LSHTM has a strong track record of conducting large-scale trials on the control of infectious diseases especially in low- and middle-income settings in collaboration with long-standing partners in West, East and Southern Africa. Many of these trials have resulted in major changes to national, regional and international policy. Tuberculosis (TB), malaria, HIV, vaccine preventable diseases and neglected tropical diseases (NTDs) have been particular areas of focus. See selected highlights from a subset of this substantial body of work.

HIV

Our work in the field of HIV has spanned all aspects of the care cascade from primary prevention through to management of complications of advanced HIV. LSHTM led the ground-breaking PopART study on community-wide implementation of HIV testing and anti-retroviral therapy in Zambia and South Africa. This trial provided crucial evidence underpinning the adoption of the universal testing and treatment strategy which now plays a key role in achieving the WHO 95-95-95 targets for HIV control. Investigators at LSHTM also co-ordinated the AMBITION study, the world’s largest trial of treatment for cryptococcal meningitis, paving the way for new therapies to be adopted worldwide for the treatment of this important HIV-associated complication. 

Tuberculosis

LSHTM's TB studies are wide-ranging, in particular in the context of HIV, including on preventative therapy, contact tracing, treatment and diagnostic strategies. The STAMP trial conducted in Malawi and South Africa was the first trial to demonstrate reduction in mortality from HIV-associated TB due to application of a diagnostic test and has had a major impact on the adoption of urine-based screening tests for TB. 

Neglected Tropical Diseases

LSHTM has run key trials on the control and elimination of NTDs. Amongst the most pivotal were a series of trials evaluating novel treatments for the elimination of trachoma, the commonest infectious cause of blindness worldwide. Much of this work was conducted in collaboration with the MRC Unit The Gambia, the Kilimanjaro Centre for Community Ophthalmology and the Ethiopian Federal Ministry of Health. These studies now underpin the SAFE WHO strategy for trachoma elimination. Currently LSHTM is leading a large study, Stronger-SAFE, which is aiming to strengthen current control efforts in order to help achieve elimination of trachoma by 2030.  

Malaria

LSHTM has played a significant role in trials of a range of strategies to control malaria. These studies have provided much of the global evidence underpinning key tools such as bed-nets, chemoprevention, vaccines and combination strategies. Recent LSHTM led studies demonstrated that combining malaria vaccines with chemoprophylaxis is a particularly effective tool for reducing mortality related to malaria.   

Vaccines

LSHTM has helped deliver critical studies on a wide range of vaccines and demonstrated the effectiveness of a new generation of conjugate vaccines. This work has underpinned their adoption by WHO. For example, LSHTM has played a leading role in research on the pneumoccocal vaccine in East and West Africa for almost two decades. Similarly, studies run by LSHTM have provided critical evidence on the effectiveness and optimal dosing schedule for controlling human papillomavirus (HPV) which is the commonest cause of cervical cancer.  

LSHTM has a strong portfolio of trials in non-communicable diseases (NCDs).

Cardiovascular disease

The Clinical Trials Unit cardiovascular team specialises in the design, conduct and analysis of multicentre clinical trials.

Alcohol reduction

LSHTM's work is centred around testing low-intensity and contextually relevant interventions aimed at improving access to care for individuals with alcohol use disorders. By focusing on interventions that are adapted to the specific context, the research aims to address the challenge of poor access to care for individuals dealing with alcohol-related issues. This approach aligns with the broader goal of making psychological treatments more widely available, particularly in routine health-care settings. The emphasis on context-specific interventions is a recognition of the importance of tailoring strategies to the unique circumstances and needs of the population. The work contributes to the ongoing efforts to bridge the treatment gap for alcohol use disorders, ultimately seeking to enhance the overall accessibility and effectiveness of interventions for individuals with harmful drinking behaviours.

Eye health

The International Centre for Eye Health has been involved with a diverse set of clinical trials for eye health. These have included: 

• mHealth solutions to identify adults and schoolchildren with eye problems and to connect them to services in Kenya
• surgical interventions such as strengthening training of eye doctors to carry out cataract surgery
• laser therapy for glaucoma in Nigeria and Tanzania
• trials for the diagnosis of diabetic eye disease in Tanzania using artificial intelligence.
   

Trials can be used to assess not only pharmacological or other bio-medical interventions but also educational, social and behavioural interventions. There is a long history of evaluating such interventions using randomised trials, for example in the fields of education and social work. 

Complex interventions 

Complex interventions involve multiple activities that interact not only with each other but also with the context in which they are delivered. Complex interventions may be used in public health to prevent diseases or promote positive health or wellbeing. They may also be used in health services or social care to educate or change the social practices or behaviours of patients, clients, carers or clinical professionals.  

For example, the Learning Together intervention to prevent bullying involved the students and staff of English secondary schools working together to plan and deliver various activities to prevent or respond to bullying. The way in which the intervention was implemented and the precise mechanisms through which this prevented bullying varied between different sorts of school, illustrating an interaction with context.

