UK Regulator Press Conference on AstraZeneca Vaccine Transcript April 7

Jonathan Van-Tam: (00:08) Welcome to the Department of Health and Social Care from where this briefing is being delivered. I'm Jonathan Van-Tam, Deputy Chief Medical Officer and this is a clinical and scientific briefing. I'm joined today on my right by Professor Wei Shen Lim, chair of the Joint Committee on Vaccination and Immunisation, the JCVI. To my immediate left by Professor Raine, Chief Executive Officer of the MHRA. And to my extreme left by Professor Munir Pirmohamed, who is chair of the Commission on Human Medicines. Jonathan Van-Tam: (00:53) So today's briefing is about the UK vaccine program. In particular, it is about the AZ vaccine. We will explain as we go through about a change of course, a course correction if you like to the UK program. Now, if you could have said to me back in March, 2020 and predicted how far we would have come so far with our vaccine program, then I'm not sure I would have believed that we would have got as far as we have. The UK vaccine program has been the most enormous success indeed. Jonathan Van-Tam: (01:40) And if you said to me that by March, 2021, we would not have needed a course correction that's also would have amazed me. So we must keep this in context of the enormous success that we've achieved so far. I'm going to stop there for now and allow Professor Raine to open the briefing by explaining her perspective from the MHRA on where we are arriving at today. Professor Raine. Professor Raine: (02:14) Thank you, Professor Van-Tam. I will now update on MHRA's rigorous scientific review of safety reports of very rare and specific blood clots with low platelet count thrombocytopenia associated with COVID-19 vaccine, AstraZeneca. Over 20 million doses of the AZ vaccine have been given in the UK. And we know that vaccines are the best way to protect people from COVID-19 and have already saved thousands of lives. And in fact, around 6,000 modeled in the UK by the end of February, but no effective medicine or vaccine is without risk. And with vaccines more complex than usual because the benefits can be to people other than the individual taking the vaccine. Professor Raine: (03:03) Well, the clinical trials of vaccines allow us to assess relatively common effects. Very rare effects are only detected when a vaccine is used at scale on a large enough number of people and that is why the UK has careful monitoring systems in place and these monitoring systems are now detecting a potential side effect of the COVID-19 vaccine, AstraZeneca in an extremely small number of people. The evidence is firming up and our review has concluded that while it's a strong possibility, more work is needed to establish beyond all doubt that the vaccine has caused these side-effects. Professor Raine: (03:45) Our role is to continually monitor safety during widespread use to confirm that the vaccines are performing as expected to identify any very rare side effects and to ensure the benefits outweigh the risks. The public's safety is at the forefront of our minds. Our teams of safety experts, scientists, clinicians, and epidemiologists have investigated, reviewed, and evaluated thoroughly and scientifically all safety reports. And our safety rubric reviews are carried out in tandem with the vaccination program. We've gathered a large amount of data on the safety profile of the available vaccines, and we've done a rigorous scientific review of all the available data with regards to suspected blood clots with low platelet count. Professor Raine: (04:35) The Commission on Human Medicines Expert Working Group has also met frequently and critically assessed all the data alongside our regulatory review. And this has also included lay representatives and advice from leading hematologists. Based on the current evidence, the benefits of the COVID-19 vaccine AstraZeneca against COVID-19 and its associated risks, hospitalization and death continues to outweigh the risks for the vast majority of people. Professor Raine: (05:09) Our review has reinforced that the risk of this rare suspected side effect remains extremely small. By the 31st of March, over 20 million doses having been given, we have had 79 case reports up to and including that date, 31st of March. All 79 cases occurred after the first dose. Of these 79 cases, 19 people have sadly died. These cases occurred in 51 women and 28 men, age from 18 to 79 years. And from these reports, the risk of this type of rare blood clot is about four people in a million who received the vaccine. Three out of the 19 were under 30 years. 