So can you start by saying your name and your position?
Yeah. Hi. My name's Carl Hennigan.
I am professor of evidence based medicine in the Department of Primary Care Health Sciences at the University of Oxford.
I also work as an urgent care general practitioner in the NHS and I do that in evenings and weekend.
Did you say urgent care or sorry? Urgent care. Right, yes.
So in the thought. Yeah. The out-of-hours setting.
Yes. The work that goes on in the evenings and the weekend. Yeah.
Okay. And without telling me your entire life story, because we don't quite have time for that.
Yeah. Can you just talk me through your career to date from where you first got interested in medicine?
Yeah, so I actually studied medicine at the University of Oxford.
I came here in 1994. So coming up for nearly three decades have been at Oxford and stayed there ever since.
And what happened? While I was a medical student, I met a certain chap called David Thacker,
who was the first ever professor of evidence based medicine and the director of the Centre for IBM.
And he had a profound impact on my whole career and what happened next,
just because of the way of thinking about decision making that you can integrate best
available evidence with your clinical experience and expertise and patient values.
You take that together. That's what evidence based medicine is how it informs decision making.
I then went on to train as a general practitioner and then ended up in an academic career pathway that led to me being
appointed as the sort of director of the Centre for Evidence based Medicine and Clinical Reader Knebworth in 2010.
And subsequent to that, I become a professor of evidence based medicine here.
But while that's been going on, I still maintain an active career as a clinician by working as a general practitioner.
And I work in the out-of-hours setting where we do generally visits and urgent care visits, for instance, into care homes.
And I like the out-of-hours because it fits with my sort of chaotic lifestyle.
So I can work it round and it works with my family. And so I tend to work evenings and weekends, and in the daytime I do.
About 50% of my time is research and about 50% of my time is teaching and building capacity and supervising.
Hmm. Very good. So let's just unpack evidence based medicine.
I mean, I think when I first heard of it, I guess for a lot of people, there'd be a kind of moment of surprise.
Yeah. What do you mean? All these years, doctors have been treating us without evidence.
So have it. How did the. The term arise? What was different about evidence?
Yeah. Is everybody think that all of healthcare is built on evidence,
but actually there's been a long history and tradition of so-called quackery in health care.
Everybody wants the silver bullet, the magic bullet to that ails and that cures, if you like.
But it was probably about the late eighties when the concept of evidence based medicine came to the fore.
Because what was happening then is lots of medicine with practised on low quality evidence, all on opinions.
I know what to do best.
And one of the key changes was with the use of high quality evidence, particularly for drugs and vaccines, the use of randomised controlled trials.
Now just to say in the current COVID pandemic,
everybody will understand the impact and you'll probably interview people who've done the recovery trial,
which looked at 13 treatments like dexamethasone.
A large national multi-centre trial provide high quality evidence about decision making, and that's a superb example of evidence based medicine.
But if you go back to the eighties and nineties, there were very few randomised controlled trials that impacted on health care and so there was a huge
growth into can we develop high quality evidence and that was the start of evidence based practice.
And there are an important aspect. How do you determine what is high quality evidence, what are the potential biases,
what are the competing interests in the conflict that might distort the evidence base?
You put all that together. My job is to try and understand how you take the evidence from the bench, if you like, to actual patient care in decisions.
And there's a huge amount of evidence out there. At any one point there's probably about 40,000 randomised controlled trials each year.
There are about 2 million articles index on PubMed, so it's like looking for the needle in the haystack if you like.
What the high quality evidence that impacts on patient care.
Now tell me about systematic review. Yeah. Yeah. So that also came.
So there's a very in about the mid nineties, Oxford was very much at the centre of the development of evidence based medicine.
David Sackett moved from Canada to Oxford to establish the first centre for
IBM in Chalmers was based on the road developed the Cochrane Collaboration,
which started up in North Oxford, actually as a group of about 70 people who were interested in systematic reviews.
And the point about systematic reviews is you really saying, look, when you have a clinical question,
what we don't want you to do is cherry pick the bits of evidence that suit your answers.
You're basically saying, let's collate. All of the evidence at certain level.
So for instance for all the randomised controlled trials and then look at the aggregate effect,
what do they say when we systematically review the evidence and it means you have a clear question,
you try and find all the evidence relevant to that question, you appraise the quality,
what's the high quality and the low quality and then you sympathise it normally with what's called a meta analysis or and we look at that,
it's called a forest plot. And when you do that that generally is the highest level of evidence that informs decision making.
