Pharmaceutical innovativeness index: methodological approach for assessing the value of medicines - a case study of oncology drugs.

BACKGROUND: We propose a framework to assess the value of pharmaceutical innovations, with explicit clinical and methodological parameters, based on the therapeutic value and health needs. RESEARCH DESIGN AND METHODS: The study was based on the adaptation of health technology assessment methods documented in the literature, which was applied to a sample of oncological drugs. Difficulties and issues during the application of those tools were identified and addressed to develop a new framework with new and revised domains and clear classification criterion for each domain. Scores were assigned to each level and domain according to their relevance to generate the final score of innovativeness. RESULTS: The Pharmaceutical Innovation Index (PII) includes four domains, two related to clinical and social dimensions - Therapeutic Need and Added Therapeutic Value - and other two about methodological features - Study Design and Quality (risk of bias). The scores combined after assigned to each domain results Index of the Innovativeness of the medicines represents the degree of pharmaceutical innovation. CONCLUSION: This work proposes a transparent methodology with well-defined criteria and script; the algorithm developed with authors' weightings and criteria may be switched to best adjust to other applications, perspective or clinical indications, while keeping the transparency and objectiveness.

Quantifying public and private investment in European biopharmaceutical research and development.

Robust biopharmaceutical research and development (R&D) ecosystems require investment from both the public and private sectors. In Europe, there is an interest in growing biopharmaceutical R&D given its contribution to public health and the economy, which requires an understanding of current public and private investment. In addition, recent European draft legislation has focused on the public sector's contributions to biopharmaceutical R&D to inform pharmaceutical prices. However, there is little empirical evidence on the specifics of public and private funding for medicine R&D in Europe. This paper performs aggregative data collection to quantify 2019 investment in biopharmaceutical R&D by the public and private sectors in 6 countries: Belgium, France, Germany, Norway, Poland, and the United Kingdom. We find that, across these countries, the private sector accounts for just under two-thirds of investment. We contrast results to those obtained using high-level R&D indicators from the Organization for Economic Co-operation and Development (OECD) and contextualize differences. We then provide 2013-2019 estimates for Belgium, France, Germany, and the United Kingdom (countries with data to support such analysis), and show that total spending grew over those years, although proportions attributable to each sector remained stable. These findings should provide further evidence for debates on policies to effectively grow the biopharmaceutical R&D sector.

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".

A prediction model based on artificial intelligence techniques for disintegration time and hardness of fast disintegrating tablets in pre-formulation tests.

BACKGROUND: The pharmaceutical industry is continually striving to innovate drug development and formulation processes. Orally disintegrating tablets (ODTs) have gained popularity due to their quick release and patient-friendly characteristics. The choice of excipients in tablet formulations plays a critical role in ensuring product quality, highlighting its importance in tablet creation. The traditional trial-and-error approach to this process is both expensive and time-intensive. To tackle these obstacles, we introduce a fresh approach leveraging machine learning and deep learning methods to automate and enhance pre-formulation drug design. METHODS: We collected a comprehensive dataset of 1983 formulations, including excipient names, quantities, active ingredient details, and various physicochemical attributes. Our study focused on predicting two critical control test parameters: tablet disintegration time and hardness. We compared a range of models like deep learning, artificial neural networks, support vector machines, decision trees, multiple linear regression, and random forests. RESULTS: A 12-layer deep neural network, as a form of deep learning, surpassed alternative techniques by achieving 73% accuracy for disintegration time and 99% for tablet hardness. This success underscores its efficacy in predicting complex pharmaceutical factors. Such an approach streamlines the drug formulation process, reducing iterations and material consumption. CONCLUSIONS: Our findings highlight the deep learning potential in pharmaceutical formulations, particularly for tablet hardness prediction. Future work should focus on enlarging the dataset to improve model effectiveness and extend its application in pharmaceutical product development and assessment.

From Pharmaceutical Innovation to Revenue Generation: The Asian Experience.

