Universal health care, genomic medicine and Thailand: investing in today and tomorrow.

One potential outcome of investing in genomic medicine is the provision of tools for creating a more cost-effective health-care system. Partly with this aim in mind, Thailand has launched two genotyping initiatives: the Thai SNP Discovery Project and the Thai Centre for Excellence in Life Sciences Pharmacogenomics Project. Together, these projects will help Thailand understand the genomic diversity of its population and explore the role that this diversity has in drug response and disease susceptibility in its population. A major future challenge will be for Thailand to integrate genomic medicine in its relatively young universal health-care system.

Genomics, public health and developing countries: the case of the Mexican National Institute of Genomic Medicine (INMEGEN).

In 2004, the government of Mexico established the National Institute of Genomic Medicine (INMEGEN), to carry out disease-related genomic studies that will address national health problems and stimulate scientific and technological development by generating new commercial products and services in genomic medicine. Towards this end, INMEGEN is carrying out a large-scale genotyping project to map genomic variation within its own population. The initiative is expected to generate a key resource for local researchers to understand disease susceptibility and variation in drug responses, which will contribute to Mexico's goal of developing public health genomics - a field in which Mexico is proving to be a leader amongst emerging economies.

Genomic medicine and developing countries: creating a room of their own.

The notion that developing countries must wait for the developed world to make advances in science and technology that they later import at great cost is being challenged. We have previously argued that developing countries can harness human genetic variation to benefit their populations and economies. Based on our empirical studies of large-scale population genotyping projects in Mexico, India and Thailand, we describe how these resources are being adopted to improve public health and create knowledge-based economies. A significant additional benefit is building the capacity for scientific research and internalizing advances in technology, whatever their source.

South Africa: from species cradle to genomic applications.

The South African government is committed to science and technology innovation, to establishing a knowledge-based economy and to harnessing life-sciences research for health and economic development. Given the constraints and the early stage of development of the field as a whole in South Africa, we found an impressive amount of research on human genomic variation in this country. Encouragingly, South Africa is beginning to apply genomics to address local health needs, including HIV and tuberculosis (TB) infections. We document a number of initiatives in South Africa that are beginning to study genetic variation within the various local indigenous populations. Other early initiatives focus on pharmacogenetic studies, mutation characterization in individual disease genes and genome-wide association studies. Public engagement in genomic issues is spear-headed by The Africa Genome Education Institute.

The next steps for genomic medicine: challenges and opportunities for the developing world.

This is a historical moment on the path to genomic medicine - the point at which theory is about to be translated into practice. We have previously described human genome variation studies taking place in Mexico, India, Thailand, and South Africa. Such investments into science and technology will enable these countries to embark on the path to the medical and health applications of genomics, and to benefit economically. Here we provide a perspective on the challenges and opportunities facing these and other countries in the developing world as they begin to harness genomics for the benefit of their populations.

From diversity to delivery: the case of the Indian Genome Variation initiative.

India currently has the world's second-largest population along with a fast-growing economy and significant economic disparity. It also continues to experience a high rate of infectious disease and increasingly higher rates of chronic diseases. However, India cannot afford to import expensive technologies and therapeutics nor can it, as an emerging economy, emulate the health-delivery systems of the developed world. Instead, to address these challenges it is looking to biotechnology-based innovation in the field of genomics. The Indian Genome Variation (IGV) consortium, a government-funded collaborative network among seven local institutions, is a reflection of these efforts. The IGV has recently developed the first large-scale database of genomic diversity in the Indian population that will facilitate research on disease predisposition, adverse drug reactions and population migration.

Top ten biotechnologies for improving health in developing countries.

Most research into genomics and other related biotechnologies is concerned with the priorities of industrialized nations, and yet a limited number of projects have shown that these technologies could help improve health in developing countries. To encourage the successful application of biotechnology to global health, we carried out a study in which we asked an international group of eminent scientists with expertise in global health issues to identify the top ten biotechnologies for improving health in developing countries. The results offer concrete guidance to those in a position to influence the direction of research and development, and challenge common assumptions about the relevance and affordability of biotechnology for developing countries.

Emergence of biopharmaceutical innovators in China, India, Brazil, and South Africa as global competitors and collaborators.

