Estimating Rebates and Other Discounts Received by Medicare Part D.

Importance: Spending in Medicare Part D continues to increase. Yet, studies of Medicare Part D are plagued by a common limitation: none can fully account for confidential rebates and other discounts that drug manufacturers and pharmacies pay to Medicare Part D plans. Objectives: To review existing methods and to propose an approach for estimating rebates and other discounts received by Medicare Part D. Evidence Review: Publicly available data from the Boards of Trustees of the Federal Hospital Insurance and Federal Supplementary Medical Insurance Trust Funds, the Centers for Medicare & Medicaid Services, the Medicare Payment Advisory Commission, the Congressional Budget Office, the Government Accountability Office, and the Office of Inspector General. Findings: Existing methods for estimating rebates and other discounts in Medicare Part D have several limitations. This analysis used an approach that aims to improve on those methods. Based on this approach, estimated discounts on brand-name drugs increased in Medicare Part D from 25.4% of gross brand-name spending in 2014 to 37.3% in 2018. There was substantial variation between classes, with estimated 2016 discounts surpassing 50% for some drugs (eg, ophthalmologic and gastrointestinal tract agents) while remaining below 10% for others (eg, antineoplastic and immunologic agents). Between 2014 and 2018, estimated net Medicare Part D spending on prescription drugs increased by 21% from $99 billion to $119 billion. With increasing enrollment, estimated annual net spending per beneficiary remained stable, increasing by just 3% from $2622 to $2694, which was below the 6% rate of inflation during the same period. Conclusions and Relevance: Models that fail to properly account for increasing rebates and other discounts will overestimate Medicare Part D expenditures. Rigorous and transparent methods for estimating discounts are critical for understanding patterns in spending and developing new cost-containment strategies.

Challenges raised by the economic evaluation of CAR-T-cell therapies. The review by the French National Authority for Health.

Since 2013, the process of pricing of innovative drugs by the French National Health Insurance has considered both cost-effectiveness and budget impact. CAR-T cell therapies were first subject to economic evaluation from 2019 in France. We aim to describe the process and results of the economic evaluation of tisagenlecleucel and axicabtagene ciloleucel as well as the challenges these evaluations raised. Evaluations submitted by the firms were reviewed by HAS and submitted to the Committee of Economic Evaluation and Public Health (CEESP). The CEESP issued opinions related to: (1) the methodological quality of economic evidence and, (2) the cost-effectiveness and budget impact of the drugs. The CEESP invalidated the estimated incremental cost-utility ratios (ICUR) of tisagenlecleucel due to the insufficient clinical evidence and methodological quality to extrapolate the long-term progression of the disease after treatment and compare tisagenlecleucel with alternatives. The CEESP concluded that tisagenlecleucel was not proven cost-effective. The estimated ICUR of axicabtagene ciloleucel at €114,509/QALY vs. chemotherapies was associated with an acceptable level of methodological quality despite being based on a weak indirect comparison and limited data on quality of life. The CEESP considered axicabtagene ciloleucel ICUR to be "very high" and questioned the societal/community willingness-to-pay of the claimed price. The primary source of uncertainty surrounding the ICUR estimates of both drugs was the lack of hindsight on effectiveness. The economic evaluation of CAR-T cell therapies highlights the risk of inefficient resource allocation driven by limited clinical data. It calls for payment schemes accounting for this risk and effective collection of post-marketing data.

How much does the hospital stay for infusion of anti-CD19 CAR-T cells cost to the French National Health Insurance?

