Tackling medicine shortages during and after the COVID-19 pandemic: Compilation of governmental policy measures and developments in 38 countries.

In response to increasing shortages of medicines, governments have implemented legislative and non-legislative policy measures. This study aimed to map these policies across high-income countries in Europe and beyond as of 2023 and to analyse developments in governmental approaches since the beginning of the pandemic. Information was collated from 38 countries (33 European countries, Australia, Brazil, Canada, Israel and Saudi Arabia) based on a survey conducted with public authorities involved in the Pharmaceutical Pricing and Reimbursement Information (PPRI) network in 2023. 34 countries requested pharmaceutical companies to notify national registers of upcoming shortages and 20 countries obliged manufacturers and/or wholesalers to stock supply reserves of critically needed medicines. Further common measures included export bans for defined medicines (18 countries), regulatory measures to facilitate import and use of alternative medicines (35 countries) and multi-stakeholder coordination (28 countries). While the legislation of 26 countries allows imposing sanctions, particularly for non-compliance to reporting requirements, fines were rather rarely imposed. Since 2022, at least 18 countries provided financial incentives, usually in the form of price increases of some off-patent medicines. Overall, several policies to address medicine shortages were taken in recent years, in some countries as part of a comprehensive package (e.g., Australia, Germany). Further initiatives to secure medicine supply in a sustainable manner were being prepared or discussed.

Lessons learned from the Canadian Fabry Disease Initiative for future risk-sharing and managed access agreements for pharmaceutical and advanced therapies in Canada.

Risk sharing agreements (RSAs) and managed access agreements have emerged as tools to overcome evidentiary uncertainty and contain costs of pharmaceuticals; however, Canada has relatively little experience with these health policy instruments. This article describes one of the few examples of national RSAs. Enzyme replacement therapies (ERT) were introduced in Canada to treat Fabry disease in the early 2000s through an RSA. Based on qualitative interviews with key participating actors, this article explains how this RSA ensured continuity of treatment for patients already on ERT, and collected robust real-world evidence to secure treatment for future Fabry patients. We show the importance of partnerships, collaborations, and active patient communities in establishing RSAs, as well as the critical role of robust registries for the collection, storage, and use of that real-world data. In doing so, this paper points to reasons that explain the relative dearth of RSAs in Canada, which can be resource (both human and finance) intensive and are difficult to broker in a federalist health system. Through these findings, policy lessons are developed concerning the need for technological and governance platforms on how RSA in Canada can be more effectively supported going forward in a broader move towards "social pharmaceutical innovation".

Problemática del acceso a los medicamentos: disponibilidad y la producción local en América latina / Problems of Access to Medicines: Availability and Local Production in Latin America

La desigualdad en el acceso a los medicamentos se percibe como un síntoma de las deficiencias del sistema sanitario y supone un incumplimiento por parte de los gobiernos de sus obligaciones para con sus ciudadanos en cuanto a su derecho a la protección de la salud.Integrar la perspectiva de la salud como derecho inherente de la población y, al mismo tiempo, la perspectiva de la salud como espacio estratégico de desarrollo de la base productiva y tecnológica, creación de valor, generación de inversiones, ingreso, empleo, conocimiento e innovación, son claves para mejorar el acceso.El objetivo de este trabajo es presentar la problemática del acceso a los medicamentos desde la perspectiva de la disponibilidad de los mismos y exponer la situación del mercado de América Latina.El escenario de América Latina es complejo: países con realidades económicas distintas, proyectos fallidos de integración, gasto en salud pública por debajo del 6%, escasa inversión en investigación y desarrollo, preferencia a las importaciones, legislación no convergente y tendencias al nacionalismo de los países de altos ingresos para el retorno de la producción al país de origen. A pesar de las limitaciones descritas, en la región existen capacidades productivas que deben ser fortalecidas. Brasil, Argentina, México, Colombia y Chile son los países llamados a liderar la producción regional a través de la diversificación. En este momento la solución pasa por que en la región se antepongan los proyectos regionales frente a los intereses individuales, para con ello lograr la autosuficiencia sanitaria.(AU)

