NIHRDataInsights/HRCSData huggingface dataset:
Title: Securing the Goalposts on Vaccine Hesitancy
Funder: The British Academy

Abstract: Amidst continually increasing evidence in favour of vaccination, hesitancy is sharply divided along political lines. This project will quantitatively assess to what degree vaccine hesitancy is driven not by a lack of information on COVID-19 and its vaccines, but by politically motivated reasoning and exposure to abundant misinformation. Using a large-scale randomized control trial, we will test scalable interventions to combat misinformation and biased reasoning on vaccination. Ultimately, we hope to deliver communication tools that allow healthcare providers to identify which individuals will be receptive to good faith conversations on the safety and efficacy of COVID-19 vaccination as well as productively engage those who are otherwise determined to reject any information that is perceived to be pro-vaccination. Our approach will adapt the communication tools of “Paradoxical Reasoning” which were developed to unfreeze entrenched beliefs in the context of the most intractable conflicts (e.g., the Israeli-Palestinian border conflict).


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Developing Anti-Viral Paints to prevent surface transmission of Covid-19
Funder: Royal Academy of Engineering

Abstract: The Covid-19 pandemic has highlighted the importance of hygiene. Surfaces around infected people have been shown to contain high levels of virus and provide a potential transmission route. This project aims to develop a novel antiviral paint that can be applied to surfaces to prevent the spread of the disease.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Genome-wide target discovery and validation for fragment-based antibiotic discovery
Funder: LifeArc

Abstract: Lung health is an area of medical need for people with cystic fibrosis (CF). Industry efforts are focused on developing new precision medicines to treat the underlying genetic mutations that cause cystic fibrosis. However, these medicines will not be able to reverse existing lung damage, or eliminate the risk of chronic infection with drug-resistant bacteria. The failure of antibiotics limits life expectancy of people with CF. New antibiotics are needed to counter the growth of antimicrobial resistance, such as Mycobacterium abscessus. Conventional screening of bacteria against chemical libraries is incredibly inefficient because a very large number of drugs are needed to screen all possible chemical shapes One solution is to break drugs down into their basic building blocks, or fragments, and use these to screen against a purified target – such as a protein that is closely associated with a particular disease process. This method enables researchers to work out where the fragments are binding and ‘grow’ or ‘link’ the fragments to build a drug that fits together perfectly. The approach has been successful in developing drugs for cancer and inflammation, but not, as yet, antibiotics. The main challenges with applying this approach to developing new antibiotics are: Finding the best target to attack within the bacteria Working out how to design the antibiotic so the bacteria cannot become resistant Designing drugs that bind to their target well but can also get inside bacteria and stay there, as bacteria are adept at pumping out antibiotics. For this project, the team is aiming to use this fragment based approach to develop novel antibiotics for the bacteria M. abscessus which presents a serious threat to people with CF. The team will systematically analyse all the genes in the bacteria to find those which are most vulnerable to chemical inhibition using advanced gene editing and silencing technologies. They will then use computational biology to discover how best to design antibiotics which are less prone to bacterial resistance. Finally, they will use artificial intelligence to develop rules for building antibiotics that actually get into the bacteria. This approach could overcome the barriers to using rational drug discovery for antibiotics, making it more straightforward to create many new drugs.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: The REACH Study: Exploring patterns of Retention and Engagement Across specialised Care services of HIV
Funder: Department of Health (England)

Abstract: The proposed study will systematically define the patterns of HIV health care attendance in the UK and increase our understanding of the characteristics and contextual factors that make patients more likely to disengage from care. This is essential to inform the design and implementation of effective interventions to improve patient retention. The research will be undertaken in three phases. The first phase will comprise of secondary analysis of the UK CHIC database to examine HIV out-patient attendance patterns. Group-based trajectory modelling will be used to identify clusters of individuals following similar distinctive patterns of outpatient attendance. Logistic regression analyses will be used to predict the probability of an individual being within a particular group according to a particular set of risk factors. In this way emerging subpopulations will be identified and characterised in detail from the complex cohort. We will investigate the potential health impact of disengaging with care in terms of mortality and disease progression and will measure the costs associated with disengagement. A tool to predict ‘retention risk’ will be devised and tested for validity. The tool will be an algorithm for use in clinical practice. The second phase explores the patient experience and uses both quantitative and qualitative methods. According to criteria outlined during phase one of the study HIV patients within each pattern of attendance will be recruited to participate in a questionnaire based survey. Five HIV outpatient centres across London have agreed to participate in the study. This will be followed by a nested sub study of 40 semi-structured interviews to gain in-depth contextual information on patients’ experiences their service preferences and perceived barriers to accessing HV services. Supplementing these will be four community focus groups used to uncover alternative perceptions that may be articulated in a different non-medicalised setting.Within the third phase ten service providers will be surveyed to provide their opinions on barriers to engagement how best to adapt services to optimise patient engagement and what service models would be operationally feasible. Throughout the study a validated framework to enable development of effective behaviour change interventions will be utilised. The outcomes will directly inform innovative service strategies streamlining and building on current initiatives. Preliminary estimates of the costs of these interventions will be determined.The outcomes of this research will represent a tailoring of national HIV services to improve patient-centred care and health outcomes. The importance of optimising service engagement is relevant across NHS services.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFECTION
Title: Therapeutic utility of HCMV strains
Funder: Division for Social Care and Health Research (Wales)