Now one of the key components also of evidence based practice and that's been interested in the COVID pandemic,
is then how do you communicate that to inform decision making?
There's been a big change probably in the three decades I've been involved in medicine from what we call a, you know, a doctor centric viewpoint.
The doctor knows best to actually more of patient centred of medicine.
We want to inform the decisions so that actually you participate in that decision.
May ultimately it's our decision and therefore communicating the better patients.
Yeah, definitely so, yeah. Our decision of patients. I'm a patient myself.
I want to be informed all the time.
So that is about informing the benefits and the harms and coming to a decision about what's the best treatment for you now.
And that's where the patient values come in, because we may look at certain treatments and look at them differently and some people
presenting with the same information will make different views about what to do next.
And that's okay because the key is, have you been fully informed?
Can you inform the decision you're about to make? And that's why I find IBN is fascinating, but actually it's still in its infancy,
much if you go to the departments, they're like physiology and anatomy.
They've been around for hundreds of years. The concept of evidence based medicine is about three decades old, really.
However, over time, people have been coming to these decisions about what type of evidence should we use to inform decisions?
And is. So you've talked about. Randomised controlled trials and obviously systematic reviews that kind of winnow those to get the answer from.
Are there other kinds of evidence? It's not the only one. No, it's not.
So it's a misnomer to think so. The key is it's the best available evidence to answer the question.
So, for instance, we have a whole part of our centre of looked at qualitative research.
You know, it's not just sometimes you might want to ask questions like, why do people not take vaccines as prescribed?
And that's a why question. Well, then you have to go and interview and you have to talk to them like this and go.
Can you talk to me about why you make these decisions, what the barrier is, what a facilitator.
So it means it's appropriate to the question. Sometimes when we look at harms, the only evidence available is observational data,
because you can't intervene when there's some harmful issue at hand.
And the best example of that will be smoking.
The one of the most famous studies ever done in Oxford was Richard Doe study, which was a 50 year cohort of doctors and their smoking habits.
When that was started in the fifties. 80% of doctors smoke.
The idea that 80% of doctors now would be ridiculous, but actually were followed up for 50 years.
And that exposure, if you were a smoker of 20 cigarettes a day, on average, you would live ten years less than somebody with never smoked.
And that was an important finding because it wasn't until the sort of 74
showing when actually warnings came on cigarette packets that this is harmful.
So the key is people say there's only randomised trials and that's all you make decision that's that's incorrect.
It's matching the evidence to the type of question you have at hand.
And then we have other studies like diagnostic studies. So we have to have the evidence base for diagnosis as well.
Is this test accurate? Do they actually pick out those with the disease or not?
And that's incredibly important to do. And people recognise that within the COVID pandemic is we've had this huge amount of testing,
whether it's PCR testing or lateral flow testing, and we ask the questions all the time about the accuracy of these testing.
Do they actually derive benefit? Do they pick out those people truly have COVID or not of be the case?
And then there's another aspect of evidence based practice and even.
Mm hmm. So what were the questions before we got to. Before we had to go with what were the main questions that you were interested in?
We've had a huge amount of questions over time. I mean, if you have to in your centre.
So there's about there's about 25 people in the centre.
We've got about 130 to 140 MSI students who would do a part time evidence based health care program and about 40 students.
So that's why it's had to do a lot of teaching and supervising.
And the questions they bring to me are all with what I call I have a light bulb moment when somebody comes in the room and says,
I have this question, I think, yeah, that's a really interesting, important question.
And if we knew the answer, we'd be able to improve practice tomorrow.
And I think that's the important. There are a lot more uncertainty for new consider in health care.
Then there also the other aspects where we may have done something and there's been harm over time.
So some of the work we've done, I've been approached by patients. We looked into the harms of metal hips or trans vaginal surgical mesh,
and recently a treatment used in the sixties and seventies called Perimeter Earth, which was a hormone pregnancy test.
So we do all that type of work. And then here we do generally work that looks at primary care in the community.
Preventive treatment, those treatments are used and we have a vast array of evidence at any one time.