Biopharmaceutical innovation has had a profound health and economic impact globally. Developed countries have traditionally been the source of most innovations as well as the destination for the resulting economic and health benefits. As a result, most prior research on this sector has focused on developed countries. This paper seeks to fill the gap in research on emerging markets by analyzing factors that influence innovative activity in the indigenous biopharmaceutical sectors of China, India, Brazil, and South Africa. Using qualitative research methodologies, this paper a) shows how biopharmaceutical innovation is taking place within the entrepreneurial sectors of these emerging markets, b) identifies common challenges that indigenous entrepreneurs face, c) highlights the key role played by the state, and d) reveals that the transition to innovation by companies in the emerging markets is characterized by increased global integration. It suggests that biopharmaceutical innovators in emerging markets are capitalizing on opportunities to participate in the drug development value chain and thus developing capabilities and relationships for competing globally both with and against established companies headquartered in developed countries.

Indian vaccine innovation: the case of Shantha Biotechnics.

BACKGROUND: Although the World Health Organization had recommended that every child be vaccinated for Hepatitis B by the early 1980s, large multinational pharmaceutical companies held monopolies on the recombinant Hepatitis B vaccine. At a price as high as USD$23 a dose, most Indians families could not afford vaccination. Shantha Biotechnics, a pioneering Indian biotechnology company founded in 1993, saw an unmet need domestically, and developed novel processes for manufacturing Hepatitis B vaccine to reduce prices to less than $1/dose. Further expansion enabled low-cost mass vaccination globally through organizations such as UNICEF. In 2009, Shantha sold over 120 million doses of vaccines. The company was recently acquired by Sanofi-Aventis at a valuation of USD$784 million. METHODS: The case study and grounded research method was used to illustrate how the globalization of healthcare R&D is enabling private sector companies such as Shantha to address access to essential medicines. Sources including interviews, literature analysis, and on-site observations were combined to conduct a robust examination of Shantha's evolution as a major provider of vaccines for global health indications. RESULTS: Shantha's ability to become a significant global vaccine manufacturer and achieve international valuation and market success appears to have been made possible by focusing first on the local health needs of India. How Shantha achieved this balance can be understood in terms of a framework of four guiding principles. First, Shantha identified a therapeutic area (Hepatitis B) in which cost efficiencies could be achieved for reaching the poor. Second, Shantha persistently sought investments and partnerships from non-traditional and international sources including the Foreign Ministry of Oman and Pfizer. Third, Shantha focused on innovation and quality - investing in innovation from the outset yielded the crucial process innovation that allowed Shantha to make an affordable vaccine. Fourth, Shantha constructed its own cGMP facility, which established credibility for vaccine prequalification by the World Health Organization and generated interest from large pharmaceutical companies in its contract research services. These two sources of revenue allowed Shantha to continue to invest in health innovation relevant to the developing world. CONCLUSIONS: The Shantha case study underscores the important role the private sector can play in global health and access to medicines. Home-grown companies in the developing world are becoming a source of low-cost, locally relevant healthcare R&D for therapeutics such as vaccines. Such companies may be compelled by market forces to focus on products relevant to diseases endemic in their country. Sanofi-Aventis' acquisition of Shantha reveals that even large pharmaceutical companies based in the developed world have recognized the importance of meeting the health needs of the developing world. Collectively, these processes suggest an ability to tap into private sector investments for global health innovation, and illustrate the globalization of healthcare R&D to the developing world.

What could infant and young child nutrition learn from sweatshops?

BACKGROUND: Adequate infant and young child nutrition demands high rates of breastfeeding and good access to nutrient rich complementary foods, requiring public sector action to promote breastfeeding and home based complementary feeding, and private sector action to refrain from undermining breastfeeding and to provide affordable, nutrient rich complementary foods. Unfortunately, due to a lack of trust, the public and private sectors, from both the North and the South, do not work well together in achieving optimal infant and young child nutrition. DISCUSSION: As the current debate in infant and young child nutrition is reminiscent of the "sweatshop" debate fifteen years ago, we argue that lessons from the sweatshops debate regarding cooperation between public and private sectors - and specific organizational experiences such as the Ethical Trading Initiative in which companies, trade unions, and civil society organizations work together to enhance implementation of labour standards and address alleged allegations - could serve as a model for improving cooperation and trust between public, civil society and private groups, and ultimately health, in infant and young child nutrition. SUMMARY: Lessons from the sweatshops debate could serve as a model to promote cooperation and trust between public and private groups, such that they learn to work together towards their common goal of improving infant and young child nutrition.