14 of the 19 were of the cerebral venous sinus thrombosis with low platelets and five were other kinds of thrombosis in major veins. Professor Raine: (06:07) The balance of benefits and risks is very favorable for older people, but it is more finely balanced for the younger people. And we at the MHRA are advising that this evolving evidence should be taken into account when considering how the vaccine is used. Today we'll be communicating information and advice to healthcare professionals on how to minimize risks. And this will provide a lot of guidance, including how to report any suspected cases. Professor Raine: (06:38) The information for healthcare professionals will be updated and there will also be information for the public. Things to look out for as we continue to monitor this issue. Anyone who has symptoms four days after vaccination or more should seek prompt medical advice. A new onset of a severe or persistent headache or blurred vision, shortness of breath, chest pain, leg swelling, persistent abdominal pain, or indeed unusual skin bruising or pinpoint spots beyond the injection site. Professor Raine: (07:10) So Professor Sir Munir will outline the Commission on Human Medicines further advice, but I'd like to reiterate again that this is extremely rare. And with the proven effectiveness against the disease that is still a huge risk to our population, the balance of benefits and known risks of the vaccine is still very favorable for the vast majority of people. So Professor Sir Munir, over to you. Prof. Munir Pirmohamed: (07:39) Thank you very much, June. So I've worked with the Commission on Human Medicines and the Expert Working Group separately to thoroughly review are all the cases coming in with the Oxford AstraZeneca vaccine in the UK. We've taken into account a wide range of data sources. We've looked at information about the usage of the vaccine on various age groups and updated incidents rates and benefit risk comparisons for different populations by age and gender. Prof. Munir Pirmohamed: (08:10) Over the last couple of weeks, the two committees have spent almost 24 hours in committee reviewing these reports. Each report has been carefully scrutinized by them MHRA and by the members of the Working Group and further information has been obtained where necessary. We've also had independent adjudication of these cases by an expert hematologist and we worked with another group of hematologists to develop a case definition of these events to make sure that the cases were identified throughout the UK and reported via the yellow card scheme. Prof. Munir Pirmohamed: (08:46) Based on the currently available data, the Commission on Human Medicines is advising the following. First, a pregnant woman should continue to discuss with the healthcare professional whether the benefits of having the vaccine outweigh the risks for them. Number two, people with a history of blood disorders that increase the risk of clotting should only have the COVID-19 vaccine AstraZeneca when the benefits outweigh any potential risks. Prof. Munir Pirmohamed: (09:14) Number three, anyone who experienced cerebral or other major blood clots occurring together with low levels of platelets after the first vaccine of COVID-19 AstraZeneca should not have the second dose. We will be continually monitoring further reports as they come in, continually monitoring other aspects to identify risk factors so that we can refine the advice that we give. At present, the data on people who've had two doses of the COVID-19 AstraZeneca vaccine are limited because these events are rare and comparatively small number of second doses have been given. Prof. Munir Pirmohamed: (09:56) Therefore, it is not possible to draw a conclusion about how frequently blood clots with a low platelet count happened following a second dose of the vaccine, but this will be monitored closely by the MHRA and by the CHM as part of the ongoing review. So just to put into context, these events are extremely rare as June has already mentioned. And I want to put it into context in relation to COVID-19 itself. Prof. Munir Pirmohamed: (10:22) It is important to remember the COVID 19 itself causes clotting and it causes lowered platelets. And I've got a few figures from a paper which was recently published. Pulmonary embolism, clots on the lungs occur in 7.8% of people who have COVID-19. DVT, deep venous thrombosis, clots in the legs occur in 11.2%. who've had COVID-19 and of those people who've been infected with SARS-COVID-2 getting COVID-19 and ending up in ITU, 23% will have some form of clot. Prof. Munir Pirmohamed: (10:59) COVID- 19 also causes strokes in about 1.6% and up to 30% of people who develop COVID-19 will get thrombocytopenia, which is lowering of the platelet count. And that puts into context that the risk of clots and load platelets is much higher with COVID-19 than these extremely rare events, which are occurring with the vaccine. So to finish off, the CHM has advised that the link between the vaccine and blood clots in the cerebral and other veins occurring together with lowered platelets is getting firmer, but absolute proof of the link between the vaccine adverse events will need extensive scientific work. Prof. Munir Pirmohamed: (11:41) Based on the currently available evidence the benefit-risks remains favorable for the vast majority of people, but as June said, is more finely balanced for the younger people. We are advising that this evolving evidence should be taken into account when considering the use of the vaccine. I'll hand back to Professor Van-Tam. Jonathan Van-Tam: (12:02) Thank you, Professor Sir Munir. Thank you, Professor Raine. You've now heard from the regulatory