMS initial price offer for the 10 drugs selected for Medicare price negotiation. METHODS: For the 10 drugs selected for negotiation, we reported (1) the list price, (2) the net price after manufacturer discounts, (3) the maximum negotiated price based on the minimum statutory discount, and (4) the ceiling of the MFP, estimated as the lowest of the latter 2. We also estimated net prices for therapeutic alternatives to the selected drugs. Net prices were estimated using peer-reviewed methodology that isolates commercial discounts negotiated between payers and manufacturers from mandatory discounts under government programs. All price benchmarks were estimated at the product level, for 30-day equivalent dosing, using 2021 data. RESULTS: 6 products (apixaban, rivaroxaban, empagliflozin, sacubitril/valsartan, etanercept, and insulin aspart) had therapeutic alternatives with lower net prices, which will be integrated with clinical benefit data in the derivation of initial price offers. The other 4 products (ustekinumab, ibrutinib, sitagliptin, and dapagliflozin) had therapeutic alternatives with higher net prices than the drugs selected for negotiation. For ibrutinib and ustekinumab, prices based on the minimum discounts were considerably lower than the estimated net prices and will likely set the starting point of the initial price offer. For dapagliflozin and sitagliptin, the starting point of the initial price offer will likely resemble their existing net prices. CONCLUSIONS: Our analyses identify different negotiation scenarios for the first 10 drugs selected for Medicare price negotiation, based on key elements involved in the derivation of the initial price offer. Our analyses can help improve transparency in the negotiation process, because the CMS is not required to reveal the information used in the derivation of price offers.

Racial and ethnic inequities in spatial access to pharmacies: A geographic information system analysis.

BACKGROUND: Pharmacy accessibility is crucial for equity in health care access because community pharmacists may reach individuals who do not have access to other health care providers. OBJECTIVE: The objective of this study was to determine whether spatial access to pharmacies differs among racial/ethnic groups across the rural-urban continuum. METHODS: We obtained a 30% random sample of the Research Triangle Institute synthetic population, sampled at the census block level. For each individual, we defined optimal pharmacy access as having a driving distance ≤2 miles to the closest pharmacy in urban counties, ≤5 miles in suburban counties, and ≤10 miles in rural counties. We used a logistic regression model to measure the association between race/ethnicity and pharmacy access, while controlling for racial/ethnic composition of the census tract, area deprivation index, income, age, gender, and U.S. region. The model included an interaction between race/ethnicity and urbanicity to evaluate whether racial/ethnic inequities differed across the rural-urban continuum. RESULTS: The sample included 90,749,446 individuals of whom 80.6% had optimal pharmacy access. Racial/ethnic inequities in pharmacy access differed across the rural-urban continuum (P value for interaction= <0.0001). In rural areas, Black (OR 0.87; 95% CI 0.86-0.87), Hispanic (OR 0.80; 95% CI 0.79-0.80), and indigenous (OR 0.47; 95% CI 0.47-0.48) individuals had lower odds of optimal pharmacy access, than White individuals. Hispanic (OR 0.96; 95% CI 0.96-0.97) and Indigenous individuals (OR 0.75; 95% CI 0.75-0.76) had lower odds of optimal pharmacy access compared to White individuals in suburban areas. In Western states, Asian had lower odds of optimal pharmacy access in suburban (OR 0.88; 95% CI 0.86-0.90) and rural areas (OR 0.91; 95% CI 0.87-0.95) compared to White individuals. CONCLUSIONS: Racial/ethnic inequities in spatial access to community pharmacies vary between urban and rural communities. Underrepresented racial/ethnic groups have significantly lower pharmacy access in rural and some suburban areas, but not in urban areas.

COVID-19 pandemic and trends in clinical outcomes and medication use for patients with established atrial fibrillation: A nationwide analysis of claims data.

