Commentary
Challenges for the Application and Development of Omics Health Technologies in Developing Countries
DDR
DRUG DEVELOPMENT RESEARCH 73 : 447–451 (2012)
Farah Huzair* and Alexander Borda-Rodriguez Development Policy and Practice, The Open University, Walton Hall Milton Keynes, MK7 6AA, UK
Strategy, Management and Health Policy Enabling Technology, Genomics, Proteomics
Preclinical Research
Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics
Clinical Development Phases I-III Regulatory, Quality, Manufacturing
Postmarketing Phase IV
ABSTRACT Omics technologies and particular applications for diagnostics and pharmacogenomics, can potentially identify disease risk, reduce disease burden, and provide better and more cost-effective health care. International institutions have recognized that global justice necessitates equity of access to medical technologies for developing and well as developed countries. The promise of the omics technologies may remain unfulfilled for developing countries unless capacities for exploitation and integration are created. These capacities are those that enable contribution efforts to upstream data collection and innovation, and downstream governance and regulation. Drug Dev Res 73 : 447–451, 2012. © 2012 Wiley Periodicals, Inc.
Key words: omics; postgenomics; global justice; developing countries; regulation; governance; capacities
THE POTENTIAL FOR OMICS TECHNOLOGIES
The publication of the full human genome sequence in 2003 by the International Human Genome Sequencing Consortium marked the culmination of the history of genetics research [NIH, 2012]. Genetics research paved the way for genomics, encompassing everything from sequencing genomes, ascribing functions to genes, and studying the structure of genes (gene architecture). Genomics is now making way for a new era of postgenomic research where focus of study moves beyond the genome to the role of genes [Archer and Dyer, 2004], how genes are transcribed into messenger RNA (transcriptomics), in the way genes are expressed as proteins (proteomics), and how they influence the chemicals that control cellular biochemistry and metabolism (metabolomics). The postgenomic era signifies not only development of these new areas of research, collectively referred to as omics technologies, but also their application to health and the development of new health technologies. A significant and rapidly advancing application is pharmacogenomics; the study © 2012 Wiley Periodicals, Inc.
of the influence of human genomic variation on drug efficacy and safety [Poland et al., 2008]. Genomics technologies support molecular diagnostics and can provide greater insights into disease risk, and so there is potential to support preventative action and reduce disease burden [Human Genomics Strategy Group, HGSG, 2012]. Pharmacogenomics and its promise of personalized medicine, recognizes individual variation in response to medicine. Treatments can therefore be tailored to genetic variation within subpopulations, therefore reducing the risk and cost associated with adverse drug reactions. Each year the costs linked to adverse drug reactions are estimated to be between
*Correspondence to: Farah Huzair, Innogen ESRC Centre, Development Policy and Practice, The Open University, Walton Hall Milton Keynes, MK7 6AA, UK. Email:
[email protected] Published online in Wiley Online Library (wileyonlinelibrary. com). DOI: 10.1002/ddr.21036
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$1.56 and $5.6 billion annually in the US and affect over 770,000 people [Agency for Healthcare Research and Quality, 2012] and are estimated to cause approximately 6.5% of all admissions to UK hospitals [HGSG, 2012]. Similar figures are not available for many developing countries but we can assume that for health systems across the world, the need to reduce costs and risk of injury is paramount. Costs of drugs may also fall if it is shown that clinical trials involving smaller populations offer the same level of safety and efficacy assurance. We argue in this paper that certain conditions need to be met to satisfy the demand for global social justice and to allow omics technologies, and in particular pharmacogenomics, to reach their full potential. First, innovation systems must be redirected to address the public health needs of developing as well as developed countries. Second, developing countries must create the capabilities and capacities to use and engage in genomics and, in particular, aspects and stages of pharmacogenomics innovation. And finally, developing countries and the international community need to have in place governance frameworks to effectively regulate use and innovation of new omics and pharmacogenomics technologies. SOCIAL JUSTICE AND THE NECESSITY TO ENGAGE THE GLOBAL SOUTH
The Global Forum for Health Research has found that only 10% of worldwide expenditure on health research and development (R&D) is devoted to the problems that primarily affect the poorest 90% of the world’s population [Chataway et al., 2010]. These trends run strongly counter to any sense of social or global justice. The work of various international development institutions, have highlighted the need to address this problem. The UNESCO [2005] Universal Declaration on Bioethics and Human Rights for example aims “to promote equitable access to medical, scientific and technological developments as well as the greatest possible flow and the rapid sharing of knowledge concerning those developments and the sharing of benefits, with particular attention to the needs of developing countries.” The Millennium Development Goals (goals 4, 5, and 6) similarly aim to reduce child mortality rates, improve maternal health, and combat HIV/AIDS, malaria, and other diseases [United Nations, 2011]. And in April of 2012, the World Health Organization’s (WHO’s) Consultative Expert Working Group on Research and Development recommended starting negotiations on a binding convention on R&D. A central idea is that governments should commit to spending 0.01% of gross domestic product on R&D that is relevant to the needs of developing countries [Dickson, 2012]. Drug Dev. Res.