experts and in a moment, I will turn to the new advice from the JCVI with Professor Lim. But before we do that, I'd like to put into context in a visual way what the data are telling us in terms of benefits and risks. So if I could have the first slide, please. Jonathan Van-Tam: (12:32) So this side, and I'll go through the first one slowly, shows you in blue type to the left of the slide, the potential benefits from COVID-19 vaccination and on the orange parts to the right, the potential harms. And you can see that as you go down the slide from top to bottom, those benefits and potential harms are arrayed by age band... Jonathan Van-Tam: (13:03) ... harms are arrayed by age band, starting at 20 to 29, young adults, through to 60 to 69, relatively old adults. And the way these data have been arrayed are in terms of intensive care admissions prevented via vaccine on the left, and serious harms potentially due to the vaccine on the right. And I thank colleagues at the Winton Centre for Risk and Evidence Communication at Cambridge University for help with getting this slide together. Jonathan Van-Tam: (13:42) This first slide is set, as you can see from the title, in a scenario of low exposure, and in actual fact, the rates of disease assumed in this scenario are lower than those we currently have in the UK at the moment. And you can see that if you look at the 20 to 29 age band, then the potential benefits amount to 0.8 ICU admissions averted compared with serious harms of potentially 1.1. Jonathan Van-Tam: (14:21) But as you go up through the age groups, the amount of serious harm declines, but the amount of benefit in terms of averted ICU admissions becomes much more pronounced. And these are arrayed over a 16 week period. Now, we don't expect vaccine to last for 16 weeks. We very confidently expect that it is going to be many, many months of protection from a vaccine. And the reason for using 16 weeks is because that is a typical pandemic wave. That's the duration of it. But you can see that at a very low exposure risk, lower than we have in the UK at the moment, the risk benefit is relatively finely balanced in those younger age groups, but it becomes very overwhelming in favor of vaccine as you go up the ages. Jonathan Van-Tam: (15:25) If we go onto the next slide, please. This is now a medium risk scenario, and it is set at 60 cases per 100,000. That is marginally higher than the UK average at the moment, but it is lower than some of the remaining hotspots in the UK. And you can see that when the disease is around us more, when there's more exposure, then the benefits, the potential benefits, start to stack up, but the potential serious harms remain static, of course. And this is still over a 16 week period, and you can see that the data become more overwhelming in terms of vaccine benefit. Jonathan Van-Tam: (16:16) Finally, let's move to a high exposure risk. And this one... Next slide, please... is set typically at where we get to in terms of a pandemic wave. This is set at the height of the second pandemic wave that we went through in the last few months, and I think is reflective of the kind of scenario we want to avoid in the forthcoming autumn and winter if we possibly can. Jonathan Van-Tam: (16:49) But here, when there's a lot of COVID-19 circulating in the population, you can see that even in the 20 to 29 group, the potential benefits in terms of intensive care admissions averted is very much higher than the serious harms due to vaccine, and that's why the regulators have concluded as they have about risk benefit for the AstraZeneca vaccine. Jonathan Van-Tam: (17:20) So, I hope that's placed it all into a bit of context for everybody. I recognize it's been a detailed, scientific discussion so far, but hopefully those figures bring it to life. And at this point, I'm going to hand over to Professor Lim to give us the JCVI advice. Thank you, Wei Shen. Professor Wei Shen Lim: (17:40) Thank you, Jonathan. JCVI has been meeting over the last two weeks and we have carefully and independently reviewed the safety evidence and the benefit evidence given to us from MHRA and Public Health England, and that includes some of the kinds of data that you seen earlier on the slide. Professor Wei Shen Lim: (18:03) We are well aware of the high level of protection that COVID-19 vaccines provide, particularly against serious disease, that is hospitalization, ITU admission, and from dying from COVID-19 disease. Against that must be balanced the uncertain occurrence of an extremely rare adverse event that may be associated with vaccination. Acting really in the interest of safety and for public benefit, JCVI feel that there are three points of advice that we would like to put across. Professor Wei Shen Lim: (18:38) The first is that information given to individuals who are being offered vaccination and information given to health professionals should be appropriately updated to reflect the latest considerations and deliberations by JCVI and by MHRA. Professor Wei Shen Lim: (18:57) The second point is that those who have received their first dose of AstraZeneca vaccine should continue to be offered the