Abstract: The virus called human cytomegalovirus (HCMV) causes life-threatening disease in patients whose immune system is not working correctly (e.g. patients with AIDS or transplant recipients). It is also the leading infectious cause of birth defects. Consequently, the US Institute of Medicine has assigned developing a vaccine against HCMV its highest priority. Producing a vaccine against HCMV poses unique problems In particular a major target of the immune response is directed against proteins that are mutated in HCMV strains that have been grown in the laboratory, thus virus grown in the laboratory cannot be used as a vaccine. We have recently generated a unique culture system that allows HCMV to be grown without risk of these proteins mutating. Using this system, the student will (1) investigate the effects of variations that we have documented in these proteins to determine which HCMV strains are most suitable for generating antibodies; (2) generate and test potential antibodies in the laboratory setting and; (3) investigate whether variations in these proteins result in strains entering cells in different ways.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Development of a new class of antivirals active against pox and herpes viruses using a novel 3D cell culture antivirals testing model
Funder: Division for Social Care and Health Research (Wales)

Abstract: There is a need for improved therapy of many viral infections. Current therapies target structural or functional components of microorganisms, an approach that inevitably leads to the development of drug resistance as the microorganism adjusts to selective pressure by mutation of epitopes and functional centers. New drug development strategies aim to inhibit pathogens by targeting host cells pathways essential for the pathogen’s lifecycle. The proposed research seeks to develop IP for a new class of nucleoside diversomers, dideoxygenated bicyclic pyrimidine nucleoside analogues (ddBCNAs). Our preliminary collaborative work suggests a new mechanism of action for ddBCNAs against human pox and cytomegaloviruses (McGuigan et al., 2004, Bugert et al., 2010). The target appears to be required early in the virus life cycle at the level of the cell cytoskeleton. The mechanism affects the rate of virus lesion development (plaque formation). For the purpose of the PhD project the effect will be further studied in 2D and 3D cell culture systems A novel 3D cell culture system (human tissue equivalent) will be custom designed for the viral agents in question. Tools and data supporting this project have been developed by the named student allowing us to rapidly progress towards our objectives.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: INFECTION
Title: IGRA in Diagnostic Evaluation of Active TB (IDEA)
Funder: Department of Health (England)

Abstract: The aim of this study is to compare the accuracy of diagnostic strategies including a comparison between existing interferon-gamma release assays (IGRAs) and conventional diagnostic testing. The role of IGRAs for participants (including HIV co-infected patients) who have been diagnosed as having suspected active tuberculosis (ATB) will also be defined.The study will determine sensitivity specificity positive and negative predictive values and likelihood ratios of the ELISpot-based IGRA and the ELISA-based IGRA for diagnosis of active tuberculosis in routine clinical practice. The study will be measured against a validated pre-defined composite reference standard for active tuberculosis. Next-generation IGRAs will be evaluated in parallel. The accuracy of these different testing strategies will be compared and an optimal testing algorithm defining the precise role of these technologies in the diagnostic work-up of suspected active tuberculosis in the NHS (National Health Service) will be developed. Health economic analysis from an NHS perspective will determine the cost-effectiveness of each testing strategy following NICE (National Institute for Health & Clinical Excellence) guidelines. The results of this study will influence tuberculosis control and elimination policy here in the UK in Europe and North America.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: CATheter Infections in Children - the CATCH trial
Funder: Department of Health (England)