Observers will question the extent to which developing countries need to engage in the development of medicines and technologies that are seen as “high tech,” particularly at a time when current discourses are highlighting the need for appropriate technologies (low-cost solutions such as treated bed nets, education programs, etc.) that can effectively reduce disease in the global south. Why not continue with the current paradigm of allowing developed countries to innovate, providing necessary advanced drugs, and developing countries to import or copy formulations in the form of generics? First, diagnostics and genomics technologies are likely to provide greater insights to disease and disease risk (risks that may not be prevalent in populations of developed countries), which could effectively target drugs, support preventative action, and reduce disease burden. Second, massive costs to health systems are incurred through adverse events associated with individual variability in response to medicine, which would continue if advanced medicines are imported without consideration of genetic variation of local populations. Third, and relatedly, if developing countries are not able or given the opportunity to contribute to innovation and development, it is possible medicines will continue to be made to treat disease largely affecting developed countries. For example, an outbreak of meningitis C in the UK in the 1990s affected about 10,000 people and killed 1,000. Three vaccine manufacturers responded immediately by developing meningitis C conjugate vaccines. In Africa in the same period, some 700,000 people were affected by group A Neisseria meningitidis, the most prevalent meningitis strain in developing countries, claiming 100,000 lives [Jódar et al., 2003] No manufacturer was interested in developing a vaccine that had such a limited commercial market. The needs of developing countries and the plight of neglected diseases—as the evidence suggests—might not influence the direction or targets of the new omics technologies, pharmacogenomics, and personalized medicine. Egalitarianism of both outcome and opportunity should contribute to a notion of global social justice. By including the needs and input of developing countries as drug and medical diagnostic innovation systems reorient around postgenomic science, not only is there a chance for greater equality in outcome, but also there is greater equality in opportunity. Equality of opportunity becomes a relatively more important factor when we consider future innovations or those that are in progress (e.g., personalized medicines), because equality in outcome and distribution can only be applied to innovations that currently exist. Of course we do not suggest that innovation of omics and pharmacogenomics technologies in-line with the needs of developing countries
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will address the whole of the global justice problem in health. We recognize that much depends on access and affordability of the innovations that are produced. Questions of affordability and distribution come later and will be addressed by work that examines public health systems, financing, patent regimes, etc. For now, and while omics is still in its early phase, it is important to address those issues that affect opportunity.
DEVELOPING CAPABILITIES AND CAPACITIES FOR RESEARCH AND INNOVATION
As mentioned previously, the promise of genomics technologies is to provide greater insights to disease risk needs. This needs to be supported by a basic platform enabling genetic testing, diagnosis, subsequent treatment, education, or preventative action. A study commissioned in the UK outlines the conditions necessary for primary health care to utilize the progress made in genomics and include the following [HGSG, 2012]:
• Rigorous and standardized processes for establishing the clinical validity and utility of genomic tests, and for quality assurance of each particular test, test centre and technology. • Clear commissioning standards for genomics and clinical genetic testing within clinical pathways, providing a straightforward and universal process for health-care professionals to request tests and receive results. • A secure and robust bioinformatics infrastructure to enable rapid, low-cost testing of genomic individual information against known variants. • A health-care workforce with the skills and knowledge to make effective use of genomic technology. This includes a strong cadre of genomics and genetics specialists in all specialties of medicine to carry out testing, manage data, and analyze results, as well as greater understanding and awareness of genomics and its role. For developing countries to contribute to the development of personalized medicine there are additional requirements. Pharmacogenomics requires human genetic banking and most collections existing worldwide (with perhaps the exception of UK Biobank and the Icelandic collection of health records—both sampling developed country populations) are too small to allow statistically meaningful research [Williams and Schroeder, 2004]. It is not necessary or indeed realistic to expect a developing country to build and establish a complete science base or entire innovation system capable of undertaking entire R&D programs for genomics and postgenomics. Health innovation systems
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are evolving to become global and collaborative [Baldwin and Von Hippel, 2009; Ozdemir et al., 2011b] and often involve public–private and product– development partnerships [Hanlin et al., 2007; Huzair et al., 2011]. Developing countries can therefore host and contribute to a small part of the upstream innovation process in order to provide population or subpopulation genetic and lifestyle data and biological material for the further development of diagnostic tools and medicines that may benefit them. This means attaining physical capacities and infrastructure for primary research involving the collection and storage of biological materials pertaining to certain ethnic groups or particular diseases. It also means building adequate human capabilities so that project personnel are appropriately trained in medical practices for sample collection, ethics procedures, genetic counseling, and procedures for handling, storage, and sharing of data. The challenges for developing countries in addressing these points are many; these include lack of absorptive and institutional capacity. The former is concerned with inadequate in-house expertise on the field of omics and public health, the latter is a core problem often referred to as “missing or perverse institutions” [North, 1990; Burnside and Dollar, 1997]. Institutions in developing countries tend to be weak and undermined by political instability. These circumstances are worsened as most developing countries are subject to unfavorable political and economic relations with developed countries. This is illustrated by the terms in which developed countries lend money and provide technical assistance. This process has been widely criticized as one in which the agenda and priorities are set up by wealthy countries [Ardndt, 2000]. Despite these circumstances, some capacity is however in place at least at the governmental level [Graham et al., 2012]. Contract or clinical research organizations (CROs) have presence in many developing countries and are experienced in undertaking large-scale clinical trials for drug R&D. Networks of universities, public research institutes, hospitals, CROs, and pharma companies already exist. The question that needs to be asked is what additional capabilities and capacities are required for genomics and postgenomics collaborative research? Standardization in data collection is one such issue. For example, research into biomarkers (disease-associated molecular changes in body tissues and fluids), has long been hailed as the key to better patient care and lower medical costs. Proteomics and DNA microarrays have contributed more than 150,000 papers documenting thousands of possible biomarkers, but fewer than 100 have been validated for routine clinical practice. A major impediment to progress is the lack of standardization in how specimens are collected. Unless Drug Dev. Res.