Chimeric antigen receptor T-cells (CAR-T cells) have the potential to be a major innovation as a new type of cancer treatment, but are associated with extremely high prices and a high level of uncertainty. This study aims to assess the cost of the hospital stay for the administration of anti-CD19 CAR-T cells in France. Data were collected from the French Medical Information Systems Program (PMSI) and all hospital stays associated with an administrated drug encoded 9439938 (tisagenlecleucel, Kymriah®) or 9440456 (axicabtagene ciloleucel, Yescarta®) between January 2019 and December 2020 were included. 485 hospital stays associated with an injection of anti-CD19 CAR-T cells were identified, of which 44 (9%), 139 (28.7%), and 302 (62.3%) were for tisagenlecleucel in acute lymphoblastic leukaemia (ALL), tisagenlecleucel in diffuse large B-cell lymphoma (DLBCL), and axicabtagene ciloleucel respectively. The lengths of the stays were 37.9, 23.8, and 25.9 days for tisagenlecleucel in ALL, tisagenlecleucel in DLBCL, and axicabtagene ciloleucel, respectively. The mean costs per hospital stay were € 372,400 for a tisagenlecleucel in ALL, € 342,903 for tisagenlecleucel in DLBCL, and € 366,562 for axicabtagene ciloleucel. CAR T-cells represented more than 80% of these costs. n=13 hospitals performed CAR-T cell injections, with two hospitals accounting for more than 50% of the total number of injections. This study provides original data in a context of limited information regarding the costs of hospitalization for patients undergoing CAR-T cell treatments. In addition to the financial burden, distance may also be an important barrier for accessing CAR T-cell treatment.

Characteristics of Clinical Trials Launched Early in the COVID-19 Pandemic in the US and in France.

Based on hierarchical classification and logistic regression of early US and French COVID-19 clinical trials we show that despite the registration of a large number of trials, only a minority had characteristics usually associated with providing robust and relevant evidence.

Why France Spends Less Than the United States on Drugs: A Comparative Study of Drug Pricing and Pricing Regulation.

Policy Points  Spending on prescription drugs is much higher per capita in the United States than in most other industrialized nations, including France.  Lower prescription drug spending in France is due to different approaches to managing drug prices, volume of prescribing, and global health budgets.  Linking a drug's price to value both at the launch of the drug and over its lifetime is key to controlling spending. Regulations on prescription volume and global spending complement the interventions on prices.  If the United States adopted the French approach to regulating drug pricing, Medicare could potentially save billions of dollars annually on prescription drug spending. CONTEXT: Prescription drug spending per capita in the United States is higher than in most other industrialized countries. Policymakers seeking to lower drug spending often suggest benchmarking prices against other countries, including France, which spends half as much as the United States per capita on prescription drugs. Because differences in drug prices may result from how markets are organized in each nation, we sought to directly compare drug prices and pricing regulations between the United States and France. METHODS: For the six brand-name drugs with the highest gross expenditures in Medicare Part D in 2017, we compared the price dynamics in France and the United States between 2010 and 2018 and analyzed associations between price changes in each country and key regulatory events. We also comprehensively reviewed US and French laws and regulations related to drug pricing. FINDINGS: Prices for the six drugs studied were higher in the United States than in France. In 2018, if Medicare had paid French prices for the brand-name drugs in our cohort, the agency would have saved $5.1 billion. We identified 12 factors that explain why the United States spends more than France on drugs, including variations in unit prices and the volume of prescriptions, driven by use of health technology assessment and value-based pricing in France. CONCLUSIONS: Key drivers of lower drug spending in France compared to the United States are that the French government regulates drug prices when products are launched and prohibits substantial price increases after launch. The regulation of prescription drugs in France is governed by rules that can inform discussions of US prescription drug policy and potential Medicare price negotiations.

Was It Worth Introducing Health Economic Evaluation of Innovative Drugs in the French Regulatory Setting? The Case of New Hepatitis C Drugs.

OBJECTIVE: This paper constitutes the first attempt to draw lessons from the recent uptake of health economic evaluation of innovative drugs in the French regulatory framework. STUDY DESIGN: Taking the example of new direct-acting antivirals against hepatitis C virus, the paper asks whether and how the cost-effectiveness (CE) opinions issued by the French National Health Authority improve the information available to support the pricing decisions. METHODS: The analysis compares the assessment of these drugs based on three different sources: CE opinions, clinical opinions, and the published cost-utility analyses (CUA) available in the literature and identified through a systematic review. RESULTS: The results show that CE opinions bring to the fore three issues prone to impact the incremental cost utility ratio and those were not available to the decision maker through clinical opinions or published CUA: the stage of treatment initiation, the modeling of the disease progression, and the uncertainty around the efficacy rates. CONCLUSIONS: France has introduced the criterion of the cost per QALY gained in the pricing and regulation of innovative pharmaceuticals since 2013. Our analysis shows that the use of CUA does enhance the information available to the decision makers on the value of the treatments.

