Special series on PAHO's Policy on Research for Health

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BMJ 2018;362:k2944 doi: 10.1136/bmj.k2944 (Published 16 July 2018)

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Editorials

EDITORIALS Research for health in the Americas OPEN ACCESS

Evolution of health research to reshape national health agendas 1

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Carissa Etienne director , Kamran Abbasi executive editor , Luis Gabriel Cuervo senior adviser

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Pan American Health Organization/World Health Organization (PAHO/WHO), Washington, DC, USA; 2The BMJ, London, UK; 3Health Systems Research, PAHO/WHO, Washington, DC, USA

Research for health is the linchpin of effective and efficient health systems. A broad range of research methods is required to improve public health and equity, and to understand the economics and mechanics of health systems. As access to scientific knowledge mushroomed in recent decades, expectations for the adoption of that knowledge for better health also grew. Societies now expect decisions to be informed by the best knowledge, but the organisation and management of the research enterprise remain inadequate. Hence, much research is wasted or is of limited value. Research sponsors don’t see that their investment affects development, and they may not even see any effect on prevention initiatives or health policies.1-5

to live fuller lives, to be more productive, and to contribute to society more widely.11 12

In 2009, member states of the Pan American Health Organization (PAHO) approved a regional policy on research for health in the Americas, the first such WHO regional policy.6 It was developed to harmonise with and complement WHO’s Strategy on Research for Health.7 This special BMJ/PAHO collection (www.bmj.com/health-research-americas) offers insights and perspectives on developments and challenges after the implementation of PAHO’s research policy. We examine what lies ahead given adoption of the United Nations Agenda 2030 and sustainable development goals, louder calls for universal health coverage and strengthening of health systems, and approval in May 2018 of WHO’s 13th Global Programme of Work 2019-2023.8

Unfortunately, research remains a weak public health function in the Americas and this must change.13 In the past decade, research reporting standards improved and trial registries brought transparency to research, but the need remains to integrate developments in ways that benefit citizens, and to do it consistently in all countries. Identifying remaining gaps will help the region tackle and eliminate established and emerging diseases as well as maintain gains in health, equity, and access. Better planning of investments is needed for discoveries to translate into public health and health system gains.14

Most PAHO member states developed national policies on research for health after the regional policy was introduced. Some of these expired or are being updated. By December 2017, 16 countries reported a national policy on research for health, and 18 Caribbean community (CARICOM) countries endorsed a common policy.9 But striking differences remain between countries in their ability to deliver, use, and organise research for health, or to monitor their research capacity. Economic and developmental returns on investment are often realised outside health, in other sectors of government, society, and the economy.10 Elimination of polio and access to HIV/AIDS treatment, for example, enabled hundreds of thousands of people

The organisation and management of research is non-existent in places, and the benefits of big data, social media, and other digital tools are waiting to be seized. Societies are yet to see the digital age reflected in monitoring and organisation of research for health. But structures and processes that better support implementation research, health systems research, and public health research are ready to be harnessed by the research community. Society, funding agencies, research sponsors, and research participants will then see the outputs and outcomes of the region’s investment in research.

This collection of articles takes stock of progress since the introduction of PAHO’s policy on research for health, identifies areas of slow progress, and discusses the challenges ahead. We also welcome contributions that add to the debate in the Americas on how to integrate research into health systems, how to organise research, and how to increase its value. How should we shape research teams in an interconnected world, and how do we capitalise on any opportunities that arise? The PAHO research policy followed a systems approach with six inter-related objectives (box 1); research is necessary to fulfil the core functions of PAHO and WHO .2 15 We seek to shape the research agenda in the Americas and globally by stimulating the generation, translation, and dissemination of valuable knowledge. We urge other regions to share their stories

Correspondence to: L G Cuervo cuervolu@paho.org No commercial reuse: See rights and reprints http://www.bmj.com/permissions

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BMJ 2018;362:k2944 doi: 10.1136/bmj.k2944 (Published 16 July 2018)

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EDITORIALS

and build a common narrative for better health systems and a healthier world. Box 1: Objectives of PAHO’s policy on health research • To promote the generation of relevant, ethical, and quality research

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• To strengthen research governance and promote the definition of research agendas • To improve competencies of and support for people involved in research

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• To seek efficiencies and enhanced impact and appropriation of research through effective and strategic alliances, collaboration, and the building of public trust and engagement in research • To foster best practices and enhanced standards for research

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• To promote the dissemination and use of research findings

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See www.bmj.com/health-research-americas for other articles in the series.

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We thank Francisco Becerra, Luis Alejandro Salicrup, and PAHO’s advisory committee on health research for their support in the development of this series.

Competing interests:We have read and understood BMJ policy on declaration of

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interests and have no relevant interests to declare. 15

This article is part of a series proposed by PAHO and commissioned by The BMJ, which peer reviewed, edited, and made the decision to publish the article with no involvement from PAHO. Open access fees for the series are funded by PAHO. Provenance and peer review: Commissioned; not externally peer reviewed. 1

2 3 4

Chalmers I, Bracken MB, Djulbegovic B, etal . How to increase value and reduce waste when research priorities are set. Lancet 2014;383:156-65. 10.1016/S0140-6736(13)62229-1 24411644 Cochrane AL. Effectiveness and efficiency: random reflections on health services. Nuffield Provincial Hospitals Trust, 1972. Smith R, Rennie D. Evidence based medicine—an oral history. JAMA 2014;311:365-7. 10.1001/jama.2013.286182 24449049 World Health Organization. The Bamako call to action on research for health: strengthening research for health, development, and equity. WHO, 2008.

No commercial reuse: See rights and reprints http://www.bmj.com/permissions

World Health Organization. Bamako call to action urges new approach to research for health. 2008. http://www.who.int/rpc/news/bamako_call_to_action/en/ Pan American Health Organization. Policy on research for health. CD49/10. 2009. http:/ /www.paho.org/hq/images/stories/KBR/Research/research%20policy%20on%20research% 20for%20health%20english.pdf?ua=1 WHO. 63rd World Health Assembly. WHO’s roles and responsibilities on health research. A63/22. 2010. http://apps.who.int/gb/e/e_wha63.html World Health Organization. Thirteenth general programme of work 2019-2023: promote health, keep the world safe, serve the vulnerable. 2018. http://www.who.int/about/whatwe-do/gpw-thirteen-consultation/en/ Cuervo LG, Bermúdez-Tamayo C. Desarrollo de la investigación para la salud en Latinoamérica y el Caribe. Colaboración, publicación y aplicación del conocimiento[Development of research for health in Latin America and the Caribbean. Collaboration, publication and application of knowledge]. Gac Sanit 2018;32:206-8. 10.1016/j.gaceta.2018.03.001 29728253 Greenhalgh T, Raftery J, Hanney S, Glover M. Research impact: a narrative review. BMC Med 2016;14:78. 10.1186/s12916-016-0620-8 27211576 Thirumurthy H, Galárraga O, Larson B, Rosen S. HIV treatment produces economic returns through increased work and education, and warrants continued US support. Health Aff (Millwood) 2012;31:1470-7. 10.1377/hlthaff.2012.0217. 22778336 Zandam H. Life after polio: towards improving the situation of polio survivors. 2015. https: //www.twigh.org/twigh-blog-archives/2015/8/25/life-after-polio-towards-improving-thesituation-of-polio-survivors Pan American Health Organization Public. health in the Americas: conceptual renewal, performance assessment, and bases for action. 2002. http://iris.paho.org/xmlui/handle/ 123456789/2748 World Health Organization. Changing mindsets—strategy on health policy and systems research. 2012. http://www.who.int/alliance-hpsr/alliancehpsr_changingmindsets_ strategyhpsr.pdf Pan American Health Organization. Values, vision and mission of the Pan American Sanitary Bureau. 2015. http://www.paho.org/hq/index.php?option=com_content& view=article&id=95%3A2008-values-vision-mission&catid=6822%3Acorporate-pages& lang=en.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/ permissionsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non Commercial No Derivs IGO License (CC BY-NC-ND 3.0 IGO), which permits distribution and reproduction for non-commercial purposes in any medium, provided the original work is properly cited. If you remix, transform, or build upon the material, you may not distribute the modified material. See: https://creativecommons.org/licenses/by-nc-nd/3.0/igo/ In any reproduction of this article there should not be any suggestion that PAHO or this article endorse any specific organisation or products

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Strengthening Research for Health in the Americas

Promoting high quality research into priority health needs in Latin America and Caribbean The region still needs to build its research capacity to inform effective public health policy and practices, say Fabio Zicker and colleagues

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cientific evidence from high quality research studies is important for improving global health and health equity.1 In resource ­constrained settings, regionally relevant knowledge and tools are essential for strengthening the effectiveness of health services and reducing the burden of disease.2 Creation of national health research systems focusing on local priorities in Latin America and the Caribbean (LAC) can facilitate high quality research and build research capacity.3 Over the past 15 years, overall expenditure on research and development in the region has increased from 0.57% to 0.8% of the gross domestic product (GDP). However, this is still far below the level of investment in countries of the Organisation for Economic Cooperation and Development (2.5-2.8% of GDP).4 Although the number of citable health science publications from LAC has tripled,5 the relevance and potential of research to address the region’s health challenges still need to improve. The disconnect between academic research and healthcare needs in the region is widely recognised.6 Overall funding for science and research infrastructure has been vulnerable to social, economic, and political instability. Science funding has been one of the first government budget lines to be cut when there is fiscal

Key messages •   Despite social, economic, and political

instability, LAC has increased its research and development expenditure and tripled health related publications in recent years •   Fostering research output relevant to public health relies on priority setting processes, strengthening national research systems, and improving collaboration between the academic community and public health implementers •   I mplementation research has an important role in improving the performance of health systems •   Sustainable investment in infrastructure and human resources is necessary for enhancing the contribution of research to public health

pressure. 7 Within this context, some initiatives have been carried out to boost the capacity and relevance of health research in the region. In this article we analyse successes, barriers, and lessons from some of these initiatives.

Strengthening national health research systems Growing global recognition of the importance of national health research programmes to improve health systems prompted the Council for Health Research for Development and Pan American Health Organisation (PAHO) to conduct a survey of research systems in 14 countries in the region in 2008. At that time, only six countries had formal research governance and management structures in place, led by either the ministry of health or the ministry of science and technology, and only nine countries reported having established priorities for national health research.8 The results were discussed at the First Latin American Conference on Research and Innovation for Health and influenced PAHO’s 2009 Policy for Research for Health.3 One of the key objectives of the policy was to establish national health research priorities. A 2014 review, five years after the policy was established, showed an increase in the number of LAC countries with research agendas. Fourteen of the 37 countries included in the review had research agendas, with wide variations in terms of objectives, content, methods, and strategic areas.9 The study highlighted a continuing need for ministries of health and stakeholders across the region to implement national research priority setting exercises using systematic methods. Aligning research priorities Ministries of health and of science and technology in LAC have steadily increased engagement with healthcare systems by defining priorities and promoting relevant health research. Research initiatives like EVIPnet (Evidence-Informed Policy Network) 10 and SORT IT (an operational research and training programme) 11 have been established within the ministries of health of 10 countries. PAHO and WHO have facilitated training, the development of web portals, and the introduction of methods to appraise scientific evidence. The aim

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of these programmes is to empower policy makers, researchers, and implementers to bridge the gap between knowledge generation and use in policy. The focus has been on areas such as access to high quality maternal and child care, prevention and control of infectious diseases, tuberculosis diagnosis and treatment, and access to high cost medicines. However, in practice, continuous competing conflicts exist between applying current knowledge and generating and testing new knowledge and evidence.3 In order to promote research on specific knowledge gaps, the Brazilian Research Program for the Unified Health System has decentralised funding ($100m over 15 years) for research, technology development, and innovation, issuing research calls on priority topics. 12 The process has included local priority setting exercises managed by state foundations for science and technology support, including policy makers, researchers, implementers, and in some instances patient associations, with the objective of proposing regionally relevant research agendas. This strategy has proved useful in increasing the demand for research on priority problems, including health technology assessment and healthcare management at point of care— for example, the testing, diagnosis, and treatment of tuberculosis at the same health centre.

Improving research quality and standards Some of the region’s most developed initiatives for strengthening research quality and standards are in the Caribbean. Caribbean academic institutions, in collaboration with the International Clinical Epidemiology Network and the Cochrane Collaboration, have promoted training to improve the quality of public health research. The focus has been on the production of systematic reviews, methods for project planning and evaluation, good clinical practice, and research ethics. The initiatives tap into fellowship programmes sponsored by the Emerging Leaders for the Americas Programme, with added support from the Universities of Ottawa, West Indies, and Johns Hopkins. More than 300 fellows have been trained so far. Other initiatives in the region, such as the Caribbean branch of the US Cochrane Centre, which was established in 2013 in Jamaica, and the Caribbean Public Health 1


Strengthening Research for Health in the Americas

Agency are also providing training in knowledge synthesis and translation. An evaluation and impact assessment report of capacity building activities in the Caribbean over the past decade documented progress in team building and developing institutional research frameworks.13 The report recognised the need to promote collaborative engagement among research and health practitioners and to optimise both human and financial resources through partnerships among Caribbean and North American institutions and global initiatives.

