Research Methodology Study for Podoconiosis Trial
Trudie Lang, Mike Clarke, Fikre Enquoselassie Gashe, Henok Negussie, Meseret Molla, Andy McKay, Esther Kivaya, Jay Berkley, Greg Fegan, Sam Frazen, Tamzin Furtado, Francois van Loggerenberg, Melanie Newport, Gail Davey.
Populations in low and middle-income countries are under-represented in research and the outcome of this inequity is lack of evidence, not just on new drugs and vaccines, but also on ways to improve disease management practices in other ways. There are many publications calling for more pragmatic trials of interventions such as enhanced hygiene measures or better ward management practices and that these need to be designed and led on the ground by those with responsibility for day-to-day care of these situations, supported by the appropriate methodological expertise. Properly conducted studies are important to show that new intervention works, whether it is a new vaccine, or showing that survival improves if you treat pneumonia at home rather than in a hospital, for example. They are also important to show that some interventions, no matter how well-meaning, do not work.
In addition to the deficit in pragmatic trials that address disease management issues there is an increasing international effort to improve clinical trial methods, through clinical trial methodology research.
Clinical trial methodology research is needed to improve the efficiency of clinical trials, which have become too expensive, too cumbersome and too bureaucratic. For these reasons would-be investigators are put off from setting up clinical trials because they perceive them to be too complex and burdensome. Therefore in resource-limited settings there is the combination of a lack of the trials needed to guide policy and practice locally (because such trials are not commercially viable), and a lack of academic-led research because there is insufficient local capacity to take on locally-led studies.
By applying the approach of action research to clinical trial research methodology we propose to examine an example of a highly pragmatic randomised trial in order to establish where the hurdles lie in setting up such a study. Through this process we aim to determine and learn from how the set-up of this study was achieved, in order to encourage and benefit future research teams. It is also hoped that documenting this example will provide a map for others to follow and demonstrate that it can be achieved, and that the processes are adaptable to any research study.
The trial that this study will be examining is called ‘GoLBet’: a randomised trial of podoconiosis treatment in northern Ethiopia. Podoconiosis is a form of lymphoedema (leg swelling) arising in people going barefoot in highland tropical areas. Although rarely a direct cause of mortality, it disables an estimated 4 million subsistence farmers in tropical Africa, greatly reducing productivity, leading to significant stigma from the community as well as health professionals, and low quality of life. Despite the high impact of podoconiosis on rural farming communities, treatment has been hampered by misdiagnosis (chiefly confusion with filarial lymphoedema) and fatalism. Only recently has any form of treatment been offered to people with podoconiosis, and this has grown from grassroots level without systematic evaluation. The intervention has not yet been evaluated through formal research and this needs to happen to provide reliable and robust information on its effects. Currently, there is no government provision of care in Ethiopia, and so for more than 95% of patients, no access to care is available.
This podoconiosis trial is a rare example of a pragmatic trial addressing a highly burdensome disease that impacts populations in very resource-limited settings in countries such as Ethiopia, Uganda and Rwanda. This will help to bring the concept and conduct of methodology research which is taking place with high profile programmes in the US and UK, to low and middle-income countries, in particular to tackle the challenges of disease management trials. Therefore this study, alongside this randomised trial, will provide an exemplar for future studies.
To conduct an action research study alongside the podoconiosis randomised trial to map the process, record and measure all the steps and processes encountered, and capture how any issues were overcome. The data from this study will be made available in as near to real time as possible to guide other researchers. Our aim is to encourage and facilitate more disease management research to benefit local public health issues in resource limited settings.
To determine the factors that impacted the set-up and operation of the GoLBet trial by constructing a process map.
- To gathers metrics data on the process of setting up a pragmatic disease management trial in resource-limited setting.
- To identify and describe the number of steps encountered in the set and conduct of a disease management trial.
- To identify and describe how challenges were overcome in the set up and operation of a pragmatic disease management trial in a resource limited setting.
- To generate guidance notes, tools (e.g. template documents) and examples from the lessons learnt to benefit future researchers.
The trial’s metrics data will be collected, starting from the point of initiation of the grant. This often happens in trials run by the pharmaceutical industry but is rarely shared or published. These data include time from draft to final protocol, number of review committees and time to first and last participant enrolled.
These metrics data will be used to construct a process map that will be developed over the course of the trial through study setup, recruitment, follow-up and closure. The process will end at the point of publication of the trial’s findings. The process map will capture the number of steps and activities along with time taken and resources needed for each of these.
After the trial is initiated and at the end of the trial, members of the research team and key stakeholders from associated organisations will complete questionnaires and some will be interviewed. This qualitative element is important to capture the experience and perspective of those involved in the conduct and management of this trial. Quantitative and qualitative data can be associated with the process map to allow for an interpretation of where issues arose and how these were solved. The solutions will help researchers planning future trials addressing local disease management questions in diseases of poverty, and are also likely to be of benefit to those working in other settings.
This minimal risk observational study will be an action research study. Action research is where the participants in the study are involved in the design, data collection and analysis, and the outcomes can be fed back in an iterative process to improve the situation being studied. We will take this model one step further by making the accumulating data available to others as it is captured in order that it can be taken and implemented in other planned or on-going research studies, without having to wait for the final publication.
This study will use an open access online platform to collect and release data, allowing the process map to be built and released in as close to real-time as possible. The experience data obtained from the interviews and questionnaires will also be added to this map, to enable recommendations to be made.