But we tend to focus on the that the evidence, like the systematic reviews that inform the guidelines, that will change patient care,
where if many people will be in the basic sciences in Oxford, translating, developing vaccines,
developing new drugs and taking them forward into the pipeline, we don't do that.
We do the applied health sciences, if you like, and we're trying to say, right, faced with this evidence, what's the decision going to be now?
And that's and you can think about it because I said there's so many new trials published every year, 40,000.
It's like a it's like a moving wheel, if you like, on the hamster on the wheel.
And the key is what we're always looking to do is if we understood the answer to this, would it actually make a difference to patient care?
And that's communicated to doctors that that's well,
actually so so what happens now is the systematic review will go into guidelines and then you've got places people like nice.
And if you think about it again, Nice has only been in operation since 1999 and so they're only three decades in.
And one of the interesting issues I gave a talk to know within the pandemic about what's next.
And they run into this problem of they've got thousands of guide and pieces of technical information and guide.
And so they've got to keep up to date with new information.
And they struggling with that because how do you maintain this knowledge base and then ultimately inform individuals in practice?
But what we teach about is the idea that you have to pull information towards you when you have a question as a clinician,
and you have to have the skills to be able to find the right evidence and in finding the right evidence to be
able to appraise the quality and understand the effect size to bring that knowledge to patients in front of you.
Some things are ingrained in the system, like what to do in a heart attack.
The evidence is very well established. You no need to question that.
But many areas, as it evolve, like cancer care, people come to me and ask all sorts of questions.
There's the new chemotherapy for breast cancer. What do you think?
And, you know, and the answer is, well, I have to look at the evidence and the story in my mind with evidence.
So what we teach is the skills of how do you access that information in evidence and in accessing it?
How can you pull it towards you and then improve the quality? And that's that's important skills for doctors.
But I think it's been interesting in the COVID pandemic, increasingly, I think the public has an appetite for evidence based practice.
They are increasingly saying, hold on a minute, I'm going to question this.
I want to understand if we're going to intervene in this way, where's the evidence?
And I found that quite invigorating, actually. The public has almost tipped itself into trying to say we want to be evidence based.
Whether that will continue will be interesting to see. But I think there's a bit of a movement from more so the public becoming more and more aware.
And I think they've become more aware because of the Internet. They can go in in a way you couldn't do two decades ago.
Yeah. You couldn't go and say, I'm going to look this help.
I'm going to. And so I think they will increasingly will be knowledgeable patients who prod and push doctors to say,
well, I've been reading a bit of evidence when that happened to me. I think that's fantastic.
But if you have to be now aware and ready for that in modern society, and I think that will continue to evolve over time.
Right. So I think we finally got to COVID. Asking everybody, can you remember where you were or what you were doing when you first heard about it?
Oh, yeah. So I first heard about it in January, you know, and it was then murmurings and it was probably January and February.
And I remember in early February doing two things. I wrote an article for the BMJ opinion about I looked at the excess mortality.
So one of the things is a clinical epidemiologist. We're interested in the data and the numbers and the Office for National Statistics,
which probably everybody is aware of now, produces great data and it produces data on things like deaths.
And he does that every week and it's been doing that for years. And we look at that.
He's interested in excess mortality. And I wrote an article about Where Are We Now?
And, and it was interesting because what was happening in early February, we had what we call normally.
So you have a five year average and you either have in excess or not in excess.
And actually with trend under at that moment in time, we'd had a very mild winter coming in.
And my point was to say, actually, it's what you really look to understand what's going on.
You have objective markers and death is a very is ultimately the objective marker.
Now we can have some arguments about the causation, but ultimately when a death is recorded, it is recorded in this country in a way that,
you know, within five days you have to go to A to certify the death that gets pulled into the earth.
And each week they produce an amazing amount of data. That is the sort of age group, the location, the facts and all.
That's really helpful. So I wrote that piece and then I remember I did a podcast with the BMJ about corona viruses and what are they?
And I was just a very interesting time because at that point I think nobody really knew very much about these features, epidemiology, viruses.
And there were very few people, I'd say a few hundred in the world who were interested in this area.
And we've been interested in it because in the last pandemic, going back to 209,
which is the swine flu pandemic, which we did a lot of work in that on the antiviral drug like Tamiflu.
Yes. And we'd spent four and a half years looking at systematically reviewing the evidence on Tamiflu.
And one of the key areas which we changed the method was we found that about 60% of the evidence had never been published.
