Medicare Part B and Part D drug eligibility for center for Medicare and Medicaid Services price negotiation under the Inflation Reduction Act: estimates using 2016-2019 data.

Background: To reduce Medicare prescription drug expenditures, the 2022 Inflation Reduction Act (IRA) allows the Centers for Medicare & Medicaid Services (CMS) to directly negotiate with drug manufacturers on Medicare prices of high-expenditure drugs (≥$200m annual spending) which meet certain eligibility criteria. However, it is unclear what proportion of high-expenditure drugs covered by Medicare, and attributable annual drug spending, would typically be eligible for CMS negotiations in a given year. Methods: We used historical Medicare drug spending data to determine how many high-expenditure drugs, and attributable drug spending, would have been eligible for CMS negotiations had the IRA been in effect from 2016-2019, while also determining which of the IRA's eligibility criteria is most restrictive. Results: From 2016-2019, approximately one third (33.3% for Part B, 32.4% for Part D) of high-expenditure Medicare drugs would have been eligible for negotiation, with ineligible drugs accounting for 75.2% and 63.8% of spending on high-expenditure drugs in Medicare Part B and D, respectively. Most ineligible high-expenditure drugs were ineligible because they launched too recently. From 2016-2019, between 59 and 74 high-expenditure drugs were eligible per year, indicating that in some years there may not be enough eligible drugs for CMS to negotiate on the maximum number of drugs allowable by law. Conclusions: The IRA's current eligibility criteria may restrict CMS from being able to negotiate drug prices on approximately two-thirds of the high-expenditure drugs covered by Medicare and may not allow CMS to negotiate on the maximum number of drugs allowable by law. Congress could consider relaxing eligibility requirements for price negotiation, such as those pertaining to launch date recency, to ensure there are a sufficient number of high-expenditure drugs eligible for negotiation or make certain ineligible drugs contributing to significant annual Medicare spending eligible for negotiation on a case-by-case basis.

Special FDA designations for drug development: orphan, fast track, accelerated approval, priority review, and breakthrough therapy.

BACKGROUND: Over the past decades, US Congress enabled the US Food and Drug Administration (FDA) to facilitate and expedite drug development for serious conditions filling unmet medical needs with five special designations and review pathways: orphan, fast track, accelerated approval, priority review, and breakthrough therapy. OBJECTIVES: This study reviews the FDA's five special designations for drug development regarding their safety, efficacy/clinical benefit, clinical trials, innovation, economic incentives, development timelines, and price. METHODS: We conducted a keyword search to identify studies analyzing the impact of the FDA's special designations (orphan, fast track, accelerated approval, priority review, and breakthrough therapy) on the safety, efficacy/clinical benefit, trials, innovativeness, economic incentives, development times, and pricing of new drugs. Results were summarized in a narrative overview. RESULTS: Expedited approval reduces new drugs' time to market. However, faster drug development and regulatory review are associated with more unrecognized adverse events and post-marketing safety revisions. Clinical trials supporting special FDA approvals frequently use small, non-randomized, open-label designs. Required post-approval trials to monitor unknown adverse events are often delayed or not even initiated. Evidence suggests that drugs approved under special review pathways, marketed as "breakthroughs", are more innovative and deliver a higher clinical benefit than those receiving standard FDA approval. Special designations are an economically viable strategy for investors and pharmaceutical companies to develop drugs for rare diseases with unmet medical needs, due to financial incentives, expedited development timelines, higher clinical trial success rates, alongside greater prices. Nonetheless, patients, physicians, and insurers are concerned about spending money on drugs without a proven benefit or even on drugs that turn out to be ineffective. While European countries established performance- and financial-based managed entry agreements to account for this uncertainty in clinical trial evidence and cost-effectiveness, the pricing and reimbursement of these drugs remain largely unregulated in the US. CONCLUSION: Special FDA designations shorten clinical development and FDA approval times for new drugs treating rare and severe diseases with unmet medical needs. Special-designated drugs offer a greater clinical benefit to patients. However, physicians, patients, and insurers must be aware that special-designated drugs are often approved based on non-robust trials, associated with more unrecognized side effects, and sold for higher prices.

The impact of drug shortages on drug prices: evidence from China.

