Estimating The Effects Of COVID-19 On Globalized Markets For Active Pharmaceutical Ingredients.

Global supply chains for active pharmaceutical ingredients (APIs) are highly centralized in certain countries and are susceptible to supply-chain shocks. However, there is no systematic monitoring or global coordination to manage risk and ensure equitable supply continuity during public health emergencies. In this study, we applied quasi-experimental methods on shipment-level customs data to determine how prices and export volume for APIs exported from India were affected by the COVID-19 pandemic. We found that API prices for key essential medicines not used for COVID-19 did not change significantly in the year after the World Health Organization pandemic declaration, but volume decreased by 80 percent. Prices for medicines speculatively repurposed for COVID-19, such as hydroxychloroquine and ivermectin, increased by as much as 250 percent compared with prices for nonrepurposed medicines, but only ivermectin saw a decrease in volume. Systematic monitoring of API markets, investments to promote supply diversification, and legal and political reforms to disincentivize price speculation could support supply-chain resilience and safeguard access to medicines.

Which roads lead to access? A global landscape of six COVID-19 vaccine innovation models.

BACKGROUND: Unequal and inequitable access to Covid-19 vaccines in low- and middle-income countries (L&MICs) was a major political, ethical and public health failure in the pandemic. However, vaccine developers' practices were not monolithic, but rather, took diverse approaches to supplying different countries, with important implications for global access. RESULTS: Using data on R&D investments, regulatory approvals, manufacturing and purchase agreements, and vaccine deliveries, we identified six distinct innovation models that apply across the 14 COVID-19 vaccines with more international presence from 2020-2022. "Western Early Arrivers" Pfizer/BioNTech and Moderna supplied the largest volumes quickly and prioritized high-income countries (HICs) from registration to vaccine delivery. "Western Latecomers" Janssen and Novavax supplied intermediate volumes later, also prioritizing HICs but with a greater proportion to L&MICs. "Major Chinese Developers" Sinopharm and Sinovac supplied intermediate volumes early, primarily to middle-income countries (MICs). "Russian Developer" Gamaleya completed development early but ultimately supplied small volumes, primarily to middle-income countries (MICs). "Cosmopolitan Developer" Oxford/AstraZeneca supplied large volumes early to HICs and MICs at the lowest prices. Finally, "Small MIC Developers" CanSino, Bharat Biotech, Medigen, Finlay Institute and the Center for Genetic Engineering and Biotechnology (CGEB), exported relatively small volumes to a few MICs. Low-income countries (LICs) were not targeted by any developer, and received far fewer doses, later, than any other income group. Almost all developers received public funding and other forms of support, but we found little evidence that such support was leveraged to expand global access. CONCLUSIONS: Each of the six innovation models has different implications for which countries get access to which vaccines, how quickly, and at which prices. Each offers different strengths and weaknesses for achieving equitable access. Our findings also suggest that Western firms had the greatest capacity to develop and deliver vaccines quickly during the pandemic, but such capacity is rapidly becoming more globally distributed with MICs playing a significant role, especially in supplying other MICs. Given the critical role of public support in enabling pandemic vaccine development and supply, governments have both the capacity and responsibility to craft international rules that will make responses to future pandemics more equitable and effective.

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.

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).

WHO guidance on COVID-19 vaccine trial designs in the context of authorized COVID-19 vaccines and expanding global access: Ethical considerations.

While the degree of COVID-19 vaccine accessibility and uptake varies at both national and global levels, increasing vaccination coverage raises questions regarding the standard of prevention that ought to apply to different settings where COVID-19 vaccine trials are hosted. A WHO Expert Group has developed guidance on the ethical implications of conducting placebo-controlled trials in the context of expanding global COVID-19 vaccine coverage. The guidance also considers alternative trial designs to placebo controlled trials in the context of prototype vaccines, modified vaccines, and next generation vaccines.

Governing the Access to COVID-19 Tools Accelerator: towards greater participation, transparency, and accountability.

The Access to COVID-19 Tools Accelerator (ACT-A) is a multistakeholder initiative quickly constructed in the early months of the COVID-19 pandemic to respond to a catastrophic breakdown in global cooperation. ACT-A is now the largest international effort to achieve equitable access to COVID-19 health technologies, and its governance is a matter of broad public importance. We traced the evolution of ACT-A's governance through publicly available documents and analysed it against three principles embedded in the founding mission statement of ACT-A: participation, transparency, and accountability. We found three challenges to realising these principles. First, the roles of the various organisations in ACT-A decision making are unclear, obscuring who might be accountable to whom and for what. Second, the absence of a clearly defined decision making body; ACT-A instead has multiple centres of legally binding decision making and uneven arrangements for information transparency, inhibiting meaningful participation. Third, the nearly indiscernible role of governments in ACT-A, raising key questions about political legitimacy and channels for public accountability. With global public health and billions in public funding at stake, short-term improvements to governance arrangements can and should now be made. Efforts to strengthen pandemic preparedness for the future require attention to ethical, legitimate arrangements for governance.