Study objective: The COVID-19 pandemic disrupted multiple aspects of the health care system, including the diagnosis and control of chronic conditions. This study aimed to quantify pandemic-related changes in the rates of clinical events among patients with atrial fibrillation (AF). Design/setting/participants: In this retrospective cohort study, we identified individuals with established AF at any time before 2019 using de-identified Optum's Clinformatics® Data Mart, and followed them from 3/18/2019 to death, or disenrollment, or the end of the study (09/30/2021). Main outcome: Rates of clinical event, including all-cause hospitalization, ischemic stroke, and bleeding. We constructed interrupted time series to test changes in outcomes after the onset of the COVID-19 pandemic (3/11/2020, date of pandemic declaration). We then identified the first month after the start of the pandemic in which outcomes returned to pre-pandemic levels. Results: A total of 561,758 patients, with a mean age of 77 ± 9.9 years, were included in the study. The monthly incidence rate of all-cause hospitalization decreased from 2.8 % in the period immediately before the pandemic declaration to 1.7 % in the period immediately after, with p-value for level change<0.001. The rate of new ischemic stroke diagnoses decreased from 0.28 % in the period immediately before pandemic declaration to 0.20 % in the period immediately after, and the rate of major bleeding diagnoses from 0.81 % to 0.59 %, both p-values for level change<0.01. The incidence rate of ischemic stroke and bleeding events returned to pre-pandemic levels in October and November 2020, respectively. Conclusions: The COVID-19 pandemic was associated with a decrease in health care visits for ischemic stroke and bleeding in a nationwide cohort of patients with established AF.

Medicare drug price negotiation: The complexities of selecting therapeutic alternatives for estimating comparative effectiveness.

Under the 2022 Inflation Reduction Act, the Centers for Medicare and Medicaid Services (CMS) are able to negotiate prices for topselling drugs in the Medicare Part B and D programs. In determining initial price offers, CMS will compare the prices and clinical benefits of the drugs subject to negotiation to the prices and clinical benefits of therapeutic alternatives. Despite the central role that the selection of therapeutic alternatives will play in the price negotiations, the available guidance published by CMS provides few details about how the organization will undertake this process, which will be particularly complex for drugs approved for more than one indication. To better inform the selection process, we identified all US Food and Drug Administration-approved indications for the first 10 drugs subject to negotiation. Using 2020-2021 Medicare claims data, we identified Medicare Part D beneficiaries using each of the 10 drugs. We extracted medical claims with diagnosis codes for each of the approved indications to report the relative treated prevalence of use by indication for each drug. We reviewed published clinical guidelines to identify relevant therapeutic alternatives for each of the indications. We integrated the evidence on the relative treated prevalence of indications and clinical guidelines to propose therapeutic alternatives for each of the 10 drugs. We describe challenges that CMS may face in selecting therapeutic alternatives.

COVID-19 pandemic and initiation of treatment for atrial fibrillation: a nationwide analysis of claims data.

BACKGROUND: The COVID-19 pandemic profoundly disrupted the delivery of medical care. It remains unclear whether individuals diagnosed with new onset disease during the pandemic were less likely to initiate treatments after diagnosis. We sought to evaluate changes in the treatment initiation of patients newly diagnosed with atrial fibrillation (AF) after the onset of the COVID-19 pandemic. METHODS: In this retrospective cohort study, we identified individuals with incident AF from 01/01/2016-09/30/2021 using Optum's de-identified Clinformatics® Data Mart Database. The primary outcome was initiation of oral anticoagulation (OAC) within 30 days of AF diagnosis. Secondary outcomes included initiation of OAC within 180 days of diagnosis, initiation of warfarin, direct oral anticoagulants (DOACs), rhythm control medications and electrical cardioversion within 30 days of diagnosis. We constructed interrupted time series analyses to examine changes in the outcomes following the onset of the pandemic. RESULTS: A total of 573,524 patients (age 73.0 ± 10.9 years) were included in the study. There were no significant changes in the initiation of OAC, DOAC, and rhythm control medications associated with the onset of the pandemic. There was a significant decrease in initiation of electrical cardioversion associated with the onset of the pandemic. The rate of electronic cardioversion within 30 days of diagnosis decreased by 4.9% per 1,000 patients after the onset of the pandemic and decreased by about 35% in April 2020, compared to April 2019, from 5.53% to 3.58%. CONCLUSION: The COVID-19 pandemic did not affect the OAC initiation within 30 days of AF diagnosis but was associated with a decline in the provision of procedures for patients newly diagnosed with AF.