Inequality in access to medicines is perceived as a symptom of the weaknesses of the health system and implies a failure on the part of governments to fulfill their obligations to their citizens in terms of their right to health protection.Integrating the perspective of health as an inherent right of the population and, at the same time, the perspective of health as a strategic space for the development of the productive and technological base, value creation, generation of investment, income, employment, knowledge and innovation, are key to improving access.The objective of this paper is to present the problem of access to medicines from the perspective of their availability and to describe the situation of the Latin American market.The Latin American scenario is complex: countries with different economic realities, failed integration projects, public health spending below 6%, low investment in research and development, preference for imports, non-convergent legislation and tendencies towards nationalism in high-income countries for the return of production to the country of origin. Despite the limitations described above, there are productive capacities in the region that need to be strengthened. Brazil, Argentina, Mexico, Colombia and Chile are the countries called upon to lead regional production through diversification. At this time, the solution is for the region to put regional projects before individual interests in order to achieve sanitary self-sufficiency.(AU)

Price negotiation and pricing of anticancer drugs in China: An observational study.

BACKGROUND: While China has implemented reimbursement-linked drug price negotiation annually since 2017, emphasizing value-based pricing to achieve a value-based strategic purchase of medical insurance, whether drug prices became better aligned with clinical value after price negotiation has not been sufficiently established. This study aimed to assess the changes in prices and their relationship with the clinical value of anticancer drugs after the implementation of price negotiations in China. METHODS AND FINDINGS: In this observational study, anticancer drug indications that were negotiated successfully between 2017 and 2022 were identified through National Reimbursement Drug Lists (NRDL) of China. We excluded extensions of indications for drugs already listed in the NRDL, indications for pediatric use, and indications lacking corresponding clinical trials. We identified pivotal clinical trials for included indications by consulting review reports or drug labels issued by the Center for Drug Evaluation, National Medical Products Administration. We calculated treatment costs as outcome measures based on publicly available prices and collected data on clinical value including safety, survival, quality of life, and overall response rate (ORR) from publications of pivotal clinical trials. The associations between drug costs and clinical value, both before and after negotiation, were analyzed using regression analyses. We also examined whether price negotiation has led to a reduction in the variation of treatment costs for a given value. We included 103 anticancer drug indications, primarily for the treatment of blood cancer, lung cancer, and breast cancer, with 76 supported by randomized controlled trials and 27 supported by single-arm clinical trials. The median treatment costs over the entire sample have been reduced from US$34,460.72 (interquartile range (IQR): 19,990.49 to 55,441.66) to US$13,688.79 (IQR: 7,746.97 to 21,750.97) after price negotiation (P < 0.001). Before price negotiation, each additional month of survival gained was associated with an increase in treatment costs of 3.4% (95% confidence interval (CI) [2.1, 4.8], P < 0.001) for indications supported by randomized controlled trials, and a 10% increase in ORR was associated with a 6.0% (95% CI [1.6, 10.3], P = 0.009) increase in treatment costs for indications supported by single-arm clinical trials. After price negotiation, the associations between costs and clinical value may not have changed significantly, but the variation of drug costs for a given value was reduced. Study limitations include the lack of transparency in official data, missing data on clinical value, and a limited sample size. CONCLUSIONS: In this study, we found that the implementation of price negotiation in China has led to drug pricing better aligned with clinical value for anticancer drugs even after substantial price reductions. The achievements made in China could shed light on the price regulation in other countries, particularly those with limited resources and increasing drug expenditures.

Achieving dynamic efficiency in pharmaceutical innovation: Identifying the optimal share of value and payments required.

