Priority setting for health research: toward a management process for low and middle income countries (Working Paper 1)

This Working Paper documents the interactions of a ‘think tank’ consultation, initiated by COHRED, bringing together health research managers from Brazil, South Africa, The Netherlands, The Philippines, the private sector, the Pan American Health Organization (PAHO), the Global Forum for Health Research and COHRED. Its purpose was to better understand the issues countries face and their needs in moving priority setting forward as well as seeking advice from professionals on how COHRED can support them in managing a process of setting and measuring progress in health research priorities. Rather than having priorities ‘reviewed’ and ‘set’ through a workshop or national activity that produces a plan reflecting the situation at one point in time, the discussion in this think tank examined what process is needed so that national health research priorities are managed in a dynamic way, and are measured, updated and can evolve with the reality of the national, operational and political context. (...)

Evaluation of regional project to strengthen national health research systems in four countries in West Africa: lessons learned.

BACKGROUND: Since the Commission on Health Research for Development (COHRED) published its flagship report, more attention has been focused on strengthening national health research systems (NHRS). This paper evaluates the contribution of a regional project that used a participatory approach to strengthen NHRS in four post-conflict West African countries - Guinea-Bissau, Liberia, Sierra Leone and Mali. METHODS: The data from the situation analysis conducted at the start of the project was compared to data from the project's final evaluation, using a hybrid conceptual framework built around four key areas identified through the analysis of existing frameworks. The four areas are governance and management, capacities, funding, and dissemination/use of research findings. RESULTS: The project helped improve the countries' governance and management mechanisms without strengthening the entire NHRS. In the four countries, at least one policy, plan or research agenda was developed. One country put in place a national health research ethics committee, while all four countries could adopt a research information management system. The participatory approach and support from the West African Health Organisation and COHRED were all determining factors. CONCLUSION: The lessons learned from this project show that the fragile context of these countries requires long-term engagement and that support from a regional institution is needed to address existing challenges and successfully strengthen the entire NHRS.

Setting research priorities across science, technology, and health sectors: the Tanzania experience.

BACKGROUND: Identifying research priorities is key to innovation and economic growth, since it informs decision makers on effectively targeting issues that have the greatest potential public benefit. As such, the process of setting research priorities is of pivotal importance for favouring the science, technology, and innovation (STI)-driven development of low- and middle-income countries. METHODS: We report herein on a major cross-sectoral nationwide research priority setting effort recently carried out in Tanzania by the Tanzania Commission for Science and Technology (COSTECH) in partnership with the Council on Health Research for Development (COHRED) and the NEPAD Agency. The first of its type in the country, the process brought together stakeholders from 42 sub-sectors in science, technology, and health. The cross-sectoral research priority setting process consisted of a 'training-of-trainers' workshop, a demonstration workshop, and seven priority setting workshops delivered to representatives from public and private research and development institutions, universities, non-governmental organizations, and other agencies affiliated to COSTECH. RESULTS: The workshops resulted in ranked listings of research priorities for each sub-sector, totalling approximately 800 priorities. This large number was significantly reduced by an expert panel in order to build a manageable instrument aligned to national development plans that could be used to guide research investments. CONCLUSIONS: The Tanzania experience is an instructive example of the challenges and issues to be faced in when attempting to identify research priority areas and setting an STI research agenda in low- and middle-income countries. As countries increase their investment in research, it is essential to increase investment in research management and governance as well, a key and much needed capacity for countries to make proper use of research investments.

Agendas de investigación priorizadas: un recurso estratégico para la salud en América Latina / Priority research agendas: a strategic resource for health in Latin America

OBJETIVO: Conocer y analizar los procedimientos de elaboración de las agendas nacionales de investigación integradas entre 2007 y 2011 en Argentina, Guatemala, México, Panamá y Paraguay. MÉTODOS: Estudio descriptivo y transversal utilizando una encuesta administrada vía internet a los participantes en la elaboración de las agendas, sobre los procesos de desarrollo, integración, instrumentación y utilización y difusión de la agenda. RESULTADOS: Los 45 participantes comunicaron haber seguido metodologías específicas para la construcción de las agendas y consideraron como buenos los aspectos organizativos en cuanto a la información previa aportada y el equilibrio entre las disciplinas y los actores clave. El 60% consideró imparciales a los coordinadores, aunque 25% señaló sesgos que favorecían algún tema. El 42% recibió apoyo técnico de consultores, lecturas y guías metodológicas. El 40% reportó haber realizado la priorización de temas. El 55% señaló haber constatado la diseminación y comunicación de la agenda, pero solo 22% comunicó la inclusión de temas de las agendas desarrolladas en convocatorias nacionales de investigación. CONCLUSIONES: El desarrollo de las agendas de investigación para la salud en los países estudiados se caracterizó por la planificación previa y la organización adecuada para lograr resultados consensuados. No obstante, las agendas no se utilizaron en las convocatorias nacionales, lo que refleja la falta de coordinación en los Sistemas Nacionales de Investigación para la Salud y la desconexión entre los financiadores y los investigadores. Se recomienda fortalecer el trabajo de integración y abogacía de actores clave para lograr modificar los procesos y estructuras de las convocatorias de investigación basadas en las agendas desarrolladas.

