Cholera vaccine clinical trials: A cross-sectional analysis of clinical trials registries.

Cholera has been one of the world's biggest public health challenges for centuries. The presence of this disease brings into focus the social determinants of health in different parts of the world. Research and development efforts to find safe and effective Cholera vaccines are critical to decreasing the disease burden from Vibrio cholerae. We searched the International Clinical Trials Registry Platform (ICTRP) and Cochrane Central Register of Controlled Trials (CENTRAL) on 5 March 2023. We included all registered randomized trials studying Cholera vaccines. We used Microsoft Excel to perform a descriptive analysis of the source registry, geographic distribution, recruitment status, phase of trials, and type of trial sponsor and presented the findings using tables and graphs. The search of ICTRP yielded 84 trials, and 315 trials were identified from CENTRAL. Seventy-four trials were included in the analysis. Most of the trials (66%, n = 49) were registered in ClinicalTrials.gov, followed by Clinical Trials Registry - India (9%, n = 7) and the Cuban Public Registry of Clinical Trials (8%, n = 6). The geographical distribution of the trials indicates that 48% (n = 36) of the trials were conducted in Asia, followed by 23% (n = 17) in North America, 15% (n = 11) in Africa, and 11% (n = 8) in Europe. Results further indicate that 81% (n = 60) of trials have a recruitment status "Not recruiting," followed by 12% (n = 9) with a status "recruiting." With the recent surge in Cholera cases and the limited supply of Cholera vaccines, research indicates the need for Cholera vaccine trials to ensure the availability of vaccines, especially in populations affected.

Rotavirus vaccine clinical trials: a cross-sectional analysis of clinical trials registries.

BACKGROUND: Rotavirus is a primary infectious virus causing childhood diarrhoea and is associated with significant mortality in children. Three African countries (Nigeria, the Democratic Republic of Congo, and Angola) are among the five countries that account for 50% of all diarrheal-related deaths worldwide. This indicates that much needs to be done to reduce this burden. The World Health Organization International Clinical Trial Registry Platform (WHO ICTRP) is a global repository for primary registries reporting on clinical trials. This study aimed to identify and describe planned, ongoing, and completed rotavirus vaccine trials conducted globally. METHODS: We searched WHO-ICTRP on 17 June 2021 and conducted a cross-sectional analysis of rotavirus studies listed in the database. Data extraction included trial location, participant age, source of the trial record, trial phase, sponsor, and availability of results. We used the Microsoft Excel 365 package to generate descriptive summary statistics. RESULTS: We identified 242 rotavirus vaccine trials registered from 2004 to 2020. Most of these trials were registered retrospectively, with only 26% of the rotavirus vaccine trials reporting the availability of results in their registries. Most of the trials are studying children aged less than 5 years. The recruitment status for these trials is currently shown in the WHO-ICTRP as "not recruiting" for 80.17% of trials, "recruiting" for 11.57% of trials recruiting, and unknown for 6.61% of trials. The continents in which these rotavirus vaccine trials have recruitment sites in Asia (41%) and North America (20%), with the maximum number of trials in the clinical trial registries coming from India (21%) and the USA (11%) with most being sponsored by the pharmaceutical industry. Our analysis shows that only 26% of the rotavirus vaccine trials report the availability of results in their registries. CONCLUSIONS: Mapping rotavirus vaccine clinical trial activity using data from the WHO ICTRP beneficial provides valuable information on planned, ongoing, or completed trials for researchers, funders, and healthcare decision-makers. Despite the high rotavirus disease burden in low- and middle-income countries, including Africa, there is minimal clinical trial activity related to the condition on the continent. The clinical trial registries as a valuable tool to share interim results of the trials.

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. METHODS AND ANALYSIS: We searched the WHO-ICTRP portal (20 January 2019) and the Russian Federation Registry (30 March 2019) to identify TB trials conducted in BRICS countries. We included only registered clinical trials conducted wholly in BRICS countries or with at least one recruitment centre in one of the BRICS countries that were investigating TB treatment. RESULTS: The search of the WHO-ICTRP yielded 408 trials and additional 32 trials were identified from the Russian registry. Of those, 253 were included in the analysis. We found that 77 trials were multicountry trials, followed by trials in China (55), India (53), South Africa (34), Russia (23) and Brazil (11). 163 trials were registered prospectively, 69 retrospectively and 21 trials had no registration status. Most trials (207) evaluated TB treatment, followed by 29 behaviour change interventions, 13 nutritional supplementation, 4 surgical treatment and 2 assessing rehabilitation. Based on ICJME recommendation of publishing 12 months after completion of trial, we found that 156 trials were completed 12 or more months by date and 101 trials had publications. Thirty-one of the 101 trials with publication had evidence of selective outcome reporting. The median time to publication was 25 months (IQR 15-37) from the time of anticipated end date stated in the registry. CONCLUSION: TB trials conducted in BRICS countries are collaborative, mostly drug treatment oriented, potentially affecting policies. Selective outcome reporting remains a problem both for prospectively and retrospectively registered trials, only small fraction of which gets to publication.

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.

Practices and trends in clinical trial registration in the Pan African Clinical Trials Registry (PACTR): a descriptive analysis of registration data.

