Falling Short of the Rights to Health and Scientific Progress

The incorporation of human rights-based approaches into TB programs is gaining traction, but little work has explored the application of human rights norms and principles to TB research (a domain traditionally left to bioethics). TB research is gravely underfunded, and the scarcity of resources for TB drug development has contributed to the stubborn persistence of the TB epidemic and helped to create the conditions under which drug-resistant TB has developed and spread. This article shows how human rights—particularly human rights standards, norms, and principles related to the rights to health and benefits of scientific progress—can provide insight into understanding how underfunding TB drug research undermines efforts to secure access to safe, effective, and optimized treatment for all people with TB. By analyzing TB research in relation to the rights to health and scientific progress, we aim to clarify the legal obligations of governments to improve the TB drug research system, fund TB research, and make medical advances that result from research available to all people with TB. Mike Frick, MSc, is the TB/HIV senior project officer at Treatment Action Group, New York, NY, USA. Ian Henry, JD, is the legal fellow at the Program on Global Health and Human Rights at the USC Institute for Global Health, Los Angeles, CA, USA. Erica Lessem, MPH, is the TB/HIV project director at Treatment Action Group, New York, NY, USA. Contact info: Please address correspondence to the authors c/o Mike Frick, Treatment Action Group, 261 5th Ave, Suite 2110, New York, NY 10016. Email: [email protected]. Competing interests: None declared. Copyright © 2016 Frick, Henry, and Lessem. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Health and Human Rights Journal HHr HHR_final_logo_alone.indd 1 10/19/15 10:53 AM M. Frick, I. Henry, and E. Lessem / TB and the Right to Health, 9-24 10 J U N E 2 0 1 6 V O L U M E 1 8 N U M B E R 1 Health and Human Rights Journal Introduction Tuberculosis (TB) has been preventable, treatable, and curable with combination drug therapy since the 1950s, but more than six decades later continues to claim 1.5 million lives a year.1 The limitations of current treatment options, and the slow pace of efforts to develop newer, better ways of treating TB, are leading factors driving the global TB epidemic, particularly in the face of rising rates of drug resistance—a human-made phenomenon. In this paper, we first discuss three treatment-related inadequacies that have hindered the response to TB: 1) inadequate options to treat TB; 2) inadequate financing for research and development (R&D) to develop better options; and 3) inadequate access to treatment options, both new and old. We argue that these shortcomings in research and access, commonly attributed to weak market incentives and the absence of political will, are the result of states’ failures to uphold their obligations under international human rights law. In particular, we examine states’ obligation to support TB research as part of meeting their commitments to fulfill the right to the highest attainable standard of health (for example, Article 12 of the International Covenant on Economic, Social and Cultural Rights or ICESCR) and the right to enjoy the benefits of scientific process and its applications (for example, Article 15 of the ICESCR).2 Considered together, the rights to health and scientific progress provide a framework—grounded in state-level legal obligations—for linking the financing, conduct, and ownership of TB research to the challenges many people with TB face in accessing adequate treatment. Under international human rights law, access is composed of multiple considerations, and “the dimensions of access require some adaptability from right to right.”3 For the right to health, General Comment 14 of the Committee on Economic, Social, and Cultural Rights (CESCR) identifies four overlapping components of access: non-discrimination, physical accessibility, economic accessibility (affordability), and access to information.4 These dimensions of accessibility join availability, acceptability, and quality of health facilities, goods, and services as essential elements of the right to health in all its forms and at all levels.5 Access considerations also form the “cornerstone” of the right to science.6 The earliest formulation of this right in Article 27 of the Universal Declaration of Human Rights points toward the right of all people to take part in cultural life, enjoy the arts, and share in the benefits of scientific progress.7 The drafting history of ICESCR Article 15 makes clear that access in this context entails enjoying the actual—and in the case of health technologies like medicines, tangible—applications of scientific progress (that is, access to the benefits of scientific progress go beyond mere sharing in the diffuse benefits that accrue from general scientific advancement).8 The text of Article 15 establishes the obligation of states to take steps “necessary for the development and diffusion of science and culture.”9 By speaking of development and diffusion together, Article 15 offers a concept of access that connects state support for research and innovation (development) to the obligation of states to ensure that all people enjoy the benefits of science and its applications without discrimination (diffusion).10 The inadequacies of TB treatment illustrate how fulfilling the rights to health and scientific progress require states to support TB research and structure this support in ways that promote both the development and diffusion of new and improved TB drugs. Inadequate treatment options for TB The majority of drugs used to treat TB are decades old, and several have never been studied for TB under the rigorous conditions of randomized, controlled trials. Only two new drugs from new drug classes have been approved to treat TB in the last 40 years. Even with these two advances, treatment for all forms of TB is long and comes with high pill burdens. Patients with drug-susceptible TB (DSTB) take treatment for six months, while those with drug-resistant TB (DR-TB) must endure treatment for up to two years. During this time, the typical multidrug-resistant TB (MDR-TB) patient will receive 240 painful drug injections and swallow M. Frick, I. Henry, and E. Lessem / TB and the Right to Health, 9-24 J U N E 2 0 1 6 V O L U M E 1 8 N U M B E R 1 Health and Human Rights Journal 11 14,600 pills.11 Many of the drugs used to treat MDRTB are poorly