Could international compulsory licensing reconcile tiered pricing of pharmaceuticals with the right to health?

BACKGROUND: The heads of the Global Fund and the GAVI Alliance have recently promoted the idea of an international tiered pricing framework for medicines, despite objections from civil society groups who fear that this would reduce the leeway for compulsory licenses and generic competition. This paper explores the extent to which an international tiered pricing framework and the present leeway for compulsory licensing can be reconciled, using the perspective of the right to health as defined in international human rights law. DISCUSSION: We explore the practical feasibility of an international tiered pricing and compulsory licensing framework governed by the World Health Organization. We use two simple benchmarks to compare the relative affordability of medicines for governments - average income and burden of disease - to illustrate how voluntary tiered pricing practice fails to make medicines affordable enough for low and middle income countries (if compared with the financial burden of the same medicines for high income countries), and when and where international compulsory licenses should be issued in order to allow governments to comply with their obligations to realize the right to health. An international tiered pricing and compulsory licensing framework based on average income and burden of disease could ease the tension between governments' human rights obligation to provide medicines and governments' trade obligation to comply with the Agreement on Trade-Related Aspects of Intellectual Property Rights

What Do Core Obligations under the Right to Health Bring to Universal Health Coverage?

Can the right to health, and particularly the core obligations of states specified under this right, assist in formulating and implementing universal health coverage (UHC), now included in the post-2015 Sustainable Development Goals? In this paper, we examine how core obligations under the right to health could lead to a version of UHC that is likely to advance equity and rights. We first address the affinity between the right to health and UHC as evinced through changing definitions of UHC and the health domains that UHC explicitly covers. We then engage with relevant interpretations of the right to health, including core obligations. We turn to analyze what core obligations might bring to UHC, particularly in defining what and who is covered. Finally, we acknowledge some of the risks associated with both UHC and core obligations and consider potential avenues for mitigating these risks

What could a strengthened right to health bring to the post-2015 health development agenda?: interrogating the role of the minimum core concept in advancing essential global health needs.

BACKGROUND: Global health institutions increasingly recognize that the right to health should guide the formulation of replacement goals for the Millennium Development Goals, which expire in 2015. However, the right to health's contribution is undercut by the principle of progressive realization, which links provision of health services to available resources, permitting states to deny even basic levels of health coverage domestically and allowing international assistance for health to remain entirely discretionary. DISCUSSION: To prevent progressive realization from undermining both domestic and international responsibilities towards health, international human rights law institutions developed the idea of non-derogable "minimum core" obligations to provide essential health services. While minimum core obligations have enjoyed some uptake in human rights practice and scholarship, their definition in international law fails to specify which health services should fall within their scope, or to specify wealthy country obligations to assist poorer countries. These definitional gaps undercut the capacity of minimum core obligations to protect essential health needs against inaction, austerity and illegitimate trade-offs in both domestic and global action. If the right to health is to effectively advance essential global health needs in these contexts, weaknesses within the minimum core concept must be resolved through innovative research on social, political and legal conceptualizations of essential health needs. SUMMARY: We believe that if the minimum core concept is strengthened in these ways, it will produce a more feasible and grounded conception of legally prioritized health needs that could assist in advancing health equity, including by providing a framework rooted in legal obligations to guide the formulation of new health development goals, providing a baseline of essential health services to be protected as a matter of right against governmental claims of scarcity and inadequate international assistance, and empowering civil society to claim fulfillment of their essential health needs from domestic and global decision-makers

Rights Language in the Sustainable Development Agenda: Has Right to Health Discourse and Norms Shaped Health Goals?

While the right to health is increasingly referenced in Sustainable Development Goal (SDG) discussions, its contribution to global health and development remains subject to considerable debate. This hypothesis explores the potential influence of the right to health on the formulation of health goals in 4 major SDG reports. We analyse these reports through a social constructivist lens which views the use of rights rhetoric as an important indicator of the extent to which a norm is being adopted and/or internalized. Our analysis seeks to assess the influence of this language on goals chosen, and to consider accordingly the potential for rights discourse to promote more equitable global health policy in the future

The SH2-containing inositol polyphosphate 5-phosphatase, SHIP-2, binds filamin and regulates submembraneous actin