It has been argued that cost-effectiveness analysis of branded pharmaceuticals only considers static efficiency, neglects dynamic effects and undermines incentives for socially valuable innovation. We present a framework for designing pharmaceutical pricing policy to achieve dynamic efficiency. We develop a coherent framework that identifies the long-term static and dynamic benefits and costs of offering manufacturers different levels of reward. The share of value that would maximise long-term population health depends on how the quantity and quality of innovation responds to payment. Using evidence of the response of innovation to payment, the optimal share of value of new pharmaceuticals to offer to manufacturers is roughly 20% (range: 6%-51%). Reanalysis of a sample of NICE technology appraisals suggests that, in most cases, the share of value offered to manufacturers and the price premium paid by the English NHS were too high. In the UK, application of optimal shares would offer considerable benefits under both a public health objective and a broader view of social welfare. We illustrate how an optimal share of value can be delivered through a range of payment mechanisms including indirect price regulation via the use of different approval norms by an HTA body.

Importance of aligning the implementation of new payment models for innovative pharmaceuticals in European countries.

INTRODUCTION: The uptake of complex technologies and platforms has resulted in several challenges in the pricing and reimbursement of innovative pharmaceuticals. To address these challenges, plenty of concepts have already been described in the scientific literature about innovative value judgment or payment models, which are either (1) remaining theoretical; or (2) applied only in pilots with limited impact on patient access; or (3) applied so heterogeneously in many different countries that it prevents the health care industry from meeting expectations of HTA bodies and health care payers in the evidence requirements or offerings in different jurisdictions. AREAS COVERED: This paper provides perspectives on how to reduce the heterogeneity of pharmaceutical payment models across European countries in five areas, including 1) extended evaluation frameworks, 2) performance-based risk-sharing agreements, 3) pooled procurement for low volume or urgent technologies, 4) alternative access schemes, and 5) delayed payment models for technologies with high upfront costs. EXPERT OPINION: Whilst pricing and reimbursement decisions will remain a competence of EU member states, there is a need for alignment of European pharmaceutical payment model components in critical areas with the ultimate objective of improving the equitable access of European patients to increasingly complex pharmaceutical technologies.

Financial Characteristics of Outcomes-Based Agreements: What Do Canadian Public Payers and Pharmaceutical Manufacturers Prefer?

OBJECTIVES: This study sought to gain insight into the financial characteristics of outcomes-based agreements (OBAs) considered most suitable to Canadian public payers and pharmaceutical manufacturers, and the rationale for their preferences. METHODS: A total of 17 public payers and pharmaceutical manufacturers participated in semistructured qualitative interviews, which assessed their knowledge of OBAs and their preferred financial characteristics. RESULTS: Payers identified 5 OBA financial models that they considered both acceptable and feasible, in no preferential order: (1) discontinuation of therapy, (2) rebates for nonresponders, (3) free trial period, (4) adjustable pricing, and (5) blended rebate. Payers had a clear preference for short-term OBAs (<1 year), whereas both payers and manufacturers agreed OBAs with longer durations (up to 5 years) would be manageable if appropriately designed. Six key success factors to design suitable and acceptable OBA financial models were identified, including the areas of interim reporting, easily measurable health outcomes, trusted data sources, engaging unbiased third-party data experts, harmonizing OBA billing methods, and the inclusion of budget caps. CONCLUSIONS: Manufacturers and payers showed high level of interest in OBAs and a robust understanding of their potential role in supporting timely market access for patients in need, with the caveat that they need to be carefully designed to provide value. Further opportunities for discussion and engagement between public payers and manufacturers are needed to establish how to implement OBAs at a pan-Canadian level and how individual provinces and territories can incorporate them within their existing governance infrastructures.

An Optional Delinked Reward System: Making Pharmaceutical Innovation Work for Everyone.

Conflicts over pharmaceutical pricing are driven by the patients' need for affordable medicines and the producer's reward for the investments in developing innovative medicines. A single price cannot achieve both goals, as it will either obstruct access by patients or provide too low a return to investors. This has led to calls to "delink" the payment for innovation from the price paid for drugs, so that both goals can be met efficiently and without conflict. However, the details of how best to do that are unclear. This paper proposes a specific implementation for delinking the Optional Delinked Reward System (ODRS), which integrates ideas from numerous pharmaceutical reimbursement systems. The ODRS would allow firms to choose either to negotiate a sales price for a drug (as is the current practice in most countries) or to sell their drug at a low "generic" price with a supplementary "delinked" reward based on assessed health benefit. This model builds on recent innovations in drug reimbursement including the UK's Antibiotic Subscription Pilot and the Pneumococcal Vaccine Advanced Market Commitment. The ODRS would ensure affordable and immediate access for patients and a fair reward for innovators.