Reimbursement to Pharmacies for Generic Drugs by Medicare Part D Sponsors.

This study evaluates whether organizations that offer Medicare Part D plans (referred to as Part D sponsors) overpay pharmacies for generic drugs.

Trends in Proportion of Medicare Part D Claims Subject to 340B Discounts, 2013-2020.

Importance: Despite controversy surrounding the 340B program, no study has analyzed trends in the proportion of Medicare Part D pharmacy claims eligible for 340B discounts. Objective: To describe trends in the proportion of Medicare Part D claims that are prescribed by 340B-affiliated clinicians and filled in 340B pharmacies. Design and Setting: This longitudinal, retrospective cohort study included 2013 to 2020 claims data from a 5% random sample of Medicare Part D beneficiaries from the Centers for Medicare & Medicaid Services and 6292 nine-digit national drug codes that were used by at least 1000 Part D beneficiaries in a given year. Data analysis was completed from November 2022 to April 2023. Main Outcomes and Measures: For each drug and year, there were 3 outcomes: (1) proportion of total Part D claims that were prescribed by a 340B-affiliated clinician; (2) proportion of claims prescribed by a 340B-affiliated clinician that were filled in a 340B pharmacy; and (3) proportion of total Part D claims under the 340B program (ie, prescribed by a 340B-affiliated clinician and filled in a 340B pharmacy). Results: The proportion of prescriptions written by a 340B-affiliated clinician doubled from 9.4% in 2013 to 19.3% in 2020. The capture of 340B prescriptions by 340B pharmacies, defined as the proportion of claims prescribed by 340B-affiliated clinicians that were filled by 340B pharmacies, increased from 18.4% in 2013 to 49.9% in 2020. As a result, the total proportion of 340B claims in Part D increased from 1.7% in 2013 to 9.6% in 2020. Rates of 340B prescribing and capture increased consistently across therapeutic classes. In 2020, the antiviral therapeutic class was the class with the largest proportion of 340B claims (16.1%), followed by targeted antineoplastics (15.7%). Conclusions and Relevance: This cohort study demonstrated that from 2013 to 2020, the share of Medicare Part D claims prescribed by a 340B-affiliated clinician increased; however, the rate at which 340B-eligible prescriptions were filled at 340B pharmacies increased at a faster rate, driving the overall increase in 340B claims. Despite these trends, only half of 340B-eligible prescriptions were subject to the 340B discount in 2020.

Nonfederal average manufacturer price to estimate savings generated by minimum discounts under the Inflation Reduction Act.

DISCLOSURES: This work was funded by the West Health Policy Center. Dr Hernandez reports consulting fees from Pfizer and BMS, outside of the submitted work. Following the submission of the original manuscript, Dr Dickson became an employee of AHIP. AHIP has had no role in reviewing this letter. The statements, findings, conclusions, views, and opinions contained and expressed herein are not necessarily those of IQVIA Inc. or any of its affiliated or subsidiary entities.