Fostering leadership and networking Research networks are an efficient way to combine different disciplines and expertise to address relevant public health problems and promote high quality research. A WHO report14 identified that successful collaboration was related to shared goals among network members, clear governance structure, strong leadership, good management practices, sustained resources, and effective communication. Social network analysis has been used to map relations between members of research networks, identifying central and influential members.15 A review of the dengue research network showed the uneven geographical distribution of research activities and near absence of engagement of the private sector, an important strategic gap in efforts to develop new approaches to tackle the growing dengue epidemic.16 Much can be learnt from the recent Zika microcephaly epidemics in north eastern Brazil. Leadership and networking were essential for sharing information, generating and disseminating new data, and defining strategic lines of research to respond to the emergency. The rapid discovery of its aetiology and the development of case management routines were facilitated by the cross-disciplinary approaches and interinstitutional collaboration of the microcephaly epidemic research group (box 1). Research on programme implementation One of the main messages of the second Latin American conference on research and innovation for health in 20116 was that innovation in research is not measured by the complexity of an intervention or solution to a problem. Innovative research may lead to simple solutions that address large social and economic burdens on the health systems. This is particularly relevant in implementation research. Implementation research is a rapidly growing area of interest in LAC, geared towards understanding both the determinants of success and barriers to the sustainable introduction or scaling-up health strategies and technologies. 18 2

Box 1: Research response to the congenital Zika syndrome epidemic in Brazil •   Response to the 2016 Zika infection epidemic involved national and state surveillance systems, the scientific community, and PAHO. Political support and funding were mobilised, with healthcare providers and the general public having high expectations. •   An interinstitutional microcephaly epidemic research group (MERG) designed and conducted a case-control study to explore possible risk factors associated with the increased incidence of microcephaly.17 These findings led to testing of 2 day old infants for Zika infection. •   Social networks helped warn about the problem but also spread unfounded rumours causing confusion about viral aetiology, vector transmission, and potential spread of the disease. The declaration of a state of emergency by the Brazilian authorities and WHO was a turning point for mobilising the public health sector, civil society, and academic community. The scientific community had a leading role in describing the congenital Zika syndrome, formulating its aetiology, and building evidence to inform policy decisions. This resulted in the Zika Preparedness Latin America Network (https:// zikaplan.tghn.org). Box 2: Improving HPV screening in Latin America—the ESTAMPA study •   ESTAMPA is led by the WHO International Agency for Research on Cancer in collaboration with various ministries of health in Latin America and with support from the US National Cancer Institute and PAHO. It is enrolling up to 50 000 participants to assess the cost effectiveness of implementing different triage methods to detect HPV infection. •   Conducting this large multicountry study has proved to be both challenging and complex, involving a network of scientists, institutions, and governments. Experience has suggested that the best results and highest quality data are largely dependent on effective planning; knowledge of local disease burden; cost-analysis for rolling out study sites; analysis of local potential for scaling up; community engagement; and interdisciplinary management. •   Because implementation research is an emerging field and training opportunities within academic institution are still being scaled up, WHO and the Special Programme for Research and Training in Tropical Disease (TDR) have developed an open online course targeted at researchers and health implementers. The aim of the course is to position implementation research as an important approach to translating innovations into policy by providing readily accessible training in LAC and other WHO regions.19

Currently, implementation research is underused in the region, but good examples include the multicentre ESTAMPA study. The study was designed to assess the performance and cost effectiveness of different algorithms and procedures for human papillomavirus (HPV) screening (box 2).

Conclusion Research has an important role in sustainable development by improving the performance of health systems and their impact on public health. Science, technology, and innovation are included in several UN sustainable development goals.20 LAC is committed to achieving these goals, but the growth of the required health research in the region is still uneven.21 National health and research systems need to review and align targets, strengthen infrastructures, and monitor mechanisms for gathering reliable data to assess progress in social development. Contributors and sources: All authors contributed to the planning and writing of the original manuscript. Celina Turchi and Enrique Vázquez provided help with the Zika example in box 1, and Rolando Herrero and Maribel Almonte helped with the study example in box 2.

Competing interests: We have read and understood BMJ policy on competing interest and declare no competing interests. FZ received research support from the Brazilian National Council for Scientific and Technological Development (CNPq), grants #458100/2014-5 and #440231/2015-9. Provenance and peer review: Commissioned; externally peer reviewed. This article is part of a series proposed by PAHO and commissioned by The BMJ, which peer reviewed, edited, and made the decision to publish the article with no involvement from PAHO. Open access fees for the series are funded by PAHO. Fabio Zicker, specialist in science, technology, and innovation in global health1 Luis Gabriel Cuervo, senior adviser for research promotion and development2 Luis Alejandro Salicrup, senior adviser for global health research3 1 Centre for Technological Development in Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil 2 Pan American Health Organization/World Health Organization, Washington, DC, USA 3 Center for Global Health, National Cancer Institute, National Institutes of Health, Bethesda, MA, USA

Correspondence to: F Zicker fabio.zicker@gmail.com 1 World Health Organization. Strategy on research for health. 2012. http://www.who.int/phi/WHO_ Strategy_on_research_for_health.pdf

doi: 10.1136/bmj.k2492 | BMJ 2018;362:k2492 | the bmj


Strengthening Research for Health in the Americas

2 Ghaffar A, Jsselmuiden I, Zicker F. Changing mindsets: research capacity strengthening in low- and middle-income countries. WHO, 2010. http://www.who.int/tdr/publications/documents/ changing_mindsets.pdf 3 Pan American Health Organization/World Health Organization. Policy on research for health. 49th Directing Council, 61st session of the regional committee. 2009. http://www.paho.org/hq/images/ stories/KBR/Research/research%20policy%20 on%20research%20for%20health%20english.pdf 4 World Bank. Research and development expenditure. https://data.worldbank.org/indicator/GB.XPD.RSDV. GD.ZS?locations=XJ 5 Scimago Journal & Country Rank. (Accessed 16 Oct 2017). http://www.scimagojr.com 6 Council on Health Research for Development (COHRED). Report to the second Latin American conference on research and innovation for health, Panama City, 2011. http://www.cohred.org/ publications/cohred-publications/joint-publications/ report-to-the-2nd-latin-american-conference-onresearch-and-innovation-for-health/ 7 Ciocca DR, Delgado G. The reality of scientific research in Latin America; an insider’s perspective. Cell Stress Chaperones 2017;22:847-52. doi:10.1007/s12192-017-0815-8 8 Alger J, Becerra-Posada F, Kennedy A, Martinelli E, Cuervo LGGrupo Colaborativo de la Primera Conferencia Latinoamericana de Investigación e Innovación para la Salud. [National health research systems in Latin America: a 14-country review (in Spanish).] Rev Panam Salud Publica 2009;26:447-57.

9 Becerra-Posada F, de Snyder NS, Cuervo LG, Montorzi G. Agendas de investigación priorizadas: un recurso estratégico para la salud en América Latina. [Priority research agendas: a strategic resource for health in Latin America.]Rev Panam Salud Publica 2014;36:361-7. 10 World Health Organization. EVIPnet. http://www.who. int/evidence/en/ 11 World Health Organization. Special programme on research and training in tropical diseases. SORT IT. 12 Ministério da Saúde Brasil. Programa de Pesquisa para o SUS (PPSUS). 2017. http://www.brasil.gov.br/ saude/2017/02/ministerio-da-saude-garante-80dos-recursos-para-pesquisa-no-setor-no-pais 13 Pan American Health Organization/ World Health Organization. Report on strengthening research capacities for health in the Caribbean, 2007-2017. 2017. http://iris.paho.org/xmlui/ handle/123456789/34342 14 World Health Organization, Special Programme for Research and Training in Tropical Diseases. Key enabling factors in effective and sustainable research networks. 2016. http://www.who.int/tdr/ publications/research-networks/en/ 15 Fonseca BdeP, Sampaio RB, Fonseca MVA, Zicker F. Co-authorship network analysis in health research: method and potential use. Health Res Policy Syst 2016;14:80. doi:10.1186/s12961-0160104-5 16 Fonseca BdeP, Zicker F. Dengue research networks: building evidence for policy and planning in Brazil. Health Res Policy Syst 2016;14:34. doi:10.1186/ s12961-016-0104-5

17 de Araújo TVB, Rodrigues LC, de Alencar Ximenes RA, et al, investigators from the Microcephaly Epidemic Research Group Brazilian Ministry of HealthPan American Health OrganizationInstituto de Medicina Integral Professor Fernando Figueira State Health Department of Pernambuco. Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study. Lancet Infect Dis 2016;16:1356-63. doi:10.1016/ S1473-3099(16)30318-8 18 Peters DH, Adam T, Alonge O, Agyepong IA, Tran N. Implementation research: what it is and how to do it. BMJ 2013;347:f6753. doi:10.1136/bmj.f6753. 19 World Health Organization, Special Programme for Research and Training in Tropical Diseases. New online course on implementation research under development. TDR News 2015. http://www.who.int/ tdr/news/2015/new-online-course/en/ 20 United Nations . Sustainable development goals: 17 goals to transform our world. http://www.un.org/ sustainabledevelopment/ 21 Becerra-Posada F, Minayo M, Quental C, de Haan S. National research for health systems in Latin America and the Caribbean: moving towards the right direction? Health Res Policy Syst 2014;12:13. doi:10.1186/1478-4505-12-13 Cite this as: BMJ 2018;362:k2492 http://dx.doi.org/10.1136/bmj.k2492

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non Commercial No Derivs IGO License  (CC BY-NC-ND 3.0 IGO), which permits distribution and reproduction for non-commercial purposes in any medium, provided the original work is properly cited. If you remix, transform, or build upon the material, you may not distribute the modified material. See: https:// creativecommons.org/licenses/by-nc-nd/3.0/igo/ In any reproduction of this article there should not be any suggestion that PAHO or this article endorse any specific organisation or products

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Strengthening Research for Health in the Americas

Advancing health research through research governance Good governance practices are crucial for advancing research for health in LAC countries, argue Luis Alejandro Salicrup and colleagues

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ountries need sustainable national health research systems to maximise the benefits of health research. Importantly, these systems should be guided by national research agendas relevant to a country’s health needs to improve the effectiveness and efficiency of the health system when responding to health priorities.1 National health research systems may be seen as primarily assisting ministries of health, but the insights they generate can inform government sectors beyond health by providing the local insight needed to tackle inequities and social injustice, especially among the most vulnerable communities.1 In Latin America and the Caribbean (LAC), better organised health research systems will enhance the ability of the countries’ health systems to produce evidence informed policy, develop health programmes, and deliver preventive and treatment services. Health research systems consist of the different institutions that support national health systems and tackle public health challenges through planning, coordinating, monitoring, and managing health research resources and activities. An important role

Key messages •   N e a r l y 1 0 y e a r s s i n c e PA H O

implemented its policy on research for health, countries in Latin America and the Caribbean have progressed, but improvements are still needed in health research governance. •   G reater coordination among all government entities overseeing health research quality is needed in countries across the region. •   The lack of adequate funding aligned with national research priorities remains a limiting factor for many national health research systems. •   Substantial gaps in research skills and capacity remain across the region. •   International organisations and other partners could have an important role in strengthening national health research governance. However, it remains crucial for LAC countries to retain their autonomy in terms of the decision making process, including financing mechanisms.

for health research systems is integrating national context with research knowledge, the local determinants of health, as well as the authorities and stakeholders that deliver healthcare and public health. The network of institutions that make up a national health research system improve public health by translating research knowledge into better policy, processes, and administrative structures. In 2009, all member states of the Pan American Health Organization/World Health Organization (PAHO/WHO) approved its policy on research for health.2 An important aim of the policy is to ensure that national health research systems have appropriate governance structures in place to enable them to function effectively. The structures that the policy aims to strengthen are those that administer and supervise how research is managed and financed, how research participants are protected, and how accountability is ensured.2 Governance related to research for health must also guarantee that national health research systems strengthen economic and social indicators 1 3 and support countries in fulfilling their commitments to regional and global policies and mandates.1 2 Health research governance is a crucial component of any national health research system, guiding the roles and actions of the different individuals, organisations, and sectors involved in health research by allocating responsibilities and resources, including funding. In settings with established research governance initiatives, health systems and services have benefited from enhanced efficiency and effectiveness, including increased competitiveness. 3 For example, health research governance practices implemented in the United States, the United Kingdom, and some European Union countries have prompted the development of innovative medicines and health technologies, as well as the ability to respond systematically to the different health challenges affecting those countries.3 4

Health research governance in LAC countries A decade ago, only a handful of LAC countries had a policy or programme on research governance for health in place.5 Now, however, a substantial number across the region have established or have started to advance research policy

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initiatives and build the necessary workforce. These include Antigua and Barbuda, Argentina, Bahamas, Bermuda, Brazil,  Cayman Islands, Chile, Colombia, Costa Rica, Dominican Republic, El Salvador, Guyana, Honduras, Mexico, Panama,  Paraguay, Peru, St Kitts, Surinam, Uruguay, and various English speaking Caribbean countries.6 As countries have developed policies and progressed at different rates, the importance of alignment and standardisation of key components of their research policies has become pressing. Key elements include the need to use research evidence to deal with the challenges presented by chronic diseases, as well as the ongoing challenges posed by infectious diseases. From our perspective, three persistent major gaps limit the role of research governance in LAC countries: the lack of effective coordination among government departments overseeing research quality; the lack of adequate funding aligned with national research priorities; and gaps in research capacity.6 Nearly 10 years after adopting the policy for research on health, LAC countries still need to improve health research governance to tackle their public health needs. However, successful initiatives and programmes in LAC countries provide learning opportunities.