"What's up with price controls?" Stakeholders' views on the regulation of pharmaceutical pricing in Malaysia.

Escalating costs have made the accessibility of drugs one of the biggest challenges faced by the Malaysian government. The government agreed to regulate drug prices by means of external reference pricing, but its proposed policy had a setback owing to much opposition from the pharmaceutical industry. The policy did gain support from the public and from non-governmental organisations because it ensured easy access to affordable medicines. Comments from public consultations with key stakeholders were used to explore stakeholders' perceptions of the external reference pricing policy. A total of 140 comments were analysed for this study. Stakeholders' views were classified as being from the Socioeconomic, industrial, and government sectors. To summarise, the government must carefully manage and consider stakeholders' views to ensure a sound policy. Using Mendelow's stakeholder mapping, this study mapped out stakeholders' views in a systematic approach. The classification of different stakeholders' views and recommendations led to suggestions for reviewing current practices in pharmaceutical pricing regulations in the Malaysian healthcare system. The analyses can be extended to other countries that face similar concerns.

The reimbursement decision speed for oncology new drugs in China and its determinant factors.

Introduction: China has initiated national price negotiations to improve access to innovative drugs. Learning the factors that contributed to the time gap from marketing authorization to reimbursement leads to more clarity to decision-making, which remains under-researched in China. Methods: We collected new oncology drug approvals that were marketed before 30 Jun 2022, using the Listed Drug Database of the Chinese drug agency. Major information of each approval was obtained from the published review report, including the first approval region (China or the US) and the receipt of expedited review pathways (priority review and conditional approval). The reimbursement lists issued by China National Healthcare Security Administration from 2015 to 2023 were used to determine the reimbursement status of drugs. The duration from marketing authorization to reimbursement was defined as the reimbursement decision speed, and the Cox regression was performed to explore the underlying factors. Results: A total of 186 oncology approvals were included. More than half of the approvals qualified for reimbursement (110[59.14%]), and the median reimbursement decision speed was accelerated from 540.5 days in the third-round negotiation to 448 days in the seventh-round. Domestic new drugs had a higher probability of being adopted by the Chinese payer than drugs developed by foreign companies (adjusted HR = 3.73, 95% CI 2.42 to 5.75; P < 0.001). Furthermore, new drug applications receiving the regular review pathway were more likely to be reimbursed (adjusted HR = 2.15, 95% CI 1.13 to 4.08; P = 0.020) compared to those approved under the conditional approval pathway. Discussion: These findings indicate that the Chinese government is actively working toward improving access to new oncology drugs. The faster reimbursement decision speed for domestic drugs might be attributed to their pricing advantages and the regulator's efforts to stimulate innovation in the domestic pharmaceutical industry. However, concerns about the uncertainty in drug benefits can affect the reimbursement decision-making, which suggests the delicate tradeoff between drug accessibility and risk involved in the reimbursement process.

Reporting reimbursement price decisions for onco-hematology drugs in Spain.