Introduction: Drug shortages pose a serious global public health challenge, affecting China and other countries. Evidence from USA shows that short-supplied drugs demonstrated a very high price growth during and after a shortage. However, the effect of shortages on drug prices in China remains unknown. This paper aims to understand the impact of drug shortages on prices and explore implications for shortage prevention policy. Methods: We collected the purchase prices and delivery rates of 120 drugs from April 2019 to December 2021 across whole China. We examined price progression of affected drugs using linear mixed-effects models and performed subgroup analyses based on the number of manufacturers and the severity of shortage. Results: Non-shortage cohort had an annual price growth of 11.62% (95% confidence interval [CI] 8.34 to 14.98). Shortage cohort demonstrated an annual price growth of 8.08% (95%CI 0.12 to 16.77) in the period preceding a shortage, 27.57% (95%CI 6.17 to 52.87) during a shortage, and 9.38% (95%CI -12.64 to 36.39) in the post-shortage period. Drug shortages' impact on prices varied across subgroups. Compared with that of drug markets supplied by a single manufacturer, the price growth rate of markets supplied by more than one manufacture declined more after the shortage resolution. Conclusion: Shortages resulted in significant price increases of study markets, especially the low-priced markets, while the shortage resolution slowed the growth. The primary shortage driver has shifted from the low price to others drivers, such as unavailability of active pharmaceutical ingredients. For currently sole-supplied drugs, the expedited review of applications from other manufacturers should be considered.

Estimated Savings From Using Added Therapeutic Benefit and Therapeutic Reference Pricing in United States Medicare Drug Price Negotiations.

OBJECTIVES: US Medicare will begin negotiating prices for top-selling drugs in 2023. This study describes and estimates potential savings from a therapeutic reference pricing approach, linking comparative effectiveness with the costs of existing therapeutic alternatives, that Medicare could use to adjust the starting point for price negotiations. METHODS: First, we identified target drugs likely to be selected for Medicare negotiation. Second, we identified comparative effectiveness ratings for target drugs based on French Haute Autorité de Santé reports. For target drugs with minor or no added benefit, we identified therapeutic alternatives based on the French reports and US clinical guidelines. For each target drug with minor or no added benefit, we computed the difference between spending based on the drug's estimated statutory ceiling price and spending based on the weighted average cost of therapeutic alternatives or the lowest cost therapeutic alternative. Finally, we calculated potential annual savings from using a starting point in negotiations based on costs of therapeutic alternatives. RESULTS: Potential drug-level savings to Medicare from using a starting point in negotiations based on average spending across therapeutic alternatives, compared with using the statutory ceiling price alone, ranged from $186 541 340 to $2 173 441 197. Potential savings from using a starting point based on the lowest cost alternative ranged from $199 872 163 to $3 605 904 765. CONCLUSIONS: Although we do not expect Medicare to rely on French comparative effectiveness assessments, this study demonstrates the potential for additional savings when using comparative effectiveness and costs of therapeutic alternatives to inform the starting price for negotiations.

Consumer expectations, drug effects, price and purity of heroin and cocaine purchased at drug consumption rooms.

BACKGROUND: Drug consumption rooms offer heroin and cocaine consumers a secure and hygienic environment including medical and social guidance. Despite the support and mentoring, only sparse information is available about how drug quality, drug prices and user expectations match at these locations. The present study reports analysis of these three parameters in two drug consumption rooms in Luxembourg. METHODS: Drug users were invited to participate in the project by handing in a few milligrams of the product they planned to consume for chemical analysis and filling out a short questionnaire about the price and their expectations. After consumption, they were asked to report the experienced effects. Drug quality was accessed using LC-Q-ToF and HPLC-UV, and a statistical analysis was carried out of the questionnaires that were correctly filled out. RESULTS: A total of 513 drug samples have been analyzed. Most consumers were looking for the relaxing/calming effects of heroin and the stimulating effects of cocaine, but they generally overestimated heroin potency and underestimated cocaine potency. No strong correlation based on Spearman's ρ between drug user estimations, drug prices and drug quality was found. CONCLUSION: To the best of our knowledge, this study is the first to combine drug analysis with heroin and cocaine user feedback about expectation, drug prices and drug effects. The analytical results were of great interest for users and the staff working at the drug consumption rooms. They may be a strong supplementary communication tool for health care workers when discussing effects and risks of highly toxic substance consumption.