Asia's pharmaceutical sector has experienced remarkable growth over the last two decades, with companies in the region producing bulk of the world's specialty generics, biologicals, and active pharmaceutical ingredients (APIs). The Asian pharma growth story has had several pillars for a strong and sustainable foundation that provided non-linear growth. This report introduces three models showing how Asian countries at different development stages - India, South Korea, and Singapore - have nurtured their own, self-sustaining pharmaceutical sectors.

Rising pharmaceutical innovation in the Global South: a landscape study.

BACKGROUND: There is growing interest in pharmaceutical innovation in low- and middle-income countries (LMICs), but information on existing activities, capacities, and outcomes is scarce. We mapped available data at the global level, and studied the national pharmaceutical innovation systems of Bangladesh and Colombia to shed light on pharmaceutical research and development (R&D) in the Global South, including challenges and prospects, to help fill existing knowledge gaps. METHODS: We gathered and analyzed data from three types of sources: literature, semi-structured interviews with key informants, and publicly available data on R&D funding, R&D scientific capacity measured by human resources, and clinical trial activities. RESULTS: Pharmaceutical R&D activities are occurring in many LMICs, but 16 countries have emerged as frontrunners. Investment in R&D in LMICs has increased in the past decade, particularly from middle-income countries (MICs). Capacity is also growing, with an increase in the number of research organizations and the amount of funding available from external sources. The total number of clinical trials and the proportion of trials in LMICs increased markedly, and there is also growing activity in the earlier, more innovative and riskier Phase 1 and 2 trials. Non-commercial entities comprise the majority of clinical trial funders and sponsors in LMICs. Finally, investments have borne fruit, as indicated by a number of innovative medicines developed in LMICs. The Bangladesh and Colombia country studies showed that there is still a need for both targeted R&D policies to strengthen capacities in the pharmaceutical sector, and more government support to overcome the challenges of a lack of funding and coordination among different actors. CONCLUSIONS: By triangulating between the data sources, it was possible to paint a broad picture of who was involved in pharmaceutical R&D in LMICs, in which particular countries, for which diseases, in which R&D phases, and with what results-as well as how these trends have changed over time. Prioritizing pharmaceutical R&D is an important strategy for better meeting health needs. The trendlines are promising, but focused attention is still needed to realize the potential for greater innovation in the Global South.

The Relationship between Health Insurance and Pharmaceutical Innovation: An Empirical Study Based on Meta-Analysis.

The growing research interest in the relationship between health insurance and pharmaceutical innovation is driven by their significant impact on healthcare optimization and pharmaceutical development. The existing literature, however, lacks consensus on this relationship and provides no evidence of the magnitude of a correlation. In this context, this study employs meta-analysis to explore the extent to which health insurance affects pharmaceutical innovation. It analyzes 202 observations from 14 independent research samples, using the regression coefficient of health insurance on pharmaceutical innovation as the effect size. The results reveal that there is a strong positive correlation between health insurance and pharmaceutical innovation (r = 0.367, 95% CI = [0.294, 0.436]). Public health insurance exhibits a stronger promoting effect on pharmaceutical innovation than commercial health insurance. The relationship between health insurance and pharmaceutical innovation is moderated by the country of sample origin, data range, journal type, journal impact factor, type of health insurance, and research perspective. Our research findings further elucidate the relationship mechanism between health insurance and pharmaceutical innovation, providing a valuable reference for future explorations in pharmaceutical fields.

Government Support of Meaningful Drug and Device Innovation: Pathways and Challenges.

The US government supports drug innovation. It is therefore crucial that it distinguish between high-value and low-value innovation in purchasing expensive prescription drugs and medical devices and ensure the continued discovery of transformative drugs and that patient and taxpayer funds are not wasted.

Pharmaceutical policy and innovation for rare diseases: A narrative review.