Current gaps in funding and coordination of health research Although LAC countries have a common historical and cultural past, they are highly diverse in many aspects—for example, language, resources, gross domestic product, and research infrastructure. On average, LAC countries invest 0.6% of their gross domestic product in research and development, far less than the 2-3% invested by the wealthiest nations, such as the US, Germany, and Japan. Brazil spends 1.15%, Chile 0.34%, Argentina 0.6%, and Mexico 0.56%.7 Mexico’s Sectoral Fund for Health and Social Security (FOSISS) is an example of a sustainable research funding model in a LAC country (box 1). Chile and Uruguay have implemented similar approaches to distributing sector funds, convening an annual call for research proposals; however, funding for health research remains limited. Argentina has increased funding for biomedical research since it established its federal Ministry of Science 1


Strengthening Research for Health in the Americas

Box 1: FOSISS: example of a successful sustainable research funding system

In Mexico, the National Council of Science and Technology (Consejo Nacional de Ciencia y Tecnología ( CONACYT)) is the leading government agency charged with formulating policies, programmes, and practices to promote and strengthen scientific research and innovation. In 2002, CONACYT established the sector funds (fondos sectoriales) as a way to integrate research into all government sectors. The Sectoral Fund for Health and Social Security (Fondo Sectorial de Investigación en Salud y Seguridad Social (FOSISS)) specifically supports research in those two sectors.8 All sector funds operate with federal secretariats/ministries and other agencies to allocate their federal research money, which CONACYT then matches and manages through a special trust for each fund. Thus, allocating funds from various sectors, CONACYT provides finance for projects that tackle the country’s needs. FOSISS is an example of a system that funds health research in a sustainable way. It provides financial support to projects responding to critical demands and priorities of the national health system, as set out in the country’s Health Sector Programme (Programa Sectorial de Salud).8 Its mission is to direct the country’s health research policy and priorities, with guidance from the national health authorities (Secretariat of Health (Secretaría de Salud)) and input from the other two Mexican health agencies involved in healthcare, the Mexican Social Security Institute (Instituto Mexicano del Seguro Social) and the Institute for Social Security and Services for State Workers (Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado). FOSISS is an effective tool to tackle major obstacles generally associated with health research governance. It has improved understanding of the benefits of research, brought adequate funding, dealt with capacity gaps, and improved integration between research for health and pressing social issues, thus tackling major public health needs.9 Moreover, the Mexican experience with handling the sector fund and its alignment with research for health priorities has improved both transparency and accountability. The policy approach used with FOSISS could easily be replicated or adapted in other LAC countries and beyond. and Technology in 2007. Under guidance from the federal Ministry of Health, the 23 provincial ministries of health and that of the Autonomous City of Buenos Aires recently held a meeting aimed at improving coordination and sharing the benefits of research agendas and specific research funding. As a result, the national authorities hope to enhance coordination of health research priorities and funding.10

Coordinating research governance in LAC countries All countries need sustainable research systems to improve the health and welfare of their populations, reduce inequalities and social injustices, and promote economic and social prosperity. In LAC countries, the governance of health research remains uneven. The lack of coordination among

relevant stakeholders, such as the ministries responsible for health, science and technology, education, and the economy, is a limiting factor hindering efforts to strengthen governance in several countries. For public health, this lack of coordination among stakeholders could affect the adequate distribution of available funding to support priority needs and challenges. Paraguay is an example of where there is a lack of adequate coordination among stakeholders regarding research policies and funding programmes. Paraguay developed its national health research agenda with stakeholders, but CONACYT, the country’s National Council of Science and Technology, is the main funding agency and operates independently. CONACYT continues to fund research, but not necessarily in line with the priorities identified in the national health

research agenda, which defeats the purpose of having one.11 More positively, the global Council on Health Research Development has spearheaded valuable efforts in conjunction with PAHO and national authorities to enhance both dialogue and coordination among the different agencies involved in health research governance in LAC countries (box 2).

Building research capacity Throughout the 1990s, LAC countries implemented a series of health sector reforms in which the goal was to increase equity, effectiveness, quality, efficiency, sustainability, and social participation. Although these reforms have had some positive outcomes in reducing inequities in access to health services and improving resource allocation,

Box 2: Role of international organisations convening cross-sector dialogues among key stakeholders in health research in LAC countries

The Council on Health Research Development, the Ministry of Health (Ministério da Saúde) of Brazil, and PAHO together hosted a discussion between the health and research sectors at a 2006 meeting in Guatemala.12 They aimed to tackle issues related to research governance, with the goal of increasing the impact of research on health and equity in Latin America. This was followed by the first Latin American Conference on Research and Innovation for Health, held in 2008 in Rio de Janeiro, Brazil, and organised by the Ministry of Health of Brazil, the Council on Health Research Development, the Global Forum for Health Research, and PAHO. Among other objectives, the conference focused on improving regional cooperation aimed at tackling and solving common problems. Discussions centred on the need to develop and strengthen national health research systems in Latin America, enhance the coordination among relevant stakeholders (eg ministries of health and ministries or councils of science and technology) and analyse different ways of financing biomedical and health research as well as the workforce required.12 Two other regional meetings were held in Cuba in 2009 and Panama in 2011.12 They provided a venue for learning about the characteristics of differing national health research systems in LAC countries, with input from delegates who completed a standardised form describing their respective system in the 23 countries they represented. All three meetings12 provided a space to build trust and professional relationships among delegates from the two main national stakeholders, the ministries of health and of science and technology (or its equivalent). A key lesson learnt was that these conferences strengthened cross-sector collaboration in research governance and national health research systems in several LAC countries. For example, Mexico’s Secretariat of Health hosted Paraguayan and Costa Rican delegations for document sharing and visiting institutions, so they could understand how the sector fund and its governance worked.12 However, a lack of sustained funding has meant that these conferences have not been held regularly, and therefore a lack of sustained coordination among stakeholders remains a limiting factor hindering research governance in LAC countries. 2

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Strengthening Research for Health in the Americas

Box 3: PAHO-OAS scholarships: for strengthening workforce capacity in research for health in LAC countries

One mechanism to tackle the staffing gap in LAC countries is the scholarship programme on research for health coordinated by PAHO and the Organization of American States (OAS). In 2014, OAS and PAHO signed and implemented a joint agreement expanding the OAS scholarship programme to cover health related graduate studies. For 60 years, this programme has been providing scholarships to students from member states to complete masters and doctorates in diverse fields, ranging from engineering to agronomy to science and technology. The aim of the PAHO-OAS programme is to train a professional workforce from different fields in methodologies on research for health to enhance national health systems in the Americas, thus fostering the connection between research and public health. The two other main partners in the programme are organisations from Brazil and Mexico, through Brazil’s Coimbra Group of Brazilian Universities (Grupo Coimbra de Universidades Brasileiras) and Mexico’s National Council of Science and Technology and the Mexican Agency of International Cooperation for Development (Agencia Mexicana de Cooperación Internacional para el Desarrollo). The agreement emphasises development of skills and competencies to promote the production and use of research for health as a tool for informing healthcare policies and prevention, increasing universal healthcare and services, and strengthening national health systems.15 Between 2014 and 2017, 683 PAHO-OAS scholarships were awarded to professionals from 27 PAHO member states. Women constituted 63% of the beneficiaries of these scholarships.16 Despite the large number of scholarships awarded, inequity remains in terms of the beneficiaries. In particular, fewer applicants are from countries in Central America and the Caribbean, where the need to strengthen health systems through research is important. Between 2014 and 2017, less than 2% of applicants came from the most vulnerable ethnicities in LAC countries—for example, indigenous peoples and Afro descendants. This gap is important because these groups are particularly affected by the disparities and inequities affecting some national health systems. Opening opportunities for higher education and participation in research for health could help tackle some of the inequities affecting them. Another challenge is the missing pathways to reintegrate trainees into the health research workforce on their return to their homeland. Argentina, Brazil, Chile, and Mexico are developing ways to reintegrate recent graduates who have received scholarships, but most LAC countries do not have a clear and efficient reintegration pathway. A solution yet to be tested could be the introduction of re-entry grants for returning graduates and researchers and the signing of fair paid licences with service contracts on return that guarantee reintegration with a job and pay scale commensurate with the new skills. This effort will require commitment from and implementation by national research funding agencies, with some support from national and/or international organisations, major donor and/or funding agencies, or private foundations. overall the reforms have not been successful in achieving the proposed goals. Reasons for this may be that research linked to public health needs and challenges was generally ignored and there is a persistent gap in skills and capacity in the research workforce of many LAC countries.13 Some LAC countries, particularly those in Central America and the Caribbean, have both an inadequate distribution and a shortage of healthcare providers. These problems are exacerbated by deficits in the skills required to advance and sustain research. Moreover, the lack of success in implementing some health system reforms has been linked to the failure to strengthen policy, planning, and management of the health workforce.14 Training scholarships are an important means of increasing research capacity in the region (box 3).

Bridging gaps in governing health research The challenges to health research governance faced by LAC countries are not unique and are shared by other regions such as South Asia and Sub-Saharan Africa.14 16 These include insufficient funding, misalignment of funding with national research priorities, lack of optimal coordination among stakeholders, and limited public health research capacity.15 Other major challenges and barriers that persistently affect health research governance in LAC countries include difficulties maintaining up -to - date information on their national health

research systems and developments. Several key issues to tackle include the need for continuity, given staff rotation; providing dedicated resources and structured processes; regular monitoring and evaluation of progress made; and incorporating new information and communication technologies to capture information systematically and in real time. Adopting a “research for health” framework, as PAHO’s policy on research for health does, means dealing with social determinants, transitioning towards a model where different sectors and fields of knowledge, including the health sector, contribute to solutions and provide expertise for meeting health needs and challenges. In LAC countries, this will mean adopting new approaches, going beyond traditional work with peers, and engaging with other sectors to strengthen health research in a sustainable way.2 The United Nations, Agenda 2030, sustainable development goals that all 193 member states signed in 2015 further underscore the need for cross-sector collaboration to improve health. The sustainable development goals are strongly aligned with PAHO’s policy on research for health and provide further impetus for international collaboration and support by encouraging reporting on important indicators. In line with sustainable development goals 3 and 17, a new proposal by the Council on Health Research Development,

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the research fairness initiative, aims to create a reporting system that encourages governments and other stakeholders to provide data on partnerships in research and innovation. 17 This could create opportunities for gathering better quality information and relevant data aimed at enhancing research for health governance worldwide. In January 2017, WHO launched its global observatory on health research and development. For its evaluation framework, the observatory follows the mandate offered in WHO’s strategy on research for health, thereby providing a centralised and comprehensive source of information and analyses on global health research and development. 18 It shows potential for guiding member states’ efforts to strengthen health research governance. The observatory seeks to collect valuable, up-to-date data from all WHO member states, including LAC countries, on national funding earmarked for health research; bridge persistent gaps in workforce development; and consolidate, monitor, and analyse relevant information on health research and development needs in developing countries, thereby guiding coordinated action. The observatory could serve as a key instrument for policy makers, research sponsors, and others to identify health research and development priorities based on public health needs and then link their indicators to the sustainable development goals. 3


Strengthening Research for Health in the Americas

Conclusions Many LAC countries have made substantial efforts to prioritise research for health and enhance research governance, establishing clear policies and programmes. However, LAC countries continue to face challenges and considerable inequities in their capacity to use and produce essential research for health; a number of countries are still searching for specific ways to develop and implement their policies. LAC countries need to harmonise their country level research governance. Pressing demands include building more human capital and adequate research infrastructure to tackle priority public health needs and developing better coordination among all relevant stakeholders—government ministries, national councils of science and technology and innovation, and major universities and research centres. Meeting these demands requires financial support to achieve the objectives set down in national strategies and agendas for health research. International agencies and other partners could assist by providing financial and technical resources. However, it is essential that LAC countries retain their autonomy in terms of the decision making process. This includes having a say in establishing priorities and financing mechanisms, as well as the means to advance research capacities and outcomes in their countries. We thank Samantha Brew, PAHO/WHO/KBR, and Suzanna Stephens for their editorial support. Contributors and sources: LAS conceived the idea and structure of this paper and wrote the first draft with assistance from the other authors; LAS developed the first literature review; and all authors contributed to writing the manuscript, commented on all drafts and revisions of the paper, and provided references. The opinions expressed in this paper are those of the authors and do not necessarily represent those of PAHO/WHO. Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; externally peer reviewed. This article is part of a series proposed by PAHO and commissioned by The BMJ, which peer reviewed,

edited, and made the decision to publish the article with no involvement from PAHO. Open access fees for the series are funded by PAHO. Luis Alejandro Salicrup, senior adviser for global health research1,2 Luis Gabriel Cuervo, senior adviser for health systems research3 Rodolfo Cano Jiménez, director of health research4 Nelly Salgado de Snyder, medical science researcher5

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Francisco Becerra-Posada, assistant director1 1

Pan American Health Organization/World Health Organization, Washington, DC, USA 2 Center for Global Health, National Cancer Institute, National Institutes of Health, Rockville, MD, USA 3 Department of Health Systems and Services, Pan American Health Organization/World Health Organization, Washington, DC, USA 4 Comisión Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud, México, Mexico 5 Sistema Nacional de Investigadores Nivel III, Programa de Salud Global/Centro de Investigación en Sistemas de Salud, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico Correspondence to: L A Salicrup salicrul@mail.nih.gov 1

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Hanney S, Kuruvilla S, Soper B, Mays N. Who needs what from a national health research system: lessons from reforms to the English Department of Health’s R&D system. Health Research Policy and Systems, 2010. https:// health-policy-systems.biomedcentral.com/ articles/10.1186/1478-4505-8-11. Pan American Health Organization/World Health Organization. Policy on research for health. Document CD49/10 of the 49th Directing Council, 61st Session of the regional committee of WHO for the Americas. PAHO/WHO, 2009. http:// www.paho.org/hq/dmdocuments/2009/CD4910-e.pdf Varkevisser C, Pathmanathan I, Brownlee A. Designing and conducting health systems research projects—volume I: Proposal development and fieldwork. KIT Publishers, Amsterdam International Development Research Centre in association with WHO Regional Office for Africa, 2003. http:// archives.who.int/prduc2004/Resource_Mats/ Designing_1.pdf Ranson MK, Bennett SC. Priority setting and health policy and systems research. Health Res Policy Syst 2009;7:27. https:// health-policy-systems.biomedcentral. com/articles/10.1186/1478-4505-7-27. doi:10.1186/1478-4505-7-27 Alger J, Becerra-Posada F, Kennedy A, Martinelli E, Cuervo LGGrupo Colaborativo de la Primera Conferencia Latinoamericana de Investigación e Innovación para la Salud. [National health research systems in Latin America: a 14-country review]. Rev Panam Salud Publica 2009;26:447-57.