OBJECTIVE: Understand and analyze procedures used to create national integrated research agendas from 2007 to 2011 in Argentina, Guatemala, Mexico, Panama, and Paraguay. METHODS: Descriptive, cross-sectional study using an online survey of agenda preparation processes; specifically, development, integration, implementation, and use and dissemination of the agenda. RESULTS: The 45 respondents reported following specific methodologies for agenda construction and had a good opinion of organizational aspects with regard to prior information provided and balance among disciplines and stakeholders. Some 60% considered the coordinators impartial, although 25% mentioned biases favoring some subject; 42% received technical support from consultants, reading matter, and methodological guidelines; 40% engaged in subject-matter priority-setting; and 55% confirmed dissemination and communication of the agenda. However, only 22% reported inclusion of agenda topics in national calls for research proposals. CONCLUSIONS: In the countries studied, development of the health research agenda was characterized by prior planning and appropriate organization to achieve ­ consensus-based outcomes. Nevertheless, the agendas were not used in national calls for research proposals, reflecting lack of coordination in national health research systems and lack of connection between funders and researchers. It is recommended that stakeholders strengthen integration and advocacy efforts to modify processes and structures of agenda-based calls for research proposals.

[Priority research agendas: a strategic resource for health in Latin America]. / Agendas de investigación priorizadas: un recurso estratégico para la salud en América Latina.

OBJECTIVE: Understand and analyze procedures used to create national integrated research agendas from 2007 to 2011 in Argentina, Guatemala, Mexico, Panama, and Paraguay. METHODS: Descriptive, cross-sectional study using an online survey of agenda preparation processes; specifically, development, integration, implementation, and use and dissemination of the agenda. RESULTS: The 45 respondents reported following specific methodologies for agenda construction and had a good opinion of organizational aspects with regard to prior information provided and balance among disciplines and stakeholders. Some 60% considered the coordinators impartial, although 25% mentioned biases favoring some subject; 42% received technical support from consultants, reading matter, and methodological guidelines; 40% engaged in subject-matter priority-setting; and 55% confirmed dissemination and communication of the agenda. However, only 22% reported inclusion of agenda topics in national calls for research proposals. CONCLUSIONS: In the countries studied, development of the health research agenda was characterized by prior planning and appropriate organization to achieve - consensus-based outcomes. Nevertheless, the agendas were not used in national calls for research proposals, reflecting lack of coordination in national health research systems and lack of connection between funders and researchers. It is recommended that stakeholders strengthen integration and advocacy efforts to modify processes and structures of agenda-based calls for research proposals.

Pacific Island publications in the reproductive health literature 2000-2011: with New Zealand as a reference.

BACKGROUND: There is a keen interest to develop research systems and increase research output in the 14 Pacific Island Forum Countries (PIFC) to support development of policies and practice based on locally relevant research evidence. AIMS: To assess the quantity and characteristics of reproductive health research output by each country (14 PIFC) from 2000 to 2011 using New Zealand's reproductive research outputs as the reference. METHODS: A systematic search of the literature using a broad definition of reproductive health. RESULTS: There were 174 papers published in the PIFC from 2000 to 2011 compared with 628 papers published in New Zealand (NZ). Most (57%) of the PIFC papers were from Papua New Guinea (PNG), although Samoa had the most papers by population (10/100,000). Five of the countries did not have a single publication. The majority of papers from both the PIFC and NZ were observational studies (72 vs 36%). Authors from Australia were responsible for 34% of PIFC publications followed by 25% from PNG. Sixty-three per cent of papers by PIFC sole and first authors were published in local journals, whereas 86% of non-PIFC authors published in international journals. CONCLUSION: There is a need for reproductive research in PIFC. PNG had the most publications on the back of a well-funded dedicated research institute and a significant collaboration with Australian researchers. The large number of papers in PIFC countries without PIFC authors raises the question about the need to require non-PIFC researchers to enter into genuine research partnerships in order to build research capacity in the PIFC.

Plaque-prone hemodynamics impair endothelial function in pig carotid arteries.

Hemodynamic forces play an active role in vascular pathologies, particularly in relation to the localization of atherosclerotic lesions. It has been established that low shear stress combined with cyclic reversal of flow direction (oscillatory shear stress) affects the endothelial cells and may lead to an initiation of plaque development. The aim of the study was to analyze the effect of hemodynamic conditions in arterial segments perfused in vitro in the absence of other stimuli. Left common porcine carotid segments were mounted into an ex vivo arterial support system and perfused for 3 days under unidirectional high and low shear stress (6 +/- 3 and 0.3 +/- 0.1 dyn/cm(2)) and oscillatory shear stress (0.3 +/- 3 dyn/cm(2)). Bradykinin-induced vasorelaxation was drastically decreased in arteries exposed to oscillatory shear stress compared with unidirectional shear stress. Impaired nitric oxide-mediated vasodilation was correlated to changes in both endothelial nitric oxide synthase (eNOS) gene expression and activation in response to bradykinin treatment. This study determined the flow-mediated effects on native tissue perfused with physiologically relevant flows and supports the hypothesis that oscillatory shear stress is a determinant factor in early stages of atherosclerosis. Indeed, oscillatory shear stress induces an endothelial dysfunction, whereas unidirectional shear stress preserves the function of endothelial cells. Endothelial dysfunction is directly mediated by a downregulation of eNOS gene expression and activation; consequently, a decrease of nitric oxide production and/or bioavailability occurs.

