Why are emerging countries popular for clinical research?

BACKGROUND: The business of clinical research has changed in the past two decades, shifting from industrialised Western countries to so-called emerging markets such as Eastern Europe, Latin America and Africa. An appraisal of the trends could identify associated factors that may have implications for the local populations and their endemic diseases. OBJECTIVES: To identify potential reasons why emerging countries have become attractive places for international sponsors to conduct their clinical trials. METHODS: Using ClinicalTrials.gov, the Pan African Clinical Trials Registry, the National Health Research Database and the Nigeria Clinical Trials Registry, trend data on clinical research development were determined for two emerging African markets, Nigeria and South Africa (SA), from 2010 to 2018. Also, health data on the two countries from the fact sheets of health statistics of the World Health Organization were compared, as well as regulatory and ethical conditions. Available data were analysed using descriptive statistics and trend analysis. RESULTS: The impact of globalisation is evident from the upward trend in clinical trials in SA before 2010, and the clear downward trend thereafter. One reason for this change could be the alignment of SA's regulatory and ethical frameworks with the Western world. In contrast, the upward trend is only just beginning in Nigeria, with the introduction of ethical/regulatory frameworks, and supportive institutions making the business of clinical research more attractive on an international level. Although the number of international and local sponsors increased in Nigeria from 2010 to 2018, only the latter increased in SA, with the former decreasing over the same period. Overall, there is a mismatch between country-specific diseases and the drugs being tested, to the extent that leprosy, which is endemic in Nigeria, and tuberculosis in SA were not in the list of top 10 study areas in either country. CONCLUSIONS: The globalisation trend is evident in the clinical trials business, but cannot be generalised to all emerging countries. Timing and intensity vary from country to country relative to factors that advance the existing profit-orientated business models of the sponsors. Furthermore, various diseases have been localised, which entails a diversely increasing need for research.

A comprehensive research agenda for zero leprosy.

BACKGROUND: Leprosy control achieved dramatic success in the 1980s-1990s with the implementation of short course multidrug therapy, which reduced the global prevalence of leprosy to less than 1 in 10 000 population. However, a period of relative stagnation in leprosy control followed this achievement, and only limited further declines in the global number of new cases reported have been achieved over the past decade. MAIN TEXT: In 2016, major stakeholders called for the development of an innovative and comprehensive leprosy strategy aimed at reducing the incidence of leprosy, lowering the burden of disability and discrimination, and interrupting transmission. This led to the establishment of the Global Partnership for Zero Leprosy (GPZL) in 2018, with partners aligned around a shared Action Framework committed to achieving the WHO targets by 2030 through national leprosy program capacity-building, resource mobilisation and an enabling research agenda. GPZL convened over 140 experts from more than 20 countries to develop a research agenda to achieve zero leprosy. The result is a detailed research agenda focusing on diagnostics, mapping, digital technology and innovation, disability, epidemiological modelling and investment case, implementation research, stigma, post exposure prophylaxis and transmission, and vaccines. This research agenda is aligned with the research priorities identified by other stakeholders. CONCLUSIONS: Developing and achieving consensus on the research agenda for zero leprosy is a significant step forward for the leprosy community. In a next step, research programmes must be developed, with individual components of the research agenda requiring distinct expertise, varying in resource needs, and operating over different timescales. Moving toward zero leprosy now requires partner alignment and new investments at all stages of the research process, from discovery to implementation.

Neglected tropical diseases in Brazil: lack of correlation between disease burden, research funding and output.