Introduction: Even using well-established technology assessment processes, the basis of the decisions on drug price and reimbursement are sometimes perceived as poorly informed and sometimes may be seen as disconnected from value. The literature remains inconclusive about how Health Technology Assessment Bodies (HTAb) should report the determinants of their decisions. This study evaluates the relationship between oncology and hematology drug list prices and structured value parameters at the time of reimbursement decision in Spain. Methods: The study includes all new onco-hematological products (22), with a first indication authorized between January 2017 and December 2019 in Spain and pricing decisions published up until October 2022. For each product, 56 contextual and non-contextual indicators reflecting the structured multiple criteria decision analysis (MCDA) - Evidence-based Decision-Making (EVIDEM) framework were measured. The relationship between prices and the MCDA-EVIDEM framework was explored using univariate statistical analyses. Results: Higher prices were observed when the standard of care included for combinations, if there were references to long-lasting responses, for fixed-duration treatment compared to treatment until progression and treatment with lower frequencies of administration; lower prices were observed for oral administration compared to other routes of administration. Statistically significant associations were observed between prices and the median duration of treatment, the impact on patient autonomy, the ease of use of the drug, and the recommendations of experts. Discussion: The study suggests that indicators related to the type of standard of care, references to long-lasting responders, the convenience of the use of the drug, and the impact of treatment on patient autonomy, as well as contextual indicators such as the existence of previous clinical consensus, are factors in setting oncology drug prices in Spain. The implementation of MCDA-EVIDEM methodologies may be useful to capture the influence on pricing decisions of additional factors not included in legislation or consolidated assessment frameworks such as the European Network for Health Technology Assessment (EunetHTA) core model. It may be opportune to consider this in the upcoming revision of the Spanish regulation for health technology assessments and pricing and reimbursement procedures.

Medical service pricing and pharmaceutical supply chain coordination contracts under the zero-markup drug policy.

To implement state policies of zero-markup drug policy and medical service fee adjustment for public hospitals, this study constructed game models of the pharmaceutical supply chain, consisting of a drug supplier and a public hospital. The study obtained the optimal medical service level and pricing under the new state drug policies. In addition, it analyzed the impacts of the degree of public benefit of hospitals on the medical service level, the medical service price, and the drug price. Finally, from the perspective of cooperation between drug suppliers and public hospitals, the specialized coordination contract was designed to maximize overall social welfare. This study found an anomalous but meaningful conclusion: in the background of the zero-markup drug policy, a higher public benefit of hospitals could increase the drug prices, but it could reduce the medical service prices further to cut down on the overall treatment fees for the patients. The novel coordination contract can optimize the pharmaceutical supply chain and achieve a win-win situation for the drug suppliers, public hospitals, and patients. When the public benefit of hospitals is higher, the profit of a decentralized decision-making supply chain is greater than a centralized one, while the pharmaceutical supply chain will not coordinate itself.

A systematic review of policies regulating or removing mark-ups in the pharmaceutical supply and distribution chain.

The regulation of mark-ups throughout the pharmaceutical supply and distribution chain may be a valuable approach to control prices of medicines and to achieve broader access to medicines. As part of a wider review, we aimed to systematically determine whether policies regulating mark-ups are effective in managing the prices of pharmaceutical products. We searched for studies published between January 1, 2004 and October 10, 2019, comparing policies on regulating mark-ups against other interventions or a counterfactual. Eligible study designs included randomized trials, and non-randomized or quasi-experimental studies such as interrupted time-series (ITS), repeated measures (RM), and controlled before-after studies. Studies were eligible if they included at least one of the following outcomes: price (or expenditure as a proxy for price and volume), volume, availability or affordability of pharmaceutical products. The quality of the evidence was assessed using the GRADE methodology. A total of 32,011 records were retrieved, seven of which were eligible for inclusion for this review. The limited body of evidence cautiously suggests that policies regulating mark-ups may be effective in reducing medicine prices and pharmaceutical expenditures. However, the design of mark-up regulations is a critical factor for their potential success. Additional research is required to confirm the effects of these policies on the availability, affordability or usage patterns of medicines and in low- and middle-income countries.

Medication adherence and pharmaceutical design strategies for pediatric patients: An overview.

Medication adherence in pediatric patients is a key factor in drug development and dosage form design. High medication adherence is not only important to achieve the expected treatment effects but can also effectively reduce medical costs. It is an ongoing task to accurately identify differences in medication adherence between children and adults and analyze the factors related to pediatric medication adherence. This is necessary to guide the development of pediatric drugs. This review focuses on factors that influence pediatric medication adherence as well as pharmaceutical design strategies to improve adherence. Current new dosage forms, new technologies, and new devices are comprehensively summarized in terms of their advantages and limitations.

Cancer Drug Prices in the United States: Efficacy, Innovation, Clinical Trial Evidence, and Epidemiology.