Government spending on antiretrovirals in Brazil and its main determinants / Gastos governamentais com antirretrovirais no Brasil e seus principais determinantes

The construction of public policies for the prevention and treatment of HIV/AIDS in Brazil is a history of struggle that unites sanitarians, researchers and activists since the 1980s. An important part of this path is linked to the production and distribution of antiretroviral drugs (ARV), initiatives to reduce the price of ARVs and civil society mobilizations for the guarantee of rights, which contributed to create one of the most successful programs to combat the disease in the country. world. Based on this history, this study aimed to analyze government spending on the acquisition of selected ARVs in the period between 2005 and 2020, making a comparison with international prices, in the light of determinants related to patent disputes, voluntary licensing, PDPs and ARV price reduction initiatives. Among other results, it was possible to observe that there was no immediate relationship between the end of the patent concession and the reduction of prices. Filings of other patent applications and the lack of nationally registered competitors, even after patent expiration, can be significant factors in maintaining high prices.

A construção de políticas públicas para a prevenção e tratamento do HIV/Aids no Brasil é uma história de luta que une sanitaristas, pesquisadores e ativistas desde os anos 1980. Parte importante desse caminho está ligado à produção e distribuição de medicamentos antirretrovirais (ARV), iniciativas de redução do preço dos ARV e mobilizações da sociedade civil pela garantia de direitos, que contribuíram para criar um dos programas mais bem-sucedidos de combate à doença no mundo. Com base nesse histórico, este trabalho teve por objetivo analisar os gastos governamentais na aquisição de ARV selecionados no período entre 2005 e 2020, fazendo uma comparação com preços internacionais, à luz dos determinantes relacionados às disputas patentárias, ao licenciamento voluntário, às PDPs e às iniciativas para redução de preços de ARVs. Entre outros resultados, foi possível observar que não houve uma relação imediata entre o fim da concessão patentária e a redução de preços. Depósitos de outros pedidos de patente e a inexistência de concorrentes registrados nacionalmente, mesmo após a expiração da patente, podem ser fatores significativos para a manutenção de altos preços.

Cost-Effectiveness of Quadruple Therapy in Management of Heart Failure With Reduced Ejection Fraction in the United States.

BACKGROUND: The 2022 clinical guidelines for management of heart failure with reduced ejection fraction call for quadruple therapy. Quadruple therapy consists of an angiotensin receptor-neprilysin inhibitor (ARNi), sodium-glucose cotransporter-2 inhibitor (SGLT2i), mineralocorticoid receptor antagonist, and beta blocker. The ARNi and sodium-glucose cotransporter-2 inhibitor are newer additions to standard of care with the ARNi replacing ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers. METHODS: We investigate the cost-effectiveness of sequentially adding the SGLT2i and ARNi to form quadruple therapy as compared with the previous standard of care with ACE inhibitor/mineralocorticoid receptor antagonist/beta blocker. Using a 2-stage Markov model, we projected the expected lifetime discounted costs and quality-adjusted life years (QALYs) of a simulated cohort of US patients who underwent each treatment option and calculated incremental cost-effectiveness ratios. We assessed incremental cost-effectiveness ratios using criteria for health care value (<$50 000/quality-adjusted life year [QALY] indicating high-value, $50 000-150 000/QALY indicating intermediate value, and >$150 000/QALY indicating low-value) and a standard $100 000/QALY cost-effectiveness threshold. RESULTS: Compared with the previous standard of care, the SGLT2i addition had an incremental cost-effectiveness ratio of $73 000/QALY and weakly dominated the ARNi addition. The addition of both the ARNi and SGLT2i for quadruple therapy offered 0.68 additional discounted QALYs over the SGLT2i addition alone at a lifetime discounted cost of $66 700, resulting in an incremental cost-effectiveness ratio of $98 500/QALY. In sensitivity analysis varying drug prices, the incremental cost-effectiveness ratio for quadruple therapy ranged from $73 500/QALY using prices available to the US Department of Veterans Affairs to $110 000/QALY using drug list prices. CONCLUSIONS: While quadruple therapy offers intermediate value, it is borderline cost effective compared with adding the SGLT2i alone to previous standard of care. Thus, its cost-effectiveness is sensitive to a payer's ability to negotiate discounts off the increasing list prices for ARNI and SGLT2is. The demonstrated benefits of ARNi and SGLT2is should be weighed against their high prices in payer and policy considerations.