ETHICS EVALUATION REVEALING DECISION-MAKER MOTIVES: A CASE OF NEONATAL SCREENING.

OBJECTIVES: This paper aims to describe the added value of combining cost-effectiveness and ethical evaluations when the preferences of the decision maker toward cost-effectiveness evaluation outcomes are not known, with the French national neonatal screening of cystic fibrosis (CF) as a case-study. METHODS: A cost-effectiveness analysis comparing four CF neonatal screening strategies, with or without DNA testing, was performed. Ethical positions toward their outcomes were described. In addition, a post-hoc analysis of the ethical issues being considered relevant from the decision-makers' perspective was conducted. RESULTS: Two strategies were found equally cost-effective. Among them, choosing the non-DNA or a DNA-based strategy constrains the decision maker to render a judgement between different ethical issues or disagreements associated with the screening program. CONCLUSIONS: The analysis supports the relevance of combining cost-effectiveness and ethics evaluation in developing health policy, as a way to reveal or clarify the motives associated with health. The choice of the decision maker to favor the DNA-based strategy, which was not originally recommended, creates the opportunity to make explicit the role played by ethical issues in the decision.

[Haute Autorite de sante opinion on cost-effectiveness of health products : results and perspectives]. / Avis d’efficience relatifs aux produits de santé à la Haute Autorité de santé?: bilan et perspectives.

Since 3rd October 2013 in France, drug companies applying for reimbursement of an innovative and expensive drug or medical device are required to provide the French National Authority for Health (HAS) with a cost-effectiveness assessment of their product. After a methodological audit of the economic evaluation submitted by the drug company, the Health Economics and Public Health Committee (CEESP) issues an opinion on the expected or observed cost-effectiveness. This opinion is sent to the Pricing Committee (CEPS) which determines the price of the product. After summarizing the French reimburse'!lent and pricing system, the objective of this article is to review the first 22 months of activity, in which HAS issued 30 cost-effectiveness opinions. The process, based on exchanges between drug companies and HAS, allowed the pricing committee to document the economic criterion in the majority of applications, while characterizing the degree of uncertainty of the results. For ten applications, major methodological concerns led the CEESP to reject the drug company's assessment.

Online dissemination of clinical practice guidelines as narrative texts and structured pathways: a case study with the treatment of type 2 diabetes.

Recently, National agencies in charge of the development of clinical practice guidelines (CPGs) have started to improve the usual narrative CPGs to provide guidance for different clinical pathways. In France, in conjunction with the development of the type 2 diabetes National CPGs, we have developed the system RecosDoc-Diabète which allows to interactively build a patient-centred pathway and get the appropriate recommendations. National narrative CPGs and RecosDoc-Diabète were published and made available online at the same time (February 2013). A questionnaire was provided to collect visitors' judgement about the system. Between February 12th and December 31st, 2013, 55,203 visitors accessed the narrative CPGs whereas 10,565 accessed the system. Among them, 186 (2%) responded to the questionnaire. One third of the comments were criticisms towards the CPG content. The system was globally positively evaluated although assessments were mixed illustrating that users' needs may be contradictory.

HTA agencies facing model biases: the case of type 2 diabetes.

When evaluating new drugs or treatments eligible for reimbursement, health technology assessment (HTA) agencies are repeatedly faced with cost-effectiveness analyses that evidence lack of adequate data and modeling biases. The case of type 2 diabetes illustrates this difficulty. In spite of its high disease burden, type 2 diabetes is poorly documented through existing cost-effectiveness analyses. We support this statement by an exhaustive literature review that enables us to precisely pinpoint the limitations of models used for the assessment of newly marketed (and expensive) drugs. We find that models are mostly restricted to surrogate endpoints and based on non-inferiority clinical trial data; they also show biases in the choice of comparators and inclusion criteria. Such limitations undermine the scope and applicability of HTA practice guidelines based on cost-effectiveness evidence. Nevertheless, cost-effectiveness models remain an opportunity to better inform decision makers and to reduce the uncertainty surrounding their decisions. HTA agencies are best placed to provide incentives for companies to improve the quality of the cost-effectiveness studies submitted for pricing and reimbursement decisions. One such incentive is to include stages of discussion between the company and the health authority during the evaluation process.