SHIP-2 is a phosphoinositidylinositol 3,4,5 trisphosphate (PtdIns[3,4,5]P3) 5-phosphatase that contains an NH2-terminal SH2 domain, a central 5-phosphatase domain, and a COOH-terminal proline-rich domain. SHIP-2 negatively regulates insulin signaling. In unstimulated cells, SHIP-2 localized in a perinuclear cytosolic distribution and at the leading edge of the cell. Endogenous and recombinant SHIP-2 localized to membrane ruffles, which were mediated by the COOH-terminal proline–rich domain. To identify proteins that bind to the SHIP-2 proline–rich domain, yeast two-hybrid screening was performed, which isolated actin-binding protein filamin C. In addition, both filamin A and B specifically interacted with SHIP-2 in this assay. SHIP-2 coimmunoprecipitated with filamin from COS-7 cells, and association between these species did not change after epidermal growth factor stimulation. SHIP-2 colocalized with filamin at Z-lines and the sarcolemma in striated muscle sections and at membrane ruffles in COS-7 cells, although the membrane ruffling response was reduced in cells overexpressing SHIP-2. SHIP-2 membrane ruffle localization was dependent on filamin binding, as SHIP-2 was expressed exclusively in the cytosol of filamin-deficient cells. Recombinant SHIP-2 regulated PtdIns(3,4,5)P3 levels and submembraneous actin at membrane ruffles after growth factor stimulation, dependent on SHIP-2 catalytic activity. Collectively these studies demonstrate that filamin-dependent SHIP-2 localization critically regulates phosphatidylinositol 3 kinase signaling to the actin cytoskeleton

The Stellenbosch Consensus on the International Legal Obligation to Collaborate and Assist in Addressing Pandemics: Clarifying Article 44 of the International Health Regulations

The International Health Regulations (IHR), of which the World Health Organization is custodian, govern how countries collectively promote global health security, including prevention, detection, and response to potential global health emergencies such as the ongoing covid-19 pandemic. While Article 44 of this binding legal instrument requires countries to collaborate and assist each other in meeting their respective obligations, recent events demonstrate that the precise nature and scope of these legal obligations are ill-understood. A shared understanding of the level and type of collaboration legally required by the IHR is a necessary step in ensuring these obligations can be acted upon and fully realized, and in fostering global solidarity and resilience in the face of future pandemics. In this consensus statement, public international law scholars specializing in global health consider the legal meaning of Article 44 using the interpretive framework of the Vienna Convention on the Law of Treaties

Inactivation of the phosphoinositide phosphatases Sac1p and Inp54p leads to accumulation of phosphatidylinositol 4,5-bisphosphate on vacuole membranes and vacuolar fusion defects

Phosphoinositides direct membrane trafficking, facilitating the recruitment of effectors to specific membranes. In yeast phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P-2) is proposed to regulate vacuolar fusion; however, in intact cells this phosphoinositide can only be detected at the plasma membrane. In Saccharomyces cerevisiae the 5-phosphatase, Inp54p, dephosphorylates PtdIns(4,5)P-2 forming PtdIns(4)P, a substrate for the phosphatase Sac1p, which hydrolyzes (PtdIns(4) P). We investigated the role these phosphatases in regulating PtdIns(4,5) P-2 subcellular distribution. PtdIns(4,5)P-2 bioprobes exhibited loss of plasma membrane localization and instead labeled a subset of fragmented vacuoles in Delta sac1 Delta inp54 and sac1(ts) Delta inp54 mutants. Furthermore, sac1(ts) Delta inp54 mutants exhibited vacuolar fusion defects, which were rescued by latrunculin A treatment, or by inactivation of Mss4p, a PtdIns(4)P 5-kinase that synthesizes plasma membrane PtdIns(4,5)P-2. Under these conditions PtdIns(4,5)P-2 was not detected on vacuole membranes, and vacuole morphology was normal, indicating vacuolar PtdIns(4,5)P-2 derives from Mss4p-generated plasma membrane PtdIns(4,5)P-2. Delta sac1 Delta inp54 mutants exhibited delayed carboxypeptidase Y sorting, cargo-selective secretion defects, and defects in vacuole function. These studies reveal PtdIns(4,5)P-2 hydrolysis by lipid phosphatases governs its spatial distribution, and loss of phosphatase activity may result in PtdIns(4,5)P-2 accumulation on vacuole membranes leading to vacuolar fragmentation/fusion defects