Dr Tommy Rampling is the lead medical doctor on the first human Ebola vaccine trial at the Jenner Institute in Oxford. The trial examines the safety of two separate vaccines, as well as their ability to generate an immune response against Ebola.
Rampling has a strong sense of purpose in the importance of this mission, telling me, “Before the latter part of 2014, these vaccines had never been given to humans. Our aim, therefore, is firstly to demonstrate that these
vaccines are safe. The next real question is whether or not this vaccine schedule will work.
“There is no safe way of definitively answering that question in the UK, but after the vaccines have been given we can look at some specific parts of the immune system, such as antibodies and T-cells, to look for activation against parts of the Ebola virus. This will give some indication as to which strategies are worth pursuing further in the countries worst affected by the current outbreak.”
The issue that seems to dominate the fight against Ebola is the problem of adapting normal clinical trial practice to the extraordinary situation of an epidemic. A key aspect is the length of time it takes to get the trial running – 18 months in normal practice. However, where there is a will, there is a way, and Rampling has been surprised by the speed of progress, “What has been exceptional for this particular trial has been the speed and flexibility of the relevant authorities in expediting our applications in the face of a global health crisis.”
Once the trial gets regulatory and ethical approval, the next step is to recruit volunteers. As this trial is for a vaccine, it can take place in Oxford, unlike Peter Horby’s trial of potential cures, which, for obvious reasons, can only test those already infected with Ebola and therefore must be based in West Africa.
The selection of volunteers is a rigorous process. As Rampling describes, “Volunteers are identified by response to ethically approved adverts, and if suitable for the trial, they are invited to attend a face-to-face screening. This involves a thorough explanation of the trial, including the risks, with one of the trial doctors.
“If they are happy to proceed, and sign the consent form, we assess their medical health through a history examination and blood and urine tests. If, after all of this, the volunteers meet all of the requirements, they are offered an appointment for vaccination.”
The initial results of these trials have been promising, and using some of the information gained from them, the Jenner Institute is now working in collaboration with the University of Maryland to run a similar trial in Mali.
The planned West African trials pose a very different set of challenges for Rampling and his colleagues, differences he is keen to stress in full. “A major difference will be the size of the studies. The African studies will need to be much larger than the early studies in order optimise the ‘power’ of the study to quantify the effect of the vaccine. Several trial designs have been proposed, each requiring several thousand subjects to be vaccinated to generate meaningful results.
“Furthermore, in order to detect a vaccine effect, the vaccinated group will need to be compared to an unvaccinated ‘control’ group who are at a similar risk of disease. This raises difficult ethical questions as to how best to fairly conduct these trials, and has been the subject of much discussion in the international scientific community.
“Finally, there are cultural differences, such as the scarcity of staff and resources, the difficulty of procedures (e.g. blood taking), all of which may put trial staff at risk of infection, and require that many adaptations to the trial design must be made to be suitable for the environment.”
Added to all of this is a new challenge, one that gets a conflicted response from Rampling, namely the recent fall in the number of new Ebola cases. For Rampling, “The decline in case incidence in the affected countries is extremely encouraging from a humanitarian and a global health perspective but it does pose novel challenges for analysing the effectiveness of drug therapies and vaccines. It is critical, therefore, to adapt scientific strategies to tackle this issue.
“Although there has been a sharp decrease in new cases in some regions of the worst affected countries, it is likely that there will continue to be sporadic outbreaks of disease in towns and villages for some time to come. New trial designs have been proposed that are suited to answering the key questions in this evolving disease burden.
“The global scientific community is in agreement that we must continue to act quickly and effectively, and glean as much information as we can from this tragic outbreak, so we can prevent similar occurrences in the future.”
Other articles in this investigation:
- “Should we give these experimental drugs to children?” – Tom Carter talks to Professor Peter Horby about his role as the head of an Oxford research group carrying out clinical trials of potential cures.
- Is it Britain’s humanitarian duty to aid affected countries?– Hannah Foxton asks whether we have a moral obligation to provide support to the Ebola-stricken countries.