This article aims to synthesize the existing literature on the implementation of public policies to incentivize the development of treatments for rare diseases, (diseases with very low prevalence and therefore with low commercial interest) otherwise known as orphan drugs. The implementation of these incentives in the United States (US), Japan, and in the European Union (EU) seems to be related to a substantial increase in treatments for these diseases, and has influenced the way the pharmaceutical research & development (R&D) system operates beyond this policy area. Despite the success of the Orphan Drug model, the academic literature also highlights the negative implications that these public policies have on affordability and access to orphan drugs, as well as on the prioritization of certain disease rare areas over others. The synthesis focuses mostly on the United States' Orphan Drug Act (ODA) as a model for subsequent policies in other regions and countries. It starts with a historical overview of the creation of the term "rare diseases", continues with a summary of the evidence available on the US ODA's positive and negative impacts, and provides a summary of the different proposals to reform these incentives in light of the negative outcomes described. Finally, it describes some key aspects of the Japanese and European policies, as well as some of the challenges captured in the literature related to their impact in Low- and Middle-Income Countries (LMICs).

Social pharmaceutical innovation and alternative forms of research, development and deployment for drugs for rare diseases.

Rare diseases are associated with difficulties in addressing unmet medical needs, lack of access to treatment, high prices, evidentiary mismatch, equity, etc. While challenges facing the development of drugs for rare diseases are experienced differently globally (i.e., higher vs. lower and middle income countries), many are also expressed transnationally, which suggests systemic issues. Pharmaceutical innovation is highly regulated and institutionalized, leading to firmly established innovation pathways. While deviating from these innovation pathways is difficult, we take the position that doing so is of critical importance. The reason is that the current model of pharmaceutical innovation alone will not deliver the quantity of products needed to address the unmet needs faced by rare disease patients, nor at a price point that is sustainable for healthcare systems. In light of the problems in rare diseases, we hold that re-thinking innovation is crucial and more room should be provided for alternative innovation pathways. We already observe a significant number and variety of new types of initiatives in the rare diseases field that propose or use alternative pharmaceutical innovation pathways which have in common that they involve a diverse set of societal stakeholders, explicitly address a higher societal goal, or both. Our position is that principles of social innovation can be drawn on in the framing and articulation of such alternative pathways, which we term here social pharmaceutical innovation (SPIN), and that it should be given more room for development. As an interdisciplinary research team in the social sciences, public health and law, the cases of SPIN we investigate are spread transnationally, and include higher income as well as middle income countries. We do this to develop a better understanding of the social pharmaceutical innovation field's breadth and to advance changes ranging from the bedside to system levels. We seek collaborations with those working in such projects (e.g., patients and patient organisations, researchers in rare diseases, industry, and policy makers). We aim to add comparative and evaluative value to social pharmaceutical innovation, and we seek to ignite further interest in these initiatives, thereby actively contributing to them as a part of our work.

Incentivizing Drug Development in Serious Mental Illness.

Serious mental illness (SMI) imposes a significant burden on individuals and society. Individuals living with SMI have worse expected health, education, and career outcomes during their lifetime. Although treatments exist, pharmaceutical innovation in this area has lagged many other disease areas, despite an important need for new treatments. This report describes barriers that have hindered innovation and the development of new drugs for SMI, including science and research, regulatory, and health system barriers. To address these barriers, this report presents policies that may incentivize investment in this area.

Assessing the Consequences of External Reference Pricing for Global Access to Medicines and Innovation: Economic Analysis and Policy Implications.

Background: External reference pricing (ERP) is used to set pharmaceutical prices to improve affordability, but its application may have negative consequences on patient access-thus, equity-across countries and on global innovation. With the United States contemplating ERP, negative effects could be magnified. Our aim: identify and quantify some major consequences of ERP. Research design, methods: Besides relying on databases and ERP modelling, we developed a heart failure case study. 4-step approach: 1) review ERP policies; 2) establish worldwide "price corridor"; 3) quantify patient access and health outcomes impact by ERP; 4) estimate ERP impact on innovation. Results: Our ERP referencing analysis highlights its perverse effects especially in lower-income countries. As counterstrategies to protect their revenues, manufacturers often implement tight list price corridors or launch avoidance/delays. Consequences include suboptimal patient access-hence, worse outcomes-illustrated by our case study: 500,000 + QALYs health loss. Additionally, the ensuing revenue reduction would likely cause innovation loss by one additional medicine that would have benefitted future patients. Conclusion: This research provides key insights on potential unintentional consequences of medicine price setting by ERP worldwide and under a new proposal for the United States. Our results can inform stakeholder discussions to improve patient access to innovative medicines globally.

