Interview: Peter Horby

The key statistic is 9,353. That is the number of people who the World Health Organisation (WHO) has estimated have died of Ebola since the beginning of the current outbreak until February 16th of this year.

In the fight against Ebola, there are two parallel efforts: the attempt to find a vaccine, and the attempt to find a cure for those already infected. Peter Horby, as the Group Leader of Oxford’s Epidemic Diseases Research Group, is leading Oxford’s contribution to finding a cure. His role involves running the clinical trials needed to establish which drugs work and are safe to use. However, with the current circumstances far from ideal for a clinical trial, these trials bring up all sorts of ethical concerns.

The first issue was about whether there should be any trials at all. For, as Horby says, “None of the Ebola specific therapies had completed safety evaluations in healthy adults, so there were some questions about whether it would be okay to go straight to Ebola patients with these drugs.” Eventually, in August last year, WHO concluded that it would be ethical to go ahead, and it was at this stage that Horby’s group first received funding from the Wellcome Trust to set up a platform to evaluate “some of the most promising experimental therapeutics”. In choosing which drugs to test, the group had to consider not only which ones were most likely to work and were safest to use, but also which ones were most readily available. ZMapp, for instance, had shown great potential in animal studies, and the two people who took it recovered fully. However, there were only enough stocks in the entire world to treat seven people and little hope of mass production anytime soon. Horby had to turn his attention elsewhere. The drug they eventually chose was brincidofovir: it ticked all the boxes, was readily available, and administered as a daily pill, thus being easy to take.

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The next step was to set up the trial. This process normally takes 18 months, but Ebola does not work to the time frame that scientists are used to. Horby’s team got the time down to three and half months, and, according to him, even that was “still too slow by the standards of an Ebola epidemic”. It was at this stage that other ethical questions arose. For instance, Horby asks, “Should we give these experimental drugs to children and pregnant women?” The drugs had never been tested on children before and there was a worry that the drug would cause foetal abnormalities if given to pregnant women. However, at the same time, both groups have high case fatalities and are therefore in need of the drugs the most. Indeed, Horby points out that the argument against giving it to pregnant women is fairly theoretical as “to date, none of the foetuses of pregnant women that have had Ebola have survived”.

The other big ethical debate focused on whether to “randomise” the trial, which means randomly giving some patients a placebo so that they can act as a control for the trial. Whilst this is fairly standard practice in normal clinical trials, the question had to be asked as to whether it would be appropriate in this one. After all, those who get the placebo would then only receive the regular standard of care for Ebola that they would have received had they not taken the trial. However, given that this standard of care, consisting of intravenous fluids and symptom relief, has a roughly 60 per cent death rate, Horby wonders if this practice is truly ethical. It is a controversial debate, and according to Horby, “In the USA, the Food and Drug Administration [FDA] have been strongly in favour of randomised trials. We have not done that because we felt it was doubtful that we would be able to implement that sort of trial design.”

He went on to point out that the trials presented practical as well as ethical problems. “You are working in an environment where you can only see the patients whilst wearing protective equipment, and you can only stay inside for about a hour because it is too hot otherwise. You have limited access to medical equipment: for instance, how do you measure blood pressure or monitor heart sounds when you cannot put a stethoscope in your ears with protective equipment on?” The team has been forced to be ‘creative’. For instance, “We have been putting scanners in the treatment centres. You take the patient records and you scan them before destroying them.”

Unfortunately, after all the work that went into the brincidofovir clinical trial, the drug company pulled out earlier this month, citing concerns about the low number of patients involved. The trial had to end. Whilst this was “very disappointing”, the research group is already setting up a different trial for a different drug, TKM-Ebola, in Sierra Leone.

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We then moved onto the question of what it is like to work with such a dangerous disease. Horby is upfront with his answer, telling me, “It is a very harrowing disease. There are a lot of children affected, a lot of families affected because of the way it is transmitted by close contact. You often get multiple family members affected, so you will get mothers, fathers, their children, and their siblings all being admitted and then dying. So, you see some very tragic situations where there will be children who will have lost most of their family members.”

However, we ended the interview on a note of hope, with Horby giving his predictions for the future. “The epidemic seems to be coming under control in Liberia, Sierra Leone and Guinea. My feeling is that it will grumble on for several more months but will likely be contained towards the second half of this year completely.”