OBJECTIVES: To assess the correlation between the burden of seven priority neglected tropical diseases (NTDs) included in the Brazilian National Agenda of Priorities in Health Research - tuberculosis, Chagas disease, leprosy, malaria, leishmaniasis, dengue and schistosomiasis - and their respective research funding and output. METHODS: This retrospective review obtained data on disease burden from the Global Burden of Disease Study and funding data from open access sources. Publications were retrieved from Scopus and SciELO, and characterised according to the type of research conducted. Correlation between funding, research output and burden was assessed by comparing the 'expected' and 'observed' values for funding and publications relative to the proportional burden for each disease. RESULTS: There was an emphasis in basic biomedical research (average 30% of publications) and a shortage of health policy and systems (average 7%) and social sciences research (average 3%). Research output and funding were poorly correlated with disease burden. Tuberculosis, Chagas disease and schistosomiasis accounted for more than 75% of total NTD-related DALYs, but accounted for only 34% of publications. Leprosy, leishmaniasis and malaria, together, received 49% of NTD-related funding despite being responsible for only 9% of DALYs. CONCLUSIONS: The analysis evidenced a lack of correlation between disease burden, research output and government funding for priority NTDs in Brazil. Our findings highlight the importance of monitoring health needs, research investments and outputs to inform policy and optimise the uptake of evidence for action, particularly in developing countries, where resources are scarce and the research capacity is limited. The results contribute to health policy by highlighting the need for improving coordination of scientific activities and public health needs for effective impact.

OBJECTIFS: Evaluer la corrélation entre la charge de sept maladies tropicales négligées (MTN) prioritaires incluses dans le programme national brésilien des priorités en matière de recherche en santé - tuberculose, maladie de Chagas, lèpre, paludisme, leishmaniose, dengue et schistosomiase - et leurs financements de recherche respectifs et les résultats. MÉTHODES: Cette revue rétrospective a obtenu des données sur la charge de morbidité de l'étude sur la Charge Globale des Maladies et des données de financement provenant de sources en accès publique. Les publications ont été extraites de Scopus et SciELO et caractérisées selon le type de recherche menée. La corrélation entre le financement, les résultats de la recherche et la charge a été évaluée en comparant les valeurs "attendues" et "observées" pour le financement et les publications par rapport à la charge proportionnel de chaque maladie. RÉSULTATS: L'accent a été mis sur la recherche biomédicale fondamentale (en moyenne 30% des publications) et une pénurie de politiques et de systèmes de santé (en moyenne 7%) et de recherche en sciences sociales (en moyenne 3%). Les résultats et le financement de la recherche étaient mal associés à la charge de morbidité. La tuberculose, la maladie de Chagas et la schistosomiase représentaient plus de 75% du total des EVCI, mais ne représentaient que 34% des publications. La lèpre, la leishmaniose et le paludisme, ensemble, ont reçu 49% des financements liés aux MTN alors qu'ils n'étaient responsables que de 9% des EVCI. CONCLUSIONS: L'analyse a mis en évidence une absence de corrélation entre la charge de morbidité, le résultat de la recherche et le financement de la plupart des MTN. Nos résultats soulignent l'importance du suivi des besoins en matière de santé, des investissements dans la recherche et des résultats pour éclairer les politiques et optimiser l'utilisation des données pour l'action, en particulier dans les pays en développement, où les ressources sont rares et la capacité de recherche est limitée. Les résultats contribuent à la politique de santé en soulignant la nécessité d'améliorer la coordination et la planification stratégique des activités scientifiques pour un impact efficace.

The Many Hosts of Mycobacteria 8 (MHM8): A conference report.

Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria (NTM) infections and Buruli Ulcer. To better understand and treat mycobacterial disease, clinicians, veterinarians and scientists use a range of discipline-specific approaches to conduct basic and applied research, including conducting epidemiological surveys, patient studies, wildlife sampling, animal models, genetic studies and computational simulations. To foster the exchange of knowledge and collaboration across disciplines, the Many Hosts of Mycobacteria (MHM) conference series brings together clinical, veterinary and basic scientists who are dedicated to advancing mycobacterial disease research. Started in 2007, the MHM series recently held its 8th conference at the Albert Einstein College of Medicine (Bronx, NY). Here, we review the diseases discussed at MHM8 and summarize the presentations on research advances in leprosy, NTM and Buruli Ulcer, human and animal TB, mycobacterial disease comorbidities, mycobacterial genetics and 'omics, and animal models. A mouse models workshop, which was held immediately after MHM8, is also summarized. In addition to being a resource for those who were unable to attend MHM8, we anticipate this review will provide a benchmark to gauge the progress of future research concerning mycobacteria and their many hosts.