Localizing pharmaceuticals manufacturing and its impact on drug security in Saudi Arabia.

Local production of pharmaceuticals plays a vital role in maintaining resilience of national healthcare systems, especially when it comes to facilitating access to needed medicines and decreasing exposure to imports and international supply chains. Pharma is a research-intensive industry and the systemic lack of governance and support to R&D activities in this sector, among other host of related issues such as unsupportive regulatory regimes and human resources capacity limitations, is one of the major impediments to the diversifying of locally produced pharmaceuticals portfolio. In this review, an overview of the current pharmaceutical production system in Saudi Arabia, its major challenges, and proposed remedies to address them will be highlighted.

Regulatory policy and pharmaceutical innovation in the United Kingdom after Brexit: Initial insights.

Brexit was presented as an opportunity to promote innovation by breaking free from the European Union regulatory framework. Since the beginning of 2021 the Medicines and Healthcare products Regulatory Agency (MHRA) has operated as the independent regulatory agency for the United Kingdom. The MHRA's regulatory activity in 2021 was analyzed and compared to that of other international regulatory bodies. The MHRA remained reliant on EU regulatory decision-making for novel medicines and there were significant regulatory delays for a small number of novel medicines in the UK, the reasons being so far unclear. In addition, the MHRA introduced innovation initiatives, which show early promise for quicker authorization of innovative medicines for cancer and other areas of unmet need. Longer-term observation and analysis is needed to show the full impact of post-Brexit pharmaceutical regulatory policy.

The Health Impact Fund: making the case for engagement with pharmaceutical laboratories in Brazil, Russia, India, and China.

Despite progress in global health, the general disease burden still disproportionately falls on low- and middle-income countries. The health needs of these countries' populations are unmet because there is a shortage in drug research and development, as well as a lack of access to essential drugs. This health disparity is especially problematic for diseases associated with poverty, namely neglected tropical diseases and microbial infections. Currently, the pharmaceutical landscape focuses on innovations determined by profit margins and intellectual property protection. To expand drug accessibility and catalyze research and development for neglected diseases, a team of researchers proposed the Health Impact Fund as a potential solution. However, the fund is predominantly considering partnerships with pharmaceutical giants in high-income countries. This commentary explores the limitations and benefits in partnering with pharmaceutical companies based in Brazil, Russia, India, and China (BRIC), with the goal of expanding the Health Impact Fund's vision to incorporate long-term, local partnerships. Identified limitations to a BRIC country partnership include lower levels of drug development expertise compared to their high-income pharmaceutical counterparts, and whether the Health Impact Fund and the participating stakeholders have the financial capability to assist in bringing a new drug to market. However, potential benefits include the creation of new incentives to fuel competitive local innovation, more equitable routes to drug discovery and development, and a product pipeline that could involve stakeholders in lower- and middle-income countries. Our commentary explores how partnership with pharmaceutical firms in BRIC countries might be advantageous for all: The Health Impact Fund, pharmaceutical companies in BRIC economies, and stakeholders in low- and middle- income countries.

R&D and market size: Who benefits from orphan drug legislation?

Since the early 80s, incentives have been introduced to stimulate R&D for rare diseases. We develop a theoretical model to study the impact of push and pull incentives on the intensive and extensive margin of optimal R&D investments. The model describes the mechanisms by which the type of incentives provided may favor R&D for orphan diseases with comparatively high prevalence. In our empirical analysis, we merge data on orphan drug designations by the Food and Drug Administration with Orphanet data on disease characteristics. In line with the theoretical results, we find evidence supporting the idea that the incentives adopted may have contributed substantially to widening the gap between more and less rare diseases classified as orphan. Our theoretical and empirical findings together suggest that, if providing some therapeutic option to patients with very rare diseases is a priority, a revision of the current system of incentives should be considered.

