Trends in Prices of Drugs Used to Treat Metastatic Non-Small Cell Lung Cancer in the US From 2015 to 2020.

Importance: Oncology drug prices are a determinant of health disparities in the US and worldwide. Several new therapeutic agents for non-small cell lung cancer (NSCLC) have become available on the US market over the past decade. Although increased competition typically produces lower prices, competition among brand-name oncology drugs has not resulted in lower prices. Objective: To assess price changes in class-specific brand-name medications used to treat metastatic NSCLC in the US from 2015 to 2020. Design, Setting, and Participants: This cross-sectional study, conducted from August 13, 2015, to August 13, 2020, used data from the Micromedex Red Book and Medi-Span Price Rx databases. The study sample was limited to 17 brand-name medications used to treat metastatic NSCLC that were available for purchase before January 1, 2019. Main Outcomes and Measures: The main outcomes were trends over time in average wholesale prices and wholesale acquisition cost unit prices and the correlation in price among the multiple brand-name medications within each therapeutic class (immune checkpoint inhibitors, epidermal growth factor receptor inhibitors, anaplastic lymphoma kinase inhibitors, ROS1 inhibitors, BRAF inhibitors, and MEK inhibitors), measured using the Pearson correlation coefficient. The compounded annual growth rates of different medication costs were compared with the annual inflation rate and the consumer price index for prescription drugs. Results: For all drug classes, the Pearson correlation coefficient approached 1.0, indicating an increase in drug list prices despite within-class drug competition. The median Pearson correlation coefficient values were 0.964 (range, 0.951-0.994) for immune checkpoint inhibitors, 0.898 (range, 0.665-0.950) for epidermal growth factor receptor inhibitors, 0.999 (range, 0.982-0.999) for anaplastic lymphoma kinase inhibitors, and 0.999 for BRAF and MEK inhibitors. The median compounded annual growth rates for most drug costs were higher than the annual inflation rate and consumer price index for prescription drugs: 1.81% (range, 1.29%-2.13%) for immune checkpoint inhibitors, 2.56% (range, 2.38%-5.26%) for epidermal growth factor receptor inhibitors, 2.46% (range, 1.75%-4.66%) for anaplastic lymphoma kinase and ROS1 inhibitors, and 3.06% (range, 0%-3.06%) for BRAF and MEK inhibitors. Conclusions and Relevance: In this cross-sectional study, prices of brand-name medications for treatment of NSCLC increased in the US from 2015 to 2020 without evidence of price competition, raising concern about the affordability of promising oncology drugs. These findings suggest that drug pricing reform is needed.

Temporal trends of adverse events and costs of nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma.

Aims: To assess grade 3/4 adverse events (AEs) and costs of first-line nivolumab plus ipilimumab versus sunitinib in advanced or metastatic renal cell carcinoma. Methods: Individual patient data from the all treated population in the CheckMate 214 trial (nivolumab plus ipilimumab, n = 547; sunitinib, n = 535) were used to calculate the number of AEs. AE unit costs were obtained from US 2017 Healthcare Cost and Utilization Project and inflated to 2020 values. Results: The proportion of patients experiencing grade 3/4 AEs decreased over time. Patients who received nivolumab plus ipilimumab had lower average per-patient all-cause grade 3/4 AE costs versus sunitinib (12-month: US$15,170 vs US$20,342; 42-month: US$19,096 vs US$27,473). Conclusion: Treatment with nivolumab plus ipilimumab was associated with lower grade 3/4 AE costs than sunitinib.

Immunotherapy combinations are now accepted as safe and effective first-line treatment options for advanced or metastatic renal cell carcinoma. This study used patient data from the CheckMate 214 clinical trial to evaluate the temporal trends and costs related to grade 3/4 adverse events (AEs) among patients treated with nivolumab plus ipilimumab versus sunitinib. We found that the proportion of patients experiencing grade 3/4 AEs decreased over time and that patients treated with nivolumab plus ipilimumab had lower AE costs compared with those treated with sunitinib (at 42 months: US$19,096 vs US$27,473 per patient). As such, nivolumab plus ipilimumab may represent a treatment option that may reduce both the clinical and economic burden among patients with advanced or metastatic renal cell carcinoma.

