Hydroxychloroquine and COVID-19 prevention and treatment. Early reports indicated benefit later observational studies showed more harm. And you're an expert in the analysis of drug trials and post-marketing surveillance for adverse effects of medications. How should one look at the evidence for and against hydroxychloroquine in COVID-19 Coronavirus infection, we should be aware of any very small studies. Random variation will mean that small studies could show dramatic benefit or dramatic harm simply by chance. And so small studies should not be used. One of the problems with observational studies is that we are never sure that those who got, let's say, hydroxychloroquine and those who didn't have the same sort of people. They may differ in number of ways. And so observational studies may show harms that are not to do with a drug, but to do with the patients who get those drugs. Or they may show benefits that are to do with a sort of patients that get those drunks. Or they may fail to show benefits. Because the patients who get the drugs are already sicker than those, who don't get the drugs. So observational studies have to be conducted extraordinarily carefully. That's why I'm in business to try and make sure that when we do observational studies, we do them very carefully. But at the end of the day, we're often rather uncertain. So I would look for the very best quality Large observational studies on hydroxychloroquine. And so far, all of these studies have failed to show any benefit for hydroxychloroquine. In COVID-19. There has been a small randomized trial in South America. And there they would, comparing not hydroxychloroquine to no hydroxychloroquine. They were comparing two different doses. And the higher dose hydroxychloroquine was shown to have adverse cardiac effects that you might expect; it is a drug that we know can affect the heart beating. Every time your heart beats, it needs to recover, and it takes a certain time to recover, and hydroxychloroquine is one of those drugs that tends to make your heart require a longer time to recover. And in the extreme, this can lead to a rhythmic cause of the heart and, in some instances, a cardiac arrest and death. So hydroxychloroquine is a drug that cannot be said to have no adverse effects but needs to be monitored carefully. It is effective in malaria, though in many places, there has been resistance to it, so it is no longer used, but in malaria, it's effective. And in some autoimmune diseases, it's effective. But in those cases, people already have a disease that you are treating. And so you can tolerate the adverse effects for the gains you have in the treatment when it comes to high hydroxychloroquine to prevent COVID-19 there, you have to be much more careful. Because you're treating people who are healthy, you don't want to bring any adverse effects to them. And we'll come to that in a minute or two; you have the same problem with vaccines. On the whole, you don't give vaccines to people who are unwell, and you give them to healthy people. Whereas if you're already unwell, you will pay a little bit more in terms of adverse effects to get rid of your disease. But if you're healthy, that's a very different kind of equation to deal with. So, the evidence against hydroxychloroquine is not particularly strong. It's a drug that we use regularly in patients who have diseases, but we don't Want to use it in patients who don't have diseases, so there is evidence for its harmfulness. And in COVID-19, we don't yet have evidence for its benefit. So the risk and benefit balance for it in prevention is simply not there. Similarly, regarding treatment, we haven't had any randomized trials that suggest that treatment with hydroxychloroquine or chlorine sulfate and all the form of the same drug essentially has any benefit at all in treating either the virus itself or the symptoms that follow from the virus. We do not know it's still possible because we've got some very large trials running including some very big ones in the UK,

in which hydroxychloroquine is being created. Paired with other treatments and also with placebo and within a month or two, I would expect us to have results that show whether it is effective, we cannot say it is not effective. We simply can say that we do not have evidence that it is effective.