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Pan American Health Organization/World Health Organization. 46th Advisory Committee on Health Research (ACHR) of the Pan American Health Organization. Washington, DC, 28-30 November 2016. 2017. https://www.paho.org/hq/index. php?option=com_content&view=article&id=13170 &Itemid=1654&lang=es Catanzaro M, Miranda G, Palmer L, Bajak A. South American science: Brazil and other big players lead in South American Science. Nature 2014;510:2046. https://www.scientificamerican.com/article/ brazil-and-other-big-players-lead-in-south-americanscience/. doi:10.1038/510204a Gobierno de México, Consejo Nacional de Ciencia y Tecnología (CONACYT). ¿Qué es el Fondo Sectorial de Investigación y Desarrollo en Salud y Seguridad Social SS/IMSS/ISSSTE-CONACYT? 2016. http:// conacyt.mx/index.php/fondos-sectorialesconstituidos2/item/ssa-imss-issste-conacyt Martínez-Palomo A. La investigación en salud. Gac Med Mex 2012;148:580-5. Gobierno de Argentina. Dirección de Investigación para la Salud. Año: 2017. MSal, 2017. www.msal. gov.ar/dis/2017/ Gobierno Nacional de Paraguay, Consejo Nacional de Ciencia y Tecnología (CONACYT). Resolución No 491/2016. http://www.conacyt.gov.py/sites/default/ files/resolucion_nro_491.pdf Executive Committee. Follow up meeting to the 1st Latin American Conference on research and innovation for health: final report. Havana, Cuba, November 2009. www.paho.org/LACRIH. Pan American Health Organization/World Health Organization. Public health capacity in Latin America and the Caribbean: assessment and strengthening. 2007. http://www.who.int/management/ publichealthcapacity.pdf Ranson MK, Chopra M, Atkins S, Dal Poz MR, Bennett SWorld Health Organization. Priorities for research into human resources for health in low- and middle-income countries. Bull World Health Organ 2010;88:435-43. doi:10.2471/ BLT.09.066290 Pan American Health Organization/World Health Organization. OAS-GCUB-PAHO scholarships to study in Brazil and Mexico. 2018. http://www. paho.org/hq/index.php?option=com_content &view=article&id=9516%3A2014-paho-andoas&catid=1484%3Apartnerships-research&Itemid=40676&lang=en Swaminathan S, Qureshi H, Jahan MU, Baskota DK, De Alwis S, Dandona L. Health research priorities and gaps in South Asia. BMJ 2017;357:j1510. doi:10.1136/bmj.j1510 Council on Health Research for Development. Research Fairness Initiative (RFI)—making research partnerships work for everyone. 2018. http://rfi. cohred.org/ World Health Organization Global observatory on health R&D. 2017. http://who.int/researchobservatory/en/

Cite this as: BMJ 2018;362:k2484 http://dx.doi.org/10.1136/bmj.k2484

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non Commercial No Derivs IGO License (CC BY-NC-ND 3.0 IGO), which permits distribution and reproduction for non-commercial purposes in any medium, provided the original work is properly cited. If you remix, transform, or build upon the material, you may not distribute the modified material. See: https://creativecommons. org/licenses/by-nc-nd/3.0/igo/ In any reproduction of this article there should not be any suggestion that PAHO or this article endorse any specific organisation or products

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Strengthening Research for Health in the Americas

Strengthening institutional capacity for equitable health research: lessons from Latin America and the Caribbean Marshall Tulloch-Reid and colleagues argue that development of research capacity in Latin America and the Caribbean requires investment in both individuals and regional institutions

T

he political, economic, environmental, and social determinants of health now receive greater recognition. This had led to an increased demand for global health research involving low and middle income countries, to meet the United Nations sustainable development goals.1 In addition to funding, sufficient human resources and infrastructure are needed so that these countries become equal partners with internationally recognised research institutions in high income countries that set research agendas and ensure that the global health research programme reflects their needs. Constrained research capacity and large disparities between high income countries and low and middle income coun-

Key messages •   Sustainable development of human

resources requires institutional strengthening and development of interdisciplinary research teams, not just training of individual scientists •   E mploying and empowering local institutions that can adapt training to meet local and international needs is a critical factor in improving research in low and middle income countries worldwide •   F a i r, re s p e c t f u l , a n d s t r a te g i c partnerships, together with financial investments in infrastructure, are necessary for implementing and maintaining sustainable training programmes in low and middle income countries •   I nv e s t m e n t s b y n a t i o n a l a n d international funding agencies in human resources and research career opportunities and physical infrastructure for health research are needed •   Formal evaluation of the success of training in low and middle income countries in Latin America and the Caribbean is necessary to better demonstrate its effect on health and research equity and encourage additional support for these efforts

tries in their capacity to produce and use research for health have contributed to a lack of evidence to inform practice and guide regional and global health policy. This has perpetuated health inequalities.2 In some Latin American countries research has increased, but several Caribbean territories are among those with the lowest level of medical research outputs.3 Through their Policy on Research for Health, the Pan-American Health Organization (PAHO), regional office of the World Health Organization (WHO), advocates strengthening in-country research in all member states to promote equity in health and socioeconomic development.2 We describe outcomes and lessons learnt from three case studies, identified by PAHO. These describe the approaches taken to develop research capacity in Latin America and the Caribbean. The first study describes building research capacity by North-South collaboration and is an example of Latin American networking. The second study was initially developed through bilateral cooperation followed by national and international networking. It has become a model for South-South collaboration. The third case study uses multiple approaches to build on existing infrastructure. It is an example of technical cooperation between PAHO and the English-speaking Caribbean.

North-South collaboration: the International Clinical Epidemiology Network (INCLEN) In the 1980s, the Rockefeller Foundation sponsored the creation of INCLEN to bridge the divide between public health and clinical medicine, to improve health in developing countries.4 INCLEN provided young clinical faculty members from medical schools in South East Asia, China, India, Africa, and Latin America with scholarships in North America and Australia to receive masters level clinical epidemiology training.4 The Rockefeller Foundation soon realised that supportive academic centres in countries other than North America and Australia were needed to sustain this INCLEN initiative. It formed partnerships with local medical and public health schools and provided financial support to establish clinical epidemiology units, encouraging the

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development of expertise in biostatistics, health economics, and social sciences.4 5 The foundation also provided leadership and management training.4 Several clinical epidemiology units were established over a period of 10 years. These became regional centres of excellence for training and research, with teams able to respond to regional research needs. To enhance regional collaboration initiatives, the Latin American Clinical Epidemiology Network (LatinCLEN) was created in 1991. LatinCLEN was not successful everywhere, but is now present in seven countries. Its member institutions provide training in clinical epidemiology, biostatistics and health economics, including one doctoral and nine masters programmes. LatinCLEN has dealt with regional needs and carried out high impact research in mental health, maternal and child health, health economic evaluation, systematic reviews, programme evaluation and clinical practice guidelines (box 1). Over the past 20 years it has successfully influenced and led cooperation with the Cochrane and Campbell collaborations.6

South-South collaboration: CIDEIM—regional training centre in the Americas The Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) in Colombia is a good example of a NorthSouth bilateral partnership evolving into a model for South-South collaboration. The centre originated as a bilateral technical assistance mission in 1961 supported by a grant to Tulane University from the US National Institutes of Health.7 The centre was broadly dedicated to health research. It formed a partnership with the Universidad del Valle Faculty of Medicine and was located within its campus until 1974. At this time COLCIENCIAS, the Colombian national agency for promotion and financing of science and technology, assumed the co-direction with Tulane University. Multilateral funding of research and institutional grants awarded during the 1980s by COLCIENCIAS and international agencies laid the foundation for transition of CIDEIM to a non-profit Colombian biomedical research institution in 1990 through a public-private 1


Strengthening Research for Health in the Americas

Box 1: The Latin American Clinical Epidemiology Network (LatinCLEN)

LatinCLEN aims at strengthening national and regional health systems through research into the effectiveness and efficiency of health interventions and the determinants of health and disease. Since its inception, LatinCLEN centres have trained over 400 clinical epidemiologists and produced over 1200 scholarly outputs.6 LatinCLEN centres and their members have provided leadership in making economic assessments of health interventions. They have refined methods for linking clinical practice guidelines with health economic evaluation, and set standards for evaluating economic evidence from different sources. The network has influenced health and research policies and the work of development agencies and intergovernmental organisations in the region. LatinCLEN’s research includes: • Development and validation of economic models to evaluate the disease burden of smoking, and the cost effectiveness of tobacco control interventions in Argentina and in six other countries in 2011 (LatinCLEN Tobacco Research Group) • Economic evaluation of exercise based cardiac rehabilitation programmes for patients with chronic heart failure in Colombia in 2016 • Determination of the impact of the Kangaroo Mother Care Program in Colombia • Evaluation of the cost effectiveness of new drugs for patients with atrial fibrillation and acute coronary syndrome in Chile6 initiative. National commitment was crucial for each stage of CIDIEM’s evolution. In 2009 CIDEIM was selected to be the regional training centre in the Americas by the Special Programme for Research and Training in Tropical Diseases (TDR). The regional training centres collaborate in improving the scientific quality and competitiveness of health research in low and middle income countries.8 9 In CIDEIM, interdisciplinary teams design and conduct basic, translational, applied and implementation research in partnership with public health authorities, universities and communities. Ongoing projects allow tr ainees to conduct supervised research alongside national and international investigator teams. Hands on research is complemented by skill building courses, which may be face to face, in a virtual format, or a combination of the two. The courses include data management , project planning, good clinical practice, data analysis planning, information and communication technology in health research, research ethics, and scientific integrity. This approach promotes compliance of research with international standards and participation in national and international research agendas. An important aspect of the courses is their design for replication through training of trainers and collaboration with regional

network institutions to develop and adapt training modules. As a regional training centre, CIDEIM’s strategy for building capacity is aimed at institutions (box 2). PAHO assists in identifying institutional participants and contributes logistical support for regional dissemination. Since 2009, CIDEIM has trained more than 2000 investigators, transferred training capacity to network institutions in Central and South America and the Caribbean and conducted interregional training in collaboration with regional training centres in Indonesia, Kazakhstan, and Ghana.10

Institutional strengthening through NorthSouth and South-South collaboration: University of the West Indies clinical epidemiology unit The University of the West Indies (UWI) epidemiology research unit was established in 1999 as part of the Tropical Medicine Research Institute, now the Caribbean Institute for Health Research (CAIHR). The need for regional training in epidemiology was recognised by the unit, which launched an MSc programme in 2005, followed by a PhD programme. In May 2007, participants at PAHO’s 40th Meeting of the Advisory Committee on Health Research proposed developing a team of epidemiologists to increase the production and use of evidence to inform

public health policy in the Caribbean.11 PAHO’s delegates committed to supporting links between INCLEN and the University of the West Indies. The meeting became the catalyst for a series of developments, with the epidemiology research unit as its focal point. The UWI clinical epidemiology unit (UWI/CEU), established in February 2009, comprised faculty members from the epidemiology unit and other university departments. 12 Members completed a training course, entitled “Effective project planning and evaluation in biomedical research,” run by CIDEIM across Latin America and the Caribbean.9 An important capacity building feature of the course is the training of local participants to deliver the course, allowing UWI to replicate the training in Jamaica and other settings. The unit has subsequently provided training in project planning and evaluation in biomedical research for over 200 Caribbean professionals. The methodology has been incorporated into graduate degree courses at UWI and St George’s University, Grenada.13 UWI staff have also received training in knowledge synthesis and translation of research into practice. This facilitated the launch of Cochrane Caribbean in June 201314 (box 3). These skills and experiences have helped strengthen UWI’s epidemiology programme. It has produced 19 epidemiologists able

Box 2: Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM)

Training is essential to the mission and research programme of CIDEIM. Research capacity is developed through a range of training approaches. These build upon and complement postgraduate programmes at national universities. Ongoing research provides a platform for mentored clinical, laboratory, and field research from the predoctoral to postdoctoral stages. Importantly, faculty members and students participate in research skill building courses and web based elective postgraduate courses. Since 2007, support has been received from the Global Infectious Disease Research Training Programme of the US National Institutes of Health Fogarty International Center for semester long, web based, postgraduate courses. These have covered advanced topics relevant to biomedicine and health science and have been organised and hosted by CIDEIM in collaboration with the Yale University School of Public Health. Live lectures and discussions are conducted virtually by national and international experts, and courses are registered for credit as electives within postgraduate programmes at participating universities. Course materials, including recorded lectures and evaluations, are accessed and managed using the open source learning Moodle platform. Over 1000 investigators and trainees from 30 Colombian universities, 12 institutes, health sector institutions, industry, and 17 Latin American and Caribbean regional universities/institutes have participated in these elective courses. 2

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Strengthening Research for Health in the Americas

Box 3: University of the West Indies clinical epidemiology unit (UWI/CEU)

Through training placements for UWI/CEU PhD candidates at the University of Ottawa and Johns Hopkins University, a special interest in systematic reviews and evidence based healthcare was developed. This led to the first training workshop in systematic review methodology in Jamaica in March 2012 (supported by faculty from the UWI/CEU, the University of Ottawa Centre for Global Health and PAHO) and the subsequent launch of Cochrane Caribbean in June 2013. Cochrane Caribbean, together with members of the UWI/CEU, have hosted annual Cochrane training workshops within the Caribbean Institute for Health Research and provided technical support for English speaking Caribbean territories. The centre also facilitates links between local and international researchers and provides training on systematic reviews and evidence-based healthcare for undergraduate and graduate students. Cochrane Caribbean has supported the development and completion of four systematic reviews initiated by local investigators, collaborated on over 20 systematic reviews, and provided evidence for the development of regional and national policy—most recently, in food industry policy and medication formularies. to deal with regional research needs in academia, health administration and delivery, and policy making. 15 Initially, many candidates pursued training to enhance performance in existing posts or fill vacant positions. Now, greater emphasis is placed on providing research development opportunities and career paths to encourage graduates to remain in the Caribbean.