Individual and social determinants of adherence to sodium-glucose cotransporter 2 inhibitor therapy: A trajectory analysis.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are known to improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). Understanding the longitudinal patterns of adherence and the associated predictors is critical to addressing the suboptimal use of this outcome-improving treatment. OBJECTIVE: To characterize the distinct trajectories of adherence to SGLT2is in patients with T2D and to identify patient characteristics and social determinants of health (SDOHs) associated with SGLT2i adherence. METHODS: In this retrospective cohort study, we identified patients with T2D who initiated and filled at least 1 SGLT2i prescription according to 2012-2016 national Medicare claims data. The monthly proportion of days covered with SGLT2is for each patient was incorporated into group-based trajectory models to identify groups with similar adherence patterns. A multinomial logistic regression model was constructed to examine the association between patient characteristics and group membership. In addition, the association between context-specific SDOHs (eg, neighborhood median income and neighborhood employment rate) and adherence to an SGLT2i regimen was explored in both the overall cohort and the racial and ethnic subgroups. RESULTS: The final sample comprised 6,719 patients with T2D. Four trajectories of SGLT2i adherence were identified: continuously adherent users (49.6%), early discontinuers (27.5%), late discontinuers (14.5%), and intermediately adherent users (8.4%). Patient age, sex, race, diabetes duration, and Medicaid eligibility were significantly associated with trajectory group membership. Areas with a higher unemployment rate, lower income level, lower high school education rate, worse nutrition environment, fewer health care facilities, and greater Area Deprivation Index scores were found to be associated with low adherence to SGLT2is. CONCLUSIONS: Four distinct trajectories of adherence to SGLT2is were identified, with only half of the patients remaining continuously adherent to their treatment regimen during the first year after initiation. Several contextual SDOHs were associated with suboptimal adherence to SGLT2is.

Role of independent versus chain pharmacies in providing pharmacy access: a nationwide, individual-level geographic information systems analysis.

Pharmacy accessibility is critical for equity in medication access and is jeopardized by pharmacy closures, which disproportionately affect independent pharmacies. We conducted a geographic information systems analysis to quantify how many individuals across the US do not have optimal pharmacy access or solely rely on independent pharmacies for access. We generated service areas of pharmacies using OpenStreetMap data. For each individual in a 30% random sample of the 2020 RTI US Household Synthetic Population™ (n=90,778,132), we defined optimal pharmacy access as having a driving distance to the closest pharmacy ≤2 miles in urban counties, ≤5 miles in suburban counties, and ≤10 miles in rural counties. Individuals were then categorized according to their access to chain and independent pharmacies. Five percent of the sample or ~15.1 million individuals nationwide relied on independent pharmacies for optimal access. Individuals relying on independent pharmacies for optimal access were more likely to live in rural areas, be 65 years or older, and belong to low-income households. Another 19.5% of individuals in the sample did not have optimal pharmacy access, which corresponds to 59.0 million individuals nationwide. Our findings demonstrate that independent pharmacies play a critical role in ensuring equity in pharmacy access.

Association Between Redlining and Spatial Access to Pharmacies.

This cross-sectional study evaluates whether there is an association between historic redlining and living within 1 or 2 miles of a pharmacy.

Changes In Net Prices And Spending For Pharmaceuticals After The Introduction Of New Therapeutic Competition, 2011-19.

Previous research has demonstrated that the introduction of a new brand-name pharmaceutical competitor does not lower list prices for existing competitive therapies. However, no study has systematically evaluated the impact of new therapeutic competition on net prices of pharmaceutical products. We identified new therapies approved during the period 2013-17 that were competitors for existing treatments. We used a novel peer-reviewed algorithm to estimate the net prices of existing therapies. We implemented regression models to estimate changes in these net prices after the approval of the new therapeutic competition during the period 2011-19. Across twelve therapeutic classes with new drug entrants in 2013-17, the introduction of new therapeutic competition was associated with a 4.2 percent decrease in annual net price growth. The introduction of new brand-name therapies in twelve therapeutic classes reduced net commercial spending on existing therapies by $10.4 billion-an 18.5 percent reduction in projected spending absent therapeutic competition. Our findings demonstrate that new therapeutic competition allows pharmacy benefit managers to use formulary management to decrease net prices and reduce drug spending, contrary to observed trends in list price increases.

Estimated discounts generated by Medicare drug negotiation in 2026.

