Planned, ongoing and completed tuberculosis treatment trials in Brazil, Russia, India, China and South Africa: A 2019 cross-sectional descriptive analysis

Tuberculosis (TB) remains a deadly challenge globally and Brazil, Russia, India, China and South Africa (BRICS) are among the countries with the highest TB burden. The objective of this study is to identify and describe ongoing, planned and completed TB trials conducted in the BRICS countries registered in WHO-International Clinical Trial Registry Platform (WHO-ICTRP); to report selective outcome reporting by comparing primary outcomes in published trials with their prespecified outcomes in registry records and to evaluate the time to publication

Randomised trials of COVID-19 vaccines in Africa – charting the path forward.

Vaccines have played a critical role in controlling disease outbreaks, hence the proliferation of the development and testing of multiple vaccine candidates during the COVID-19 pandemic. Randomised trials are gold standards for evaluating the safety and efficacy of pharmaceutical interventions such as COVID-19 vaccines. However, contextual differences may attenuate effects of COVID-19 vaccines. Thus, the need to conduct COVID-19 vaccine trials in all settings, including in Africa. We conducted a crosssectional analysis of planned, ongoing, and completed COVID-19 vaccine trials in Africa. We searched the South African National Clinical Trials Register, Pan African Clinical Trials Registry, and International Clinical Trials Registry Platform (ICTRP) on 12 January and 30 April 2022; and complemented this with a search of ClinicalTrials.gov on 17 May 2022. We screened the search output and included randomised trials with at least one recruitment site in Africa. We identified only 108 eligible trials: 90 (83%) evaluating candidate COVID-19 vaccines, 11 (10%) assessing if existing vaccines could prevent SARS-CoV-2 infection, and 7 (7%) evaluating interventions for improving COVID-19 vaccination coverage. South Africa had the highest number of trials at 58 (54%). Beyond South Africa, countries with more than 10 trial sites include Kenya, Ghana, Egypt, Uganda, and Zimbabwe. Among the trials, 14 (13%) do not have principal investigators based in Africa, 39 (30%) are funded by industry, and 91 (84%) are funded by institutions based outside the host country. COVID-19 vaccine trials with recruitment sites in Africa represented only 7% of the 1453 COVID-19 vaccine trials in the ICTRP. The paucity of COVID-19 vaccine trials conducted on the African continent is a cause for concern. This has implications for the role that Africa may play in future pandemics.Significance:• There are generally very few vaccine trials conducted in Africa, relative to the rest of the world.• The limited vaccine trials in Africa could be attributed to limited expertise and resources, both human and material, as well as lack of perceived market.• It is reassuring that many COVID-19 vaccines are planned, being conducted, or have been conducted in multiple African countries; but there is a need for more African public sector funding for vaccine trials on the continent

Clinical trial registration during COVID-19 and beyond in the African context: what have we learned?

Since the outbreak of COVID-19, many lives have been impacted especially on the African continent which is already fighting the burden of multiple diseases of poverty. However, clinical research has offered hope for treatment and prevention options for this infectious disease. Despite many COVID-19 clinical trials conducted globally, three countries in Africa account for more than 80% of all trials from the continent registered trials in clinical trial registries. This indicates geographic disparity among COVID-19 research in Africa. From the perspective of clinical trial registration, transparency in clinical research and the availability of data became important for making informed decisions to manage the pandemic. Registries serve as a source of planned, ongoing, and completed trials while allowing efficient funding allocation for research that would not duplicate efforts. Additionally, research gaps can be identified, which provide opportunities for collaboration among researchers. Therefore, a critical lesson learnt during this pandemic is that clinical trial registration is important in facilitating the process of tracking changes made to protocols and minimizing publication bias, thereby promoting and advocating for clinical research transparency. Moreover, registration in a clinical trial registry is a condition for publication and allows for trial summary results to be publicly available. Adhering to the principle of results sharing is especially important for the rapidly growing clinical research activities racing to find evidence-based interventions to end the COVID-19 pandemic

