Managed Entry Agreements: Policy Analysis From the European Perspective.

BACKGROUND: Mounting pressures on the healthcare system, such as budget constraints and new, costly health technologies reaching the market, have pushed payers and manufacturers to engage in managed entry agreements (MEAs) to address uncertainty and facilitate market access. OBJECTIVES: This study was conducted to illustrate the current landscape of MEAs in Europe and to analyze the main hurdles they face in implementation, providing a policy perspective. METHODS: We conducted a health policy analysis based on a literature review and described the emergence, classification, current use, and implementation obstacles of MEAs in Europe. RESULTS: Throughout Europe, uncertainty and high prices of health technologies have pushed stakeholders towards MEAs. Two main types of MEAs were applied heavily, finance-based agreements (FBAs) and performance-based agreements, including individual performance-based agreements and coverage with evidence development (CED). Service-based agreements have not been as heavily considered so far, yet are increasingly used. Many European countries are turning to CEDs to address uncertainty and facilitate market access while negotiating the pricing and reimbursement rates of products. Despite the interest in CEDs, European countries have moved toward FBAs due to the complexities and burdens associated with PBAs. CONCLUSIONS: Ultimately, in Europe, with the exception of Italy, where MEAs have proven to be inefficient, MEAs are predominantly FBAs dedicated to addressing cost containment from payers' perspective and external reference pricing from the manufacturers' perspective. It has been speculated that MEAs will disappear in the medium-term as they are counterproductive for extending patient access and emergence of innovation. To inform value-based decision making and allow early access to innovative medicines, CEDs should be revisited.

Heterogeneous Recommendations for Oncology Products Among Different HTA Systems: A Comparative Assessment.

Rising budget constraints and demands for healthcare services create additional complexity within the decision process for resource allocation. Innovations and scientific progress have been shown to be key drivers of the increase in healthcare expenditures (1). In the context of rising medical care costs and limited resources, Health Technology Assessment (HTA) was developed as a tool to inform decision-making and to provide the rationalization behind these decisions driving resource allocation and spending for health technology products. Furthermore, HTA agencies make the decision-making process more transparent. The HTA approach involves evaluating multiple aspects of a new product's value in order to maximize health gain provided within the setting of limited resources.

The impact of amortization of gene therapies funding on the results and conclusions of CEMs and BIMs.

BACKGROUND: Gene replacement therapy (GRT) is a treatment method used to combat or prevent various diseases. Its high one-off cost constitutes a major obstacle for successful market access. This paper aims to assess and discuss the applicability of amortization in models, such as cost-effectiveness models (CEMs) and budget impact models (BIMs) informing HTA recommendations and reimbursement decisions. METHODS AND FINDINGS: A hypothetical CEA and BIA were considered. The objective was to compare the GRT with and without amortization. A straight-line amortization model was used. The CEM and BIM were considered and assessed based on two set of scenarios: considering different amortization duration or different discounting rate. The impact of amortization against the total cost of gene therapy was assessed for all the scenarios. The cost difference between GRT with and without amortization in relation to its total cost was -$58,855, thus amortization does not have a significant impact on the results and conclusions of the cost-effectiveness analysis. For BIM in the base case, amortization had no impact on the results. CONCLUSION: Amortization has negligible impact on the results of CEM and total BIM and no impact on the conclusions from the model. One exception is the budget impact in case of an amortization period longer than the time horizon of BIM, where a half of the GRT price is moved beyond the model time horizon. Amortization has a distinguishing effect from an accounting perspective, but it does not have any implication for payers.

Amortization of gene replacement therapies: A health policy analysis exploring a mechanism for mitigating budget impact of high-cost treatments.

With gene replacement therapies (GRTs) increasingly and rapidly reaching the healthcare marketplace, the vast potential for improving patient health is matched by the potential budgetary impact for healthcare payers. GRTs are highly valuable given their potential life-extending or even curative benefits and may provide significant cost-offsets compared with standard of care. Current healthcare systems are, however, struggling to fund such valuable but costly therapies. Some payers have already implemented specific financing models to account for the new treatment paradigms, but these do not address the budget impact in the year of acquisition or administration of these costly technologies. This health policy analysis aimed to assess the rationale and feasibility of amortization, within the context of financing healthcare technologies, and specifically GRTs. Amortization is an accounting concept applied to intangible assets that allows for spreading the cost an intangible asset over time, allowing for repayment to occur via interest and principal payments sufficient to repay the intangible asset in full by its maturity. Our systematic scoping review on the amortization of healthcare technologies found a very small literature base with even that being unclear and inconsistent in its understanding of the issues. Where amortization was proposed as a solution for funding costly, but highly valuable GRTs, the concept was not fully investigated in detail, nor was the feasibility of the approach fully challenged. However, by providing clear definitions of relevant concepts along with an example of amortization models applied to some example GRTs, we propose that amortization can offer a promising method for funding of extraordinarily high-value healthcare technologies, thereby increasing market and patient access for these technologies. Nonetheless, healthcare accounting principles and financing guidelines must evolve to apply amortization to the rapidly developing GRTs.