An empirical study of the impact of generic drug competition on drug market prices in China.

Introduction: Generic substitution is encouraged to reduce pharmaceutical spending in China, and with incentive policies, the market size of the generic drug continues to rise. To find out how the generic competition affects drug price in this area, this study examines how the quantity of generic drug manufacturers can influence average drug price in the Chinese market. Methods: This study uses a rigorous selection of drugs from the 2021 China's National Reimbursement Drug List (NRDL), and uses drug-level fixed effects regressions to estimate the relationship between competition and price within each drug. Results: We note that drug prices decline with increasing competition in the Chinese market, but not in a perfectly linear manner, with marginal price declines decreasing after the fourth entrant and "rebounding" at subsequent entrants, especially the sixth. Discussion: The findings suggest the importance of maintaining effective competition between suppliers to control prices, and that the government needs to further control generic pricing, especially for late entry generics, to ensure effective competition in the Chinese market.

The Inflation Reduction Act: How Will Medicare Negotiating Drug Prices Impact Patients with Heart Disease?

PURPOSE OF REVIEW: Cardiovascular medications improve health and prevent early death. However, high drug prices reduce the use of these medications and strain the health system. The Inflation Reduction Act (IRA) of 2022 allows Medicare to negotiate drug prices with manufacturers and reduces out-of-pocket drug costs for Medicare beneficiaries. This article explores the potential impact that the IRA will have on the treatment of cardiovascular disease. RECENT FINDINGS: Cardiovascular disease medications are likely to be selected for price negotiations under the IRA, leading to savings for patients and for Medicare. Recent work suggests that the IRA's reforms to the Medicare Part D drug benefit will meaningfully reduce out-of-pocket costs for important cardiovascular medications. The IRA is expected to impact cardiovascular disease treatments via price negotiations and through the broader access to medications afforded by improvements to Part D coverage design.

The price, efficacy, and safety of within-class targeted anticancer medicines between domestic and imported drugs in China: a comparative analysis.

Background: Affordability to novel anticancer drugs has become a major health issue in China. It is encouraging to note that China initiated its drug regulatory reform and national price negotiation policies since 2015. As a growing number of domestic within-class targeted anticancer drugs are approved in China, it is expected that this may reduce the price of novel anticancer drugs and improve the affordability of anticancer drugs. This study aimed to evaluate the price, efficacy, and safety of the within-class anticancer drugs between domestic and imported drugs approved in China from 2010 to 2022. Methods: The domestic and imported within-class targeted drugs for solid cancers approved in China between 2010 and 2022 were extracted. We classified it as a class of anticancer drugs based on the same indication and similar biological mechanism. The published literature derived from pivotal clinical trials of these domestic and imported drugs was identified based on the review report and the latest labels issued by the China National Medical Products Administration. We evaluated the monthly treatment price at launch and the latest (2022), primary efficacy endpoint and safety between domestic and imported anticancer drugs. Meta-analyses were further employed to evaluate the efficacy and safety of the domestic and imported anticancer drugs, including pooled hazard ratios (HR) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR) for solid cancers, and relative risk for serious adverse events (SAE) and Grade ≥3 adverse events (AEs). Findings: In our cohort study, 12 within-class anticancer drugs with 7 cancer diseases were analyzed, including 18 domestic (21 indications; 21 pivotal trials) and 18 imported (21 indications; 27 pivotal trials) novel anticancer drugs, respectively. The median monthly treatment price of domestic and imported drugs from the years of launch to 2022 had significantly decreased by 71% and 62%, respectively. Moreover, the median monthly treatment price of domestic targeted anticancer drugs on the market at launch ($3786 vs. $5393, P = 0.007) and the latest ($1222 vs. $2077, P = 0.011) was significantly lower than that of imported drugs. No significant differences in median PFS gains (9.0 vs. 11.0 months; P = 0.24), OS gains (9.3 vs 10.6 months; P = 0.66), and ORR (57% vs 62%, P = 0.77) of targeted anticancer drugs in their pivotal trials were observed between the domestic and imported drugs. Additionally, there was no significant difference between domestic and imported drugs in the incidence of SAE (23% vs. 24%; P = 0.41) and Grade ≥3 AEs (59% vs. 57%; P = 0.45). These findings were also further confirmed in the meta-analyses for primary efficacy endpoints and safety outcomes. Interpretation: The prices of both domestic and imported anticancer drugs significantly decreased after market entry mainly due to the role of national price negotiations. The median monthly treatment price of domestic within-class targeted anticancer drugs was significantly lower than that of imported drugs. Furthermore, the efficacy and safety of domestic anticancer drugs were comparable to that of imported drugs. This evidence implicated that the development of within-class anticancer drugs with national price negotiations in China significantly improved the affordability for patients. Funding: This study was supported by postdoctoral fellowship from Tsinghua-Peking Joint Centers for Life Sciences (CLS).

