A process for breakthroughs in medical research around the global snakebite crisis
When it comes to breakthroughs in medical research, the coveted ‘eureka’ moment is rare. Instead, a meticulous process of strategic phases must be applied to make progress. Here, Hamish Ogston CBE and his team of expert advisors explain how the Hamish Ogston Foundation and partner organisations are looking to solve the global snakebite crisis through such a process.
The Hamish Ogston Foundation seeks to identify areas where it can make a lasting contribution to medical research which focuses on improving the existence of the many impoverished and often disregarded people in this world.
To select these areas, the Hamish Ogston Foundation adheres to strict research best practice protocols, and consults with experts in the relevant fields. It was this stringent process which led us to the decision to fund snakebite research in three of the Asian countries worst affected by this neglected tropical disease.
But how do you get to this stage of having unassailable evidence to change practice?
First, let us consider the wise words of some of history’s most revered scientists. It is said that Archimedes reached his conclusion about displacement suddenly, and was so excited that he jumped out of the bath and ran home through the streets of Syracuse naked shouting “eureka!”.
However, there are not many “eureka” moments in medical research, which depends almost entirely on meticulously grinding out data and building up to a conclusion based on evidence. Experts, through a process of peer-review, can discredit your methods and pick holes in your statistical evidence, forcing you to return to the drawing board and reconsider.
Indeed, Francis Bacon said: “If a man will begin with certainties, he shall end in doubts; but if he will be content to begin with doubts, he shall end in certainties.” He was intimating that advances in learning have their snakes and ladders, and that conclusions are reached gradually.
Ultimately, the objective of research is to publish findings and conclusions in the most revered and respected medical journals and to present your findings for scrutiny at scientific meetings at home and abroad. Subsequently, a change in practice following a research conclusion may follow through the recommendations of government health agencies, such as the World Health Organisation.
The research process
The Hamish Ogston Foundation snakebite antivenom research will comply with these best practice protocols. The effectiveness of an antivenom may be very clear at an early stage on an individual basis, but it is still important to have a large number of patients to give the study more strength or “power”. This is why multi-centre trials are important, as they recruit large numbers of patients more rapidly than single centres.
The first hurdle is obtaining approval for the research project from the local Research Ethics Committee. The Committee will look at, for example, how the volunteers might be harmed and how this can be controlled. Nobody can take part in a trial without having the appropriate information to register their consent to do so. Ethics Committees can be slow in granting approval: 6-8 months might be an average time to get it.
First, the scientists will take approximately 15 volunteer patients and use a very small concentration of the antivenom being tested to make sure it is not obviously harmful to humans at this very low dose stage. This is often referred to as Phase 0.
Phase 0 is often not carried out in favour of going straight to Phase I. This stage elicits the same information but uses 20-80 patients who have no health problems to be sure that a side effect is not due to the underlying health condition. If unacceptable side effects or a disappointing lack of effectiveness unexpectedly occurs at this stage it is possible that the trial may be stopped.
Phase II involves studying several hundred patients to see if the antivenom has no unacceptable side effects by following them up for a year. Information gained at this stage can guide the investigators as to what to look for in Phase III.
Phase III involves 2-3000 patients and may involve comparing two antivenoms in a so-called double blind trial. This means that the actual antivenom randomly administered is unknown to the scientists and can be identified later only by a third party through a code on the vial. Being aware of which of two antivenoms being studied for comparison has the potential for introducing bias in identifying side effects and effectiveness. This phase can take approximately three years.
Phase IV occurs after approval has been given and lasts for many years. It is a formal way of detecting any long-term safety and effectiveness concerns.
Then, results are written up and published, in scientific paper format. This process can take 6-9 months. The research has to be accepted for publication, requiring approval by several expert assessors.
This meticulous medical research process may not quite be to the taste of Archimedes – but the HOF is committed to supporting only the most robust scientific methods.