Dr Trudie Lang
| Research Area: | Global Health |
|---|---|
| Technology Exchange: | Drug discovery and Medical statistics |
| Keywords: | clinical trials, GCP, Informed consent, Trial design, Trial operations and Trial regulations |
Global Health Clinical Trials
Principal Investigator Trudie Lang
The goal of Global Health Trials is to promote and make easier the conduct of non-commercial clinical research across all diseases in resource-poor settings.
Background
Clinical trials establish the evidence base for prevention and treatment of disease and are critically important in the field of Global Health. This importance is threefold: there is the greatest potential for improving health in numerical terms, there is enormous potential gain from relatively simple interventions, and developing countries have been under represented in clinical trials to date.
Clinical trials in developing countries typically have endpoints that are severe disease outcomes or mortality. They more often involve children and are sponsored by not-for-profit organisations. There are also specific situations that merit more and better clinical trials to inform policy such as disease outbreaks, including those with pandemic potential, in displaced populations, refugee camps and natural disasters. These very specialist situations and environments need a research focus in order to identify highly practical and appropriate interpretation of guidelines and regulations to enable rapid and flexible trial implementation whilst maintaining the same degree of attention to ethical standards and to quality of processes and data as any international trial.
There is a high level of activity with externally sponsored product development trials. However disease management trials are equally important and product development trials alone do not leave sites with the ability to run their own broad programmes. To encourage more locally led trials we need to support researchers and provide skills and guidance in setting questions and operating protocols.
Objectives
We have established a dedicated, collaborative, non-disease-specific web forum to help clinical researchers with trial operations, design, methods and interpretation of regulations. Global Health Trials offers guidance whilst also identifying problems and potential solutions and encouraging the sharing of best practices. Using a participatory mixed methods action research approach we are conducting methodology research to identify the real barriers and issues. The data gathered is being used to continuously update the web forum and to develop resources and guidance to enable the conduct of clinical trials to be both appealing and straightforward.
The main objective of this research is to identify where the interpretation of GCP and other regulatory requirements is problematic in resource poor settings and quantify the impact these issues are having. The identification of the problems will lead to studies that will generate new tools that will be made available on the web forum. This is a continuous iterative process so continuing the theme of participatory action research, with the web forum providing the open-access, open source and fully collaborative vehicle.
There is a need for well trained and qualified clinical trialists to lead and design their own trial programmes in developing countries in order to catch up with the career structures in the west. Therefore another aim of this collaboration is to develop training courses and resources to meet specific gaps. At present there are diplomas and MSc clinical trial courses that are taught and available through distance learning. Whilst these are good, they are focused on industry and US/European regulatory needs. Our research will also help to guide the design and content of courses specifically focused on developing country clinical trials based on what we have shown to work locally in vulnerable populations.
Our findings will also enable funders interested in capacity building to direct their resources appropriately and product developers to select trial sites. Although we are focusing our research on tropical medicine we expect some of our findings to be generally applicable to anyone engaged in non-commercial trials.
| Name | Department | Institution | Country |
|---|---|---|---|
| Kathryn Maitland | FEAST trial | Uganda, Tanzania, Kenya | |
| Dr Raghib Ali MRCP | Cancer Epidemiology Unit | Oxford University | UK |
| Prof Jeremy Farrar | Tropical Medicine | Oxford University | UK |
| Prof Rosanna Peeling | London School Hygiene and Tropical Medicine | UK | |
| Dr Catherine (Sassy) Molyneux | Tropical Medicine | Oxford University | UK |
2011. Strengthening the informed consent process in international health research through community engagement: The KEMRI-Wellcome Trust Research Programme Experience. PLoS Med, 8 (9), pp. e1001089. | Read more
2011. Use of deferred consent for severely ill children in a multi-centre phase III trial. Trials, 12 pp. 90. Read abstract | Read more
Voluntary participation of a subject in research respects a subject's rights, strengthens its ethical conduct, and is formalized by the informed consent process. Clinical trials of life-saving interventions for medical emergencies often necessitate enrollment of patients where prior written individual informed consent is impossible. Although there are regulations and guidelines on protecting subjects in emergency research, these have been criticised for being limited and unnecessarily restrictive. Across Europe and the United States stringent regulations have resulted in a substantial decline of clinical trials involving emergency interventions. Hide abstract
2011. Clinical research: time for sensible global guidelines. Lancet, 377 (9777), pp. 1553-1555. | Read more
2011. Advancing global health research through digital technology and sharing data. Science, 331 (6018), pp. 714-717. Read abstract | Read more
The imperative for improving health in the world's poorest regions lies in research, yet there is no question that low participation, a lack of trained staff, and limited opportunities for data sharing in developing countries impede advances in medical practice and public health knowledge. Extensive studies are essential to develop new treatments and to identify better ways to manage healthcare issues. Recent rapid advances in availability and uptake of digital technologies, especially of mobile networks, have the potential to overcome several barriers to collaborative research in remote places with limited access to resources. Many research groups are already taking advantage of these technologies for data sharing and capture, and these initiatives indicate that increasing acceptance and use of digital technology could promote rapid improvements in global medical science. Hide abstract
2011. Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial. Lancet Infect Dis, 11 (2), pp. 102-109. Read abstract | Read more
RTS,S/AS01E is the lead candidate malaria vaccine. We recently showed efficacy against clinical falciparum malaria in 5-17 month old children, during an average of 8 months follow-up. We aimed to assess the efficacy of RTS,S/AS01E during 15 months of follow-up. Hide abstract
2010. Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children. PLoS One, 5 (11), pp. e14090. Read abstract | Read more
The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1∶1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme. Hide abstract
2010. Diverse ethics of translational research in the developing world. Am J Bioeth, 10 (8), pp. 41-42. | Read more
2010. Clinical research in resource-limited settings: enhancing research capacity and working together to make trials less complicated. PLoS Negl Trop Dis, 4 (6), pp. e619. | Read more
2009. Malaria vaccine trial endpoints - bridging the gaps between trial design, public health and the next generation of vaccines PARASITE IMMUNOL, 31 (9), pp. 574-581. | Read more
2006. A phase 2b randomised trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya. PLoS Clin Trials, 1 (6), pp. e29. Read abstract | Read more
The objective was to measure the efficacy of the vaccination regimen FFM ME-TRAP in preventing episodes of clinical malaria among children in a malaria endemic area. FFM ME-TRAP is sequential immunisation with two attenuated poxvirus vectors (FP9 and modified vaccinia virus Ankara), which both deliver the pre-erythrocytic malaria antigen construct multiple epitope-thrombospondin-related adhesion protein (ME-TRAP). Hide abstract
2006. Beyond registration - measuring the public-health potential of new treatments for malaria in Africa LANCET INFECT DIS, 6 (1), pp. 46-52. | Read more
2005. New TB vaccine granted orphan drug status BRIT MED J, 331 (7530), pp. 1476-1476. | Read more
The Global Health Clinical Trials : Clinical Trial Research Methods
The Global Health Clinical Trials Programme is led from the University of Oxford's Centre for Tropical Medicine and aims to facilitate the conduct of high quality and diverse clinical research in resource limited settings. We do this through our web-based platform that provides resources, guidance, networking, e-learning and career support for researchers based in developing countries. The ability to design, manage and govern clinical research in developing countries lags behind wealthier ...