The complexity in the Learning Together intervention is probably true of many public health, health services and social care interventions involving social interactions. Even where interventions involve administering a medicine or undertaking a clinical procedure, they will tend to involve social interactions and so in this sense are complex. If interventions are complex, it is important that trials do more than just evaluate overall effectiveness.

Trials of complex interventions often include process evaluations to examine intervention delivery and mechanisms of action, and how these vary between different sites and populations. Because complex interventions are rooted in social interactions, it is likely that qualitative research (interviews or observations) will be a necessary part of process evaluations to understand these interactions. It is important that trials evaluate educational, social and behavioural interventions both to ensure effective interventions are scaled up appropriately and that harmful interventions are stopped.

The Programme for Evidence to Inform Disability Action (PENDA) incorporates much of LSHTM’s research on disability, including through the conduct of impact evaluations of interventions, primarily using randomised controlled trials (RCTs).

PENDA is a consortium led by the  International Centre for Evidence in Disability and funded by the UK Foreign, Commonwealth and Development Office (FCDO). Part of the PENDA project is conducting impact evaluations (primarily RCTs) of interventions designed to improve the well-being of people with disabilities in low- and middle-income countries. The interventions assessed include programmes focused on livelihood development, access to health and addressing violence and discrimination.

PENDA trials include:  

• A non-randomised control trial of a “Cash-Plus” programme in the Xiengkhouang Province of Laos. The programme involves a regular cash transfer, family support delivered to caregivers to improve their skills and understanding of disability and provision of assistive devices for children with disabilities. The evaluation will assess the impact of the programme on child and caregiver well-being and household poverty. The follow-up period is two years.  
• A cluster RCT of the Paediatric Development Clinic/Baby Ubuntu programme implemented by Partners in Health in Rwanda. The Paediatric Development Clinic provides early care for young children at risk of developmental disability and monitors development and growth, whilst providing support to caregivers. Baby Ubuntu is a structured programme for children with a developmental disability and their caregivers, provided over 11 sessions by a health professional and trained caregiver. The study will adopt a cluster randomised controlled design across three districts of Rwanda, with a 12-month follow-up period. Key outcomes include the participation of children in family and community life, caregiver knowledge and family quality of life. 
• A cluster RCT of an inclusive sexual and reproductive health programme that was developed to increase access to modern contraceptive methods and reduce unmet need for family planning for women of reproductive age with disabilities in Kaduna city, Nigeria. The trial has a 12-month follow-up and the primary outcome measure is access to family planning.  

The Nutrition Group has expertise in designing and conducting clinical trials to generate evidence for improved nutrition outcomes. Topics span fundamental nutrition metabolism, severe malnutrition treatment programme design, and the design and evaluation of complex multisectoral interventions. The group works primarily in resource-poor contexts, with a range of partners including universities, government departments, NGOs and multilateral organisations.

Micronutrient supplementation and metabolism 

Several trials in the Nutrition Group have focused on micronutrient supplementation and health outcomes. The Nutrition & Planetary Health team based at the MRC Unit The Gambia conducts micronutrient trials in mothers and babies with a major focus on preventing iron deficiency and anaemia. The ENID and INDiGO trials test the individual and additive effects of multiple micronutrient supplementation in pregnancy and infancy. The Vitality trial has tested whether supplementation with vitamin D and calcium optimises musculoskeletal health among peripubertal children with HIV in Zimbabwe and Zambia. Comprehensive Anaemia Programme and Personalised Therapies (CAPPT) was a cluster-randomised controlled trial testing home visiting, iron supplementation, participatory learning and action groups, plus routine antenatal care on haemoglobin among pregnant women in southern Nepal. 

Treatment of severe malnutrition 

Members of the Nutrition Group are lead investigators on trials which aim to improve the management of severe malnutrition in infants and children. For example, the team is working with Jimma University Ethiopia, Goal Ethiopia and the Emergency Nutrition Network on a large cluster- randomised trial exploring a new care pathway to improve the management of small and nutritionally at-risk infants aged under 6 months.

Food and agriculture interventions 

The Nutrition Group has run several trials to generate evidence on food and agriculture-led interventions to improve nutrition and health. The Action Against Stunting Hub is conducting two trials on the impacts of an egg intervention on pregnancy outcomes in Indonesia and on infant growth, development and micronutrient status in India. The cluster-randomised Upscaling Participation and Videos for Agriculture and Nutrition (UPAVAN) trial demonstrated that a set of nutrition-sensitive agriculture interventions was effective at improving child and maternal diet diversity in rural India. The Addressing Hidden Hunger with Agronomy (AHHA) trial demonstrated that consumption of maize flour, biofortified with selenium fertiliser, was effective at correcting selenium deficiency among women and children in a rural community setting in Malawi.  

LSHTM is involved in a wide range of trials in maternal, newborn and child health (MNCH), often involving multi-disciplinary teams and contributing to complex interventions.

