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Risk and complexity-based assessment of trials would improve trial conduct, reduce costs, and enable key elements such as quality management to be more likely to pick up real issues that impact trial outcomes, rather than the one-size-fits-all approach to clinical trial monitoring (often described as \"tick box checking\") [14]. [...]the globalisation of clinical trials should not be about running inexpensive trial sites to benefit distant people, but should focus on bringing research to populations who have previously been under-represented in clinical trials, and enabling these same communities the benefits resulting from new drugs, vaccines, and improvements in managing health.

The next emergent novel pathogen is likely to occur where the ability to undertake health research and collect life-saving data is lacking. Without embedded and ongoing research activities in place spotting and stopping a new threat is not possible, thereby enabling undetected infection and unchecked transmission within a community. Without local existing capabilities to collect such data delay is catastrophic. Fundamental goals in pandemic preparedness should be to stop an outbreak before it becomes a pandemic. This requires immediate action from teams already in place with the right skills, this could be readily achieved if we shift our thinking and enable research capabilities to be present in every healthcare setting. Addressing fundamental gaps in health research capacity and equity could tackle this and then we would be better prepared, globally.

ObjectivesA key barrier in supporting health research capacity development (HRCD) is the lack of empirical measurement of competencies to assess skills and identify gaps in research activities. An effective tool to measure HRCD in healthcare workers would help inform teams to undertake more locally led research. The objective of this systematic review is to identify tools measuring healthcare workers’ individual capacities to conduct research.DesignSystematic review and narrative synthesis using Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for reporting systematic reviews and narrative synthesis and the Critical Appraisals Skills Programme (CASP) checklist for qualitative studies.Data sources11 databases were searched from inception to 16 January 2020. The first 10 pages of Google Scholar results were also screened.Eligibility criteriaWe included papers describing the use of tools/to measure/assess HRCD at an individual level among healthcare workers involved in research. Qualitative, mixed and quantitative methods were all eligible. Search was limited to English language only.Data extraction and synthesisTwo authors independently screened and reviewed studies using Covidence software, and performed quality assessments using the extraction log validated against the CASP qualitative checklist. The content method was used to define a narrative synthesis.ResultsThe titles and abstracts for 7474 unique records were screened and the full texts of 178 references were reviewed. 16 papers were selected: 7 quantitative studies; 1 qualitative study; 5 mixed methods studies; and 3 studies describing the creation of a tool. Tools with different levels of accuracy in measuring HRCD in healthcare workers at the individual level were described. The Research Capacity and Culture tool and the ‘Research Spider’ tool were the most commonly defined. Other tools designed for ad hoc interventions with good generalisability potential were identified. Three papers described health research core competency frameworks. All tools measured HRCD in healthcare workers at an individual level with the majority adding a measurement at the team/organisational level, or data about perceived barriers and motivators for conducting health research.ConclusionsCapacity building is commonly identified with pre/postintervention evaluations without using a specific tool. This shows the need for a clear distinction between measuring the outcomes of training activities in a team/organisation, and effective actions promoting HRCD. This review highlights the lack of globally applicable comprehensive tools to provide comparable, standardised and consistent measurements of research competencies.PROSPERO registration numberCRD42019122310.

Infectious disease burden is dynamic and devastating across the globe. We need to better understand and predict these threats to mitigate harm from new, re-emergent and endemic pathogens. 3,752 globally diverse participants took part in this two-step, mixed-methods adapted Delphi study. Firstly, an online survey asked health workers and researchers to identify the infectious diseases they considered to be at greatest risk of escalation in their setting, along with the factors driving this. Secondly, structured thematic workshops were hosted in Africa, Asia and Latin America, to allow in-depth exploration of the factors driving the prioritisation of these diseases. Participants considered the primary threat to be the escalation of high burden, endemic diseases, rather than emerging or re-emerging pathogen outbreaks. This was driven by the high prioritisation of vector-borne diseases (primarily malaria and dengue), tuberculosis, and HIV/AIDS. Whilst the main finding from survey responses (n = 3,700) identified growing concern over tuberculosis, participants in the subsequent workshops (n = 169) emphasised the increasing threat of vector-borne diseases. Participants considered the impact of climate change, socioeconomic factors and increasing drug resistance patterns to be driving the escalation of these diseases. This study provides striking new insight into priority infection threats due to the large scale of participation, breadth of stakeholder experience, and wide global representation. These factors allowed us to accurately determine the consensus of a substantial component of the global infectious disease research community and share unprecedented insights from the lived experience of researchers and health workers in low resource settings. We consider these perspectives particularly valuable given the absence of biological data that concurrently assesses all infectious diseases across global regions at a single point in time. Our findings represent an important new evidence-based alarm call; the next pandemic may not be a sudden event, but a slow, ‘creeping catastrophe’, impacting the most impoverished regions and communities. We need to respond now, having heard these important, consistent opinions from these previously unheard and collective voices.

Many studies needed to quell this and future pandemics are not being done, and the chance is ebbing away. Many studies needed to quell this and future pandemics are not being done, and the chance is ebbing away. “We need to start asking the right questions, right now.”

TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Pan African Clinical Trials Registry PACTR201501000997429.

When people fail to stay at home or seek medical care, is it because they do not trust public-health messages or because they need to earn money for food? Without effective drugs or vaccines, we rely on case detection, contact tracing and public-health measures such as social distancing and stay-at-home orders. By seeing ideas as a portfolio, we'll avoid pouring funds into so many hospital-based clinical trials assessing essentially the same interventions while neglecting research on public trust, transmission from animals or lab-based tests on stored samples.

Background There is vast global inequality regarding where health research happens, who leads the research, and who benefits from the evidence. Globally, wealthier nations drive and influence data-driven research and how it is structured institutionally. Key barriers to high-quality research being undertaken in and led by low-resource settings are well reported. These barriers persist, thereby perpetuating a lack of locally generated data and/or evidence to tackle diseases that bring the greatest burden. Our aim was to design a tool to capture best practices in the production of data-driven health research, to advance both quality and quantity of research being conducted where it is needed most. Methods An expert group of senior global health researchers from Asia, Africa, Europe, and Latin America and the Caribbean (LAC) convened to discuss potential solutions to addressing this imbalance in both quality and quantity of global health research. This study documents how a novel approach was developed, informed by this discussion, to support research teams in low-resource settings. The new approach, called “Pathfinder”, is a process-mapping tool wherein teams document key steps of their research projects flow to produce quality data and subsequent studies. Results The Pathfinder methodology is a novel tool to be used alongside planned studies to guide teams through each step of their research, from setting their research question, to identifying the best methods needed to complete each step, to translating research outputs into impactful policy and practice. It is a standardized framework, which can be applied or adapted to specific settings for research teams track to key steps, challenges, solutions, and tools throughout their planned study’s process. Pathfinders can also be applied to studies that have already been completed, retroactively documenting their key components. Several global research institutes are piloting the Pathfinder methodology. Conclusions Pathfinders can help inform future studies by capturing best practices, thereby removing barriers to research, and addressing global inequality in this domain. Specifically, Pathfinders can help identify the methods and skills needed for teams to produce safe, ethical, and accurate data-driven health research.

The nucleotide analogue brincidofovir was developed to prevent and treat infections caused by double-stranded DNA viruses. Based on in vitro data suggesting an antiviral effect against Ebola virus, brincidofovir was included in the World Health Organisation list of agents that should be prioritised for clinical evaluation in patients with Ebola virus disease (EVD) during the West African epidemic. In this single-arm phase 2 trial conducted in Liberia, patients with laboratory-confirmed EVD (two months of age or older, enrolment bodyweight ≥50 kg) received oral brincidofovir 200 mg as a loading dose on day 0, followed by 100 mg brincidofovir on days 3, 7, 10, and 14. Bodyweight-adjusted dosing was used for patients weighing <50 kg at enrolment. The primary outcome was survival at Day 14 after the first dose of brincidofovir. Four patients were enrolled between 01 January 2015 and 31 January 2015. The trial was stopped following the decision by the manufacturer to terminate their program of development of brincidofovir for EVD. No Serious Adverse Reactions or Suspected Unexpected Serious Adverse Reactions were identified. All enrolled subjects died of an illness consistent with EVD. Due to the small sample size it was not possible to determine the efficacy of brincidofovir for the treatment of EVD. The premature termination of the trial highlights the need to establish better practices for preclinical in-vitro and animal screening of therapeutics for potentially emerging epidemic infectious diseases prior to their use in patients. Pan African Clinical Trials Registry PACTR201411000939962.

Schistosomiasis control mainly relies on preventive chemotherapy with praziquantel (PZQ) distributed through mass drug administration. With a target of 260 million treatments yearly, reliably assessing and monitoring efficacy is all-important. Recommendations for treatment and control of schistosomiasis are supported by systematic reviews and meta-analyses of aggregated data, which however also point to limitations due to heterogeneity in trial design, analyses and reporting. Some such limitations could be corrected through access to individual participant-level data (IPD), which facilitates standardised analyses. A systematic literature review was conducted to identify antischistosomal drug efficacy studies performed since 2000; including electronic searches of the Cochrane Infectious Diseases Group specialised register and the Cochrane Library, PubMed, CENTRAL and Embase; complemented with a manual search for articles listed in past reviews. Antischistosomal treatment studies with assessment of outcome within 60 days post-treatment were eligible. Meta-data, i.e. study-level characteristics (Schistosoma species, number of patients, drug administered, country, etc.) and efficacy parameters were extracted from published documents to evaluate the scope of an individual-level data sharing platform. Out of 914 documents screened, 90 studies from 26 countries were included, enrolling 20,517 participants infected with Schistosoma spp. and treated with different PZQ regimens or other drugs. Methodologies varied in terms of diagnostic approaches (number of samples and test repeats), time of outcome assessment, and outcome measure (cure rate or egg reduction rate, as an arithmetic or geometric mean), making direct comparison of published data difficult. This review describes the landscape of schistosomiasis clinical research. The volume of data and the methodological and reporting heterogeneity identified all indicate that there is scope for an individual participant-level database, to allow for standardised analyses.