Regenerative medicine regulatory policies: A systematic review and international comparison.

BACKGROUND: A small number of regenerative medicines (RMs) have received market authorization (MA) worldwide, relative to the large number of clinical trials currently being conducted. Regulatory issues constitute one major challenge for the MA of RMs. OBJECTIVE: This study aimed to systematically review the regulation of RMs internationally, to identify the regulatory pathways for approved RMs, and to detail expedited programs to stimulate MA process. METHODS: Official websites of regulatory authorities in 9 countries (United States (US), Japan, South Korea, Australia, Canada, New Zealand, Singapore, China, and India) and the European Union (EU) were systematically browsed, and was complemented by a systematic literature review in Medline and Embase database. RESULTS: Specific RM legislation/frameworks were available in the EU, US, Japan, South Korea and Australia. A risk-based approach exempting eligible RMs from MA regulations were adopted in the EU and 6 countries. All investigated regions have established accelerated review or approval programs to facilitate the MA of RMs. 55 RMs have received MA in 9 countries and the EU. Twenty-three RMs received Priority Medicine designation, 32 RMs received Regenerative Medicine Advanced Therapy designation, and 11 RMs received SAKIGAKE (fore-runner initiative) designation. CONCLUSION: Regulators have adopted proactive strategies to facilitate RM approval. However, addressing the discrepancies in regulatory requirements internationally remains challenging.

Use of Patient Preference Information in Benefit-Risk Assessment, Health Technology Assessment, and Pricing and Reimbursement Decisions: A Systematic Literature Review of Attempts and Initiatives.

Objectives: Inclusion of patient preference (PP) data in decision making has been largely discussed in recent years. Healthcare decision makers-regulatory and health technology assessment (HTA)-are more and more conscious of the need for a patient-centered approach to decide on optimal allocation of scarce money, time, and technological resources. This literature review aims to examine the use of and recommendations for the integration of PP in decision making. Methods: A literature search was conducted through PubMed/Medline in May 2019 to identify publications on PP studies used to inform benefit-risk assessments (BRAs) and HTAs and patient-centered projects and guidelines related to the inclusion of PPs in health policy decision making. After title and abstract screening and full-text review, selected publications were analyzed to retrieve data related to the collection, use, and/or submission of PPs informing BRA or HTA as well as attempts and initiatives in recommendations for PPs integration in decision-making processes. Results: Forty-nine articles were included: 24 attempts and pilot project discussions and 25 PP elicitation studies. Quantitative approaches, particularly discrete choice experiments, were the most used (24 quantitative elicitation studies and 1 qualitative study). The objective of assessing PPs was to prioritize outcome-specific information, to value important treatment characteristics, to provide patient-focused benefit-risk trade-offs, and to appraise the patients' willingness to pay for new technologies. Moreover, attempts and pilot projects to integrate PPs in BRAs and HTAs were identified at the European level and across countries, but no clear recommendations have been issued yet. No less than seven public and/or private initiatives have been undertaken by governmental agencies and independent organizations to set guidance targeting improvement of patients' involvement in decision making. Conclusion: Despite the initiatives undertaken, the pace of progress remains slow. The use of PPs remains poorly implemented, and evidence of proper use of these data in decision making is lacking. Guidelines and recommendations formalizing the purpose of collecting PPs, what methodology should be adopted and how, and who should be responsible for generating these data throughout the decision-making processes are needed to improve and empower integration of PPs in BRA and HTA.

Chinese guidelines related to novel coronavirus pneumonia.

Background and Objective: China has managed to control the coronavirus disease (COVID-19) with confinement measurements and treatment strategies, while other countries are struggling to contain the spread. This study discusses the guidelines related to COVID-19 in China in order to provide important references for other countries in the fight against COVID-19. Methods: Chinese guidelines relevant to COVID-19 were systematically searched via the China National Knowledge Infrastructure database, YiMaiTong database, and World Health Organization (WHO) COVID-19 database on March 20th, 2020. Guideline information was extracted, including date of publication, source, objectives and the target population. Guidelines specific to the pharmacological treatment of COVID-19 were further investigated to identify the types of antivirus drugs recommended and to report on how treatment recommendations for COVID-19 have evolved overtime. Results: A total of 100 guidelines were identified, of which 74 were national guidelines and 26 were regional guidelines. The scope of included guidelines consisted of: the diagnosis and treatment of COVID-19, the management of hospital departments and specific diseases during the outbreak of COVID-19. Fifty-one of the included guidelines targeted overall COVID-19 patients, while the remaining guidelines concentrated on special patient populations (i.e. geriatric population, pediatric population, and pregnant population) or patients with coexisting diseases. Fifteen guidelines focused on the pharmacological treatments for all COVID-19 patients. Interferon, Lopinavir/Ritonavir, Ribavirin, Chloroquine, and Umifenovir represented the most recommended antivirus drugs. Among them, 7 Chinese guidelines have recommended Chloroquine Phosphate or Hydroxychloroquine for the treatment of COVID-19. Conclusions: China has generated a plethora of guidelines covering almost all aspects of COVID-19. Chloroquine, as one widely affordable treatment, was recommended by Chinese national guidelines and provincial guidelines. Considering the continuous debates around Chloroquine, confirmatory studies with robust methodology are awaited to address the unanswered questions on its potential benefits and risks on COVID-19.

