European & Developing Countries Clinical Trials Partnership

Abstract Research ethics and integrity codes lay the foundation for ethical research. However, stakeholders in research may struggle to move from reading codes to applying them, especially during times of crisis when there is increased uncertainty and risk. To bridge this gap, the PREPARED project team has developed adaptable tools to support implementation of the PREPARED Code for research ethics and research integrity during pandemics. These include training clips to accompany each code article, an experiential learning app, and how-to style guidelines for enhancing the resilience of stakeholder-specific processes. In this chapter, we summarise PREPARED’s approach to code implementation, elaborate on each tool developed, and provide tips for future initiatives seeking to improve the practical application of ethics codes. We also present an example of how our tools were utilised during an African Vaccine Regulatory Forum (AVAREF) training session and provide a resource bank to support the integration of our materials into ethics training programmes.

Aims & Objectives: High pediatric mortality rates are seen in low-resource settings like Malawi. Early recognition of deterioration risks and prioritization of care can help reduce such deaths. Our study predicted factors associated with deterioration in critically ill children in two high-dependency units in Malawi. Methods: A clinical study analyzed 779 children (28 days to 60 months) admitted to paediatric HDUs in Zomba and Blantyre hospitals. The study used Random Forest and XGboost. Data was split into 0.3, and transfer learning was used to create a model on one site and validate on the other Results: Between July 2022 and June 2023, 779 patients were admitted to the HDU and 73(9%) experienced severe events. The child’s temperature (importance score: 0.07), age (0.05), diarrhoea upon admission (0.035), weight (0.034), and the mother’s employment (0.031) were found to predict deterioration. Continuous vital signs also played a crucial role in predicting outcomes, with features such as ECG respiratory rateSD (0.05), SPO2SD(0.032), maximum ECG respiratory rate (0.03), and ECG Heart Rate SD(0.03) demonstrating significance. Both random forest and XGBoost had high accuracy of 0.98 and 0.99, respectively. Precision values were 1 and 0.94, respectively, while recall rates stood at 0.49 and 0.48 for the two models, indicating their ability to capture relevant instances of deterioration. The ROC AUC for the random forest was 0.746, and XGBoost was 0.7393. Conclusions: Our study found predictors of at-risk children in two Malawian HDUs. The model can help in early identification and intervention, reducing adverse outcomes and child mortality.Keywords: Transfer learning, deterioration, High Dependency Unit, Pediatric, Machine Learning

Abstract Background Social network-based interventions can improve uptake of health interventions. However, limited evidence exists on their feasibility and acceptability in fishing community settings. We assessed the feasibility, acceptability and preliminary effects of a social network-based, peer-led HIV self-testing (HIVST) intervention among men in Uganda. Methods The PEer-led HIVST intervention for MEN (PEST4MEN) is a pilot intervention conducted among men (15 + years) in Kalangala and Buvuma island districts. Data were collected between July and September 2022. The intervention was implemented through 22 “peer-leaders” who were trained in HIVST use and distribution processes and requested to refer at least 20 members from their social networks. A total of 475 men were referred; of these, 400 met the study enrolment criteria. Enrolled men were administered a baseline questionnaire and requested to pick two kits from their peer-leaders. The intervention was deemed feasible if > 80% of the kits given to the peer-leaders were distributed to men within their social networks and acceptable if > 80% of those who received the kits used them to self-test for HIV. First-time HIV-positive testers were asked if they linked to HIV care. Data were analyzed using STATA version 16.0. Results Of 400 men, 272 (67.9%) were aged 18–34 years; 227 (56.7%) were engaged in fishing or fishing-related activities while 328 (82%) had ever tested for HIV. Of 361 men (90.2%) interviewed at follow-up, 355 (98.3%) reported that they received kits from their peer-leaders; 352 (99.1%) used them to self-test for HIV. Of those who self-tested, 339 (96.3%) returned used kits for re-reading. Fifty-one men (14.5%) had reactive self-test results; of these, 16 men (31.4%) were first-time HIV-positive testers. Of first-time HIV-positive testers, 14 men (87.5%) went for confirmatory HIV testing, seven men (50%) were confirmed as HIV-positive and five men (71.4%) were linked to HIV care. Conclusion Our peer-led HIVST intervention was feasible and acceptable and identified a sizeable proportion of previously undiagnosed HIV-positive men who were linked to HIV care. However, while these results are promising, we recommend additional research in a large study, preferably in other fishing community settings, prior to the roll-out of this intervention. Trial registration ClinicalTrials.Gov: NCT05685498 (retrospectively registered on January 17, 2023).