Durable cell and gene therapy potential patient and financial impact: US projections of product approvals, patients treated, and product revenues.

Durable cell and gene therapies potentially transform patient lives, but payers fear unsustainable costs arising from the more than 1000 therapies in the development pipeline. A novel multi-module Markov chain Monte Carlo-based model projects product-indication approvals, treated patients, and product revenues. We estimate a mean 63.5 (54-74 5th to 95th percentile range) cumulative US product-indication approvals through 2030, with a mean 93000 patients treated in 2030 generating a mean US$24.4 billion (US$17.0B-35.0B, US$73.0B extreme) list price product revenues not including ancillary medical costs or cost offsets. Thus, the likely dozens of durable cell and gene therapies developed through 2030 are unlikely to threaten US health system financial sustainability.

Projected impact of biosimilar substitution policies on drug use and costs in Ontario, Canada: a cross-sectional time series analysis.

BACKGROUND: Several Canadian provinces have introduced reimbursement policies mandating substitution of innovator biologics with lower-cost biosimilars. We estimated the number of patients affected and cost implications if such policy changes were to be implemented in Ontario, Canada. METHODS: We conducted a cross-sectional time series analysis of Ontarians dispensed publicly funded biologics indicated for inflammatory diseases (rheumatic conditions, inflammatory bowel disease: infliximab, etanercept, adalimumab) between January 2018 and December 2019, and forecasted trends to Dec. 31, 2020. The primary source of data was pharmacy claims data for all biologics reimbursed by the public drug program. We modelled the number of patients affected and government expenditures (in nominal Canadian dollars) of several biosimilar policy options, including mandatory nonmedical biosimilar substitution, substitution in new users, introduction of a biosimilar for adalimumab, and price negotiations. In a secondary analysis, we included insulin glargine. RESULTS: In 2018, 14 089 individuals were prescribed a publicly funded biologic for inflammatory diseases. A mandatory nonmedical biosimilar substitution would potentially have affected 7209 patients and saved $238.6 million from 2018 to 2020. A new-user substitution would have affected 757 patients and saved $34.2 million. If an adalimumab biosimilar were to become available, 12 928 patients would be affected by a mandatory nonmedical substitution and the 3-year savings would increase to $645.9 million (all biosimilars priced at 25% of innovator biologics). Finally, an expanded nonmedical substitution policy including insulin glargine would affect 115 895 patients and save $288.7 million (not including adalimumab). INTERPRETATION: Policies designed to curb rising costs of biologics can have substantially different effects on patients and government expenditures. Such analyses warrant careful consideration of the balance between cost savings and effects on patients.

Price trends of reimbursed oncological drugs in Switzerland in 2005-2019: A descriptive analysis.

Increasing oncological treatment costs are a major global concern with the risk of entailing two-tiered health care. Among cost determining factors is the price of individual drugs. In recognition of the central role of this factor, we present a comprehensive overview of the development of monthly prices of oncological drugs introduced over the last 15 years in Switzerland. We identified all oncological drugs newly reimbursed by mandatory health insurance in 2005-2019, and searched public repositories for their package prices, indications with approval dates, and treatment regimens for the calculation of (indication-specific) monthly prices. We found 81 products covering 77 different substances (39.5% protein kinase inhibitors, 21.0% monoclonal antibodies). Most indications related to the topography "blood", followed by "lung and thorax" and "digestive tract". From 2005­2009 to 2015­2019, the median monthly product price over all distinct indications of all products decreased by 7.56% (CHF 5,699 [interquartile range 4,483­7,321] to CHF 5,268 [4,019­6,967]), whereas it increased by 73.7% for monoclonal antibodies. In December 2019, six products had monthly prices over CHF 10,000, all approved for hematological or dermatological cancers. Our analysis suggests that individual price developments of oncological drugs are presently not the major driver of rising cancer treatment costs. However, rising launch prices of some new, mostly hematological drugs are of concern and require continued monitoring.