President Trump's prescription to reduce drug prices: from the campaign trail to American Patients First.

Background: Drug prices in the United States are the highest in the world, restricting access to the domestic lower income population. President Trump campaigned heavily on promises to reduce drug prices.Methods: A literature review was conducted through PUBMED, EMBASE, Media and grey literature to consolidate and analyze publications addressing President Trump's promises from the campaign trail as well as the shortcomings and achievements of the Trump administration.Results: Major promises ranged from repealing and replacing Obamacare, expanding coverage, allowing cross-state insurance purchasing, and reducing drug prices. Main accomplishments of the Trump administration have been two executive orders (13765 and 13813), the proposition of the American Health Care Act, and the passing of the Tax Cuts and Jobs Act of 2017. The American Patients First blueprint further revealed the administration's strategies for lowering drug prices. The administration has also engaged in unconventional strategies, such as via bilateral leverage directly with trade partners.Conclusion: The Trump administration has not yet been able to fulfill the major campaign promises, primarily the ones requiring legislative and/or administrative action. If enough legislative action is accomplished to implement the Trump administration's promises, the effects on the pharmaceutical industry could be direct, yet minimal, unless Medicare can directly negotiate with manufacturers.

Why "American Patients First" is likely to raise drug prices outside of the United States.

Background: The Trump administration's 'American Patients First' blueprint proposes to reduce drug prices in the USA by increasing drug prices abroad, ex USA. The possibility of the Trump administration to raise drug prices ex USA through legal action via the WTO and bilateral negotiations with foreign trade partners was reviewed. Methods: A literature review was conducted through PUBMED, EMBASE, Media and grey literature to consolidate publications of the Trump administrations' policies and strategies towards foreign countries and drug prices. Results: The Trump administration has withdrawn from and halted major multilateral agreements including the TPP, Paris Agreement, TTIP, UNESCO, NAFTA (now USMCA), and NATO. The Trump administration has been successful in bilateral negotiations for pharmaceuticals' pricing, as seen with Japan, South Korea, Germany, and Mexico and Canada. Conclusion: The objective of raising prices abroad is attainable. Action through the WTO is unlikely, due to its nondiscriminatory principle. Bilateral trade negotiation have proven more promising. In this bilateral framework, financial security and military protection are strong assets for the USA to levy higher drug prices abroad. Although raising drug prices ex USA is possible, further questions as to whether this will directly translate into lower drug prices for American patients are raised.

Chinese Guidelines related to Novel Coronavirus Pneumonia

China has managed to control the coronavirus disease (COVID-19) with confinement measurements and treatment strategies, while other countries are struggling to contain the spread. This study discussesthe guidelines related to COVID-19 in China in order to provide important references for other countries in the fight against COVID-19. Chinese guidelines relevant to COVID-19 were systematically searched via the China National Knowledge Infrastructure database, YiMaiTong database, and World Health Organization (WHO) COVID-19 database on March 20th , 2020. Guideline information was extracted, including date of publication, source, objectives and the target population. Guidelines specific to the pharmacological treatment of COVID-19 were further investigated to identify the types of antivirus drugs recommended and to report on how treatment recommendations for COVID-19 have evolvedovertime. A total of 114 guidelines were identified, of which 87 were national guidelines and 27 were regional guidelines. The scope of included guidelines consisted of: the diagnosis and treatment of COVID-19, the management of hospital departments and specific diseases during the outbreak of COVID-19. Sixty-four of theincluded guidelines targeted all COVID-19 patients, whilethe remainingguidelines concentrated onspecialpatientpopulations (i.e., geriatric population, pediatric population, and pregnant population) or patients with coexistingdiseases. Twenty-three guidelines focused on the pharmacological treatments for all COVID-19 patients.Interferon, Lopinavir/Ritonavir, Ribavirin, Chloroquine, and Umifenovir represented the most recommended antivirus drugs. With the emergence of encouraging results from preclinical and preliminary clinical studies, Chloroquine Phosphate was recommended in the national Diagnosis and Treatment Protocol for NovelCoronavirus Pneumonia (6th version) on February 19th, 2020. Thereafter, more detailed guidelines regarding theadjustment of dosage regimens and the monitoring of adverse events of Chloroquine Phosphatewere published. To date, 8 Chinese guidelines have recommendedChloroquine Phosphate or Hydroxychloroquine as mainstream antivirusdrug for the treatment of COVID-19. China has generated a plethora of guidelines covering almost all aspects of COVID-19. Chloroquine, as one widely affordable treatment, holds great potential to become the gold standard choice as more clinical evidence is shared by researchers from China as well as other countries.