second dose of AstraZeneca vaccine, according to the set schedule. Professor Wei Shen Lim: (19:11) And the final bit of advice is that adults who are aged 18 to 29 years old, who do not have an underlying health condition that puts them at higher risk from serious COVID-19 disease should be offered an alternative COVID-19 vaccine in preference to the AstraZeneca vaccine, where such an alternative vaccine is available. Professor Wei Shen Lim: (19:36) And perhaps it's useful to state what is not advised as well. We are not advising a stop to any vaccination for any individual in any age group. We are advising a preference for one vaccine over another vaccine for a particular age group, really out of the utmost caution, rather than because we have any serious safety concerns. This will obviously have some implications in terms of operation and deployment of vaccines and I'm just going to hand back, therefore, to Jonathan, to set those out for us. Jonathan Van-Tam: (20:16) Thank you, Wei Shen. So, I'm going to round off the last part of this briefing now. People out there listening to this will say, "Well, what does this mean for me and what should I now do?" Jonathan Van-Tam: (20:32) So, let me begin with the deployment piece. This is a change in clinical advice for the under thirties. It will require some changes in the way that the National Health Service operationalizes the vaccine rollout program, but I've spoken to my colleagues in the NHS in some detail this morning, and I am assured that actually, because of our supply situation in relation to alternative vaccines, the effect on the timing of our overall program should be zero or negligible. That of course is contingent upon getting the supplies that we expect to get of the alternative vaccines, which are the Pfizer vaccine currently in use and the Moderna vaccine that we hope to bring into deployment from mid April in England. Jonathan Van-Tam: (21:33) So, that's the kind of, "What does it mean for me?" On the, "What should I do?" Please be reassured that two sets of independent experts on the regulatory side, the MHRA and the CHM, and on the clinical advice side, the JCVI, are all over this, and I can testify to the many, many hours of work they have been putting into getting this advice to you in the last week or so, really almost working without a break. And my thanks to the members of those various committees and organizations who've worked honestly night and day behind the scenes to get to this point. Jonathan Van-Tam: (22:24) This is a course correction. There's no question about that, but it is in a sense in medicine, quite normal for physicians to alter their preferences for how patients are treated over time. It's happened with vaccines only a few years ago. Up until a few years ago, the advice to the elderly and flu vaccines was, "Get your vaccine," and then the JCVI then changed its advice and said, "Our preference is now for the adjuvanted vaccine for the elderly." So, changes in preference for vaccines are business as usual and this is a course correction. But this is a kind of massive beast that we are driving along at enormous pace with enormous success, this vaccine program. You know, if you sail a massive liner across the Atlantic, then it's not really reasonable that you aren't going to have to make at least one course correction during that voyage, and I frame this very much in those terms. Jonathan Van-Tam: (23:36) The NHS has a message that we will get the right vaccine to you in the right time, according to the new JCVI advice. There might be a small delay sometimes. There might be a slightly greater distance that some people are asked to travel. But the NHS is all over this and understands the challenge of making the advice from JCVI truly operational in a smooth way. Jonathan Van-Tam: (24:07) So, I'm going to sum up there by saying this is a course change. It is based on a clinical preference based on newly emerging data. It will be kept under very careful review. Please remember that the benefits of vaccine accrue over a very long period of time. We are fairly confident that it's months and months, whereas the event of vaccination is a brief moment. Vaccines continue to be the way out for the UK. They continue to be the way in which we can get our lives back to normal and our economy opened up again in the shortest time possible. Jonathan Van-Tam: (25:01) Thank you very much for listening and we will now take some questions. I think the first question is from Fergus Walsh at the BBC. Hello, Fergus. Fergus Walsh: (25:12) Right. Thank you very much, indeed. Can I ask two questions? Are you worried that this change of course might damage vaccine confidence, especially in the young, and can you just be specific on the risks? Are the risks to those from the vaccine in the under thirties significantly higher than among older age groups? Jonathan Van-Tam: (25:40) Thank you. So, on the first point, I will answer that question and say that clearly this is a course change. We don't want it to result in a loss of vaccine confidence. I hope I've reassured you that these are really carefully considered decisions and it remains vitally