Trends in Use and Expenditures for Brand-name Statins After Introduction of Generic Statins in the US, 2002-2018.

Importance: The high and increasing expenditures for prescription medications in the US is a national problem. Objective: To explore the association of generic statin competition on relevant use and cost savings and to provide use and expenditure trends for all available statins for private and public payers and for out-of-pocket spending. Design, Setting, and Participants: This survey study evaluated data from the January 1, 2002, to December 31, 2018, Medical Expenditure Panel Survey by using a difference-in-differences analysis. Participants included noninstitutionalized individual statin users. Data were analyzed from November 1, 2020, to March 30, 2021. Exposures: The market entry of 5 generic statin medications (atorvastatin, rosuvastatin, simvastatin, lovastatin, and pravastatin). Main Outcomes and Measures: National- and individual-level reductions in the annual number of statin purchases and total expenditures across private insurance, public insurance (Medicaid and Medicare), and out-of-pocket spending (presented in 2018 US dollars). Results: Between January 1, 2002, and December 31, 2018, an average of 21.35 million statins (95% CI, 16.7-25.5 million) were purchased annually, with an average total annual cost of $24.5 billion (95% CI, $18.2-$28.8 billion). The number of brand-name statin purchases decreased by 90.9% (95% CI, 56%-98%) nationally and 27.4% (95% CI, 13%-40%) individually after the end of market exclusivity. Among major payers, the end of market exclusivity was associated with individual cost savings of $370.00 (95% CI, $430.70-$309.20) for private insurers, $281.00 (95% CI, $346.80-$215.30) for Medicare, $72.34 (95% CI, $95.22-$49.46) for Medicaid, and $211.90 (95% CI, $231.20-$192.50) for out-of-pocket spending. Combining all payers, the decrease translates to $925.60 (95% CI, $1005.00-$846.40) of annual savings per individual and $11.9 billion (95% CI, $10.9-$13.0 billion) for the US. Conclusions and Relevance: Results of this survey study suggest that full generic competition of statins was associated with significant cost savings across all major payers within the US health care system.

Out-of-pocket medical expenses compared across five years for patients with one of five common cancers in Australia.

BACKGROUND: Patient medical out-of-pocket expenses are thought to be rising worldwide yet data describing trends over time is scant. We evaluated trends of out-of-pocket expenses for patients in Australia with one of five major cancers in the first-year after diagnosis. METHODS: Participants from the QSKIN Sun and Health prospective cohort Study with a histologically confirmed breast, colorectal, lung, melanoma, or prostate cancer diagnosed between 2011 and 2015 were included (n = 1965). Medicare claims data on out-of-pocket expenses were analysed using a two-part model adjusted for year of diagnosis, health insurance status, age and education level. Fisher price and quantity indexes were also calculated to assess prices and volumes separately. RESULTS: On average, patients with cancer diagnosed in 2015 spent 70% more out-of-pocket on direct medical expenses than those diagnosed in 2011. Out-of-pocket expenses increased significantly for patients with breast cancer (mean AU$2513 in 2011 to AU$6802 in 2015). Out-of-pocket expenses were higher overall for individuals with private health insurance. For prostate cancer, expenses increased for those without private health insurance over time (mean AU$1586 in 2011 to AU$4748 in 2014) and remained stable for those with private health insurance (AU$4397 in 2011 to AU$5623 in 2015). There were progressive increases in prices and quantities of medical services for patients with melanoma, breast and lung cancer. For all cancers, prices increased for medicines and doctor attendances but fluctuated for other medical services. CONCLUSION: Out-of-pocket expenses for patients with cancer have increased substantially over time. Such increases were more pronounced for women with breast cancer and those without private health insurance. Increased out-of-pocket expenses arose from both higher prices and higher volumes of health services but differ by cancer type. Further efforts to monitor patient out-of-pocket costs and prevent health inequities are required.