BACKGROUND: Starting in 2026, Medicare will be able to negotiate drug prices. Although recent reports have identified the drugs that will likely face negotiation, no study has estimated the maximum negotiated price according to guidance from the Centers for Medicare and Medicaid Services. OBJECTIVE: To identify the maximum negotiated price for the 10 drugs expected to be negotiated by Medicare in 2026. METHODS: We apply peer-reviewed methodology to estimate 2020 rebates for the 10 drugs anticipated to be negotiated by Medicare in 2026. We compare rebates to the statutory minimum discounts to identify the maximum negotiated price in 2026 and estimate savings. RESULTS: The minimum discount stipulated by the Inflation Reduction Act exceeds 2020 rebates for 4 of the 10 drugs expected to be negotiated in 2026, including etanercept, which is subject to a minimum discount of 60%, compared with an estimated rebate of 39.1%, and the cancer drugs ibrutinib, palbociclib, and enzalutamide, all of which will be subject to a minimum discount of 25%, compared with estimated rebates of 9%, 5.7% and 15.0%, respectively. Based on 2020 gross spending, the minimum required discount on these 4 drugs would generate savings of $1.8 billion. CONCLUSIONS: In 2026, minimum discounts will only apply to 4 of 10 drugs likely subject to negotiation. For most drugs, net prices will establish the ceiling for the negotiated price. To achieve the savings projected by the Congressional Budget Office ($3.7 billion), negotiated prices will have to fall below the ceiling for the negotiated price established by the statute. DISCLOSURES: This work was funded by the West Health Policy Center. Dr Hernandez reports consulting fees from Pfizer and Bristol Meyers Squibb, outside of the submitted work. Following the submission of this manuscript, Mr Dickson became an employee of American's Health Insurance Plans. American's Health Insurance Plans had no role in reviewing this manuscript. The statements, findings, conclusions, views, and opinions contained and expressed herein are not necessarily those of IQVIA Inc. or any of its affiliated or subsidiary entities.

Contextualizing the Price of Biosimilar Adalimumab Based on Historical Rebates for the Original Formulation of Branded Adalimumab.

This cross-sectional study compares recent list and net prices for Humira after rebates with announced prices of interchangeable biosimilar Humira formulations.

Estimated Changes in Insulin Prices and Discounts After Entry of New Insulin Products, 2012-2019.

Importance: Despite the political salience of insulin prices, no study to date has quantified trends in insulin prices that account for manufacturer discounts (net prices). Objective: To describe trends in insulin list prices and net prices faced by payers from 2012 to 2019 and estimate changes in net prices after the 2015 to 2017 entry of new insulin products. Design, Setting, and Participants: This longitudinal study included an analysis of Medicare, Medicaid, and SSR Health drug pricing data from January 1, 2012, to December 31, 2019. Data analyses were performed from June 1, 2022, to October 31, 2022. Exposures: US sales of insulin products. Main Outcomes and Measures: Net prices faced by payers were estimated for insulin products as list prices minus manufacturer discounts negotiated in commercial and Medicare Part D markets (ie, commercial discounts). Trends in net prices were evaluated before and after the entry of new insulin products. Results: Net prices of long-acting insulin products increased at an annual rate of 23.6% from 2012 to 2014 but decreased at an annual rate of 8.3% after the introduction of insulin glargine (Toujeo and Basaglar) and degludec (Tresiba) in 2015. Net prices of short-acting insulin increased at an annual rate of 5.6% from 2012 to 2017 but then decreased from 2018 to 2019 after the introduction of insulin aspart (Fiasp) and lispro (Admelog). For human insulin products, which did not experience entry of new products, net prices increased at an annual rate of 9.2% from 2012 to 2019. From 2012 to 2019, commercial discounts increased from 22.7% to 64.8% for long-acting insulin products, from 37.9% to 66.1% for short-acting insulin products, and from 54.9% to 63.1% for human insulin products. Conclusions and Relevance: In this longitudinal study of US insulin products, results suggest that insulin prices substantially increased from 2012 to 2015, even after accounting for discounts. The introduction of new insulin products was followed by substantial discounting practices that lowered net prices faced by payers.