important... Jonathan Van-Tam: (26:03) ... decisions, and it remains vitally important that people who are called back for their second dose come for it, and it remains vitally important that all adults in the UK come forward for vaccination when they are offered it. On the points about risk, I think I will defer to Professor Lin. Professor Wei Shen Lim: (26:23) Thank you. The importance really is not simply the risk to an individual. There is a slight gradation in the risk of the serious adverse event occurring in younger people compared to older people, but it's really the benefit-risk balance, which is most important here. The benefit from vaccination is, as we know, very, very high in older people and decreases as age goes down, because the risks from COVID-19 goes down with age. But there is still a benefit to younger people from being vaccinated. Overall, that benefit is still in favor of being vaccinated. It happens that where we have an alternative vaccine, we feel, on balance, it would be preferable to offer the very youngest people who have no other health conditions, the alternative vaccine instead of the AstraZeneca vaccine, really just on the side of safety, rather than because of any particular significant concern about the risk from the vaccine itself. Jonathan Van-Tam: (27:39) Thank you. Fergus, I think I'd just add that the slides that I showed to you were based on ICU admissions and didn't take into account the additional benefits of vaccine in terms of preventing long COVID, which we know is quite a significant problem after this illness, the costs of the illness itself, and the costs of potentially passing on the infection to family and friends. Thank you. Tom Clarke, ITV. ( silence) Professor Wei Shen Lim: (28:48) That's a very good question. In fact, we were just discussing that earlier because we know somebody whose daughter is around 30, 31, and that is a relevant and important question. One of the really fundamental things about the vaccine program is that it's shown to be fair and it's transparent. That's precisely why we want to have this briefing now to demonstrate what the risks and the benefits are so that everybody is informed before they come for their vaccination. We have set up quite clearly what the benefits are against the risk and why we've made a decision about the 30-year-old who is healthy and otherwise well. Professor Wei Shen Lim: (29:36) For somebody who's 31 and 32, I think they have to make their own decision as to what they want to do about vaccination. We would still say that the balance is in favor of being vaccinated because of the risks from COVID-19 and the protection that the vaccine offers. Tom Clarke: (29:55) Can I just have one follow-up question, if I may? (silence) Professor Wei Shen Lim: (30:25) Indeed, I wonder whether in the moment, Sir Munir will want to come back and just discuss the risk signal from the ages in terms of thrombocytopenia and blood clots. But in terms of moving into pediatric vaccination, JCVI has not made any firm decision yet on when to move into vaccination for children. The clinical trials are still ongoing regarding the safety of vaccines in children, so no decision made on that point yet. Jonathan Van-Tam: (31:02) Thank you, Wei Shen. Tom, in passing the baton back to Professor Sir Munir on the numbers, I will in this passing through me, as it were, say that the JCVI's decision to give advice for the under 30s was taken fully cognizant of the fact that their advice would therefore apply above the age of 30 to 31 year olds. That was part of the consideration. We are talking here in the context of extremely small numbers by age, and that makes the data very difficult to interpret, but I'm sure Sir Munir will elaborate much better on this. Prof. Munir Pirmohamed: (31:54) Thank you. There is a slightly higher risk in the younger age group compared to the old age group. Obviously, as has been already said, that we do need to look at the relative benefits versus the risks in different age groups. The reason why it's a higher risk in the younger age group is not clear. As I said earlier, we need to undertake much more scientific work to understand why this sort of link between the vaccine and particularly the younger age group is occurring. That will help us in the future to be able to then refine the advice that we give in terms of product information. Further work needs to be done on all of that. Prof. Munir Pirmohamed: (32:37) With regard to the children, the trial has been paused by the Data Safety Monitoring Board for an abundance of caution, really. We know that children are at much lower risk of these clots and so on. As we are able to accumulate more data over the next few weeks, the MHRA and the expert working groups will be liaising with the trialists at Oxford, and then to be able to determine whether the trial can start again based on the data that's available. Jonathan Van-Tam: (33:13) Thank you, Tom. On children, I will just add that there are multiple manufacturers with different types of vaccines, all working to do trials in children. This is not the only show in town in terms of trying to establish