Tuberculosis treatment intervention trials in Africa: A cross-sectional bibliographic study and spatial analysis

Background Mycobacterium Tuberculosis (TB) poses a substantial burden in sub-Saharan Africa and is the leading cause of death amongst infectious diseases. Randomised controlled trials (RCTs) are regarded as the gold standard for evaluating the effectiveness of interventions. We aimed to describe published TB treatment trials conducted in Africa. Methods This is a cross-sectional study of published TB trials conducted in at least one African country. In November 2019, we searched three databases using the validated Africa search filter and Cochrane’s sensitive trial string. Published RCTs conducted in at least one African country were included for analysis. Records were screened for eligibility. Co-reviewers assisted with duplicate data extraction. Extracted data included: the country where studies were conducted, publication dates, ethics statement, trial registration number, participant’s age range. We used Cochrane’s Risk of Bias criteria to assess methodological quality. Results We identified 10,495 records; 175 trials were eligible for inclusion. RCTs were published between 1952 and 2019. The median sample size was 206 participants (interquartile range: 73–657). Most trials were conducted in South Africa (n = 83) and were drug therapy trials (n = 130). First authors were from 30 countries globally. South Africa had the most first authors (n = 55); followed by the United States of America (USA) (n = 28) and Great Britain (n = 14) with fewer other African countries contributing to the first author tally. Children under 13 years of age eligible to participate in the trials made up 17/175 trials (9.71%). International governments (n = 29) were the most prevalent funders. Ninety-four trials provided CONSORT flow diagrams. Methodological quality such as allocation concealment and blinding were poorly reported or unclear in most trials. Conclusions By mapping African TB trials, we were able to identify potential research gaps. Many of the global north’s researchers were found to be the lead authors in these African trials. Few trials tested behavioural interventions compared to drugs, and far fewer tested interventions on children compared to adults to improve TB outcomes. Lastly, funders and researchers should ensure better methodological quality reporting of trials

Description of vaccine clinical trials in Africa: a narrative review

Clinical research is important in establishing the effects of health-care interventions. Vaccine clinical trials are to examine the effectiveness and safety of vaccines for the prevention of diseases. Africa has a high burden of infectious diseases such as malaria, tuberculosis, HIV/AIDS, and Ebola virus disease. Here we report a database surveillance study of vaccine-related clinical trials conducted in Africa. An objective is to address and profile vaccine clinical trials conducted in Africa. Data were extracted from the WHO International Clinical Trials Registry Platform on 22 July 2018 and updated on 05 September 2019. We found that 61% of the 377 clinical trials were registered prospectively and 35% registered retrospectively. About 72% of the trials were single-country studies and within the country, most trials (86%) were single-center studies. The proportion of trials involving multiple African countries was 11% and that of trials involving countries outside of Africa was 16%. The biggest funder of the vaccine trials (34%) was industry, followed by governments (25%) and universities (21%). The most studied diseases were malaria (20%), HIV/AIDS (15%), tuberculosis (7%), and Ebola virus disease (6%). Most of the vaccine trials were conducted in adults (42%). The trials ranged from phase I to phase IV, with most of the trials being in phase I (18%) and phase III (18%). The conduct of vaccine clinical trials in Africa seeks to address the disease epidemics faced by the continent. There is a need for more investments from governmental bodies toward vaccine research in Africa. Further, African country collaborations are needed in efforts to find African solutions to the current infectious disease threats faced by the continent

A systematic review of strategies for reducing missed opportunities for vaccination