Research for health and development (R4HD) acknowledges that many of the determinants of health lie outside the boundaries of the health system. The size and quality of the health and care workforce (HCWF) are key drivers towards the future trajectory of many of these factors. We consider researchers for health and development an abiding, pervasive but neglected constituent part of this HCWF. This workforce straddles many professional groups and sectors. The diversity of occupations, lack of standardization in occupational cadres, the complexity and gendered aspects of the labour market, and the variable demographic, epidemiological, socio-economic and health systems’ contexts in the global south and the global north, led to a kaleidoscopic perception of the health research workforce that have kept it hidden from public opinion. This led to neglect by science as well as health policymakers and created an orphan sub-set of the HCWF. Understanding the health researchers’ labour market will help to identify means to develop, retain and utilize the health research workforce, addressing size, composition, role, skills transferability, careers and social impact through building, enabling or sustaining its research functions, capacity, employment opportunities and career tracks, among other issues. This thematic series of the Human Resources for Health Journal, calls for papers that go beyond narrow conceptual approaches and professional understandings of health care workers and the health research workforce, and requests that contributors examine important workforce issues through the broad lens of R4HD within a sustainable development goals framework.

There is stark global inequity in health research in terms of where studies happen, who leads the research and the ultimate beneficiaries of the results generated. Despite significant efforts made, limited research ideas are conceptualised and implemented in low-resource settings to tackle diseases of poverty, and this is especially true in sub-Saharan Africa. There is strong evidence to show that the barriers to locally led research do not vary largely between disease, study type and location and can be largely solved by addressing these common gaps. The European & Developing Countries Clinical Trials Partnership (EDCTP) was established in 2003 as a European response to the global health crisis caused by the three main poverty-related diseases HIV, tuberculosis and malaria. EDCTP has established a model of long-term sustainable capacity development integrated into clinical trials which addresses this lack of locally led research in sub-Saharan Africa, supporting the development of individual and institutional capacity and research outputs that change the management, prevention and treatment of poverty-related and neglected infectious diseases across Africa. In recognition of emergent data on what the barriers and enablers are to long-term, sustainable capabilities to run studies, EDCTP formed a new collaboration with The Global Health Network (TGHN) in September 2017, with the aim to make a set of cross-cutting tools and resources to support the planning, writing and delivery of high-quality clinical trials available to research staff wherever they are in the world, especially those in low- and middle-income countries (LMICs) via TGHN platform. These new resources developed on the ‘EDCTP Knowledge Hub’ are those identified in the mixed method study described in this commentary as being key to addressing the gaps that the research community report as the most limiting elements in their ability to design and implement studies. The Knowledge Hub aims to make these tools freely available to any potential health research team in need of support and guidance in designing and running their own studies, particularly in low-resource settings. The purpose is to provide open access to the specific guidance, information and tools these teams cannot otherwise access freely. Ultimately, this will enable them to design and lead their own high-quality studies addressing local priorities with global alignment, generating new data that can change health outcomes in their communities.

Abstract Mycoplasmas have exceptionally streamlined genomes and are strongly adapted to their many hosts, which provide them with essential nutrients. Owing to their relative genomic simplicity, Mycoplasmas have been used for the development of chassis to deploy tailored vaccines. However, the dearth of robust and precise toolkits for genomic manipulation and tight regulation has hindered any substantial advance. Herein we describe the construction of a robust genetic toolkit for M. pneumoniae, and its successful deployment to engineer synthetic gene switches that control and limit Mycoplasma growth, for biosafety containment applications. We found these synthetic gene circuits to be stable and robust in the long-term, in the context of a minimal cell. With this work, we lay a foundation to develop viable and robust biosafety systems to exploit a synthetic Mycoplasma chassis for live attenuated vaccines or even for live vectors for biotherapeutics.