Correlation of Anticancer Drug Prices with Outcomes of Overall Survival and Progression-Free Survival in Clinical Trials in Japan.

Drug pricing methods vary extensively across countries. Japan calculates drug prices using cost accounting and based on the efficacy of similar drugs. This study investigated the relationship between drug prices and their clinical efficacy and usefulness using public information on anticancer drugs reimbursed by the National Health Insurance price listing between January 2009 and March 2020. We investigated drug characteristics, prices, and clinical benefits based on overall survival (OS) and progression-free survival (PFS). Eighty anticancer drugs were approved in Japan during the study period. The largest number (28 drugs, 35.0%) was approved based on PFS, 18 (22.5%) were approved based on OS, and 13 (16.3%) based on the response rate. The mean (±SD) drug price was JPY 88,416.2 (±148,974.7), while the median drug price (with quartiles) was JPY 21,694 (JPY 4855.0-JPY 93,396.8). Drug prices were significantly higher for PFS than for OS, while cost index-the drug price to extend PFS or OS by one day-did not differ significantly between PFS and OS. The relationship between the 46 drugs approved based on OS or PFS and their prices was examined. A correlation was found between drug prices and their clinical usefulness in terms of OS but not PFS.

The impact of conventional cost-effectiveness analysis on pricing dynamics in the market of new medicines: a proposed countervailing approach.

BACKGROUND: Countries using cost effectiveness ratio as a decision tool for price and reimbursement decisions still witness accelerating price increases. The objective of this paper is to propose a change in the application of the incremental cost effectiveness ratio as a criterion for price policy. RESEARCH DESIGN: We develop a model that sets a price for marginal effectiveness equal to the marginal willingness to pay, but it reimburses average effectiveness according to the size of increased QALY gain. RESULTS: This new formula also allows to split the economic value of drug between patients and the industry and creates a reward to invest into QALY gains. We show some empirical data of the new prices derived from the application of the new formula, as well as the implications in terms of the consumer and manufacturer´s surplus based on two potential scenarios of the incentives generated by this new formulation. DISCUSSION: We propose that small increases in life expectancy be priced differently from substantial as a way of containing the price dynamics. CONCLUSIONS: A change in the application of the ICER threshold will help to reduce the price pressure on public budgets.

Two views of cancer medicines: Imagery versus evidence.

Despite advertising imagery portraying cancer medicines as offering substantial improvement or cure, most patients can expect modest or no incremental benefit from most new treatments, according to pre-specified criteria. When improvements in overall survival are demonstrated, they average just 2.1 months. Despite limited benefits, drug prices have risen while median household incomes have remained largely unchanged, and these higher prices are poorly correlated with improved outcomes. Better alignment of perception with demonstrated drug benefit could be achieved by limitations on advertising and improved labeling or other disclosures. Reforms are also needed to remove financial incentives to prescribe costlier drugs.

Comparative price analysis of biological medicines: disparities generated by different pricing policies.