Viewing the global health system as a complex adaptive system - implications for research and practice.

The global health system (GHS) is ill-equipped to deal with the increasing number of transnational challenges. The GHS needs reform to enhance global resilience to future risks to health. In this article we argue that the starting point for any reform must be conceptualizing and studying the GHS as a complex adaptive system (CAS) with a large and escalating number of interconnected global health actors that learn and adapt their behaviours in response to each other and changes in their environment. The GHS can be viewed as a multi-scalar, nested health system comprising all national health systems together with the global health architecture, in which behaviours are influenced by cross-scale interactions. However, current methods cannot adequately capture the dynamism or complexity of the GHS or quantify the effects of challenges or potential reform options. We provide an overview of a selection of systems thinking and complexity science methods available to researchers and highlight the numerous policy insights their application could yield.   We also discuss the challenges for researchers of applying these methods and for policy makers of digesting and acting upon them. We encourage application of a CAS approach to GHS research and policy making to help bolster resilience to future risks that transcend national boundaries and system scales.

Non-commercial pharmaceutical R&D: what do neglected diseases suggest about costs and efficiency?

Background: The past two decades have witnessed significant growth in non-commercial research and development (R&D) initiatives, particularly for neglected diseases, but there is limited understanding of the ways in which they compare with commercial R&D. This study analyses costs, timelines, and attrition rates of non-commercial R&D across multiple initiatives and how they compare to commercial R&D. Methods: This is a mixed-method, observational, descriptive, and analytic study. We contacted 48 non-commercial R&D initiatives and received either quantitative and/or qualitative data from 13 organizations. We used the Portfolio to Impact (P2I) model's estimates of average costs, timelines, and attrition rates for commercial R&D, while noting that P2I cost estimates are far lower than some previous findings in the literature. Results: The quantitative data suggested that the costs and timelines per candidate per phase (from preclinical through Phase 3) of non-commercial R&D for new chemical entities are largely in line with commercial averages. The quantitative data was insufficient to compare attrition rates. The qualitative data identified more reasons why non-commercial R&D costs would be lower than commercial R&D, timelines would be longer, and attrition rates would be equivalent or higher, though the data does not allow for estimating the magnitude of these effects. Conclusions: The quantitative data suggest that costs and timelines per candidate per phase were largely in line with (lower-end estimates of) commercial averages. We were unable to draw conclusions on overall efficiency, however, due to insufficient data on attrition rates. Given that non-commercial R&D is a nascent area of research with limited data available, this study contributes to the literature by generating hypotheses for further testing against a larger sample of quantitative data. It also offers a range of explanatory factors for further exploration regarding how non-commercial and commercial R&D may differ in costs and efficiency.

Travel restrictions and infectious disease outbreaks.

BACKGROUND: A key purpose of the International Health Regulations (IHR) is to prevent unwarranted interruptions to trade and travel during large and/or transnational infectious disease outbreaks. Nevertheless, such outbreaks continue to disrupt the travel industry. This aspect of the IHR has received little attention in the academic literature despite its considerable impact on affected States and commercial activity. This article outlines the challenges and gaps in knowledge regarding the relationship between outbreaks and the travel sector and discusses the opportunities for further research and policy work to overcome these challenges. METHODOLOGY: We conducted a literature review on the relationship between outbreaks and travel restrictions, with a particular focus on the 2014-16 Ebola epidemic in West Africa. This review was complemented by an expert roundtable at Chatham House and further supported by case studies and qualitative interviews. RESULTS: Numerous travel stakeholders are affected by, and affect, large-scale infectious disease outbreaks. These stakeholders react in different ways: peer pressure plays an important role for both governments and the travel sector, and the reactions of the media and public influence and are influenced by these stakeholders. While various data sources on travel are available, and World Health Organization is mandated to work with States, there is no recognized coordinating body to disseminate timely, consistent, reliable and authoritative information and best practices to all stakeholders. CONCLUSION: This article highlights the interdependent relationship between various travel stakeholders. The reasons for interruption of travel during the 2014-16 Ebola outbreak were complex, with decisions by States only partly contributing to the cessation. Decisions by non-state actors, particularly the travel industry itself, contributed significantly and were based on a variety of factors. Further research, analysis and policy development are required to mitigate the health and economic consequences of infectious disease outbreaks. Any further research will also need to take account of COVID-19 travel-related issues.