CITATION: Jaca, A. et al. 2018. A systematic review of strategies for reducing missed opportunities for vaccination. Vaccine, 36(21):2921-2927, doi:10.1016/j.vaccine.2018.04.028.The original publication is available at https://www.sciencedirect.com/journal/vaccineBackground: Missed opportunities for vaccination (MOVs) occur when persons eligible for vaccination visit a health facility and do not get the vaccines they need. We conducted a systematic review to assess effects of interventions for reducing MOVs. Methods: We searched PubMed, Scopus, and the Cochrane Central Register of Controlled Trials in April 2017. Three authors independently screened search outputs, reviewed potentially eligible papers, assessed risk of bias, and extracted data; resolving disagreements by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Results: Six studies (five trials and one cohort study) met our inclusion criteria, all conducted in the United States of America. All six studies had various limitations and were classified as having a high risk of bias. We found moderate certainty evidence that the following interventions probably improve vaccination coverage: patient education (RR 1.92, 95% CI 1.38–2.68), patient tracking using community health workers (RR 1.18, 95% CI 1.11–1.25), and patient tracking and provider prompts (RR 1.24, 95% CI 1.18–1.31). In addition, we found low certainty evidence that concurrent interventions targeting health-facility (education, prompts, and audit and feedback) and family settings (phone calls) may increase vaccination coverage (RR 1.25, 95% CI 1.08–1.46). Conclusions: The currently available evidence suggests that patient education, patient tracking, outreach sessions, and provider prompts reduce missed opportunities for vaccination and improve vaccination coverage. Rigorous studies are required to confirm these findings and increase the certainty of the current evidence base. WHO is currently coordinating efforts to generate such evidence, especially from low-income and middle-income countries, and it is likely that the data will be available in the next few years.https://www.sciencedirect.com/science/article/pii/S0264410X18305115Publisher's versio

Randomised trials of COVID-19 vaccines in Africa – charting the path forward

Vaccines have played a critical role in controlling disease outbreaks, hence the proliferation of the development and testing of multiple vaccine candidates during the COVID-19 pandemic. Randomised trials are gold standards for evaluating the safety and efficacy of pharmaceutical interventions such as COVID-19 vaccines. However, contextual differences may attenuate effects of COVID-19 vaccines. Thus, the need to conduct COVID-19 vaccine trials in all settings, including in Africa. We conducted a cross-sectional analysis of planned, ongoing, and completed COVID-19 vaccine trials in Africa. We searched the South African National Clinical Trials Register, Pan African Clinical Trials Registry, and International Clinical Trials Registry Platform (ICTRP) on 12 January and 30 April 2022; and complemented this with a search of ClinicalTrials.gov on 17 May 2022. We screened the search output and included randomised trials with at least one recruitment site in Africa. We identified only 108 eligible trials: 90 (83%) evaluating candidate COVID-19 vaccines, 11 (10%) assessing if existing vaccines could prevent SARS-CoV-2 infection, and 7 (7%) evaluating interventions for improving COVID-19 vaccination coverage. South Africa had the highest number of trials at 58 (54%). Beyond South Africa, countries with more than 10 trial sites include Kenya, Ghana, Egypt, Uganda, and Zimbabwe. Among the trials, 14 (13%) do not have principal investigators based in Africa, 39 (30%) are funded by industry, and 91 (84%) are funded by institutions based outside the host country. COVID-19 vaccine trials with recruitment sites in Africa represented only 7% of the 1453 COVID-19 vaccine trials in the ICTRP. The paucity of COVID-19 vaccine trials conducted on the African continent is a cause for concern. This has implications for the role that Africa may play in future pandemics. Significance: There are generally very few vaccine trials conducted in Africa, relative to the rest of the world. The limited vaccine trials in Africa could be attributed to limited expertise and resources, both human and material, as well as lack of perceived market. It is reassuring that many COVID-19 vaccines are planned, being conducted, or have been conducted in multiple African countries; but there is a need for more African public sector funding for vaccine trials on the continent