Incentives to promote the US pharmaceutical innovation: empirical research based on the case of Epogen.

OBJECTIVE: This study aims at emphasizing the significant impact of the incentives to promote the United States (US) pharmaceutical innovation. METHODS: We carried out a retrospective single-case study. We analyzed the innovation process of Epogen: basic research, applied research, regulatory, and marketing. RESULTS: Incentives and policies of pharmaceutical innovation significantly facilitates the entire life cycle of Epogen. The transfer of patent presented by the Bayh-Dole Act allowed Amgen to purchase the research results of Epogen. Relying on the intellectual property mechanisms and financing incentives, Amgen raised the funds needed for Epogen in applied research. Special review shortened the regulatory of Epogen. Epogen obtained orphan drug designation twice and 8 years of market exclusivity. Tax deduction and research funding provided direct economic compensation. The patent system enabled Epogen to obtain 32 years of patent protection (1983-2015). Monopoly pricing was a significant determinant to increase the sales of Epogen through pricing strategies. CONCLUSION: We pointed out that Amgen has developed the successful innovation of Epogen taking advantages of the incentives. Effective and flexible incentives and policies are essential to support the entire life cycle of new drugs, ultimately forming a sustainable driver for the long-run pharmaceutical innovation.

Unpacking the effects of adverse regulatory events: Evidence from pharmaceutical relabeling.

We provide causal evidence that regulation induced product shocks significantly impact aggregate demand and firm performance in pharmaceutical markets. Event study results suggest an average loss between $569 million and $882 million. Affected products lose, on average, $186 million over their remaining effective patent life. This leaves a loss of between $383 million and $696 million attributable to declines in future innovation. Our findings complement research that shows drugs receiving expedited review are more likely to suffer from regulation induced product shocks. Thus, it appears we may be trading off quicker access to drugs today for less innovation tomorrow. Results remain robust to variation across types of relabeling, market sizes, and levels of competition.

Disease burden metrics and the innovations of leading pharmaceutical companies: a global and regional comparative study.

BACKGROUND: The recent innovation activities of global top-tier pharmaceutical companies in accordance with global and regional health concerns were investigated in order to identify their innovations contributing to population health. METHODS: "Innovation activity" was defined as the number of drugs for which R&D activities have been reported within the last three years. Such activities were measured by collecting the data on drug developments and classifying them by developer company, phase of development, therapeutic use, and the country in which the development conducted. Subsequently, we examined and compared the correlations between the global innovation activities of the top 20 pharmaceutical companies and the disease burden measured in disability-adjusted life years (DALYs) by income level and region. In addition, this study analyzed the association between country-specific innovations and DALYs in the corresponding countries. RESULTS: At a global level, the innovation activities were not associated with global DALYs. However, when analyzed by income level, the innovation activities were associated with DALYs in high income and upper middle income countries while it was not associated with DALYs in low middle income and low income countries. In terms of region, correlations were found between the innovation activities and DALYs in the European region, the Americas, and the Western Pacific region whereas such correlations were not found in the African, Eastern Mediterranean, and South-East Asian regions. Similar to the analyses by income level and region, correlations between country-specific innovations and DALYs were only found in high income or high GDP countries. In addition, an empirical analysis of several cases including Canada, Germany, South Korea, and the United Kingdom revealed that pharmaceutical innovation is more closely related to market size than disease burden. CONCLUSIONS: This study identified that discrepancies between pharmaceutical innovation and public health needs, i.e., disease burden values, have persisted until recently. To alleviate this imbalance, both public and private sectors should not only fulfill their respective roles and responsibilities regarding these issues, but also make strategic and collaborative efforts such as Product Development Partnerships (PDPs) directed toward public health improvement.