Introduction: Biological medicines have been assuming an important role among the therapeutic options for several diseases, however, due to their complex production process, the products obtained from this technology have a high added value and do not reach the purchasing power of most patients, which overwhelms the budget of health systems. With the development of biosimilars, which have reduced production costs, it is expected that access to biological medicines will become broader. However, in Brazil, the criteria for determining the price of biosimilars, unlike the generic policy in the country, do not foresee a price reduction due to the reduction of development costs. Objective: To understand the impact of the current model of economic regulation on the availability and access of these products in the country, based on a comparative analysis in selected countries, and identify trends that can help to expand the availability and access to biological medicines. Method: Quantitative and qualitative study, to identify the variation between the entry prices of biological medicines in Brazil and in selected countries, as well as the differences in the economic regulation policies established in these countries. Results: The results demonstrate that the current pricing model in Brazil has generated distortions in the prices of biosimilars in the market, which, consequently, makes it difficult for the population to access this category of products, in addition to allowing unsustainable market practices for the systems of public and private health in Brazil. It was also found that most of the analyzed countries, unlike Brazil, seek to harmonize the prices of different brands of the same molecule marketed in the country and with the international market, in addition to establishing incentive policies for indication and replacement by biosimilars, which expands the participation of biosimilars in the market significantly. Conclusion: Based on the data presented, it is concluded that it is essential to build a broader political and regulatory debate on the market for biologicals and biosimilars in the country to guarantee the access of the Brazilian population to more cost-effective technologies, generate a more competitive market and consequently contribute to the financial sustainability of health systems.

Can Drug Price Controls Help Patients Get a Better Deal? A SWOT Analysis

@#Introduction: Due to the increasing rate of drug prices and overall healthcare inflation, stakeholders from the pharmaceutical industry and non-governmental organisations (NGOs) are voicing their concerns about the possible reciprocal effects in the long run. Drug price controls (DPCs) regulation is crucial to ensure affordability and indirectly reduce congestion in public healthcare facilities. This study aims to identify the SWOT analysis of the DPCs in Malaysia and how it will impact the drug supply chain. Methods: The study adopted a subjective environmental scanning method and a SWOT analysis tool to examine the Malaysian pharmaceutical DPCs in the healthcare supply chain (HSC) ecosystem through both intrinsic and extrinsic perspectives. Results: The immediate effect of DPCs would be beneficial, especially to the patients and the government. Balancing the right amount of control and liberalization of the market is seen to be the biggest factor contributing to the policy’s effect on the drug supply chain. The main concern would be the long-term effect as mixed results are coming from a group of countries that had implemented a similar policy. Conclusion: Notwithstanding the qualitative methodology of the paper, the findings could provide a better understanding of the price of drugs in Malaysia’s HSC and serve as a foundation for future studies. This paper proposes a new way to diversify the DPCs economy by entering the HSC chain industry.

Correlation between clinical trial endpoints of marketed cancer drugs and reimbursement decisions in China.

Objective: This study aimed to assess whether different clinical trial endpoints in pivotal trials of cancer drugs were associated with reimbursement decisions in China. Materials and methods: Cancer drugs marketed before June 30th, 2021 with publicly available technical review reports for application of drug registration on Center for Drug Evaluation (CDE) website were reviewed. The trial design characteristics and relevant clinical outcomes [e.g., overall survival (OS), progression-free survival (PFS) and objective response rate (ORR)] were extracted from the technical review reports, while the reimbursement decisions were reviewed from National Healthcare Security Administration (NHSA) website. The differences in trial characteristics and clinical outcomes between drugs with positive reimbursement decisions and negative ones were compared by hypothesis test (Pearson's chi-squared test, Fisher's exact test, independent samples t-test and Mann-Whitney U test). The correlation between different clinical trial endpoints and reimbursement decisions was analyzed by multivariate logistic regression. Results: There were 112 cancer drug indications included in this study. Among these indications, 76 received a positive reimbursement decision, and the most common primary endpoints of them were PFS (42.1%) and ORR (30.3%). Taking PFS (OR = 7.333) and ORR (OR = 5.271) as the primary endpoints were more likely to receive a positive reimbursement decision compared with OS (P = 0.003). The proportion of drugs marketed with phase I (75.0%) and phase II (85.7%) clinical trials receiving positive reimbursement decisions are significantly higher than those marketed with phase III clinical trials (61.3%, P = 0.043). The magnitude of clinical benefit only had subtle influences (Prisk benefit - OS = 0.627, Prisk benefit - PFS = 0.087, Psurvival benefit - OS = 0.545, Psurvival benefit - PFS = 0.189) on the drug reimbursement decisions, however, the drug prices and clinical needs also made a difference on that. Conclusion: This study found that, in Chinese drug price negotiations from 2017 to 2021, policymakers have focused more on meeting clinical needs and filling therapeutical gaps in National Reimbursement Drug List (NRDL), while requirements for the selection of primary endpoints, clinical trial phases, and clinical benefits have been reduced. In the future, emphasis should be put on the use of surrogate endpoints and clinical benefits.