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specimens are taken from people who are matched for as many variables as possible (including sex, age, weight, ethnicity, previous treatments, and lifestyle factors such as smoking and alcohol use) all the subsequent steps in efforts to correlate biomarkers with a patients condition and response to treatments, are compromised [Poste, 2011]. REGULATION AND GOVERNANCE
Regulation in biotechnology has been viewed by various authors and perspectives as both enabling and stifling for innovation, and the balance has been difficult to strike. This is the case even for developed countries and is seen for example in the new regulatory frameworks currently being produced for biosimilars across the world. As so often is the case with new or emerging technologies [Collins and Evans, 2002], omics technologies, and the development and use of personalized medicine requires anticipatory governance and participatory foresight to manage uncertainty [Ozdemir et al., 2011a]. At this early stage, users, public interest groups, and policy makers are demanding governance mechanisms that will ensure the ethical collection and use of data. The UK study on the future of genomics in primary care published in 2012 demands the development of a legal framework to adequately address the challenges created by genomic medicine and the availability of genomic information [HGSG, 2012]. Given the key role we have outlined for developing countries in addressing global justice as beneficiary of and contributor to research, there is the same need for adequate legal frameworks. Legal frameworks need to not only ensure patient safety, confidentiality, and allow for research, but also have mechanisms for enforcement. A necessary starting point for the writing of good regulation and its enforcement is the need to have a sufficiently funded and competent national regulatory authority (NRA). NRAs perform a central role in collecting, monitoring, and assessing all safety-related information submitted by health manufacturers, national, local hospitals, and health-care institutions operating in the country. NRAs in developing countries are largely challenged by the quality and completeness of field evidence, weak and uniformed monitoring systems, poor surveillance mechanisms, underreporting of serious health cases, and lack of infrastructure. NRAs may be assisted by overarching governing bodies such as the WHO and The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), which can provide training for regulators, guidance documents for regulatory frameworks and standard setting in data collection and sharing. Drug Dev. Res.
Good governance also requires a coordinated and consistent approach to engaging with the public to promote understanding of genomics and what it means for health care [HGSG, 2012]. Generally, the process of translating knowledge from bench to bedside is complex. The WHO has, e.g., identified Knowledge Translation (KT) as a practice that should be used in health-care settings [WHO, 2004]. The WHO suggests a stronger emphasis on translating knowledge into action to improve public health by bridging the gap between what is known and what is actually done. KT requires synthesis, dissemination, exchange, and ethically sound application of knowledge to improve health [CIHR, 2008]. At the center of this process lays effective exchanges between researchers and end users. KT is a process rarely used; in addition, developing countries face two further problems. Public engagement, education, or consultation exercises are costly particularly if there are various “publics” to engage or bring together, if the target population is large and widely distributed, or if there are several languages in use. Second, public engagement to introduce new health biotechnologies may face an uphill struggle in developing countries due to a controversial history of past clinical trial work resulting in mistrust and “a fear of white coats” [Upton, 2011]. CONCLUSIONS
Omics technologies and applications in diagnostics and health represent a bundle of technologies that have the potential to either exacerbate or reduce inequality, depending on whether a country can access the technology and shape its development. The challenges for developing countries in creating the capacities and capabilities for using and engaging genomic and postgenomic technologies are not insurmountable. For example, development of capacities for research, and the funding of physical infrastructure may be provided by global collaborative innovation networks and public–private partnerships. And capability development, the training of personnel, and the creation of regulatory frameworks may be assisted by international organizations such as the WHO and the ICH. Most important, however, is that both developed and developing country agencies realize the potential for omics technologies to reduce cost and disease burden and contribute to global social justice. Fulfilling potential will require a planned and coordinated approach to ensure that none of the issues discussed here are missed. The involvement of developing countries in upstream research should be facilitated and the capability for technology adoption needs to be developed.
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