Challenges to sustaining capacity building Financial support to maintain many of these initiatives is insufficient. Loss of support from the Rockefeller Foundation has significantly restricted the activities of INCLEN and LatinCLEN. PAHO contributes to the regional training initiatives of CIDEIM and UWI/CEU, through support of workshops and investigator exchanges. However, training and capacity building depend on stable institutional funding and career opportunities that will attract new generations of health researchers. Key personnel at UWI/ CEU and virtually all personnel in CIDEIM are dependent on funding for projects. This means that delivery of project results must be balanced with capacity building activities, which is a challenge to sustainability. Additionally, critical shortages of skilled personnel remain in some fields, including biostatistics, implementation science, research management, and health economics. Capacity building currently focuses on human resources, but there is also a critical need for investment in, and renewal of, institutional infrastructure. Discussion The case studies presented here illustrate distinct approaches to developing research capacity in low and middle income countries. 16 These include vertical research projects where investigators from high income countries lead and conduct targeted research in low and middle income countries; centres of excellence concentrating investment in a few institutions; NorthSouth partnerships focusing on a specific research question and networks and consortiums linking multiple research institutions with complementary skills to deal with research challenges.16 Each case study used

combinations of all approaches over time to build individual and institutional capacities. Although vertical projects can meet project objectives, they do not usually produce sustainable capacity in low and middle income countries once completed. INCLEN initially focused on building capacity through individual scholarships. However, it found that strengthening institutions by creating clinical epidemiology units with multidisciplinary teams was critical for sustaining gains in capacity development and retaining talent.4 CIDEIM’s experience illustrates how North-South collaborations can lead to enduring centres of excellence. CIDEIM has evolved over 57 years to become a centre of innovative research capacity building with regional and global influence. Through partnership with PAHO and Latin American and Carribean regional institutions, CIDEIM provides a cost sharing model for research training. Incorporation of the content of short courses on good research practices into the curriculums of postgraduate programmes in the region further extends and sustains research capacity building. UWI/CEU illustrates use of a combination of capacity building measures to build regional institutional capacity. Locating the UWI/ CEU at CAIHR, an institution whose primary role is producing research, has been critical in allowing practitioners protected time for research. PAHO, together with regional and international partners, by supporting UWI/CEU in building a team of regional epidemiologists in the Caribbean, has enabled a larger and more sustainable impact.13 The current constraints on national and international funding for research do not encourage investment in building local in-country capacity, which requires many years of sustained support. Latin American and Caribbean research networks continue to look to North-South collaborations for funding. A recent systematic review that examined research capacity development found that most research on North-South collaborations focused on problems with these relationships. Many publications argued that too few benefits accrue to the southern partner.16

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Sever al organisations worldwide call for capacity building to be a key component of global research funding to reduce “brain drain” from low and middle income countries.17 Stable research career opportunities are a major determinant of sustainable research and research training capacity. Funding schemes for capacity building could strategically leverage existing strengths in Latin American and Caribbean institutions. A postdoctoral funding scheme for low and middle income countries could begin to deal with this critical transition stage in career development, particularly in this region where most countries have postgraduate training programmes. Some international agencies have instituted funding schemes that target research teams in low and middle income countries. These include the International Research in Infectious Diseases and Tropical Medicine Research Centres grant schemes of the US National Institutes of Health, and Fogarty training programmes. The Wellcome Trust offers a range of international fellowship programmes, collaborative projects and even multi-user equipment grants.18 Institutions in low and middle income countries, particularly those in Latin America and the Caribbean, need to improve their ability to provide consistent accurate forecasts of total research costs to funding agencies and to obtain adequate reimbursement of indirect costs.20 21 Some funding agencies recognise the constraints imposed by limited support for operational costs and are willing to negotiate higher indirect costs for such institutions; others, however, cap these resources at a lower rate than for high income countries. 19 Severely restricting indirect costs has a negative impact on administrative support and capital expenditure on infrastructure and equipment. It is a disincentive for investigators and faculty to participate in non-profit training activities. Institutions in low and middle income countries need this support to achieve recognition as credible focal points for creating and sustaining change.20 National and regional solutions to financing institutions in Latin America and 3


Strengthening Research for Health in the Americas

the Caribbean include investment in their own capacity development by dedicating a proportion of national budgets or special taxation to finance research and research infrastructure. There is also an opportunity for collaboration with scientists of the national research diaspora.17 In addition to dealing with urgent health problems, improving the assessment of the pivotal role that research institutions play in national development may encourage policy makers to recognise research for health as an investment rather than an expense.2

Conclusions Despite the diverse challenges of building research capacity in low and middle income countries, the three case studies presented here show that positive outcomes through coordinated use of existing networks and limited funds are possible. They also highlight the importance of North-South and South-South collaboration in increasing research capacity to improve health throughout the Americas. Key components of their success include supporting committed leaders, providing training by building upon existing regional training initiatives and creating good regional and international partnerships. The presence of capable research institutions in Latin America and the Caribbean will be crucial for sustainable and equitable research for health in the future. Contributors and sources: All authors have led or facilitated many of the initiatives described in this paper and participated in conceptualising, drafting and revising the text, approving the final version of the article submitted for publication, and are accountable for all parts of the work they have contributed. MKT-R is the guarantor of the article. Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; externally peer reviewed. This article is part of a series proposed by PAHO and commissioned by The BMJ, which peer reviewed, edited, and made the decision to publish the article with no involvement from PAHO. Open access fees for the series are funded by PAHO. Marshall K Tulloch-Reid, professor1 Nancy Gore Saravia, director 2,3 Rodolfo J Dennis, professor4

Andres Jaramillo, coordinator research and training portfolio2,3 Luis Gabriel Cuervo, senior adviser, health systems research5

8

Susan P Walker, professor Luis Alejandro Salicrup, senior adviser for global health research5,6

9

1

1 Caribbean Institute for Health Research, University of the West Indies, Kingston, Jamaica 2

Centro Internacional de Entrenamiento e Investigaciones Médicas, Cali, Colombia 3

Universidad Icesi, Cali, Colombia Departamento de Epidemiología Clínica y Bioestadística, Pontificia Universidad Javeriana, Bogotá, Colombia

10

4

5

Health Services and Access Unit, Department of Health Systems and Services of the Pan American Health Organization/World Health Organization, Washington DC, USA

11

6

Center for Global Health, National Cancer Institute, United States National Institutes of Health, USA Correspondence to: M K Tulloch-Reid marshall.tullochreid@uwimona.edu.jm 1

2

3

4

5

6

7

World Health Organization. Closing the gap in a generation: health equity through action on the social determinants of health. Final Report of the Commission on Social Determinants of Health. 2008. http://www.who.int/social_determinants/ thecommission/finalreport/en/ Pan American Health Organization/World Health Organization. PAHO Policy on Research for Health. Document CD49/10 of the 49th session of PAHO’s Directing Council. 2009. https://www.paho.org/hq/ index.php?option=com_content&view=article&id=1 414%3A2009-policy-on-research-health&catid=25 02%3Apublications&lang=en McKee M, Stuckler D, Basu S. Where there is no health research: what can be done to fill the global gaps in health research? PLoS Med 2012;9:e1001209. http://journals. plos.org/plosmedicine/article?id=10.1371/ journal.pmed.1001209. doi:10.1371/journal. pmed.1001209 Halstead SB, Tugwell P, Bennett K. The International Clinical Epidemiology Network (INCLEN): a progress report. J Clin Epidemiol 1991;44:579-89. doi:10.1016/0895-4356(91)90222-U Morrow RHJr, Lansang MA. The role of clinical epidemiology in establishing essential national health research capabilities in developing countries. Infect Dis Clin North Am 1991;5:235-46. Gómez Restrepo C, Muñoz N S, Ruiz AJ, Lanas F. Latin American Clinical Epidemiology Network Series Paper 1: The Latin American Clinical Epidemiology Network “LatinCLEN”. J Clin Epidemiol 2017;86:71-4. doi:10.1016/j.jclinepi.2016.10.002 Board on Science and Technology for International Development, Institute of Medicine National Academy of Sciences. The US capacity to address tropical infectious disease problems. National Academy Press, 1987. https://books.google.co.uk/ books?id=CpYrAAAAYAAJ&pg=PR2&lpg=PR2&d q=The+US+Capacity+to+Address+Tropical+Infe ctious+Disease+Problems.+National+Academy+

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of+Science+1987.+Report+No.&source=bl&ots =HsxQz52EoX&sig=Cb5u1-65MEE4PTSqcpTo_ d4Y0MY&hl=en&sa=X&redir_esc=y World Health Organization. Regional training centers. An introduction to the TDR network. 2015. www.who. int/entity/tdr/news/2015/en/ Ogundahunsi OA, Vahedi M, Kamau EM, et al. Strengthening research capacity—TDR’s evolving experience in low- and middle-income countries. PLoS Negl Trop Dis 2015;9:e3380. doi:10.1371/ journal.pntd.0003380http://journals.plos. org/plosntds/article?id=10.1371/journal. pntd.0003380. Alger J, Gómez L, Jaramillo A, Saravia NG, Cuervo LG. Reunión de la Red Inter-Regional de Planeación y Evaluación Efectivas de Proyectos de Investigación para la Salud, Cali, Colombia, Abril 2010. Rev Med Hondur 2010;78:97-100. http://www.paho.org/hq/ index.php?option=com_docman&task=doc_view&gi d=17086&Itemid=270&lang=en Advisory Committee on Health Research (ACHR). Pan American Health Organization/World Health Organization (PAHO/WHO). 40th ACHR: An overview of health research policy in the Americas and a proposal for PAHO/WHO’s research policy. 2007. http://www1.paho.org/english/DD/IKM/RC/ACHR2007-40-05-Policy.pdf?ua=1 University of the West Indies. UWI admitted to International Epidemiology Network. Press release. https://www.mona.uwi.edu/marcom/uwinotebook/ entry/3492 Pan American Health Organization/World Health Organization. Report on strengthening research capacities for health in the Caribbean, 2007-2017. Washington, DC: PAHO/WHO, 2017. http://iris.paho. org/xmlui/handle/123456789/34342 Cochrane Caribbean. Cochrane Caribbean launch. Press release, 2013. http://caribbean.cochrane.org/ cochrane-caribbean-launch Tulloch-Reid MK. The University of the West Indies Clinical Epidemiology Unit: collaborating to improve health. J Clin Epidemiol 2015;68:1099-100. doi:10.1016/j.jclinepi.2015.04.012 Franzen SR, Chandler C, Lang T. Health research capacity development in low- and middle-income countries: reality or rhetoric? A systematic metanarrative review of the qualitative literature. BMJ Open 2017;7:e012332. doi:10.1136/ bmjopen-2016-012332. Saravia NG, Miranda JF. Plumbing the brain drain. Bull World Health Organ 2004;82:608-15. Wellcome Trust. Scheme finder. United Kingdom: Research Council UK, 2018. https://wellcome.ac.uk/ funding/scheme-finder United States National Institutes of Health. NIH grants policy statement. 2017. https://grants.nih.gov/grants/ policy/nihgps/html5/section_7/7.4_reimbursement_ of_facilities_and_administrative_costs.htm Lucas S. How to fund think tanks effectively even when you can’t. William and Flora Hewlett Foundation, 2017. https://www.hewlett.org/fundthink-tanks-flexibly-even-cant/ Council on Health Research and Development. Fair research contracting. Geneva, Switzerland, 2018. http://www.cohred.org/frc/

Cite this as: BMJ 2018;362:k2456 http://dx.doi.org/10.1136/bmj.k2456

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non Commercial No Derivs IGO License (CC BY-NC-ND 3.0 IGO), which permits distribution and reproduction for non-commercial purposes in any medium, provided the original work is properly cited. If you remix, transform, or build upon the material, you may not distribute the modified material. See: https://creativecommons. org/licenses/by-nc-nd/3.0/igo/ In any reproduction of this article there should not be any suggestion that PAHO or this article endorse any specific organisation or products 4

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Strengthening Research for Health in the Americas

academic research evaluations of different public health programmes, leading to federal and national scale-up in Brazil of programmes offering physical activity classes in the community (Academia da Cidade) and programmes encouraging physical activity through provision of public spaces and resources (Academia da Saúde). Similar programmes in other countries, such as Colombia and Chile, are also being evaluated and scaled up.6 Project GUIA was funded and coordinated by the Centers for Disease Control and the Prevention Research Centre in Saint Louis, US, in partnership with three universities in Brazil.6 The project made use of established public health ties and collaborations between the countries’ governments that existed before the project started. A diverse network of partners in academia, government (at all levels), and non-governmental institutions (for example, the PAHO and CELAFISC (Centro de Estudos do Laboratório de Aptidão Física de São Caetano do Sul)) were invited to take part in the project. An important part of its success was the project’s approach to cultural sensitivity, which enabled recipient partners to identify or prioritise research efforts according to the local context.6 Project GUIA exemplifies the importance of interacting with stakeholders from the outset, strengthening the capacity of researchers and policymakers to use and generate practice based evidence. Disseminating findings for use by regional entities and implementing them within programmes has been recognised as an important aspect of the partnership.6 Reflections on the success of Project GUIA have also highlighted the importance of timing. The project began as Brazilian public health agencies were ready to embrace initiatives for non-communicable disease prevention6 and at a time when a pool of talented young investigators in Latin America was emerging,7 showing that investment in researchers early on in their career can develop into larger initiatives. However, retaining such talent requires further investment. Without such support, it will be a challenge to maintain a flow of talent for working, innovating, and advancing public health efforts to tackle non-communicable diseases in the region. A critical mass of talent is key in using their experience to promote the lessons learnt or sustain knowledge and policy engagement at various levels.

Partnerships for more appropriate and affordable technologies Transferring innovations from one region to another does not simply result in desired outcomes, and developing new medical 2

technologies costs time and money. Partnership will therefore be crucial for implementing appropriate and affordable medical technology in Latin America. Partnerships between academia and industry, including north-south and south-south collaboration, could lead to more cost effective, appropriate, affordable, and sustainable interventions for the region’s major public health challenges. Moreover, by engaging multiple entities within and between institutions these partnerships can help to build capacity for interdisciplinary research and researchers in Latin America who engage in research and development and innovation. One example in the region where partnership is being encouraged for global health research innovation is the competitive funding provided by the National Institutes of Health, through its National Cancer Institute. These partnerships are especially relevant given the disease burden in the region: 85% of cervical cancers worldwide occur in low and middle income countries, with 16% of cases in the Americas.8 One of the current partnerships supported by National Institutes of Health/National Cancer Institute funding includes public and private institutions in Latin America and the US looking at the accessible and affordable use of molecular diagnostics in the early detection of human papillomavirus (HPV) subtypes that can lead to cervical cancer. Specifically, researchers from Latin America and the International Agency for Research on Cancer are working to develop an HPV test based on detecting the activity of oncoprotein E6/E7, which is present in the eight most common HPV subtypes associated with cervical cancer. The study will use pre-existing clinical research networks in Latin America to assess the test’s potential as the standard screening tool for cervical cancer.9 Another example of a partnership supported by this programme which built on existing networks in Latin America includes the transformation of a non-gas based ablative device, the CryoPen(R) Cryosurgical System, into an inexpensive and portable cryotherapy device that can be operated by any healthcare provider.10 The industry, academia, and government partnerships, as described in the policy on Research for Health, rely on setting a joint agenda clarifying responsibilities, strengthening capacity, and sharing data and networks for a long lasting impact on current and emerging public health challenges. However, these partnerships could be at risk if multiple agencies cannot match or align priorities, and changes in political agendas may create obstacles. The development of these partnerships relies on existing and future funding opportunities.

Unless the partners concerned have a sustained product development plan, there is the risk that when the funding ends the interactions facilitated by the partnerships may cease, putting at risk the research and innovation process and, therefore, its targeted products.