whether a vaccine can be authorized and suitable for children. That's an unfolding story that we'll have to leave to another day. Jonathan Van-Tam: (33:39) Another Tom now. Tom Moore from Sky. Tom Moore: (33:43) Thank you very much. You very much presented... (silence) Jonathan Van-Tam: (34:14) Would you like to begin on that, Wei Shen? Professor Wei Shen Lim: (34:15) Sure. Thank you. Every country has to make their own decision regarding what is best for their own population. That takes into account the kind of disease that we have in our country, the size of the wave, the risk of a next wave occurring, the amount of vaccines we have, how well the vaccine program is being delivered, and obviously the values of our own people, whether we want to accept the vaccine or not. I believe that every country will, in the end, have to make their own decision regarding the risk and benefit. Just as an example, it's sad to say but true, that in some countries, life expectancy is not as good as it is in the UK. People may live to a mean age of about 50. For them, their life expectancy will mean that their risk-benefit in terms of when to draw the line against a particular vaccine, it may be any of the vaccines that are available, will be different from another country where life expectancy may be different. Professor Wei Shen Lim: (35:26) It's taking all of these things into account that we've come to the decision in the UK, given our vaccine availability, our supply, the kind of pandemic that we're having, the B117 variant that we've had, all of these together, we thought that the correct judgment was that it is around the 30-year threshold where the younger people who do not have any health conditions, where we would offer the alternative vaccine, rather than saying everybody in the country should be offered an alternative vaccine, because, really, this is an extremely rare adverse event. We do not know for sure that it's related to one vaccine or not yet. It may also be relevant to some other vaccine. It may not even be related to a vaccine. It may be related to COVID itself. We're just unsure. The advice we're giving is really based very much on protecting the population and working on a principle that safety is our biggest concern. Jonathan Van-Tam: (36:36) Thank you, Wei Shen. Tom, I'm going to reinforce the point about context. Wei Shen has kind of stolen the example about a low income country where sadly life expectancy is not the same as the UK. The context of risk and benefit is going to be very different in each population. The JCVI was entirely free to make its own advice and recommendation to us as it saw fit. That has always been the way with JCVI. They are always independent and they can say and do as they wish. Jonathan Van-Tam: (37:12) That having been said, if you look at some of my slides and if you look, for example, at the high exposure risk category, then the idea of withholding a vaccine where a potential harm, for example, in the 40 to 49 group, is 0.5 harms per 100,000 people versus 51.5 intensive care admissions averted. That's not taking into account hospitalizations, long COVID, and spreading to others. Then the notion that you would clip a vaccine at that point is pretty absurd, really. It is very much an independent decision, but I think it's been taken in an extremely rational way. Tom Moore: (38:04) But he's not decision driven by... (silence) Jonathan Van-Tam: (38:10) No, it isn't. It absolutely wasn't. As I've explained to you all, the program should not be delayed because of this changing course. Everything should stay on course. Thank you. All right. We'll now turn to Nick McDermott at The Sun. Nick McDermott: (38:31) [inaudible 00:38:31]. (silence) Jonathan Van-Tam: (39:41) Thank you, Nick. I will pass the first part of the question to my regulatory colleagues. I'm not sure who wants to go first on that one. June. Professor Raine: (39:49) The important question of how firm is the evidence, yes, the evidence has accrued not only in numbers and kinds of cases, but the pattern of those cases. So we feel it's a much more solid basis in our regulatory world to put in the side effect into our product information. And that tells us that it's a reasonably plausible link, but there needs to be much more work on the scientific understanding of this new constellation of symptoms to give us that feeling of the proof that you would expect. And that work will go on at pace. And I would like to hand to Sir Munir to tell you more about that. Prof. Munir Pirmohamed: (40:32) Yeah. So the early evidence suggests that this constellation of symptoms is caused by an immune response against platelets, which allows the platelets to then lead to clotting in different parts of the body. But what we don't have clearly is the link between the vaccine and how the immune response becomes activated against the platelets. And that's where the scientific work needs to go on to identify what that link is so that we can then develop ways and strategies to be able to overcome this adverse event for the future. Jonathan Van-Tam: (41:10) Thank you. Now on your second part of your question, Nick, about other