Real-World Outcomes and Costs Following 6 Months of Treatment with the Long-Acting Injectable (LAI) Aripiprazole Lauroxil for the Treatment of Schizophrenia.

BACKGROUND: Continuous antipsychotic therapy is recommended as part of long-term maintenance treatment of schizophrenia, and gaps in antipsychotic treatment have been associated with increased risks of relapse and rehospitalization. Because the use of long-acting injectable (LAI) antipsychotics may reduce the likelihood of undetected medication gaps, initiating an LAI medication may affect resource utilization and costs. The LAI aripiprazole lauroxil (AL) was approved in the United States (US) in 2015 for the treatment of schizophrenia in adults. OBJECTIVE: The objective of this retrospective observational cohort study was to examine treatment patterns, resource utilization, and costs following initiation of AL for the treatment of schizophrenia in adults. METHODS: A retrospective analysis of Medicaid claims data identified a cohort of patients (N = 485) starting AL shortly after Food and Drug Administration approval in October 2015. Treatment patterns, resource utilization, and costs were compared 6 months before and after treatment initiation. Subgroup analyses were conducted based on the type of antipsychotic (LAI, oral, or none) received before initiation of AL. RESULTS: Over 6 months of follow-up, patients received an average of 4.6 injections out of a maximum of six (77%). After initiating AL, all-cause inpatient admissions decreased by 22.4%; other significant reductions were observed in mental health-related admissions and emergency room (ER) visits. All-cause inpatient costs decreased by an average of US$2836 per patient (p < 0.05) in the 6-month post-AL period, whereas outpatient pharmacy costs increased by US$4121 (p < 0.05), resulting in no significant difference in overall costs between the pre- and post-AL periods. The subgroup of patients who had been prescribed an oral antipsychotic before starting AL had significant reductions in proportion of patients with inpatient and ER visits and costs, but also reported a significant increase in pharmacy costs. CONCLUSIONS: AL was associated with a significant reduction in inpatient costs and an increase in outpatient pharmacy costs, resulting in no changes in total healthcare costs over 6 months. The adherence rate and reductions in inpatient use may indicate the potential for greater clinical stability among patients initiated on AL compared with their previous treatment.

Pharmaceutical drug development: high drug prices and the hidden role of public funding.

In 2019, the record for the most expensive drug was broken at US$2.1 million per patient. The high costs of new drugs are justified by the pharmaceutical industry as the expense required for maintaining research and development (R&D) pipelines. However, this does not take into account that globally the public pays for between one to two-thirds of upfront R&D costs through taxpayers or charitable donations. Governments are effectively paying twice for medicines; first through R&D, and then paying the high prices upon approval. High drug prices distort research priorities, emphasising financial gains and not health gains. In this manuscript, issues surrounding the current patent-based drug development model, public funding of research and pharmaceutical lobbying will be addressed. Finally, innovations in drug development to improve public health needs and guaranteeing medication access to patients will be explored.

Pursuing Value-Based Prices for Drugs: A Comprehensive Comparison of State Prescription Drug-Pricing Boards.