The recognition and progression of an academic or research career is hinged on the number and quality of publications in high-impact journals. Open access publication, especially in high-impact journals, confers a significant citation (ie, recognition and progression) advantage.1 However, there is increasing demand for publication fees or article processing charges (APCs), by high-impact open access journals. Where does this leave African researchers who earn too little (personal income or research grants) to publish in such top-tier open access journals? Already, Africa contributes much too little (1.3% in one estimate) to research publication output globally,2 of which 52% are accounted for by just three middle-income countries—South Africa, Nigeria and Kenya. The local and global challenges that limit the publication and citation potential of African researchers are well known. For example, at the local level, there are very few full-time researchers (5 per million people in low-income countries vs 363 per million people in high-income countries),3 with weak investment in research (and academic writing) capacity,4 research infrastructure and research governance.5 And at the global level, there are exploitative international research collaborations, gender constraints affecting female researchers6 and inability to attract global research funding. Now, APCs are systematically excluding African researchers from publishing in high-impact open access journals. Researchers in Africa are typically not in a position to win or have access to grants that cover APCs as eligible research expenditure. A 2018 analysis showed that countries of the WHO African region received only 0.65% of global research grants.3 This is not peculiar to Africa—for example, in Pakistan, only 2% of researchers had received more than two research grants 15 years after doctoral training.7 In 2008, WHO African region adopted the Algiers Declaration—to invest 2% of member countries’ national health budget in health research. But …

More than 40 agencies that fund health research capacity strengthening in low- and middle-income countries (LMICs) participate in the ESSENCE Health Research initiative, which has established a mechanism for reviewing and coordinating their funding. Taken together, the expected outcomes of implementation of the review mechanism are increases in the efficiency and equity in health research capacity strengthening activities with decreased duplication of efforts. The overall goal is increased support of research on national health priorities as well as improved pandemic preparedness in LMICs, and, eventually, fewer countries with very limited research capacity.

BackgroundHealth challenges and health systems set-ups differ, warranting contextualised healthcare interventions to move towards universal health coverage. As such, there is emphasis on generation of contextualized evidence to solve local challenges. However, weak research capacity and inadequate resources remain an impendiment to quality research in the African region. WHO African Region (WHO AFR) facilitated the adoption of a regional strategy for strengthening national health research systems (NHRS) in 2015. We assessed the progress in strengthening NHRS among the 47 member states of the WHO AFR.MethodsWe employed a cross sectional survey design using a semi structured questionnaire. All the 47member states of WHO AFR were surveyed. We assessed performance against indicators of the regional research strategy, explored facilitating factors and barriers to strengthening NHRS. Using the research barometer, which is a metric developed for the WHO AFR we assessed the strength of NHRS of member states. Data were analysed in Excel Software to calculate barometer scores for NHRS function and sub-function. Thematic content was employed in analysing the qualitative data. Data for 2014 were compared to 2018 to assess progress.ResultsWHO AFR member states have made significant progress in strengthening their NHRS. Some of the indicators have either attained or exceeded the 2025 targets. The average regional barometer score improved from 43% in 2014 to 61% in 2018. Significant improvements were registered in the governance of research for health (R4H); developing and sustaining research resources and producing and using research. Financing R4H improved only modestly. Among the constraints are the lengthy ethical clearance processes, weak research coordination mechanisms, weak enforcement of research laws and regulation, inadequate research infrastructure, limited resource mobilisation skills and donor dependence.ConclusionThere has been significant improvement in the NHRS of member states of the WHO AFRO since the last assessment in 2014. Improvement across the different objectives of the regional research strategy is however varied which compromises overall performance. The survey highlighted the areas with slow improvement that require a concerted effort. Furthermore, the study provides an opportunity for countries to share best practice in areas of excellence.

The European and Developing Countries Clinical Trials Partnership (EDCTP) was established in 2003 to accelerate the development of medical interventions for tuberculosis (TB), human immunodeficiency virus (HIV) and malaria, with a particular focus on Phase II and III clinical trials. Between 2003 and 2015, the first EDCTP programme committed €65.6 million to research on TB and TB-HIV co-infection. The programme made a significant contribution to the first three elements of the DOTS TB control strategy, which mobilised European and African funding for TB-related research and generated important evidence on TB diagnostics and treatment regimens. As well as informing the development of international policy on TB diagnosis and treatment, the programme also significantly enhanced the capacity of countries in sub-Saharan Africa to undertake clinical trials and associated clinical research. The lessons learned from the first EDCTP programme have informed the development of a second, expanded EDCTP programme, EDCTP2, which was launched in 2014, and is due to run until 2024. One key lesson is the need for continued partnerships to fight the global threat of TB.