Assessment of Commercial and Mandatory Discounts in the Gross-to-Net Bubble for the Top Insulin Products From 2012 to 2019.

Importance: Insulin list prices have grown substantially since 2010, but net prices have declined since 2015 because of manufacturer discounts, leading to an increasingly large difference between list and net prices of drugs often called the gross-to-net bubble. It remains unclear to what extent the gross-to-net bubble represents voluntary manufacturer discounts negotiated in commercial and Medicare Part D markets (hereafter called commercial discounts) vs mandatory discounts under the Medicare Part D coverage gap, Medicaid, and the 340B program. Objective: To decompose the overall gross-to-net bubble of leading insulin products into discount types. Design, Setting, and Participants: This economic evaluation obtained data from Medicare and Medicaid claims and spending dashboards, Medicare Part D Prescriber Public Use File, and SSR Health for the top 4 commonly used insulin products: Lantus, Levemir, Humalog, and Novolog. The gross-to-net bubble, which represents total discounts, was estimated for each insulin product and year (from 2012 to 2019). Analyses were conducted in June to December 2022. Main Outcomes and Measures: The gross-to-net bubble was decomposed into 4 discount types: (1) Medicare Part D coverage gap discounts, (2) Medicaid discounts, (3) 340B discounts, and (4) commercial discounts. Coverage gap discounts were estimated using Medicare Part D claims data. Medicaid and 340B discounts were estimated using a novel algorithm that accounted for best prices set by commercial discounts. Results: Total discounts for the 4 insulin products increased from $4.9 billion to $22.0 billion. Commercial discounts represented a majority of all discounts, increasing from 71.7% of the gross-to-net bubble in 2012 ($3.5 billion) to 74.3% ($16.4 billion) in 2019. Among mandatory discounts, coverage gap discounts remained relatively consistent as a proportion of discounts (5.4% in 2012 vs 5.3% in 2019). Medicaid rebates decreased as a proportion of total discounts, from 19.7% in 2012 to 10.6% in 2019. The 340B discounts increased as a proportion of total discounts from 3.3% in 2012 to 9.8% in 2019. Results for the contribution of discount types to the gross-to-net bubble were consistent across insulin products. Conclusions and Relevance: Results of a decomposition of the gross-to-net bubble for leading insulin products suggest that commercial discounts play a growing role in lowering net sales compared with mandatory discounts.

Variation in Statewide Intravesical Treatment Rates for Non-Muscle Invasive Bladder Cancer During the Bacillus Calmette-Guerin Drug Shortage.

OBJECTIVE: To measure the changes in treatment patterns for non-muscle invasive bladder cancer before and during the Bacillus Calmette-Guerin (BCG) drug shortage. MATERIALS AND METHODS: We used a 5% random sample of Medicare beneficiaries and identified 7971 bladder cancer patients (2648 pre-BCG shortage and 5323 during the shortage) ≥66 years of age who received intravesical treatment within 1 year of diagnosis between 2010 and 2017. The BCG shortage period was defined from July 2012 ongoing. Full induction treatment with BCG, mitomycin C, gemcitabine, or other intravesical agents was defined as receiving ≥5 of 6 treatments within 60 days. State-level BCG use before and during the drug shortage was compared in US states reporting at least 50 patients in each period. Independent variables included year of index date, age, sex, race, rurality, and region of residence. RESULTS: BCG utilization rates decreased 5.9% in the shortage period (95% CI (-8.2%)-(-3.7%)). The proportion of patients that completed a full induction course of BCG decreased from 31.0% in the pre-shortage period to 27.6% in the shortage period (P = .002). 84% of reporting states (16 of 19) had decreased BCG utilization ranging between 5% and 36% compared to pre-shortage rates. CONCLUSION: During the BCG drug shortage, eligible bladder cancer patients were less likely to receive gold standard intravesical BCG with a large variation in treatment patterns between US states.