Policy Points In the absence of federal action on rising prescription drug costs, we reviewed the details of five states that have enacted prescription drug-pricing boards seeking to lower drug prices based on products' value. Within these states, six such boards are currently authorized; they have similarities but vary in terms of structure, authority, scope, and leverage. As of June 2021, only one of the boards in our sample has conducted pricing reviews; legislators in other states can learn from the successes and challenges of existing boards. Prescription drug-pricing boards represent a novel and promising way to curb state spending and pay for value in prescription drugs but face legal and political barriers in implementation. CONTEXT: Rising prescription drug costs are consuming a growing proportion of state and private budgets. In response, lawmakers have experimented with a variety of policies to contain spending and achieve value in prescription drugs. As part of this series of reforms, some state legislatures have recently authorized prescription drug-pricing boards to address the high prices of brand-name prescription drugs and assess the value of those drugs. METHODS: We identified state prescription drug-pricing boards in the United States, defined as any agency authorized by a state legislature to review specific drugs and pursue value-based drug prices. To describe the characteristics of the boards, we obtained public records of authorizing legislation, guidance documents, and board meeting minutes. We compared the boards' powers and responsibilities and analyzed completed pricing reviews. FINDINGS: Six state drug-pricing boards in five states met our definition; their design varied substantially. Two of the boards (New York Medicaid and Massachusetts) have authority over drug rebates paid by state Medicaid programs, one (New York Drug Accountability Board) has jurisdiction over state-regulated commercial insurance, and another three (Maine, Maryland, and New Hampshire) oversee non-Medicaid, state-funded insurance. Three boards are authorized to require manufacturers to confidentially submit information related to the pricing and clinical effectiveness of reviewed drugs to inform value determinations. Only one board (New York Medicaid) had completed pricing reviews as of June 3, 2021. CONCLUSIONS: Boards' structure, scope, and statutory leverages to compel manufacturers to negotiate lower net costs are key factors that influence whether and to what extent boards can achieve cost savings for states. Though legal constraints may limit the effective reach of prescription drug-pricing boards, these agencies can enable states to address rising prescription drug costs, in part by virtue of their very existence. To overcome practical limitations, states seeking to implement similar policies can build on the experiences and designs of current boards.

Cost drivers in the pharmacological treatment of interstitial lung disease.

INTRODUCTION: Treatments of interstitial lung diseases (ILDs) mainly focus on disease stabilization and relief of symptoms by managing inflammation or suppressing fibrosis by (in part costly) drugs. To highlight economic burden of drug treatment in different ILD-subtypes we assessed cost trends and therewith-associated drivers. METHODS: Using data from the German, observational HILDA study we estimated adjusted mean medication costs over 36-month intervals using one- and two-part Generalized Estimating Equation (GEE) regression models with a gamma distribution and log link. Next, we determined factors associated with costs. RESULTS: In Idiopathic pulmonary fibrosis (IPF) mean per capita medication costs increased from €1442 before to €11,000€ at the end of study. In non-IPF subtypes, the increase took place at much lower level. Mean per capita ILD-specific medication costs at the end of the study ranged between €487 (other ILD) and €9142 (IPF). At baseline, higher FVC %predicted values were associated with lower medication costs in IPF (-9%) and sarcoidosis (-1%). During follow up higher comorbidity burden escalated costs in progressive fibrosing ILD (PF-ILD) (+52%), sarcoidosis (+60%) and other ILDs (+24%). The effect of disease duration was not uniform, with cost savings in PF-ILD (-8%) and sarcoidosis (-6%), but increased spending in IPF (+11%). CONCLUSION: Pharmacological management of ILD, in particular of IPF imposes a substantial economic burden on the healthcare system. Strategies to reduce comorbidity burden and early treatment may reduce the impact of ILDs on the healthcare system.

Evaluation of availability, price, and affordability of cardiovascular, diabetes, and global medicines in Abuja, Nigeria.