Abstract: The trial is a pragmatic Phas III 3-arm randomised controlled clinical trial. Treatment allocation cannot be blinded to the clinician responsible for randomising a patient and inserting the central venous catheter (CVC) but will be concealed from patients their parents and PICU personnel responsible for their care.Population:The study population is 1200 children less than 16 years of age admitted to PICU who require insertion of a polyurethane CVC for at least 3 days and who weigh more than 3 kg. We will recruit children from two broad clinical groups: children admitted as planned surgical admissions (about one-third of all admissions) and children admitted as an emergency from the same or another hospital. Approximately 40% of PICU admissions are expected to be eligible. Recruitment targets will be reached if 1 in 4 of these patients are enrolled. As this study involves treatment in an emergency situation we will be requesting ethical approval for a deferred consent process for children admitted as an emergency. The line can then be inserted without any delay and consent/assent will be sought at 48 hours post randomisation or once the patients condition allows. The study will involve 10 UK Paediatric Intensive Care Units (PICUs). Study Duration:Patient follow-up until 48 hours after removal of the randomised CVC will be by the research nurse. Follow-up at 6 months will be ascertained from routine administrative data.Description of Agent/ Intervention: We will randomly allocate children to a standard polyurethane CVC antibiotic impregnated CVC (minocycline and rifampicin) or heparin bonded polyurethane CVC. in a ratio of 1:1:1. Objectives:Primary: To determine the effectiveness of heparin bonded or antibiotic impregnated CVCs compared with standard CVCs for preventing hospital acquired blood stream infection.Secondary Objectives include: Cost effectiveness effectiveness of type of CVC in 3-way comparison for preventing hospital acquired blood stream infection effect of type of CVC on clinical measures of care (duration of CVC insertion antibiotic use and stay) mortality at 30 days and adverse events on pathogen selection antibiotic resistance clinical evidence of CVC thrombosis and thrombocytopenia.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Observational study to estimate the changes in the efficacy of BCG with time since vaccination
Funder: Department of Health (England)

Abstract: Two analytic observational studies will be conducted comparing the frequency of the BCG vaccine in people in people with and without a history of illhealth. Both studies will evaluate how the effect of BCG vaccine changes with time since vaccination. The first study will examine children aged from 0-17 years born when BCG can be given in infancy. The second study will examine an adult age range from 23 to 37 years and aged 13-years old when the pre-2005 school aged BCG programme existed


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Paediatric European Network for the Treatment of AIDS (PENTA)PENTA 16 Trial: Short-Cycle Therapy (SCT) (5 days on/2 days off) in young people with chronic HIV-infection
Funder: Department of Health (England)

Abstract: 160 HIV-1 infected males and females aged 8-21 years will be recruited from paediatric and adolescent hospital clinics in the UK and other European countries as well as Brazil Thailand and Uganda and randomised into two groups:1. Continuous ART2. Short-Cycle therapy (5 days on ART (Mon-Fri or Sun-Thurs) and 2 days off (Sat-Sun or Fri-Sat).Participants will be seen for clinic visits until the last young person recruited has completed 48 weeks of follow-up. Measures such as height weight tanner scales and blood tests are part of their normal routine visit however they will also be asked to complete questionnaires and attend more regular visits for the first 12 weeks.The adherence (MEMS cap) substudy will be carried out in a subset of 60 participants from the UK and Uganda. The study will use Medication Event Monitoring Systems (MEMS) to measure adherence to the protocol for both arms of the trial.The qualitative substudy aims to understand the way in which SCT is experienced and valued and looks at the factors that may hinder SCT implementation into routine therapy through interviews audio diaries and focus groups in 40 participants (20 from UK 20 from Uganda) exploring how young people understand and orientate to the process of adaption and the acceptability of the SCT against continuous treatment along with lifestyle and contextual factors linked to adherence. The trial is funded by the NIHR Health Technology Assessment for UK and Ireland sites only. Funding for other countries will be from the PENTA Foundation.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Adjunctive Rifampicin to Reduce Early mortality from Staphylococcus aureus bacteraemia: a multi-centre randomised double blind placebo controlled trial (the ARREST trial)
Funder: Department of Health (England)