vaccines and, in particular, the Janssen vaccine, in terms of the immediately available alternatives, the immediately available alternative right now, already in deployment in the UK is the Pfizer vaccine. We do expect to have quantities of Moderna beginning to be deployed from mid-April in England. And those will be the two for the next few weeks as it were. It's common knowledge and public information that the UK has placed orders with Janssen. We do not yet have certainty on the timing of delivery, but that vaccine could become available over the summer and is indeed a one dosed schedule. Therefore, it must be part in the frame, if you like, or in the mix, for solutions, for vaccine requirements going forwards, and indeed for the young people you refer to. Jonathan Van-Tam: (42:17) But that's always been part of the UK strategy to have multiple horses in the race so that we would always be in a good position if we needed flexibility to be able to exercise it. But my final cautionary point for you is that this is a vanishingly rare, but sadly, quite serious adverse event, but it is vanishingly rare. And you can't pick these kind of things up until you have literally deployed tens of millions of doses of vaccine. And therefore, for the vaccines not yet deployed in large numbers around the world, we have to wait and see if we are going to see or not see similar signals. And therefore, it again reinforces the message that it's important to have many horses in this race. Thank you. We're going to Tom Whipple at The Times next. Thank you, Tom. That's a very mechanism-based question. I'm going to pass that straight to Sir Munir. Prof. Munir Pirmohamed: (44:01) Thank you. So the early evidence is suggesting that there is an immune response which is occurring in relation to whatever the event is. It may be the vaccine or it may be a previous COVID infection, for example. But the way that, that immune response then targets the platelets and why it targets the platelets in the very small number of individuals we are not clear about. And that further work is ongoing at the moment. I think it is really important to understand the mechanisms because it might provide us with ways of being able to prevent this in the future. Prof. Munir Pirmohamed: (44:38) For example, if you were able to identify the mechanisms, you'll be able to refine the advice that's given so we can actually identify risk factors for example, and then try to prevent it in individuals who have those risk factors. It may also allow us to be able to then think about modified vaccines, which do not cause this particular adverse event in the future. You mentioned the adenoviral vector, and yes, there are several vaccines with adenoviral vectors, but we don't know whether it is related adenoviral vector or it is related to something else at the moment. And again, that's part of the scientific work that needs to undergo at the moment. Jonathan Van-Tam: (45:18) Thank you. We will now move to Hannah Geissler at The Express. Thank you, Hannah. I'm going to pass to Sir Munir first of all, for the question about women. And then to the Yellow Cards to Professor Raine. Thank you. Prof. Munir Pirmohamed: (46:10) Sure. So of the 79 cases, 51 were in women and 28 were in men. The numbers are quite small and that may reflect actually who's getting the vaccine because many of the healthcare workers for example are women. But if you actually look at the incidence rate according to the number of vaccines administered, there's actually no difference between men and women. So we will need to continue to monitor this and see whether there is a gender predilection to developing this particular adverse event. But at the moment, we do not have any evidence to say that either men or women are more likely to get this. Professor Raine: (46:48) On the Yellow Card Scheme, every week, we publish all the reports in summary form, but also the report on a Thursday talks about any trends that have come up. So I really can't do any better than encourage people to read it, but also, to encourage everyone to report to us. Every report matters and every report will be carefully looked at. Thank you. Jonathan Van-Tam: (47:14) Thank you, Hannah. So that brings us to the end of the questions posed by the media today. I would like to conclude at this point by thanking my colleagues for their time. And more importantly than that time today, for the immense amount of hours and effort they and their assistants have put in behind the scenes to get us to this point. I want to emphasize to everybody that COVID-19 remains a serious illness that, unfortunately, as Professor Whitty has said, it is something we're going to have to live with in the long-term. Vaccine is likely to be, and continue to be, extremely important in this country in getting life back to normal. We are managing this very carefully. I hope you've seen real evidence today of authentic experts looking after your interest, doing the very best they can. It is a course correction, but nevertheless, it is full speed ahead with the UK vaccine program so that we can get life back to normal. Thank you. This briefing is concluded.