Maternal health

The WOMAN trial showed that early administration of tranexamic acid reduces death from bleeding in trauma and postpartum haemorrhage. Advocacy on the importance of tranexamic acid for treatment of postpartum haemorrhage and further research through WOMAN-2 continue to promote the role of tranexamic acid in addressing global maternal mortality.

Newborn health

Neonatal trials include the Operationalising Kangaroo Mother Care Before Stabilisation Amongst Low Birth Weight Neonates in Africa (OMWaNA) trial of early kangaroo mother care for hospitalised neonates weighing less than 2000 g in The Gambia; and the Pre-delivery Administration of Azithromycin to Prevent Neonatal Sepsis & Death (PregANZI-2) trial of azithromycin during labour to reduce neonatal deaths in Burkina Faso and The Gambia. 

Child health

LSHTM has extensive experience in researching new treatments for childhood infections including neglected tropical diseases such as schistosomiasis. This includes the ‘Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance’ (MORDOR) trial of mass administration of azithromycin to young children in Malawi and the Praziquantel in Preschool Children (PIP) trial, a randomised controlled trial aiming to find the right dose of the only available drug to treat schistosomiasis in preschool children in Uganda and the Philippines. Results of the PIP trial will inform WHO policies on schistosomiasis control.

LSHTM has led the development and evaluation of tools for preventing major childhood infections including vaccines, insecticide-treated nets and drugs for prophylaxis. The Vaccine Centre and the Malaria Centre at LSHTM act as the focal areas for research on vaccines and malaria.

Examples include large trials of new generation pyrethroid-piperonyl butoxide nets to prevent malaria in Tanzania, South Africa and Uganda; vaccine trials such as the Pneumovac trials in The Gambia; and cluster randomised controlled trials of seasonal malaria chemoprophylaxis in West Africa.

The Child Health Intervention for Developmental Outcomes (CHIDO) trial in Zimbabwe explored early childhood development, parenting, economic resilience, retention in HIV care, and care outcomes among HIV-exposed and infected infants aged 0-2 years.

LSHTM has numerous projects in the area of early child development. The Sustainable Program Incorporating Nutrition and Games (SPRING) trial is a recently completed seven-year research programme funded by the Wellcome Trust that brought together researchers from the UK, India and Pakistan. Every Newborn – Simplified Measurement Integrating Longitudinal Neurodevelopment & Growth (EN–SMILING) extends other EN–BIRTH research to include metrics for child development and promotes early identification of adverse developmental outcomes. Building on this, Every Newborn – Reach up Early Education intervention for All Children (EN–REACH) is a randomised trial of 150 clusters in three countries evaluating a preschool readiness package.

Sexual and reproductive health (SRH) is a long-standing focus area for LSHTM with trials of multi-faceted approaches and covering different areas of SRH and in different settings, including health facilities, schools and other community-based settings in the UK and internationally.  

A major area is sexual health promotion: Examples include a whole-school social marketing intervention to promote sexual health among secondary school students (the Positive Choices Trial) and the use of mhealth technologies such as text messages to promote safer sex, provide support and information to prevent unplanned pregnancies in the UK (safetxt), and a trial to promote uptake and continuation of contraception use among women in Bangladesh. Seminal trials are focusing on menstrual health, a hugely neglected issue.  The MENISCUS trial is evaluating the impact of a multi-component menstrual health intervention in Ugandan secondary schools on girls’ education, health and wellbeing.  

HIV prevention 

LSHTM has a well-established track-record of highly impactful work on HIV prevention with trials of biomedical, social and structural interventions. Examples of ongoing trials include: 

• A trial evaluating demand for HIV pre-exposure prophylaxis (PREP) in Uganda and South Africa and an HIV prophylactic vaccine trial in Uganda 
• A trial of differentiated prevention and care to reduce the risk of HIV acquisition and transmission among female sex workers as part of the AMETHIST consortium in Zimbabwe. 

Sexually transmitted infections 

LSHTM is a world-leader in research on sexually transmitted infections (STIs) and is a WHO collaborating Centre for STIs. The STI Research Interest Group at LSHTM promotes and disseminates research, facilitates cross-disciplinary and cross-faculty research work on STIs and HIV and facilitates internal and external collaborations.  LSHTM has been involved in policy-changing studies of the human papillomavirus (HPV) vaccine. 

Major trials include: 

• a cluster randomised controlled trial investigating the impact of point-of-care testing and treatment of STIs in antenatal care on birth outcomes in Papua New Guinea 
• the IMPROVE trial focusing on preventive therapy for malaria combined with azithromycin for prevention of STIs 
• a trial in Zambia is investigating self-sampling for schistosomiasis as well as other genital tract infections 
• the STICH trial investigating the impact of community-based screening for STIs among youth on population-level prevalence. The STICH trial is embedded in a larger trial (CHIEDZA) which is investigating the provision of a comprehensive package of SRH services with integrated HIV services.