Trends in anti-HER2 drugs consumption and influencing factors.

Background: Human epidermal growth factor receptor 2 (HER2) inhibitors have been approved to treat various cancers with HER2 amplification. The Chinese government has made great efforts to improve the availability and affordability of these drugs. This study aimed to analyze the trends in anti-HER2 drug consumptions in Nanjing from 2012 to 2021, and explore influencing factors. Methods: Data about use of anti-HER2 drugs in 2012-2021 were extracted from Jiangsu Medicine Information Institute. Six types of anti-HER2 drugs were included. Drug consumption was expressed as defined daily doses (DDDs) and expenditure. Time series analysis was adopted to find trends in consumption, while interrupted time series was used in analyzing the impact of policy on consumption. The correlation between DDDs and defined daily cost (DDC) was analyzed by Pearson's correlation test. Results: The DDC, DDDs, and expenditure of anti-HER2 drugs changed little from 2012 to 2016. The DDC decreased intermittently, while the DDDs and expenditure of these drugs grew continuously from 2017 to 2021. The anti-HER2 monoclonal antibodies contributed to the majority of total consumption in 2012-2019. The DDDs of anti-HER2 tyrosine kinase inhibitors surpassed the DDDs of monoclonal antibodies in 2020-2021. Trastuzumab was the predominantly prescribed drug in 2012-2019, but the DDDs of pyrotinib surpassed the DDDs of trastuzumab in 2020-2021. The ln value of DDC or self-paid DDC of trastuzumab was negatively correlated with the ln value of its DDDs. The national health insurance coverage (NHIC) and national drug price negotiation policy about anti-HER2 drugs were initiated in 2017. Low-price generics and biosimilar of trastuzumab came into the market in 2020 and 2021, separately. Interrupted time series analysis showed that the DDDs increased significantly after the implementation of NHIC, price negotiation or generic drug replacement. Conclusion: The consumption of anti-HER2 drugs has significantly increased and their DDC has decreased after the implementation of NHIC, price negotiation, or low-price generic drug replacement since 2017. Further efforts are needed to translate the high consumption into clinical benefits.

Antihypertensive prescribing pattern, prescriber adherence to ISH 2020 guidelines, and implication of outpatient drug price on blood pressure control at selected hospitals in Southern Ethiopia.

PURPOSE: To determine the impact of drug prescribing pattern, outpatient drug price of medicines, and level of adherence to evidence-based international guidelines on blood pressure (BP) control at selected hospitals in Southern Ethiopia. METHODS: Hospital-based cross-sectional study was conducted. The data entry and analysis were done by using SPSS version 21.0. RESULTS: A mean age of participants was 55.87 ± 11.02 years. The rate of BP control was 17.5% based on International Society of Hypertension (ISH) guidelines 2020. In about two-thirds of patients, 270 (66.5%) were taking combination therapy. Mean annual cost of drugs for hypertension was 11.39 ± 3.98 US dollar (USD). Treatment was affordable for only 91 (22.4%) of patients. There was considerable variation on prescriber's adherence to evidence-based guidelines. Body mass index (BMI) of 18-24.9 kg/m2, adjusted odds ratio (AOR) = 3.63 (95% confidence interval (C.I), 1.169-11.251, p = 0.026), physically activity, AOR = 12.69 (95% C.I, 1.424-113.17, p = 0.023), presence of no comorbidity, AOR = 12.82 (95% C.I, 4.128-39.816, p = 0.000), and taking affordable antihypertensive regimen, AOR = 3.493 (95% C.I, 1.4242-9.826, p = 0.018), were positively associated BP control. CONCLUSION: The level of BP control, affordability of drugs for the management of hypertension and related comorbidities, and the prescriber's adherence to evidence-based guidelines were inadequate. Therefore, addressing factors associated with good BP control including affordability and clinician adherence to evidence-based guidelines by responsible stakeholders could improve BP control and reduce associated complications.