Discussion Multidisciplinary partnerships promote greater understanding among stakeholders across public and private sectors both nationally and internationally. They are key to tackling current and future health challenges: treating communicable diseases and non-communicable diseases, sustaining public health interventions, and creating innovative solutions for common problems that can be applied in low and middle income countries. For partnerships to be effective, stakeholders need to agree a shared vision and mission; negotiate roles, responsibilities, and actions; define aims; and establish processes for negotiations and sharing power. 11 Creating strategic alliances with all potential stakeholders (governments, universities, private sector, funders, international organisations, professional societies, community based organisations, and patient groups) is necessary to tackle national priorities through research for health. Partnerships between different stakeholders are also crucial in achieving the aims of the policy on research for health: improving equity, health, and development.12 Nascent research partnerships often fail because of unrealistic budgets and a lack of leadership, negotiation, teamwork, and management skills. Such skills are currently acquired by researchers in Latin America in a learning-by-doing fashion, late on in a professional’s career. Introducing and building such skills during undergraduate and postgraduate training could lead to long lasting and sustainable relationships of equals, a prerequisite for meaningful partnerships. Incorporating these skills into the curriculum will require another partnership: one between academic institutions and governments for capacity building. The Latin America region can take advantage of its diverse population and common languages, mainly Spanish and Portuguese, to build partnerships that would be unlikely to work otherwise. We will have to adapt, as existing challenges (that is, the unfinished agenda of infectious diseases, strengthening health systems, and achieving universal healthcare) will be paired with newer ones, such as multimorbidity, non-communicable diseases, and big data approaches for

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Clinical trial transparency in the Americas: the need to coordinate regulatory spheres Numerous initiatives have contributed to health data transparency in the Americas, but further coordinated effort is needed to ensure the reliability of research for health, argue Trudo Lemmens and Carlos Herrera Vacaflor

I

n its 2009 Policy on Research for Health, the Pan American Health Organization/World Health Organization (PAHO/WHO) reiterated the key role of transparency in ensuring reliable research for health.1 In the wake of several high profile controversies, transparency has been particularly promoted in the context of industry sponsored pharmaceutical trials aimed at producing data for drug regulatory approval.2 In response to these controversies, various stakeholders have pushed for clinical trial registration and access to data submitted to drug regulatory agencies as key transparency tools, to enhance evidence informed decision making by clinicians, regulators, and society.2 Notwithstanding widespread support for transparency, its implementation faces significant challenges. Transparency of pharmaceutical data has been hampered by the qualification of such data as commercially confidential information and by inconsistencies in overlapping regulatory spheres. This article will first discuss key developments related to registering

pharmaceutical clinical trials and sharing data submitted to drug regulatory agencies in the Americas. Then, reports from three countries will show how they have implemented key transparency measures and what challenges remain. Finally, the paper will suggest how research ethical review, present in all jurisdictions, could play a role in moving forward with data transparency. The three selected countries, representing the four major language groups in the Americas, have strong pharmaceutical industries at different stages of development: mature market (Canada), emerging market (Brazil), and second tier emerging market (Argentina). Most Latin American countries are in the last category. Argentina and Brazil represent countries with a growing number of clinical trials. 3 The drug regulatory agencies of all three countries are recognised as regional reference authorities (box 1). Given the region’s diversity in terms of industry development and regulatory review, these case studies are neither exhaustive nor fully representative. Rather, they shed light on various initiatives, outcomes, and challenges.

Key messages •   National health regulatory agencies

involved in health related research governance should harmonise a n d st re a m l i n e b ot h re s e a rch ethics committee governance and transparency requirements in different regulatory regimes •   D rug regulatory agencies in Pan American Health Organization member states should follow the approach taken by the European Medicines Agency with respect to clinical data used for a regulatory decision—that the data do not constitute commercially confidential information and that the burden of proof is on drug companies to argue why specific data should be kept confidential •   Research ethics committees can play a coordinating role in the promotion of transparency standards to the extent that the governance structure of committees reflects their public interest nature

Developments in trial transparency in the Americas Over the past decade, WHO, PAHO, national governments, funding agencies, scientific journals,4 and some pharmaceutical sponsors in the Americas have taken steps to promote transparency.2 5 Clinical trial registration, the first initiative to get widespread support, is now required in many countries, despite clear gaps (box 2).2 WHO recognises the registries of Brazil, Cuba, and Peru as primary registries in the PAHO region for its International Clinical Trials Registry Platform.4 Concurrently, there has been a significant increase in trial registration in the Americas.8 Regarding pharmaceutical data sharing, no national regulatory authority from the Americas has yet followed the example of the European Medicines Agency (EMA), which first facilitated data access in 2010, followed in 2014 by a policy which embraced as a principle that all clinical trials data from phase 1, 2, and 3 studies submitted for drug regulatory approval will be made public.5

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The 2014 policy starts from the premise that clinical data are not commercial confidential information, shifting the burden to companies to show why secrecy of specific data components is needed. In the Americas, even the United States—with disclosure obligations in its Food and Drug Administration Amendments Act (FDAAA) of 2007— does not require registration of all clinical trials, nor does it prospectively publish all trial data.9 National freedom of information acts in various countries provide some level of access to data held by governments, but in those regimes, drug regulators have wide discretionary powers over data access requests.

Brazil Since 2010, Brazil has implemented relatively successful transparency and data access policies. The Brazilian Registry of Clinical Trials (ReBEC) aims to make information for all studies available in English, Portuguese, and Spanish.10 Registration with ReBEC is mandatory for all clinical trials involving drugs not yet officially approved and involving Brazilian researchers or participants. Brazilian journals indexed in Literatura Latino Americana em Ciências da Saúde and Scientific Electronic Library Online, and journals associated with the International Committee of Medical Journal Editors (ICMJE) require trial registration as condition for publication.11 Proof of registration with WHO’s International Clinical Trials Registry Platform (ICTRP) or another registry recognised by the ICMJE is mandatory for national regulatory authority authorisation.12 From 2010 to 2015, 3112 protocols were registered with ReBEC,8 with an increase in the registration of both state funded and pharmaceutical industry funded trials.13 For 2016 and 2017, the number of registered trials was 1162 and 1279, respectively. ReBEC gives access to clinical trial summaries in accordance with WHO’s Trial Registration Data Set. Clinical trial reports are submitted to Brazil’s National Health Surveillance Agency (ANVISA), but can only be accessed on request.14 ANVISA coordinates data access under Brazil’s access to information law. Anyone can request research data for use, re-use, or redistribution providing they cite authorship 1


Strengthening Research for Health in the Americas

Box 1: National regulatory authorities (NRAs) in the America NRAs recognised by PAHO as regional references of medicines and biological products •   Argentina: National Administration of Drugs, Food, and Medical Technology (ANMAT) •   Brazil: National Health Surveillance Agency (ANVISA) •   Canada: Health Canada (HC) •   Chile: Public Health Institute (ISP) •   Colombia: National Institute of Food and Drug Surveillance (INVIMA) •   Cuba: Center for State Control of Drug Quality (CEMED) •   Mexico: Federal Commission for Protection against Sanitary Risks of the United Mexican States (COFEPRIS) •   United States of America: Food and Drug Administration (FDA) NRAs recognised by PAHO as regional references of medicines and biological products •   Argentina: National Administration of Drugs, Food, and Medical Technology (ANMAT) •   Bahamas: Bahamas National Drug Agency (BNDA) •   Barbados: Barbados Drug Service (BDS) •   Bolivia: Medicines and Health Technology Unit (UNIMED) •   Brazil: National Sanitary Surveillance Agency—Ministry of Health (ANVISA) •   Canada: Health Canada (HC) •   Chile: Public Health Institute (ISP) •   Costa Rica: National Board of Health Research (CONIS), University RECs, Costa Rican Social Security Fund (CCSS) •   Cuba: Center for State Control of Drug Quality (CEMED) •   Dominican Republic: General Directorate of Medicines, Food, and Health Products (DIGEMAPS) •   Ecuador: National Institute for Hygiene and Tropical Medicine—Ministry of Health •   El Salvador: National Directorate of Medicines •   Guatemala: Department of Regulation and Control of Pharmaceutical and Related Products (MEDICAMENTOS) •   Guyana: Food and Drug Department (FDD) •   Haiti: Direction de la Pharmacie, du Médicament et de la Médicine Traditionnelle (DNM/MT) •   Honduras: Health Secretariat, General Directorate of Sanitary Regulations •   Jamaica: Standards and Regulation Division (DSR) •   Mexico: Federal Commission for Protection against Sanitary Risks of the United Mexican States (COFEPRIS) •   Panama: Directorate of Pharmacy and Drugs •   Paraguay: National Directorate of Health Surveillance •   Peru: General Board of Medicines, Supplies, and Drugs (DIGEMID) •   Suriname: National Regulatory Authority •   Trinidad and Tobago: National Regulatory Agency •   United States of America: Food and Drug Administration (FDA) •   Venezuela: Rafael Rangel National Institute of Hygiene (IHRR) Note: All the above agencies operate as part of the national ministries of health. In the English speaking Caribbean, PAHO’s Caribbean Public Health Agency (CARPHA) is involved in establishing uniform standards. There is also PAHO’s Pan American Network for Drug Regulatory Harmonization (PANDRH).

and data origin. ANVISA has created an open data repository, Plano de Dados Abertos, which meets quality standards under current regulations. Data access may be restricted based on protection of fundamental rights or the interest of society or the state.15 A National Health Council regulation requires researchers involved in public or privately funded research to publish their results. Interruption of research and failure to publish must be explained to the Research Ethics Committee (REC) and the national REC agency, CONEP. Progress in promoting transparency appears threatened by ReBEC’s budget restrictions and staff shortages. At the regulatory level, data sharing may further be affected by ANVISA’s confidentiality ag re e m e n t s w i t h o t h e r regu l a to r y agencies.16

Argentina Argentina has developed policies for mandatory clinical trial registration and access to research data. These initiatives have been 2

timidly implemented, however, in part hindered by jurisdictional problems. Argentina created its National Registry for Health Research (RENIS) to increase clinical trial and other health research registration.17 Health research funded by the Ministry of Health or conducted under National Administration for Drugs, Food, and Medical Technology (ANMAT) regulations must be registered in order to receive authorisation. The implementation of registration requirements of other clinical trials taking place in the provinces depends on the local health authorities. RENIS also contains information on research ethics boards, sponsors, researchers, and contract research organisations. For 2016 and 2017, RENIS contains 145 and 180 registered research projects,9 respectively, while 191 and 125 clinical trials were entered into ANMAT’s database for clinical pharmacology studies18 for the same period. ANMAT’s guidelines contain rules about patient confidentiality and reporting data (such as clinical trial reports) to ANMAT, but not to the public.

Different statutes impact on access to research data. Laws governing access to information need government, state, and decentralised agencies to provide access to any data under their control.19 A ‘Habeas Data Law’ also regulates data access.20 There are further privacy obligations regarding personal data. If data are de-identified, however, access cannot be restricted if such access is for scientific purposes or is in the public interest. De-identified data can also be shared and transferred internationally without consent.21 The law characterises safety and efficacy data submitted to ANMAT as trade secrets or commercial data.22 This may create challenges for implementing data sharing with independent researchers and the public. Argentina is among the countries with the highest clinical trial registration rate by population,8 making RENIS a valuable effort. Even though the registry displays clinical trial summary data, RENIS neither fulfils the WHO dataset standard, nor does it provide access to data in PAHO languages doi: 10.1136/bmj.k2493 | BMJ 2018;362:k2493 | the bmj


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Box 2: Status of PAHO member states States with formal, mandatory clinical trial registration requirements* •   Brazil •   Colombia •   El Salvador •   Guatemala •   Panama •   Peru •   Uruguay •   USA States with national registries† •   Argentina •   Brazil •   Cuba •   Mexico •   Peru •   USA *Compiled on the basis of WHO survey of national pharmaceutical profiles in the Americas, with verification of country information submitted with its current policies on national regulatory agency websites. The site contains only countries that have mandatory registration in their drug regulatory structure. Some countries (such as Canada) have partial registration requirements through funding agency guidelines that are also part of good clinical practices.6 †The registries of Argentina, Mexico, and the US are not recognised as WHO primary registries.7

(English, Portuguese, and French) other than Spanish. 23 This may impede the visibility of local research for attracting international trials.11 Furthermore, access to research data is regulated under multiple legal frameworks. This creates confusion regarding researchers and civil society organisations’ rights to access data.

Canada Canada does not have its own comprehensive trial registry. Health Canada’s Clinical Trials Database provides information on clinical trials but primarily aims to stimulate research enrollment.24 Trial registration and public reporting of results are mandatory in federally funded institutions through the federal funding agencies’ research ethics standard, the Tri Council Policy Statement (TCPS2),25 and specific funding agency requirements.26 However, Health Canada’s Health Products and Food Branch, the federal drug regulator, does not explicitly require registration of clinical drug and medical device trials. Health Canada’s Good Clinical Practice Guidelines27 refer to the principles of the Declaration of Helsinki (DOH) as part of the history of good clinical practices, and Health Canada’s own REC follows the TCPS2. Both DOH and TCPS2 require trial registration and results reporting. Such indirect references are not legally enforceable, even though they could perhaps still be seen as part of good clinical practice. Official reports have long emphasised the need to improve transparency in

the regulatory record for clinical trials.28 Trials tend to be registered on the US FDA registry and prior registration is also required by most, if not all, Canadian medical journals. Access to information legislation can be used to request data access, but Health Canada has insisted in the past that applicants show how their information needs outweigh the potential commercial harm to the data submitting company— thus hindering data transparency. A 2014 amendment to the Food and Drug Act creates a legal basis for disclosure of data from clinical trials without consent from the sponsor once a drug receives approval, and could be used for further regulations about trial registration.29 Yet, the law refers to clinical trials data as commercially confidential information—seemingly undermining the concept of data as a public good. Health Canada currently also requires a signed confidentiality agreement before providing access to data, thus delaying access and subsequent sharing of data.30 A draft regulation 21 reveals, however, a potential shift in the regulatory approach about data transparency. Seemingly inspired by the EMA’s approach, the draft regulation states that “clinical summaries, reports, and supporting data of clinical trials” submitted in the drug evaluation process will not be considered commercial confidential information following a final regulatory decision. This would shift the burden of proof to pharmaceutical sponsors to show why the regulator must keep specific data confidential. The regulation remains silent about the requirement for researchers to sign a confidentiality agreement, a practice that may continue to hinder access and sharing of data. The draft regulation also does not tackle the matter of trial registration, which would need another new regulation.