Arterial wall response to ex vivo exposure to oscillatory shear stress.

BACKGROUND: The aim of this study was to analyze the arterial wall response to plaque-prone hemodynamic environments, known to occur mainly in areas of arterial trees such as bifurcations and branching points. In these areas, the vasculature is exposed to cyclically reversing flow that induces an endothelial dysfunction predisposing thus arteries to local development of atherosclerotic plaques. METHODS: We used an ex vivo perfusion system that allows culturing arterial segments under different hemodynamic conditions. Porcine carotid arteries were exposed for 3 days to unidirectional high and low shear stress (6 +/- 3 and 0.3 +/- 0.1 dyn/cm(2)) as well as to oscillatory shear stress (0.3 +/- 3 dyn/cm(2)). This latter condition mimics the hemodynamics present at plaque-prone areas. At the end of the perfusion, the influence of different flow patterns on arterial metabolism was assessed in terms of matrix turnover as well as of smooth muscle cell function, differentiation and migration. RESULTS: Our results show that after 3 days of perfusion none of the applied conditions influence smooth muscle cell phenotype retaining their full contraction capacity. However, an increase in the expression level of matrix metalloproteinase-2 and -9, as well as a decrease in plasminogen activator inhibitor-1 expression were observed in arteries exposed to oscillatory shear stress when compared to arteries exposed to unidirectional shear stress. CONCLUSION: These observations suggest that plaque-prone hemodynamic environment triggers a vascular wall remodelling process and promotes changes in arterial wall metabolism, with important implication in atherogenesis.

Functional, mechanical and geometrical adaptation of the arterial wall of a non-axisymmetric artery in vitro.

OBJECTIVE: Vascular remodeling is an adaptive response to variations in the hemodynamic environment acting on the arterial wall. Remodeling translates into changes of structure, geometry and mechanical properties of the artery. Our aim was to study the remodeling response of pig right common carotid arteries in vitro. METHODS: In vivo right carotid arteries are exposed to a non-uniform hemodynamic environment and exhibit a strong wall asymmetry in the circumferential direction that allows the study of two regions separately, as the artery remodels under in vitro perfusion. Porcine right common carotid arteries were cultured during 1 day (n = 6), 3 days (n = 6) or 8 days (n = 6) in an in vitro organ culture system, at a constant perfusion pressure of 100 mmHg. Geometrical, histological, biomechanical and biological analysis of the perfused segments was performed at the end of each study. RESULTS: Smooth muscle cell nuclei density and wall thickness remain constant along the culture periods. Elastin and collagen are significantly redistributed to equilibrate their relative content along the vessel circumference. The distensibility profile is significantly different at day 8. Matrix metalloproteinase-2 expression and activity increase significantly at days 3 and 8. CONCLUSION: The non-axisymmetric arterial wall adapts to a uniform hemodynamic environment by redistributing the structural components of the extracellular matrix. The changes of collagen and elastin density may result from a vascular remodeling process involving matrix metalloproteinase-2 up-regulation and enzymatic activity. The remodeling response results in a new vascular wall configuration that is more distensible at physiological pressures (30-120 mmHg) and stiffer at higher pressures.

Biomechanical adaptation of porcine carotid vascular smooth muscle to hypo and hypertension in vitro.

Previous research in arterial remodeling in response to changes in blood pressure seldom included both hyper- and hypotension. To compare the effects of low and high pressure on arterial remodeling and vascular smooth muscle tone and performance, we have utilized an in vitro model. Porcine carotid arteries were cultured for 3 days at 30 and 170mmHg and compared to controls cultured at 100mmHg for 1 and 3 days. On the first and last day of culture, pressure-diameter and pressure-wall thickness curves were measured under normal smooth muscle tone using a high-resolution ultrasonic device. Last-day experiments included measurements where vascular smooth muscle was contracted or totally relaxed. From the data wall cross-sectional area, Hudetz elastic modulus and a contraction index related to the diameter reduction under normal smooth muscle tone were calculated. We found that although wall cross-sectional area (indicating wall mass) did not change much, Hudetz elastic modulus was significantly reduced in the 3-day hypotension group. Inspection of the wall contraction index suggests that this is due to a reduction in the vascular smooth muscle tone. Further, the peak of contraction index was found to be shifted to higher pressures in the 3-day 170mmHg group. We conclude that vascular smooth muscle performance adapts to both hypo- and hypertension at short time scales and can alter the biomechanics of the vascular wall in vitro.