The case for conducting first-in-human (phase 0 and phase 1) clinical trials in low and middle income countries.

BACKGROUND: Despite the increase in the number of clinical trials in low and middle income countries (LMICs), there has been little serious discussion of whether First in Human (FIH; phase 0 and phase 1) clinical trials should be conducted in LMICs, and if so, under what conditions. Based on our own experience, studies and consultations, this paper aims to stimulate debate on our contention that for products meant primarily for conditions most prevalent in LMICs, FIH trials should preferably be done first in those countries. DISCUSSION: There are scientific and pragmatic arguments that support conducting FIH trials in LMIC. Furthermore, the changing product-development and regulatory landscape, and the likelihood of secondary benefits such as capacity building for innovation and for research ethics support our argument. These arguments take into account the critical importance of protecting human subjects of research while developing capacity to undertake FIH trials. SUMMARY: While FIH trials have historically not been conducted in LMICs, the situation in some of these countries has changed. Hence, we have argued that FIH should be conducted in LMICs for products meant primarily for conditions that are most prevalent in those contexts; provided the necessary protections for human subjects are sufficient.

Access and use of human tissues from the developing world: ethical challenges and a way forward using a tissue trust.

BACKGROUND: Scientists engaged in global health research are increasingly faced with barriers to access and use of human tissues from the developing world communities where much of their research is targeted. In part, the problem can be traced to distrust of researchers from affluent countries, given the history of 'scientific-imperialism' and 'biocolonialism' reflected in past well publicized cases of exploitation of research participants from low to middle income countries. DISCUSSION: To a considerable extent, the failure to adequately engage host communities, the opacity of informed consent, and the lack of fair benefit-sharing have played a significant role in eroding trust. These ethical considerations are central to biomedical research in low to middle income countries and failure to attend to them can inadvertently contribute to exploitation and erode trust. A 'tissue trust' may be a plausible means for enabling access to human tissues for research in a manner that is responsive to the ethical challenges considered. SUMMARY: Preventing exploitation and restoring trust while simultaneously promoting global health research calls for innovative approaches to human tissues research. A tissue trust can reduce the risk of exploitation and promote host capacity as a key benefit.

Postoperative GH and Degree of Reduction in IGF-1 Predicts Postoperative Hormonal Remission in Acromegaly.

Purpose: Determine predictive factors for long-term remission of acromegaly after transsphenoidal resection of growth hormone (GH)-secreting pituitary adenomas. Methods: We identified 94 patients who had undergone transsphenoidal resection of GH-secreting pituitary adenomas for treatment of acromegaly at the USC Pituitary Center from 1999-2019 to determine the predictive value of postoperative endocrine lab values. Results: Patients underwent direct endoscopic endonasal (60%), microscopic transsphenoidal (38%), and extended endoscopic approaches (2%). The cohort was 63% female and 37% male, with average age of 48.9 years. Patients presented with acral enlargement (72, 77%), macroglossia (40, 43%), excessive sweating (39, 42%), prognathism (38, 40%) and frontal bossing (35, 37%). Seventy-five (80%) were macroadenomas and 19 (20%) were microadenomas. Cavernous sinus invasion was present in 45%. Available immunohistochemical data demonstrated GH staining in 88 (94%) and prolactin in 44 (47%). Available postoperative MRI demonstrated gross total resection in 63% of patients and subtotal resection in 37%. Most patients (66%) exhibited hormonal remission at 12 weeks postoperatively. Receiver operating characteristic (ROC) curves demonstrated postoperative day 1 (POD1) GH levels ≥1.55ng/mL predicted failure to remit from surgical resection alone (59% specificity, 75% sensitivity). A second ROC curve showed decrease in corrected insulin-like growth factor-1 (IGF-1) levels of at least 37% prognosticated biochemical control (90% sensitivity, 80% specificity). Conclusion: POD1 GH and short-term postoperative IGF-1 levels can be used to successfully predict immediate and long-term hormonal remission respectively. A POD1 GH cutoff can identify patients likely to require adjuvant therapy to emphasize clinical follow-up.

Shared principles of ethics for infant and young child nutrition in the developing world.