Implementation challenges and regional strategies A key challenge to a coherent data transparency strategy, particularly regarding access to clinical trials data on pharmaceuticals, is the fact that distinct but overlapping regulatory regimes determine whether, and to what extent, data sharing may occur. Most countries have specific ethics guidelines for publicly funded research. Inspired by international guidelines, like the frequently referenced Declaration of Helsinki31 and the Council for International Organizations of Medical Sciences,10 they increasingly include transparency obligations such as registration and summary results reporting. In countries like Canada, commercially funded pharmaceutical clinical trials undertaken in federally funded institutions must abide by these guidelines. Food and drug regulations, including good clinical practice requirements, often

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refer to international ethics guidelines.32 Nonetheless, industry sponsors insist— and regulatory regimes often accept—that clinical trials data constitute commercially confidential information. This creates barriers to data sharing, although access to information regimes often allow researchers to request access to regulatory data following product approval. In such cases, however, regulatory agencies tend to exercise discretionary power and are often under pressure to respect industry’s insistence on secrecy. RECs could play a role by insisting on data access as a key ethical requirement and by ensuring that transparency commitments are added to the consent forms of research subjects. Ensuring individual consent for data sharing may also help tackle potential concerns about privacy of personal health information contained in clinical trials data. In all countries, pharmaceutical clinical trials must receive REC approval before recruiting human subjects. There is widespread recognition, including in international good clinical practice standards, of RECs having key obligations to protect research subjects’ rights, safety, and wellbeing. 33 If—as national and international ethics guidelines recognise— transparency is a key component of ethical research, RECs should require researchers and sponsors to make specific transparency commitments as a condition for ethics approval. Additionally, considering the growing recognition of RECs post-approval role, arguably they should actively verify and, to the fullest extent possible, enforce transparency standards.32 We recognise the difficulties in achieving this. Even in Europe, where transparency faces fewer regulatory barriers, RECs lack adequate procedures to verify results publication or minimise selective reporting.34 In the Americas, different countries’ substantive rules on research transparency are also reflected in different REC governance regimes. Some countries have a coherent, centralised administrative structure with uniform rules for RECs that may facilitate the enforcement of transparency standards. For example, in Brazil, all institutional RECs are responsible for reviewing trials conducted at their site. However, CONEP reviews the RECs’ decisions and may request changes. It also authorises, registers, and monitors institutional RECs. Although Brazil’s structure creates public accountability and coherent REC review, CONEP remains underfunded.23 RECs for industry sponsored trials in other jurisdictions follow a more market oriented structure. In countries like Canada (in some major provinces), the US, and Argentina (except the Province and City of Buenos Aires), 35 most industry sponsored trials 3


Strengthening Research for Health in the Americas

are reviewed by commercial RECs. These are in a direct client-provider relationship with industry sponsors and compete for their business.36 They are stakeholders in the knowledge production industry that supports pharmaceutical and medical device industries and operates under the same commercial market norms—including commercial confidentiality norms.16 Market oriented REC governance for industry sponsored research appears ill suited for enforcing and promoting trial registration and data sharing. Jurisdictional matters may create additional barriers to attempts to promote a publicly accountable REC structure. This is the case, for example, in Argentina and Canada. In each Argentinean province, institutional and commercial RECs are coordinated by central RECs. Resolution 1002/2016 created the National Advisory Committee on Research Ethics, which collaborates with provincial RECs and promotes coordination. Its mandate includes registering RECs operating at national institutions or decentralised agencies of the Ministry of Health; yet it does not cover private RECs. A recent Argentinean case study on industry sponsored trials documents the failure of the government and a commercial REC to enforce basic transparency rules. 37 In Canada, there is also no federal regulation or federal monitoring of RECs.38 The most populated provinces with the highest pharmaceutical clinical trials activities, Ontario and Quebec, largely rely on private commercial RECs to review pharmaceutical clinical trials. Only one province, Newfoundland and Labrador, enacted legislation that explicitly mandates a central Health Research Ethics Authority to organise the review of all research in the province by one central REC.39

Conclusion Countries in the Americas have taken ­important steps in implementing transparency standards. Some have achieved significant progress in implementing mandatory clinical trial registration and a level of transparency. Nonetheless, some leading countries still fail even to impose registration with a publicly accessible registry. While data sharing initiatives have been undertaken in several countries, the transparency of pharmaceutical clinical trials data has been hindered by its characterisation as commercially confidential information. Nevertheless, most jurisdictions recognise the strong ethical basis for data transparency, often with explicit reference to international research ethics guidelines. This is also reflected in human rights and public goods approaches to data sharing. If countries in the region were to streamline the different overlapping regulatory fields that govern clinical trials data, and follow 4

the EMA’s lead in creating a presumption that data should be publicly accessible, they would take an important step towards the implementation of comprehensive data transparency. To implement coherent transparency of health data in the Americas, countries need to juggle different applicable rules, guidelines, and governance tools successfully. This means different regulatory agencies and funding agencies coordinating applicable transparency rules at each national level. The further development of publicly accountable REC systems, directly accountable to the state, must be part of promoting meaningful transparency. We thank Luis Salicrup, Luis Gabriel Cuervo, editors of The BMJ, and reviewers for feedback about the paper and Suzanne Stephens for editing. We acknowledge the financial support of the Contributions Program of the Office of the Privacy Commissioner of Canada, for a project on Access to Clinical Drug Trials Data and Privacy. Contributors and sources: Both authors declare that they made substantial contributions to the conception and design of the work; to the acquisition, analysis, or interpretation of data for the work; and to the drafting of the article and critical revision. They both approve the final version and agree to be accountable for its content and for ensuring that any questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; externally peer reviewed. This article is part of a series proposed by PAHO and commissioned by The BMJ, which peer reviewed, edited, and made the decision to publish the article with no involvement from PAHO. Open access fees for the series are funded by PAHO. Trudo Lemmens, professor and Scholl chair in health law and policy1 Carlos Herrera Vacaflor, researcher2 1 Faculty of law and Dalla Lana School of Public Health, University of Toronto, Canada 2

Faculty of law, University of Toronto, Canada

Correspondence to: T Lemmens Trudo.Lemmens@ utoronto.ca 1 Pan American Health Organization/World Health Organization. Policy on research for health: document 49/10 of the 49th directing council, 61st session of the regional, committee of WHO for the Americas. 2009. www.paho.org/hq/images/stories/ KBR/Research/research%20policy%20on%20 research%20for%20health%20english.pdf. 2 Krleža-Jeriç K, Lemmens T, Reveiz L, Cuervo LG, Bero LA. Prospective registration and results disclosure of clinical trials in the Americas: a roadmap toward transparency. Rev Panam Salud Publica 2011;30:87-96. 3 Rodríguez-Feria P, Cuervo LG. Progress in trial registration in Latin America and the Caribbean, 2007-2013. Rev Panam Salud Publica 2017;41:e31. 4 Registro Peruano de Ensayos Clínicos. El REPEC ahora es un registro primario de la OMS. 21 Febrero 2017. www.ensayosclinicos-repec.ins.gob.pe/86-slideshow/270-el-repec-ahora-es-un-registro-primariode-la-oms. 5 European Medicines Agency. European Medicines Agency policy on publication of clinical data for medicinal products for human

use: policy/0070. 2013. www.ema.europa.eu/ docs/en_GB/document_library/Other/2014/10/ WC500174796.pdf. 6 WHO. Pharmaceutical sector country profiles data and reports. Region of the Americas. AMRO/PAHO, 2010.www.who.int/medicines/areas/coordination/ coordination_assessment/en/index1.html 7 Rodríguez-Feria P, Cuervo LG. Progress in trial registration in Latin America and the Caribbean, 2007-2013. Rev Panam Salud Publica 2017;41:e31. 8 Organização Pan-americana da Sáude/Organização Mundial da Saúde. Relatório de gestão dos termos de cooperação 2015 [Cooperation Terms Management Report 2015]. 2015. www.paho.org/bra/images/ relatorio_gestao_2_sem_2015_o16.pdf?ua=1. 9 ReNIS: Registro Nacional de Investigaciones en Salud. www.argentina.gob.ar/salud/ registroinvestigaciones 10 Freitas CBD, Hossne WS, Dutra S. Progress and challenges of clinical research with new medications in Brazil. In: Homedes N, Ugalde A, eds. Clinical trials in Latin America: where ethics and business clash. Springer. 2014:151-71 11 US Food and Drug Administration. FDA 801 requirements. 2017. https://clinicaltrials.gov/ct2/ manage-recs/fdaaa. 12 Agência Nacional de Vigilância Sanitária. Perguntas e responstas RDC 9/2015: resolução RDC No 9 art.2-3 (2015). 2015. http://portal.anvisa.gov.br/ documents/33836/2492465/Perguntas+e+respo stas+sobre+a+RDC+09+de+2015/b14fa962-c1e941f5-9524-a290c5b4e98e. 13 Silva LR, Laguardia J, Bastos Alves MRA, et al. ReBEC em números: reflexos da política mandatória em pesquisa clínica na trajetória do Registro Brasileiro de Ensaios Clinicos. Cadernos BAD 2014;2 juldez:107-14. https://www.bad.pt/publicacoes/index. php/cadernos/article/view/1187. 14 Ferreira da Silva C, Ventura M, Castro C. Bioethical perspective of justice in clinical trials. Rev Bioet 2016;24:292-303. 15 Agência Nacional de Vigilância Sanitária. Brasil. Sobre a Lei de Acesso a Informação. 2011. http:// portal.anvisa.gov.br/sobre-a-lei-de-acesso-ainformcao. 16 Agência Nacional de Vigilância Sanitária, Brasil; Medicines and Healthcare Products Regulatory Agency, United Kingdom. Termos de confidencialidade entre a Agência Nacional de Vigilância Sanitária do Brasil e a da Agência Reguladora de Medicamentos e Produtos para a Saúde do Reino Unido Grã Bretanha e Irlanda do Norte. 26 Nov 2012. http://portal.anvisa.gov.br/ documents/33788/3043011/ANVISA_MHRA++Acordo+de+confidencialidade+%28BR% 2C+2012%29+%282%29.pdf/45ef580e-cca94998-ad3f-3a6462c54258. 17 Resolución 1480/2011, Apruébase la guía para investigaciones con seres humanos. Objetivos. Bs.As., 13/9/2011. http://servicios.infoleg.gob.ar/ infolegInternet/anexos/185000-189999/187206/ norma.htm 18 Estudios Clinicos. www.anmat.gov.ar/aplicaciones_ net/applications/consultas/ensayos_clinicos/ Consulta_EC.asp#. 19 Ministerio de Justicia y de Derechos Humanos de la Presidencia. Argentina, InfoLEG: Información Legislativa. Ley 27275: Derecho de Acceso a la Información Pública, 29 Septiembre 2016. http://servicios.infoleg.gob.ar/ infolegInternet/anexos/265000-269999/265949/ norma.htm. 20 Ministerio de Justicia y de Derechos Humanos de la Presidencia. Argentina, InfoLEG: Información Legislativa. Ley 25.326: Protección de Datos Personales. 30 Oct 2000. Buenos Aires: InfoLEG; 2016. http://servicios.infoleg.gob.ar/infolegInternet/ anexos/60000-64999/64790/texact.htm 21 Outomuro D, Mirabile LM. Confidencialidad y Privacidad en la medicina y en la investigación científica: desde la bioética a la ley. Rev Bioet 2015;23:238-44. www.scielo.br/pdf/ bioet/v23n2/1983-8034-bioet-23-2-0238. pdf10.1590/1983-80422015232062.

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22 Ministerio de Justicia y de Derechos Humanos de la Presidencia. Argentina, InfoLEG: Información Legislativa. Ley de confidencialidad sobre información y productos que estén legítimamente bajo control de una persona y se divulgue indebidamente de manera contraria a los usos comerciales honestos: Ley 24-766, 20 dic 1996. Buenos Aires: InfoLEG; 1996. http:// servicios.infoleg.gob.ar/infolegInternet/ anexos/40000-44999/41094/norma.htm 23 Pan American Health Organization/World Health Organization. Advisory committee on health research: a review of its contributions to health and research for health in the Americas 2009-2015. 2016. www.paho.org/hq/ index.php?option=com_docman&task=doc_ download&gid=36641&Itemid=270. 24 Lemmens T, Gibson S. Decreasing the data deficit: improving post-market surveillance in pharmaceutical regulation. McGill Law J 2014;59:943-88. doi:10.7202/1026134ar . 25 Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Social Sciences and Humanities Research Council of Canada. Tri-council policy statement: ethical conduct for research involving humans. 9 Dec 2014. www.pre.ethics.gc.ca/pdf/eng/ tcps2-2014/TCPS_2_FINAL_Web.pdf. 26 Canadian Institutes of Health Research. Section 2: grants and awards management—CIHR’s grants and awards guide. 2013. www.cihr-irsc.gc.ca/e/22631. html#2-A20.

27 Health Canada. Notice: ICH guideline E6: good clinical practice: consolidated guideline. 2004. www. hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/ prodpharma/e6-eng.pdf. 28 Standing Senate Committee on Social Affairs, Science, and Technology. Canada’s clinical trial infrastructure: a prescription for improved access to new medicines. 2012. www.aihealthsolutions.ca/ media/Senate-report.pdf. 29 Herder M. The opacity of Bill C-17’s transparency amendments. Impact Ethics Blog 23 June 2014. https://impactethics.ca/2014/06/23/the-opacity-ofbill-c-17s-transparency-amendments. 30 Herder M, Lemmens T, Lexchin J, et al. Pharmaceutical transparency in Canada: tired of talk. BMJ Blog 6 June 2016. http://blogs.bmj.com/bmj/2016/06/06/ pharmaceutical-transparency-in-canada-tired-of-talk. 31 World Medical Association. WMA declaration of Helsinki: ethical principles for medical research involving human subjects. 2013. www.wma.net/ policies-post/wma-declaration-of-helsinki-ethicalprinciples-for-medical-research-involving-humansubjects. 32 Kolstoe SE, Shanahan DR, Wisely J. Should research ethics committees police reporting bias? BMJ 2017;356:j1501. doi:10.1136/bmj.j1501 33 International Conference on the Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practices (E6R1). 2016. www.ich.org/fileadmin/ Public_Web_Site/ICH_Products/Guidelines/Efficacy/ E6/E6_R1_Guideline.pdf.