Randomised trials of COVID-19 vaccines in Africa – charting the path forward

Vaccines have played a critical role in controlling disease outbreaks, hence the proliferation of the development and testing of multiple vaccine candidates during the COVID-19 pandemic. Randomised trials are gold standards for evaluating the safety and efficacy of pharmaceutical interventions such as COVID-19 vaccines. However, contextual differences may attenuate effects of COVID-19 vaccines. Thus, the need to conduct COVID-19 vaccine trials in all settings, including in Africa. We conducted a crosssectional analysis of planned, ongoing, and completed COVID-19 vaccine trials in Africa. We searched the South African National Clinical Trials Register, Pan African Clinical Trials Registry, and International Clinical Trials Registry Platform (ICTRP) on 12 January and 30 April 2022; and complemented this with a search of ClinicalTrials.gov on 17 May 2022. We screened the search output and included randomised trials with at least one recruitment site in Africa. We identified only 108 eligible trials: 90 (83%) evaluating candidate COVID-19 vaccines, 11 (10%) assessing if existing vaccines could prevent SARS-CoV-2 infection, and 7 (7%) evaluating interventions for improving COVID-19 vaccination coverage. South Africa had the highest number of trials at 58 (54%). Beyond South Africa, countries with more than 10 trial sites include Kenya, Ghana, Egypt, Uganda, and Zimbabwe. Among the trials, 14 (13%) do not have principal investigators based in Africa, 39 (30%) are funded by industry, and 91 (84%) are funded by institutions based outside the host country. COVID-19 vaccine trials with recruitment sites in Africa represented only 7% of the 1453 COVID-19 vaccine trials in the ICTRP. The paucity of COVID-19 vaccine trials conducted on the African continent is a cause for concern. This has implications for the role that Africa may play in future pandemics. SIGNIFICANCE: • There are generally very few vaccine trials conducted in Africa, relative to the rest of the world. • The limited vaccine trials in Africa could be attributed to limited expertise and resources, both human and material, as well as lack of perceived market. • It is reassuring that many COVID-19 vaccines are planned, being conducted, or have been conducted in multiple African countries; but there is a need for more African public sector funding for vaccine trials on the continent.hj2022Paediatrics and Child Healt

Mobile reporting of vaccine stock-levels in primary health care facilities in the Eastern Cape Province of South Africa: perceptions and experiences of health care workers

The use of mobile and wireless digital technologies – mobile health (mhealth)- is increasingly been adopted in low- and middle-income countries (LMICs) to improve data visibility, improve decision-making, and consequently help ensure availability of health commodities in health facilities. In a bid to improve availability of medicines in primary health care facilities, the South African department of Health launched the Stock Visibility Solution (SVS), a mobile application developed for the purpose of capturing and monitoring stock levels of medicines including vaccines using mobile phones. The stock levels of medicines in facilities are usually uploaded to the central stock management system so that managers can act promptly to address stock-out situations. Pilot studies show that the SVS has the potential to reduce stock-outs from occurring. This study aimed to explore the perceptions and experiences of the SVS system amongst healthcare workers (HCWs) who are involved with managing stock levels of medicines in primary health care facilities in the Eastern Cape Province. This will help identify potential barriers and facilitators to implementation of the system and contribute to the development of strategies to improve its efficiency and effectiveness. A qualitative research design was employed, including semi-structured interviews with 64 HCWs working in primary health care facilities in the OR Tambo district, Eastern Cape Province in South Africa. Data was transcribed verbatim and analyzed using thematic analysis. Most HCWs understood the SVS as a system for reporting stock levels to managers and conveyed commitment to ensuring the system works. However, they highlighted a number of factors that demotivated efficient usage of the system: inadequate training, staff shortages and high staff turnover, lack of responses from the managers, the extra workload that comes with the system, amongst others. HCWs made various suggestions for how the system might be improved, most pertinently the need for more pharmacists and pharmacy assistants and for these cadres to be primarily in-charge of stock management and the use of the SVS. While HCWs are committed to addressing vaccine stock-outs, they face various barriers to an effective and efficient implementation of the SVS system. We make various recommendations for how these barriers might be addressed