Efectividad de la formación de técnicos de laboratorio para la baciloscopia cutánea y nasal en una institución para la investigación de la lepra en India / No disponible

Durante 2 días, un total de 155 técnicos de laboratorio empleados en distintos laboratorios públicos del gobierno de Tamil Nadu, India, con una experiencia entre 3-25 años, se formaron en la técnica de toma de muestras cutáneas y nasales en el Centro de Enseñanza e Investigación de Chengalpattu entre 2013 y 2014. El objetivo de la formación era centrar su atención en las técnicas de frotis cutáneo y nasal. La formación consistió en demostraciones directas in vivo y formación práctica, evaluación y clasificación de las muestras. Se llevó a cabo una evaluación pre y post formación de cada uno de los participantes. La efectividad de la formación se analizó y había una significativa evidencia (P = 0.004) de que la formación mejor. el conocimiento de los participantes. De promedio, el nivel de conocimientos se incrementó en 10 puntos

A total number of 155 Laboratory Technicians working for the Government of Tamil Nadu, India having an experience of 3 to 25 years in various Public Health Laboratories of the state were deputed to undergo 2 days’ orientation training programme on skin smear and nasal smear techniques at the Central Leprosy Teaching and Research Institute, Chengalpattu in 2013–2014. The aim of the orientation training was to focus their attention on quality skin smear and nasal smear techniques reported by Laboratory Technicians working in various public health laboratories of the state. The training was conducted through live hands-on demonstration, practical performance of trainees and module reading. Pre- and post assessment was carried out for every Laboratory Technician trainee. The effectiveness of this training was analysed and showed that there was strong evidence (P .0.004) that the teaching intervention improves the knowledge of the trainees. On average the level of knowledge improved by approximately 10 points

Onchocerciasis, an undiagnosed disease in Mozambique: identifying research opportunities.

BACKGROUND: The objective of this paper is to summarise and critically review the available data about onchocerciasis in Mozambique, in order to report epidemiological and clinical aspects related to the disease and identify gaps in knowledge. The paper is intended to raise awareness of the existence and importance of this disease and to define research priorities. METHODS: We examined the scarce epidemiological data at our disposal: two diagnostic studies in 1997 and 1998 (first reports on the existence of onchocerciasis in Mozambique), and two Rapid Epidemiological Mapping of Onchocerciasis (REMO) surveys in 2001 and 2007. We examined differences in study designs and methodologies as well as the differing geographical locations to explain the divergence in findings among the studies. RESULTS: Evidence indicates that onchocerciasis is hypoendemic in Mozambique (with national and imported cases), but still largely remains an undiagnosed illness. There is no awareness of the clinical aspects of the disease and nor of the differential diagnosis with lepromatous leprosy and dermatitis caused by Scabies spp. The use of skin biopsy and a symptom screening questionnaire, combined with nodule rate, in the first two studies may have captured even atypical or subacute presentations. Both REMO surveys relied solely on nodule detection and in the six years between the two studies, the prevalence of nodules detected more than doubled. CONCLUSIONS: The epidemiology and clinical aspects of the disease are unknown in Mozambique. Since the last REMO took place in 2007 and since the population is subject to large-scale movement and displacement, it is important to develop tools to identify and analyse populations that are at high risk for onchocerciasis. Cases of onchocerciasis may be misdiagnosed as leprosy or scabies that fail to improve despite being subjected to treatment against leprosy. Techniques to enable a differential diagnosis need to be established by training health professionals on the recognition of this undiagnosed disease. It is equally necessary to identify the blackfly vectors and where they breed.

Leveraging Advances in Tuberculosis Diagnosis and Treatment to Address Nontuberculous Mycobacterial Disease.