Abstract: Background: Around 12500 cases of Staphylococcus aureus bacteraemia occur each year in the United Kingdom with an associated mortality of about 30% yet the evidence guiding optimum management is poor. We hypothesise that adjunctive rifampicin will enhance killing of Staphylococcus aureus early in the course of antibiotic treatment of bacteraemia sterilise infected foci and blood faster and thereby reduce the risk of dissemination metastatic infection and death.Design: A randomised blinded placebo controlled trial. Eligible patients will be randomised to two parallel arms in a 1:1 ratio: standard intravenous antibiotic therapy of the attending physician’s choice plus either 14 days of placebo or rifampicin (900mg/24hrs if >60kg; 600mg/24hrs if <60kg). Setting: 17 large acute NHS Trusts. Target population: All adults (=18 years) with a pure culture of S. aureus (meticillin-susceptible or resistant) grown from their blood will be eligible. Patients will be excluded if they have received >96 hours of active antibiotic therapy for the current infection. Outcome measurements: The trial’s co-primary outcomes will be (i) all-cause mortality through 14 days and (ii) death or bacteriological failure (microbiologically confirmed treatment failure or disease recurrence) by 12 weeks from randomisation. The secondary endpoints will include duration of bacteraemia; treatment failure by 12 weeks adjudicated by an independent endpoint committee blind to treatment allocation; the development of rifampicin resistant S. aureus; and serious adverse events and reactions. Healthcare-related resource use and EQ-5D will be collected during the trial to determine the cost-effectiveness of rifampicin for S. aureus bacteraemia treatment in the NHS.Sample size: Current data indicate 16% and 24% of all cases of S. aureus bacteraemia die by 14 days and 12 weeks respectively; a further 10% of patients have repeat isolation of S. aureus over the 12 weeks following initial bacteraemia. Assuming at least 80% power two-sided alpha 0.025 and a 10% loss to follow-up by 12 weeks we would need to randomise 940 patients to detect a 30% relative reduction in death/bacteriological failure by 12 weeks and a 45% reduction in death by 14 days.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Update and amalgamation of two Cochrane Reviews: neuraminidase inhibitors for preventing and treating influenza in healthy adults and children
Funder: Department of Health (England)

Abstract: Neuraminidase inhibitors (NIs) have become global public health drugs stockpiled against possible influenza outbreaks. Despite their popularity the discovery of sizeable reporting bias uncertainty over the number of trials run ghost authorship and widespread discrepancies between published and unpublished versions of the same trials have led to a reappraisal of the published evidence and calls for public release of hitherto confidential data. The project aims to review unpublished data on effectiveness and harms of NIs for influenza in all age groups updating and amalgamating two established Cochrane reviews on adults and children. The review will be in two stages. Stage one will identify reconstruct and assess all NI trials conducted to January 2010 using regulatory and pharmaceutical reports. Only reliable* trial data will be included in the second phase of the review (an analysis following standard Cochrane methods).Because of the complexity of our task we have devised four additional types of tools for data management and information: a directory mapping citations to clinical trials in our data sources; its expanded version with annotations; a narrative of our review documenting the evolution of methods and detailed summary of the regulatory documents and a reference resource holding details of all trials. In addition we have created a tool for assessing all known types of reporting bias in trials and sub-trials programmes.*Reliability is made up of 5 aspects:1.Completeness - there is sufficient material to assess the other reliability criteria.2. Internal consistency - all parts of the same CSR/unpublished pharma report are consistent and coherent.3. External consistency - all versions of the various CSR/unpublished pharma reports are consistent and coherent.4. Clarity - all parts and versions allow understanding of the design and conduct of the trial.5. Robustness - exposure of reconstructions to regulatory comments do not lead the majority of voters (at least 4 of 7 in the team) to change the study conclusions or their trustworthiness.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION;6.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Real-time Modelling of a Pandemic Influenza Outbreak
Funder: Department of Health (England)

Abstract: During the 2009 outbreak of pandemic A/H1N1 influenza much attention was devoted to the problem of capturing the epidemic dynamics through real-time modelling. The aim of such modelling was to provide up-to-the-moment assessments of the present and future state of the epidemic based upon continually updated streams of information.In practice as illustrated by the 2009 outbreak direct data are seldom available and multiple sources of data exist each indirectly informing the epidemic development each subject to possible sources of bias. This calls for more complex epidemic modelling that can synthesise the information held within a range of data sources to compensate for the lack of direct observation of the infection process. As a result of this real-time modelling of the 2009 A/H1N1 outbreak proved to be more challenging than had been anticipated.A complex model for epidemic assessment was developed in 2009 integrating a multiplicity of epidemic surveillance data within a statistical modelling framework that accounts for the transmission dynamics of the virus and the healthcare seeking behaviours of a population. The Markov chain-Monte Carlo techniques used require that as new data become available the model has to be re-run in its entirety a computationally expensive process. Therefore as data accumulate more sophisticated algorithms might prove more efficient than this current approach.We believe the application of such algorithms to the problem of real-time epidemic modelling represents a significant challenge yet has the potential to make the process of real-time modelling more tractable permitting the incorporation of larger amounts of data without the attendant computational expense. We propose to build a system which can supply a timely monitoring of any emerging pandemic to policymakers developing a statistical modelling approach that synthesises a wide range of surveillance data as well as prior beliefs from historical epidemics.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: INFECTION