OBJECTIVES: Rising cancer drug prices challenge patients and healthcare systems. Although prices are routinely assigned to original drug indications receiving US Food and Drug Administration (FDA) approval, the pricing of supplemental indication approvals remains uncertain. This study identifies and quantifies factors associated with cancer drug prices, distinctly analyzing original and supplemental indications. METHODS: Clinical trial evidence and epidemiologic data supporting new indications' FDA approval (2003-2022) were collected from the Drugs@FDA database, ClinicalTrials.gov, and Global Burden of Disease study. Indication-specific monthly treatment costs were calculated for Medicare patients. The association between log-prices and collected variables were assessed in regression analyses. RESULTS: We identified 145 drugs approved across 373 cancer indications. Drugs were priced at $24 444 per month on average (median = $16 013). For original indications, prices weakly correlated to improvements in overall survival (ß = 0.28, P = .037) and progression-free survival (ß = 0.16, P = .001). Original indications' prices were as follows: (1) negatively associated with disease incidence (ß = -0.21, P < .001) and prevalence; (2) positively correlated with first-in-class drugs (26%, P = .057), gene and cell therapies (176%, P < .001), hematologic cancers (62%, P < .001), and severe diseases with substantial unmet needs (6% per disability-adjusted life-year, P < .001); and (3) negatively correlated to indications with randomized-controlled phase 3 trials. Prices were poorly associated with supplemental indications' efficacy, clinical evidence, and epidemiology. CONCLUSIONS: Cancer drug prices are set based on the original indication's characteristics, thereby omitting the value of supplemental indications. Indication-specific pricing, coverage, and reimbursement policies considering each indication's safety, efficacy, innovativeness, and unmet needs are necessary to align a drug's value and price.

Interface policies bridging outpatient and hospital sectors in Europe: can cross-sectorial collaboration in reimbursement and procurement improve access to affordable medicines?

INTRODUCTION: Pharmaceutical systems are frequently characterized by fragmentation, and competences for outpatient and inpatient sectors sit with different authorities, payers, and purchasers. This fragmentation of responsibilities can incentivize shifting expensive therapies and thus patients from one sector to the other. AREAS COVERED: Reimbursement and procurement policies in Europe addressing unwanted consequences of this fragmentation were identified through literature reviews and surveys with policy-makers. Good practice examples include cross-sectorial reimbursement lists managed by committees with representatives from the outpatient and hospital sectors, specific funding mechanisms, joint procurement involving purchasers from both sectors, actions against procurement contracts prohibiting generic competition, and an extension of Health Technology Assessment to the hospital sector. EXPERT OPINION: Recognizing fragmentation as a major challenge for pharmaceutical systems, policy-makers in some countries reacted by implementing policies to support cross-sectorial collaboration. However, only a handful of good practice examples exist for reimbursement and procurement policies in Europe. Though robust evaluations are lacking, there are indications that pharmaceutical policies which ensure collaboration at the interface of the outpatient and inpatient sectors would likely result in efficiency gains and better use of public budgets and may serve as lever to improve access to medicines.

In several European countries, the decision which medicines are funded by public money (reimbursement) and purchased by public institutions (public procurement) is taken independently for the outpatient sector and the hospital sector. There are different payers and procurers per sector, and even within a sector. Patients may be transferred between the sectors for financial reasons because one payer aims to shift the financial burden for the medication to the other sector.Policy-makers have understood the importance of better collaboration between the sectors, and some European countries introduced policies addressing the issue.The article presents examples of how reimbursement and procurement policies can be designed to improve the collaboration between the outpatient and hospital sectors. Committees that decide whether or not a medicine should be covered may contain representatives from both sectors; they may be mandated to take decisions that apply to medicines for outpatient use and administered in hospitals. Purchasers of both sectors may procure jointly a medicine. Supporting tools, such as the assessment of a medicine to support the decision on coverage and the price, may be used in both sectors. Financing solutions can reduce the incentive for one sector to shift a medicine to the other sector.These measures can help that patients gain improved access to affordable medicines. However, despite the introduction of such interface policies in some countries, policy-makers still need to continue working on overcoming the fragmentation in the pharmaceutical system.