34 Strech D, Littmann J. The Contribution and attitudes of research ethics committees to complete registration and non-selective reporting of clinical trials: a European survey. Res Ethics Rev 2016;12:123-36. doi:10.1177/1747016115626497 . 35 Sabio MF, Bortz JE. [Structure and functioning of research ethics committees in the Autonomous City of Buenos Aires and Greater Buenos Aires]. Salud Colect 2015;11:247-60. http://www.scielosp.org/ pdf/scol/v11n2/v11n2a08.pdf. doi:10.18294/ sc.2015.687 36 Lemmens T, Freedman B. Ethics review for sale? Conflict of interest and commercial research review boards. Milbank Q 2000;78:547-84, iii-iv. doi:10.1111/1468-0009.00185 37 Homedes N, Ugalde A. The evaluation of complex clinical trial protocols: resources available to research ethics committees and the use of clinical trial registries–a case study. J Med Ethics 2015;41:464-9. doi:10.1136/ medethics-2013-101381 38 Lemmens T. Federal regulation of REB review of clinical trials: a modest but easy step towards an accountable REB review structure in Canada. Health Law Rev 2005;13:39-50. 39 Newfoundland and Labrador: health research ethics authority act. http://assembly.nl.ca/Legislation/sr/ statutes/h01-2.htm Cite this as: BMJ 2018;362:k2493 http://dx.doi.org/10.1136/bmj.k2493

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non Commercial No Derivs IGO License  (CC BY-NC-ND 3.0 IGO), which permits distribution and reproduction for non-commercial purposes in any medium, provided the original work is properly cited. If you remix, transform, or build upon the material, you may not distribute the modified material. See: https:// creativecommons.org/licenses/by-nc-nd/3.0/igo/ In any reproduction of this article there should not be any suggestion that PAHO or this article endorse any specific organisation or products

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Strengthening Research for Health in the Americas

Improving public health and health systems through evidence informed policy in the Americas Translating knowledge into policy and practice can improve public health and health systems in the Americas, say Tomás Pantoja and colleagues

T

he evidence informed policy making approach—where policy decisions are informed by the systematic and transparent use of evidence—captured a great deal of international attention at the beginning of the millennium. The movement was spurred on by the 2004 World Report on Knowledge for Better Health and the statements issued at the Ministerial Summits on Health Research in Mexico City in 2005 and Bamako, Mali, in 2008, both convened by the World Health Organization.1 2 More recently, the United Nations’ Agenda 2030 for sustainable development formulated 17 goals for global development, and policies informed by research will be key. In this context, the Pan American Health Organization/World Health Organization (PAHO/WHO) developed its “Policy on Research for Health” in 2009.3 The policy stressed the need for minimum quality standards and relevance in the research being conducted to inform health policy. It also outlined the environment needed to produce impactful research, which is effective research governance and a skilled workforce working in partnership networks.3 The policy’s objective of attaining a positive health impact through research relies on

Key messages •   Many policy makers in the Americas

acknowledge the relevance of using research to inform decisions made for their health systems •   Knowledge translation is much more accepted, however, in clinical and public health policy making compared with the health systems field •   I n the Americas, the growth and consolidation of national health research systems to generate research evidence has been uneven and based on isolated capacity building initiatives •   Some countries have established a formal infrastructure to implement research translation efforts at national level •   Despite this, in most cases, activities are developed as one-off projects with no sustainable funding beyond the specific project life cycle

establishing constructive communication between the different stakeholders who fund, produce, and use research. This entails empowering civil society organisations to set research priorities, and making research findings available in formats appropriate for different audiences. The objective of this article is to examine current challenges to research for health and describe successful initiatives implemented in the Americas that aim to make a positive impact on population health.

Main challenges Researchers have identified challenges and limitations that hinder efforts to link research to policy action at the country level.4 These challenges can be grouped into three main areas: the sociopolitical climate for research use; the research production process; and the translation of research findings. Research is often undervalued, seen as irrelevant, or too difficult to use to inform policy making. Although policy makers in many countries in the Americas acknowledge the benefits of using research to guide decisions to improve health systems, current actions still pale in comparison to the achievements by the evidence based medicine movement. Research producers and users are still struggling to work out the scientific foundations of health policy and systems research. 5 Additionally, the systematic use of research in health system decision making processes has not been formally established in policy making schemes. It is, currently, greatly dependent on the background of decision makers and their personal relationships with researchers and healthcare practitioners.6 The Americas, including the Caribbean region, produce 46% of the world’s public health research—but most of that (37%) comes from the United States,7 and it is not always directly relevant to PAHO member states. 8 A more systematic approach is needed to generate priorities and fund research that is relevant and useful to the Americas. National health research systems, people, institutions, and activities that generate high quality research to promote, restore, and maintain the health status of populations, are one way to ensure that research will meet national public health needs. The growth and consolidation of

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these systems in the Americas has been uneven, however, and based on individual or isolated capacity building initiatives.9 In 2005, the World Health Assembly urged countries to create national infrastructures to promote evidence based policy and evidence based public health and healthcare delivery systems. 10 In practice, such infrastructure consists of programmes, interventions, and tools that disseminate and facilitate access to research information, foster knowledge exchange between stakeholders, and use evidence to inform healthcare organisations and health systems. 11 Such formal infrastructure, however, is not currently in place in many countries in the Americas.12 In most cases, activities are developed as one-off projects with no sustainable funding beyond the project life cycle. Although some initiatives have promoted dialogue between research producers and users, the high turnover of public health authorities, and even of technical teams within the health and technology sectors, hinder the development of long term knowledge translation activities. 12 Additionally, the lack of a formal infrastructure to coordinate national efforts to translate research into policy and promote exchange of experiences between the countries of the Americas has limited collective learning and resource sharing in the area of knowledge translation.

Successful initiatives Knowledge translation initiatives in the Americas have not undergone a comprehensive review. However, there are cases in Brazil, Chile, and Peru where the challenges faced when attempting to link research to policy action have been tackled. These case studies were selected by the authors based on their direct knowledge of them. In Peru, in recent years, the sociopolitical climate for research use has improved thanks to the work of non-academic research units that promote the use of research evidence in the health system. Following two initiatives where research findings helped to inform policy decisions, Peru’s Ministry of Health established formal processes for demanding research evidence. The two initiatives focused on the abortive effects of the morning after contraceptive pill, and the potential health impact of transgenic foods.13 Research evidence is now required 1


Strengthening Research for Health in the Americas

to inform decisions on programme budgets, the redesign of health programmes at national and subnational levels, and the selection of specific health interventions to be funded by the ministry. In order to tackle Peru’s need for evidence, the Unit for Generation and Analysis of Evidence in Public Health has been set up at the National Institute of Health.14 Furthermore, these formal processes have been expanded to other directorates in the Ministry of Health, and collaboration between groups working on clinical guidelines and health technology assessment has started. In Chile, the National Health Research Fund (FONIS) is a cost effective initiative that was set up to produce relevant research to aid decision makers tackling problems in the country’s health system.15 Since 2003, FONIS has competitively funded projects in the areas of the effectiveness of clinical and public health interventions; environmental and occupational health; equity in access to healthcare; health promotion and risk factor control; quality of healthcare and user satisfaction with health services; and methods for measuring the impact on health of public policies implemented by the nonhealth sector. Over its first 10 years, FONIS funded 300 projects costing around $10m (£7.5m; €8.6m) in total. Research funded by FONIS has had an impact on national policy. Changes in the tobacco law in Chile, for example, were informed by FONIS funded research.16 17 In 2006, WHO launched its evidence informed policy network (EVIPNet) to tackle the challenge of translating research into policy in the Americas and worldwide. EVIPNet develops sustainable partnerships between policy makers, researchers, and civil society to increase the capacity of countries to develop health policies using research evidence. 18 PAHO launched EVIPNet in the Americas in 2007 and by the end of 2013 there were teams in 12 countries.12 EVIPNet country teams form the institutional infrastructure necessary to translate research findings into effective policies. The two main outputs from EVIPNet’s country teams are contextualised, user friendly evidence briefs for policy that present a research synthesis of different policy options; and policy dialogues, which are structured discussions focused on an evidence brief that are used to formulate policy. 19 By 2013, over 700 country officers and experts had participated in training, developed 14 evidence briefs, and conducted 10 deliberative dialogues in eight countries. 12 Brazil has led the way in implementing successful EVIPNet activities and products (box 1).20 Although EVIPNet is not the only initiative tackling the challenge of translating research into policy, it has provided a template for organising 2

Box 1: The experience of EVIPNet-Brazil •   In 2016, EVIPNet-Brazil published a series of eight health evidence syntheses for policy in key public priority areas. High infant mortality rates in north and northeastern Brazil were the impetus behind this push to use evidence. The evidence showed how high infant mortality bore a direct correlation to poor quality of care during labour and delivery, with insufficiently trained healthcare workers neglecting to follow established protocols and guidelines for care. In the low resource municipality of Piripiri, research showed that 60% of all newborn deaths were preventable. •   EVIPNet-Brazil approached this issue by presenting evidence informed policy options in partnership with the local health council. Policy dialogues led to the selection of options with the greatest potential impact, involving complex local planning for more than 30 interventions based on the best available evidence. This work helped to successfully reduce infant mortality rates in Piripiri from 21 per 1000 live births in 2009, to 7 per 1000 live births in 2011. •   EVIPNet-Brazil is currently adapting this evidence into a policy model so that it can be replicated in several other Brazilian localities, where local working groups will tackle their own health issues, prepare evidence syntheses, and organise policy dialogues on the matters affecting them. Other public health priority issues include sickle cell anaemia, air pollution, congenital heart disease, tuberculosis in the homeless population, early childhood development, and road traffic deaths.

activities in other countries in the Americas (Chile, for example).21 It has also provided field opportunities for capacity building, assisting both researchers and decision makers through the network of the global EVIPNet initiative.

Pending agenda In order to produce relevant research to inform decision making in health, countries need to adopt a systematic approach to strengthening national health research systems.22 This requires a well defined policy or programme linked to national priorities for research for health; structures for coordinating and managing research; sustainable financing mechanisms; and a defined set of indicators for monitoring and evaluation. PAHO is well positioned to promote the adoption of this approach in the countries of the Americas, building on successful experiences and connecting systematically and consistently current isolated initiatives. Despite some success in knowledge translation in the Americas, 20 21 in most countries the research translation infrastructure still needs strengthening. Countries also need to promote and support the development of research translation teams. This is crucial in countries where some translation activities have been carried out, but where no formal infrastructure has been established for regional or global collaboration. Beyond funding issues, taking stock of successes and failures after 10 years of effort in this area will constitute a short term priority. PAHO is attempting to tackle the challenges hindering knowledge translation by working closely with partners and developing strategic alliances. These include working with Canada’s McMaster University and Brazil’s Latin American and Caribbean Center for Health Science Information; making the regional virtual

health library and comprehensive system of literature databases available; and working with WHO’s Alliance for Health Policy and Systems Research. There has been no formal assessment across the Americas of the sociopolitical climate in relation to the use of research to inform policy, with data on this matter scattered across policy documents in different countries. Nor has there been a systematic effort to collect information about the prevailing attitudes towards knowledge translation, such as efforts made in the Middle East and some African countries.23 24 This type of information could enable the design of tailored strategies. PAHO is well placed to mobilise groups of regional experts working in the field and tackle this issue.

Conclusion At a country level, there are a number of challenges to linking research to policy action. These concern the sociopolitical climate related to research use; the production of relevant research; and the translation of research findings. PAHO’s Policy on Research for Health has provided a general framework for developing successful initiatives in the Americas. Over the past decade, progress has been made in the establishment of national health research systems; and in the availability of country level teams with the skills to identify, assess, summarise, and package research evidence. Progress has also been made in establishing standardised processes for the use of evidence in policy making (for example, EVIPNet processes) with teams of regional experts supporting these efforts. However, obstacles to generating impact through research remain embedded within the region’s health systems. PAHO and its Policy on Research for Health will be key in delineating the next steps in

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Strengthening Research for Health in the Americas

achieving a positive health impact through research on health systems in the Americas. Acknowledgements: We thank Luis Gabriel Cuervo and Luis Alejandro Salicrup, Office of Knowledge Management, Bioethics and Health Research, PAHO/ WHO, and Lisa Bero from the University of Sydney. Contributors and sources: TP is an academic family physician and health system researcher. JB previously worked as a decision maker in the Municipality of Piripiri in north eastern Brazil and at the Brazilian Ministry of Health as national coordinator of EVIPNetBrazil. UP previously worked as a senior officer at WHO in Geneva, where he coordinated the Global Secretariat of EVIPNet. The article is based on case studies published in peer reviewed journals, on policy documents, and on the experience of the authors as researchers and decision makers at different levels of the health system. All authors have contributed to this paper and concur in its content. TP is guarantor. The views are those of the authors and not necessarily those of the institutions with which they are affiliated. Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; externally peer reviewed. This article is part of a series proposed by PAHO and commissioned by The BMJ, which peer reviewed, edited, and made the decision to publish the article with no involvement from PAHO. Open access fees for the series are funded by PAHO. Tomás Pantoja, associate professor1 Jorge Barreto, researcher

2

Ulysses Panisset, adjunct professor3 1

Department of Family Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile 2

Oswaldo Cruz Foundation (Fiocruz), Brasília, Brazil Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

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Correspondence to: T Pantoja tpantoja@med.puc.cl 1 The Mexico statement on health research: knowledge for better health: strengthening health systems. From the Ministerial Summit on Health Research. 2004. www.who.int/rpc/summit/agenda/en/mexico_ statement_on_health_research.pdf. 2 Lancet. The Bamako call to action: research for health. Lancet 2008;372:1855. doi:10.1016/ S0140-6736(08)61789-4

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Cite this as: BMJ 2018;362:k2469 http://dx.doi.org/10.1136/bmj.k2469

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