An integrated valuation model for payer and investor.

Background: In order to optimize positioning and associated drug price for both payer and investor, it is for a company essential to forecast the potential market access attractiveness for the new drug for different indications at the early onset of the clinical development program. This analysis must include the constraints from the perspective of the payer, but also the biotech companies, who require a minimum drug price to satisfy their investors. This paper aims to provide an Integrated Valuation Model for payer and investor, bridging concepts from health economics and economic valuation reflecting the perspectives of the payer and the investor for a drug in early clinical development phase. The concept is illustrated for a new hypothetical drug (Product X) in advanced breast cancer in 1-line, 2-line, and 3-line position. Methods: The Integrated Valuation Model includes the outcomes of the budget impact model, pricing matrix model, and cost-effectiveness model reflecting the payer's perspective. These models are interacted and linked with a discounted cash flow model in order to reflect also the economic value from the investor's perspective. Results: The maximum price in 1-line position is €269.7 for the payer and the minimum price is €14.7 for the investor, which are unit prices per administration corresponding with treatment regimens for the comparative treatments. In 2-line position, the maximum price is €274.1 for the payer and the minimum price for the investor increases to €184.5 for the investor because of the smaller market size in 2-line position, which leads to a smaller pricing corridor to satisfy both payer and investor. Consequently, Product X has market access attractiveness for both payer and investor in 1-line and 2-line position. However, the minimum price €942.7 in 3-line position for the investor is higher than the maximum price €283.3 for the payer, which means there is no market potential. Conclusion: The practical strategic application of the Integrated Valuation Model is optimization of positioning and price of Product X. Hence, it can be a transparent tool in early-stage development of a compound based on upfront assessment of market access attractiveness for the payer and the investor.

Utilization, Spending, and Price of Opioid Medications in the US Medicaid Programs Between 1991 and 2019.

Background: The opioid epidemic and drug abuse are critical public health challenges in the United States. The number of deaths from exceeding the recommended opioid dose is increasing. Objective: To describe the recent trends in utilization, spending, and cost of opioid medications in the US Medicaid population between 1991 and 2019. Methods: This retrospective, descriptive study was designed to evaluate the utilization of, spending on, and cost of opioids from 1991 to 2019 in the Medicaid population. We extracted data from the Centers for Medicare & Medicaid Services national Medicaid pharmacy files. The opioids received included fentanyl, meperidine, morphine, hydromorphone, oxymorphone, hydrocodone, hydrocodone plus acetaminophen, oxycodone, oxycodone plus acetaminophen, tapentadol, and tramadol. The number of prescriptions and reimbursement spending were calculated for each medication per quarter year. The average per-prescription reimbursement as a proxy of drug price was calculated as the reimbursement amount divided by the number of prescriptions per quarter year. The market shares by spending and utilization were also calculated for each opioid medication. Results: The number of all opioid prescriptions in Medicaid increased from approximately 2.1 million in 1991 to approximately 41.6 million in 2015, and then reduced to approximately 19.1 million in 2019. During this 29-year study period, the opioid medications that were used as monotherapy were hydrocodone (246.8 million prescriptions), oxycodone (111.9 million prescriptions), and tramadol (75.2 million prescriptions). The total spending in the Medicaid population on opioids was $19.4 billion, including approximately $7.3 billion spending on oxycodone, approximately $3.7 billion on fentanyl, and approximately $3.3 billion on hydrocodone. The majority of opioid prices increased over time, and the highest average costs per opioid prescription in 2019 were $1188 for oxymorphone, $641 for tapentadol, and $198 for fentanyl. Conclusions: The utilization of and spending on opioid medications in Medicaid increased over time, peaked in 2015, and then declined with the initiation of nationwide programs to combat the opioid epidemic. Effective cost-containment strategies and programs to combat the abuse of opioids are warranted in Medicaid programs.