The nontuberculous mycobacteria (NTM), defined as any mycobacterial pathogen other than Mycobacterium tuberculosis or Mycobacterium leprae, are a diverse group of pathogens that collectively cause a substantive but often unappreciated worldwide burden of illness. Although NTMs may cause illness similar to M. tuberculosis, these pathogens generally do not respond to classic tuberculosis (TB) drug regimens, resulting in misdiagnosis and poor treatment, particularly in resource-poor settings. Although a few high-quality epidemiologic surveys have been made on the topic, existing evidence suggests that NTM-associated disease is much more common than previously thought: more common than TB in the industrialized world and likely increasing in prevalence globally. Despite this evidence, these organisms remain markedly understudied, and few international grants support basic science and clinical research. Here we suggest that the considerable efforts in developing new treatments and diagnostics for TB can be harnessed in the fight against NTM-associated illnesses.

Comparing cutaneous research funded by the US National Institutes of Health (NIH) with the US skin disease burden.

BACKGROUND: Disease burden should be an important component for guiding research funding. OBJECTIVE: We sought to examine the relationship between dermatologic research funded from 2012 to 2013 by the National Institutes of Health (NIH) and US skin disease burden as measured by disability-adjusted life years in the Global Burden of Disease 2010 study. METHODS: A cross-sectional analysis was independently performed by 2 researchers who matched projects from the 2012 to 2013 NIH Research Portfolio Online Reporting Tools with 15 skin conditions and their respective disability-adjusted life years from Global Burden of Disease 2010. RESULTS: The NIH funded 1108 projects spanning the 15 skin conditions. Melanoma received almost half of the total skin condition budget (49.5%). Melanoma, nonmelanoma skin cancer, and leprosy were funded above what would be suggested by their disease burden, whereas dermatitis, acne vulgaris, pruritus, urticaria, decubitus ulcer, fungal skin diseases, alopecia areata, cellulitis, and scabies appeared underfunded. Bacterial skin diseases, viral skin diseases, and psoriasis were well matched with disease burden. LIMITATIONS: Disease burden is one of many factors that may be used to guide priority-setting decisions. CONCLUSION: Skin disease burden measured by disability-adjusted life year metrics partially correlates with NIH funding prioritization. Comparing US disease burden with NIH funding suggests possible underfunded and overfunded skin diseases.

Research ethics review practices: experiences of the Armauer Hansen Research Institute/All Africa Leprosy and Tuberculosis Rehabilitation and Training Center Ethics Review Committee, Ethiopia.

The need for ethics review committees (ERCs) is imperative in the conduct of research to ensure the protection of the rights, safety and well-being of research participants. However, the capacities of most ERCs in Africa are limited in terms of trained experts, competence, resources as well as standard operating procedures. The aim of this report is to share experiences of one of the local institutional ERCs, the Armauer Hansen Research Institute (AHRI)/All Africa Leprosy and Tuberculosis Rehabilitation and Training Center (ALERT) Ethics Review Committee (AAERC), to other ERCs found in academic and research institutions in the Country. In this report, we used an empirical approach to review archived documents of the AAERC Secretariat to assess the Committee's strengths and weaknesses. The experiences of the AAERC in terms of its composition, routine work activities, learning practices and pitfalls that require general attention are summarized. In spite of this summary, the Committee strongly acknowledges the functions and roles of other ERCs in the Country. In addition, an independent assessment of the Committee's activity in general is warranted to evaluate its performance and further assess the level of awareness or oversights among researchers about the roles of ERCs.

The pits and falls of graphical presentation.

Graphics are powerful tools to communicate research results and to gain information from data. However, researchers should be careful when deciding which data to plot and the type of graphic to use, as well as other details. The consequence of bad decisions in these features varies from making research results unclear to distortions of these results, through the creation of "chartjunk" with useless information. This paper is not another tutorial about "good graphics" and "bad graphics". Instead, it presents guidelines for graphic presentation of research results and some uncommon, but useful examples to communicate basic and complex data types, especially multivariate model results, which are commonly presented only by tables. By the end, there are no answers here, just ideas meant to inspire others on how to create their own graphics.