tolerated and carry the potential for serious—and in some cases irreversible—toxicities, including peripheral neuropathy, hearing loss, and psychosis. Even then, the effectiveness of MDR-TB treatment is low, with global cure rates persisting at 48%.12 Poor MDR-TB cure rates are attributable not only to the challenges of completing therapy (such as pill burden, toxicities, and length of treatment), but also to the poor anti-TB activity of the drugs themselves. The majority of drugs the World Health Organization (WHO) recommends to treat MDRTB are not even demonstrated to be bactericidal (capable of killing bacteria), but rather are added onto a backbone of other drugs to protect against the amplification of resistance.13 Over time, the limitations of TB treatment have changed the nature of TB disease itself, whereby drug-sensitive strains have become chronic and deadly by developing resistance to existing antibiotics. By leaving patients reliant on lengthy, difficult-to-tolerate regimens that complicate adherence, the weak R&D environment has helped to create the conditions under which DR-TB strains arise and are transmitted in communities.14 In other words, the failures of the R&D system have contributed to the successful adaptation of the TB pathogen, and have continued to permit its flourishing, at the expense of human health and life. This biosocial phenomenon has been driven by human activity, but the attribution of responsibility has wrongly zeroed in on TB patients themselves.15 The oft-voiced idea that most drug resistance results when patients fail to adhere to therapy is challenged by research tracing a majority of DR-TB cases in some settings to primary transmission.16 In addition, whole-genome sequencing of clinical isolates from DR-TB outbreaks suggest that “drug-resistant strains circulating today reflect not only vulnerabilities of current TB control efforts but also those that date back 50 years.”17 This evidence underscores the need to shift the frame of analysis away from the behaviors of individual TB patients today to focus on the continuing legacy of government failures to prevent and respond to DR-TB by providing adequate treatment. By focusing on the obligations of governments, human rights offer a more suitable framework for holding the relevant actors accountable for addressing the emergence of DR-TB through research and treatment scale-up. Inadequate funding for TB R&D Over the past decade, funding for TB R&D has fallen far short of the resources required to improve TB treatment by developing new drugs and repurposing older ones. The Stop TB Partnership’s Global Plan to Stop TB, 2011–2015 estimates that the world needed to spend USD$9.8 billion between 2011 and 2015 to develop the new tools we need to eliminate TB.18 This covers spending across six areas of TB research: basic science, diagnostics, drugs, vaccines, operational research/epidemiology, and infrastructure. To create accountability toward this goal, Treatment Action Group (TAG) has tracked global spending on TB R&D every year since 2005 using a survey sent to funding organizations in the public, private, philanthropic, and multilateral sectors. (A detailed description of TAG’s resource-tracking methodology is published in the 2015 Report on Tuberculosis Research Funding Trends).19 Resource tracking conducted by TAG shows that by the end of 2014, the world had invested $2.7 billion in TB R&D, less than one-third of the $9.8 billion goal. In each of the 10 years TAG has tracked TB R&D funding, annual spending on all forms of TB research by public, private, philanthropic, and multilateral institutions together has never exceeded $700 million. Alarmingly, funding for TB R&D appears to be flatlining. After increasing from $358.5 million in 2005 to $636.7 million in 2009, funding for TB R&D has remained stagnant since the global financial crisis (see Figure 1). As many observers have pointed out, flat funding is essentially falling funding, since inflation decreases the purchasing power of flat budgets.20 Moreover, the costs of biomedical research have risen faster than inflation, at least in the United States—the country that accounts for over half of all public spending for TB research.21 This underfunding is especially acute M. Frick, I. Henry, and E. Lessem / TB and the Right to Health, 9-24 12 J U N E 2 0 1 6 V O L U M E 1 8 N U M B E R 1 Health and Human Rights Journal for TB drug research, which in 2014 received $243.3 million in funding, one-third of the Global Plan’s annual target of $740 million for TB drug R&D.22 In addition to its low absolute level, funding for TB R&D is highly concentrated among a small pool of donors, most of them public institutions in high-income nations. Sixty percent of TB research funding comes from public agencies, and 62% of public funding comes from a single country: the United States. Mirroring the global trend, US government funding for TB R&D has remained flat since 2009, when US government agencies spent $255.4 million on TB R&D. In 2014, the US government spent $248.5 million.23 This dependency on public funding from a small number of country governments is heightened by the high degree of concentration of available funding in other sectors. For example, the Gates Foundation gave 86% of philanthropic support for TB R&D in 2014, and Otsuka contributed 54% of pharmaceutical industry funding.24 This leaves public agencies with few industry and philanthropic partners, and has left the field vulnerable to shifting donor priorities and even the withdrawal of major funders. This withdrawal has been most pronounced in the pharmaceutical sector. Since 2012, three major pharmaceutical companies (Pfizer, AstraZeneca, and Novartis) have closed their TB research programs as part of an industry-wide pivot away from anti-infectives research.25 (Although Novartis is renewing investment in the development of clofazimine for TB, it is not pursing new TB drug candidates.) The atrophying state of anti-infectives research has generated warning cries for over a decade.26 Newly developed antibiotics are not expected to generate blockbuster sales, leading major pharmaceutical companies to focus on developing new treatments for chronic illnesses or new biologics such as vaccines. In 2014, the pharmaceutical sector spent just $98.6 million on TB drug develop$100,000,000 $200,000,000 $300,000,000 $400,000,000 $500,000,000 $600,000,000 $700,000,000 $0 $358,476,537 $418,928,300 $478,343,421 $494,576,235 $636,979,349 $643,360,390 $675,328,887 $638,783,272 $686,303,295 $674,036,492