BACKGROUND: The defining event in the area of infant feeding is the aggressive marketing of infant formula in the developing world by transnational companies in the 1970s. This practice shattered the trust of the global health community in the private sector, culminated in a global boycott of Nestle products and has extended to distrust of all commercial efforts to improve infant and young child nutrition. The lack of trust is a key barrier along the critical path to optimal infant and young child nutrition in the developing world. DISCUSSION: To begin to bridge this gap in trust, we developed a set of shared principles based on the following ideals: Integrity; Solidarity; Justice; Equality; Partnership, cooperation, coordination, and communication; Responsible Activity; Sustainability; Transparency; Private enterprise and scale-up; and Fair trading and consumer choice. We hope these principles can serve as a platform on which various parties in the in the infant and young child nutrition arena, can begin a process of authentic trust-building that will ultimately result in coordinated efforts amongst parties. SUMMARY: A set of shared principles of ethics for infant and young child nutrition in the developing world could catalyze the scale-up of low cost, high quality, complementary foods for infants and young children, and eventually contribute to the eradication of infant and child malnutrition in the developing world.

'Relief of oppression': an organizing principle for researchers' obligations to participants in observational studies in the developing world.

BACKGROUND: A central question in the debate about exploitation in international research is whether investigators and sponsors from high-income countries (HIC) have obligations to address background conditions of injustice in the communities in which they conduct their research, beyond the healthcare and other research-related needs of participants, to aspects of their basic life circumstances. DISCUSSION: In this paper, we describe the Majengo sexually transmitted disease (STD) Cohort study, a long-term prospective, observational cohort of sex workers in Nairobi, Kenya. Despite important scientific contributions and a wide range of benefits to the women of the cohort, most of the women have remained in the sex trade during their long-standing participation in the cohort, prompting allegations of exploitation. The Majengo STD cohort case extends the debate about justice in international research ethics beyond clinical trials into long-term observational research. We sketch the basic features of a new approach to understanding and operationalizing obligations of observational researchers, which we call 'relief of oppression'. 'Relief of oppression' is an organizing principle, analogous to the principle of harm reduction that is now widely applied in public health practice. Relief of oppression aims to help observational researchers working in conditions of injustice and deprivation to clarify their ethical obligations to participants. It aims to bridge the gap between a narrow, transaction-oriented account of avoiding exploitation and a broad account emphasizing obligations of reparation for historic injustices. We propose that relief of oppression might focus researchers' consideration of benefits on those that have some relevance to background conditions of injustice, and so elevate the priority of these benefits, in relation to others that might be considered and negotiated with participants, according to the degree to which the participating communities are constrained in their realization of fundamental freedoms. SUMMARY: The over-arching aim of relief of oppression is that, within the range of benefits negotiated over time with the local communities and organizations, an increasing proportion reflects a shared interest in improving participants' fundamental freedoms. We describe how harm reduction serves as a useful analogy for how we envision relief of oppression functioning in international research.

Evaluating priority setting success in healthcare: a pilot study.

BACKGROUND: In healthcare today, decisions are made in the face of serious resource constraints. Healthcare managers are struggling to provide high quality care, manage resources effectively, and meet changing patient needs. Healthcare managers who are constantly making difficult resource decisions desire a way to improve their priority setting processes. Despite the wealth of existing priority setting literature (for example, program budgeting and marginal analysis, accountability for reasonableness, the 'describe-evaluate-improve' strategy) there are still no tools to evaluate how healthcare resources are prioritised. This paper describes the development and piloting of a process to evaluate priority setting in health institutions. The evaluation process was designed to examine the procedural and substantive dimensions of priority setting using a multi-methods approach, including a staff survey, decision-maker interviews, and document analysis. METHODS: The evaluation process was piloted in a mid-size community hospital in Ontario, Canada while its leaders worked through their annual budgeting process. Both qualitative and quantitative methods were used to analyze the data. RESULTS: The evaluation process was both applicable to the context and it captured the budgeting process. In general, the pilot test provided support for our evaluation process and our definition of success, (i.e., our conceptual framework). CONCLUSIONS: The purpose of the evaluation process is to provide a simple, practical way for an organization to better understand what it means to achieve success in its priority setting activities and identify areas for improvement. In order for the process to be used by healthcare managers today, modification and contextualization of the process are anticipated. As the evaluation process is applied in more health care organizations or applied repeatedly in an organization, it may become more streamlined.