Comparing cutaneous research funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases with 2010 Global Burden of Disease results.

IMPORTANCE: Disease burden data helps guide research prioritization. OBJECTIVE: To determine the extent to which grants issued by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) reflect disease burden, measured by disability-adjusted life years (DALYs) from Global Burden of Disease (GBD) 2010 project. DESIGN: Two investigators independently assessed 15 skin conditions studied by GBD 2010 in the NIAMS database for grants issued in 2013. The 15 skin diseases were matched to their respective DALYs from GBD 2010. SETTING: The United States NIAMS database and GBD 2010 skin condition disability data. MAIN OUTCOME(S) AND MEASURE(S): Relationship of NIAMS grant database topic funding with percent total GBD 2010 DALY and DALY rank for 15 skin conditions. RESULTS: During fiscal year 2013, 1,443 NIAMS grants were issued at a total value of $424 million. Of these grants, 17.7% covered skin topics. Of the total skin disease funding, 82% (91 grants) were categorized as "general cutaneous research." Psoriasis, leprosy, and "other skin and subcutaneous diseases" (ie; immunobullous disorders, vitiligo, and hidradenitis suppurativa) were over-represented when funding was compared with disability. Conversely, cellulitis, decubitus ulcer, urticaria, acne vulgaris, viral skin diseases, fungal skin diseases, scabies, and melanoma were under-represented. Conditions for which disability and funding appeared well-matched were dermatitis, squamous and basal cell carcinoma, pruritus, bacterial skin diseases, and alopecia areata. CONCLUSIONS AND RELEVANCE: Degree of representation in NIAMS is partly correlated with DALY metrics. Grant funding was well-matched with disability metrics for five of the 15 studied skin diseases, while two skin diseases were over-represented and seven were under-represented. Global burden estimates provide increasingly transparent and important information for investigating and prioritizing national research funding allocations.

Canada's neglected tropical disease research network: who's in the core-who's on the periphery?

BACKGROUND: This study designed and applied accessible yet systematic methods to generate baseline information about the patterns and structure of Canada's neglected tropical disease (NTD) research network; a network that, until recently, was formed and functioned on the periphery of strategic Canadian research funding. METHODOLOGY: MULTIPLE METHODS WERE USED TO CONDUCT THIS STUDY, INCLUDING: (1) a systematic bibliometric procedure to capture archival NTD publications and co-authorship data; (2) a country-level "core-periphery" network analysis to measure and map the structure of Canada's NTD co-authorship network including its size, density, cliques, and centralization; and (3) a statistical analysis to test the correlation between the position of countries in Canada's NTD network ("k-core measure") and the quantity and quality of research produced. PRINCIPAL FINDINGS: Over the past sixty years (1950-2010), Canadian researchers have contributed to 1,079 NTD publications, specializing in Leishmania, African sleeping sickness, and leprosy. Of this work, 70% of all first authors and co-authors (n = 4,145) have been Canadian. Since the 1990s, however, a network of international co-authorship activity has been emerging, with representation of researchers from 62 different countries; largely researchers from OECD countries (e.g. United States and United Kingdom) and some non-OECD countries (e.g. Brazil and Iran). Canada has a core-periphery NTD international research structure, with a densely connected group of OECD countries and some African nations, such as Uganda and Kenya. Sitting predominantly on the periphery of this research network is a cluster of 16 non-OECD nations that fall within the lowest GDP percentile of the network. CONCLUSION/SIGNIFICANCE: The publication specialties, composition, and position of NTD researchers within Canada's NTD country network provide evidence that while Canadian researchers currently remain the overall gatekeepers of the NTD research they generate; there is opportunity to leverage existing research collaborations and help advance regions and NTD areas that are currently under-developed.