OBJECTIVE: To assess the availability, price, and affordability of cardiovascular, diabetes, and global medicines in Abuja, Nigeria. METHODS: A cross-sectional survey involving 27 private pharmacies, 13 public pharmacies, and 25 private hospital pharmacies in Abuja was conducted using the standardized World Health Organization/Health Action International methodology. The availability percentage for each pharmacy sector and each medicine was analyzed. The median price ratio (MPR) (ratio of the median price to the international reference prices) of the medicines were evaluated accordingly. Affordability was assessed by calculating the number of days' wages the lowest-paid unskilled government worker required to purchase a month worth of the standard treatment for a chronic condition. RESULTS: The availability of cardiovascular (CV) medicines ranged from 28.4% (in private hospital pharmacies) to 59.9% (in private pharmacies). There was mixed variability in the mean availability of Originator Brands (OBs) and Lowest Priced Generics (LPGs) anti-diabetic drugs with the highest availability being OBs 36% and LPGs 40.2%, in private pharmacies and public pharmacies, respectively. The availability of global drugs ranged from 49.7% in private hospitals to 68.8% in private pharmacies. Two cardiovascular and four global medicines had greater than 80% availability across the pharmaceutical sectors. The median price ratio for OBs and LPGs was 9.60 and 1.72 for procurement, it was 8.08 and 2.60 in private pharmacies, 13.56 and 2.66 in public hospitals, and 16.38 and 7.89 in private hospitals. The percentage markup on LPG was 49.4% in public hospitals, 51.4% in private pharmacies, and 323% in private hospitals. Only nine medicines in both public hospitals and private pharmacies and two in the private hospital pharmacies required less than the daily wage of the lowest-paid government worker. CONCLUSION: The availability of cardiovascular, diabetes, and global medicines was below 80% across the different pharmaceutical sectors in Abuja and the medicines were unaffordable. Although the prices were generally exorbitant, private pharmacies offered the best options in terms of availability, pricing, and affordability of medicines. Therefore, the results of this study emphasize the pertinence of enforcing policies that facilitate the availability, pricing, and affordability of cardiovascular, diabetes, and global medicines.

Factors Associated With Generic Drug Uptake in the United States, 2012 to 2017.

OBJECTIVES: In the United States, brand-name prescription drugs remain expensive until market exclusivity ends and lower-cost generics become available. Delayed generic drug uptake may increase spending and worsen medication adherence and patient outcomes. We assessed recent trends and factors associated with generic uptake. METHODS: Among 227 drugs facing new generic competition from 2012 to 2017, we used a national claims database to measure generic uptake in the first and second year after generic entry, defined as the proportion of claims for a generic version of the drug. Using linear regression, we evaluated associations between generic uptake and key drug characteristics. RESULTS: Mean generic uptake was 66.1% (standard deviation 22.1%) in the first year and 82.7% (standard deviation 21.6%) in the second year after generic entry. From 2012 to 2017 generic uptake decreased 4.3% per year in the first year (95% confidence interval, 2.8%-5.8%, P < .001) and 3.2%/year in the second year (95% confidence interval, 1.2%-5.1%). Generic uptake was lower for injected than oral drugs in the first year (38.5% vs 70.0%, P < .001) and second year (50.3% vs 86.9%, P < .001). In the second year, generic uptake was higher among drugs with an authorized generic (86.1 vs 80.1%, P = .045) and those with ≥3 generic competitors (87.7% vs 78.6%, P = .055). CONCLUSION: Early generic uptake decreased over the past several years. This trend may adversely affect patients and increase prescription drug spending. Policies are needed to encourage generic competition, particularly among injected drugs administered in a hospital or clinic setting.

Assessing the pricing and benefits of oncology products: an update.

Introduction: Oncology expenditure is outperforming all other health care sectors. In particular, the cost of oncology pharmaceuticals is soaring as it is fueled both by incremental costs and the introduction rate of new products. Due to the particularities of cancer as a disease, a significant multilayer of pressure is exerted toward the reimbursement of new treatments. Nevertheless, if the expenditure increase is left unattended, it may hamper the viability of any health care system worldwide.Areas covered: A literature review of the expenditure on oncology pharmaceuticals and the exploration of the root causes for the increase in expenditure was performed.Expert commentary: The surging oncology expenditure demonstrates a multi-layer causality that encompasses prices, the uncertainty of clinical trials, the specificities of cancer as a disease, and the artificial monopoly of oncology modalities. Moreover, laxity in the regulatory approval of new products was noted. In addition, the study design should be adequately justified. Finally, new reimbursement schemes, that explicitly reward and promote clinically meaningful and measurable outcomes, are also imperative.