BACKGROUND: The Pan African Clinical Trials Registry (PACTR) is a WHO International Clinical Trials Registry Platform primary register, which caters for clinical trials conducted in Africa. PACTR is the first and, at present, the only member of the Network of WHO Primary Registers in Africa. The aim is to describe and report on the trends of trial records registered in PACTR. METHODS: PACTR was established in 2007 as the AIDS, Tuberculosis, and Malaria Clinical Trials Registry. The scope of the registry was then expanded in 2009 to include all diseases. This is a cross-sectional study of trials registered in PACTR from inception to 18 August 2021. A descriptive analysis of the use and trends of the following data fields: study intervention, disease condition, sex of the participants, sample size, ethics, funding and availability of results was conducted using Microsoft Excel. RESULTS: The number of trials registered has increased year on year, reaching 606 trials registered in 2020. The total number of trials registered at the time of the analysis was 2998. More than half of the trials in the registry (1655 of 2998, ie, 55%) were prospectively registered. Ethical approval was received by 90% (2691 of 2998) of the registered trials. Factorial assignment as an intervention model was in 20% (589 of 2998) of the trials registered. There were 36% (1083 of 2998) completed trials, of which 3% (94 of 1083) had results available in the registry. The most dominant funding source indicated was self-funding in 23% (693 of 2998) of the registered trials, and 55% (1639 of 2998) had no funding. CONCLUSION: Registration on PACTR continues to grow; however, our analysis shows that researchers' capacity-building is needed to understand the importance of the registry and how this information informs healthcare decisions. Promoting prospective trial registration remains critical to avoid selective reporting bias to inform research gaps.

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.

Cochrane corner: rapid point-of-care antigen and molecular-based tests for the diagnosis of COVID-19 infection.

INTRODUCTION: the COVID-19 pandemic, which results from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents important diagnostic challenges. Diagnostic strategies available to identify or rule out current infection, or to identify people in need of care escalation, or to test for past infection and immune response have become available, to reduce household and community transmission. We highlight a Cochrane review, published in September 2020, on the assessment of diagnostic accuracy of point-of-care antigen and molecular-based tests to determine current SARS-CoV-2 infection. METHODS: the authors of the Cochrane review searched multiple electronic databases for studies, which assessed SARS-CoV-2 infection with a diagnostic test. Eligible participants for the review included people with suspected current SARS-CoV-2 infection, known to have, or not to have COVID-19 infection, or where tests were used to screen for infection. RESULTS: the authors included 18 studies of point-of-care tests conducted in various parts of the world, with none from Africa. The review shows that there is considerable variability in sensitivity and specificity of the antigen tests. The review also shows that molecular tests had less variability in sensitivity and specificity. CONCLUSION: the review suggests that the current evidence is not strong enough to determine the usefulness of point-of-care tests in all settings. However, the benefits are likely to be more noticeable in countries, like Africa where community transmission is high. An impact evaluation would be warranted when rapid point-of-care tests are implemented in African countries.

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.

Cochrane corner: universal screening for SARS-CoV-2 infection.

INTRODUCTION: coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most people infected with SARS-CoV-2 have mild disease with non-specific symptoms, although a few becoming critically ill with septic shock and multiple organ failure. There is an unknown proportion of infected individuals who remain asymptomatic and infectious. Universal screening for COVID-19 infections to detect individuals who are infected before they present clinically could therefore be an important measure to contain the spread of the disease. We highlight a Cochrane rapid review which assessed the effectiveness and accuracy of universal screening for COVID-19 infection. METHODS: the authors of the Cochrane review searched multiple electronic databases to identify studies reporting on the effectiveness of universal screening and reporting on screening test accuracy. Eligible participants for the review included people who had not sought care for potential COVID-19 symptoms. RESULTS: the authors included 22 publications, with none of them conducted in Africa. Two modelling studies reported on the beneficial and negative effects of screening; and 20 studies (cohort and modelling) reported data on the accuracy of screening tests. The included studies had wide variability in the baseline prevalence of COVID-19 infection as well as study settings and methods. All cohort studies compared screening strategies to reverse transcriptase-polymerase chain reaction (RT-PCR) as the gold standard. The rapid review suggests that there is low certainty of evidence that screening at travel hubs may slow the importation of infected cases. Furthermore, the review highlights the uncertainty and variation in the accuracy of screening. CONCLUSION: given the low accuracy of the tests included in this review, a high proportion of COVID-19 infected individuals may be missed and go on to infect others. In addition, some healthy individuals may be falsely identified as positive, requiring confirmatory testing and potentially leading to the unnecessary isolation of these individuals.

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.

Effects of vaccines in protecting against Ebola virus disease: protocol for a systematic review.

INTRODUCTION: Ebola virus disease is one of the most devastating infectious diseases in the world with up to 90% case fatality observed. There are at least 13 candidate vaccines developed and being tested to prevent the occurrence of the Ebola virus disease. While none of these candidate vaccines has received regulatory approval for use, one candidate vaccine (rVSVΔG-ZEBOV-GP) has been granted access for emergency use. Two other candidate vaccines (GamEvac-Combi and Ad5-EBOV) have been licensed for emergency use in their countries of origin. The objective of this systematic review is to summarise the effects of the Ebola candidate vaccines in humans. METHODS AND ANALYSIS: We will search for potentially eligible studies, with no language or date restrictions, in the Cochrane Central Register of Controlled Trials, PubMed, Scopus, the WHO International Clinical Trial Registry Platform, and reference lists of relevant publications. The Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effect (DARE) will be searched for related reviews. Two review authors will independently screen search records, assess study eligibility, perform data extraction, and assess the risk of bias; and reconcile their findings. We will pool data from similar studies using Mantel-Haenszel's fixed-effect model. ETHICS AND DISSEMINATION: This study is exempted from ethical consideration since the data collected are publicly available and at no point will confidential information from human participants be used. We will disseminate our results through publications in peer-reviewed journals and relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42018110505.

A systematic review of strategies for reducing missed opportunities for vaccination.

BACKGROUND: 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.