And that's called publication bias. And we went and got from the manufacturer manufacturers.
The Clinical study of study reports, which are huge documents, but they're the documents that underlie all what happens in the trial.
And we used them and it took a few years to produce that systematic review.
So it's interesting, many of the interesting people who were the big names you'll hear like the chief scientific officer,
like Patrick Vallance with the head of GSK at the time. And GSK produced the name of it and the name of it with one of the drugs that we looked at.
And he his company supplied us with the full study report.
And I contacted him at that moment in time. So there was a group of people that we were aware coming in, and I think so it was that February.
But I think I think it's fair to say in that February that there was a certain element of is this going
to be a bit like the fourth one outbreak where there was a lot of noise and actually it petered out.
And I think, you know, where it all started to change was when you sort of thought the the significant outbreaks in northern Italy.
And I think that Northern Italy moment, which was about three or four weeks preceding where we were in in the UK,
was a significant game changer in sort of what's going to come next.
And I think there are interesting features about the outbreak in northern Italy that actually
could explain a lot of interesting issues about what happened in that period in time.
But I think then it moved on very rapidly. For me.
Interestingly, I worked, uh, the week preceding lockdown.
I think that was about the 16 to 17 the weekend before we started to go into lockdown.
I remember I work the weekend at an urgent care GP and that involved me doing visits and that's a very interesting position to be a physician.
When visits that we get, call them will go out and I'll go out to a care home and you'll go to a care home and on the door it will be like,
we've got COVID in this care home.
And that gives you a very you know, it makes you it makes you think and reflect about everything you're about to do.
The will tell you not to go into these places and you're going, Oh, I'm thinking I booked the shift today.
Was that a good idea? But actually the problem was at that moment in time,
and this is one of the contributors to I think what I consider the panic measures
is we didn't have any personal protective equipment and neither did the care home.
And there didn't seem to be any planning place.
And that lack of equipment meant that there was a real big hole in the floor plan,
that somehow something was missing because when faced with an unknown,
you do want to be in that position at that moment in time to say, look, I need to take precautions.
And actually, many of my colleagues were in a position that we just didn't have the equipment.
And I think that was, for me, a real position where I said, we've got a problem.
And in that problem, there were two issues. There seemed to be a huge knowledge deficit.
As I said, there were just lots of issues that people weren't aware of.
And secondly, there wasn't a very clear plan about the action of what to do next.
And about 72 hours later on a Tuesday, I got a fever cough and, uh, took care of it, and so did my wife.
And when the world country went into lockdown, we were already in our 14 days quarantine at that moment in time.
And, you know, and so a lot of the issues and thought processes were coming together for what the position I took next and what I thought,
what the major need was for us to use our skills to produce things like the evidence with service,
but also many features that had been in the last two years have been trying to improve the decision making and through informing the decision,
because I think a lot of people and journalists, particularly politicians, the public, have had to come to what is a respiratory pathogen?
What does it mean? How do they act? What can you do to make a difference and how should you go about that?
So that's sort of the journey in, if you like.
And and I guess, you know, very profound thinking about in that moment in time where we were in what was happening.
Mm hm. Why? Is it?
I was going to say, why is it so difficult? Is it is it is it is it actually very difficult to get certainty over a new disease like that?
Yeah. Look, there are many areas of health care where there's more uncertainty than you consider.
Particularly in terms of prevention, you know, treating people with high blood pressure.
The majority of people who have drug treatment for high blood pressure will never benefit from that treatment.
And so in certain areas, there's much more uncertainty now at the outset of a new pathogen.
And there are 13 questions that you want to start asking about the behaviour of the virus and try to understand that very quickly.
So for instance, one of the key attributes of a virus, if it's pandemic and pandemic theory,
suggest that all members of society should be equally affected.
So if you go back to the 1918 influenza outbreak, the Spanish flu, you see that actually young people were actually infected and many of those died.
And so when you have that so for instance, if you see children and young people dying,
you know, you've got a new pathogen and it has a severity that actually is a real problem.
But actually, it was very quickly aware and we looked at the data and said, actually, there's a very significant problem here with age.
That the mortality as you get older significantly goes up and actually in young people are virtually unaffected.
In particular in terms of mortality, which is not the same for all respiratory viruses.
So there are influenza attacks on the fires and particularly on the ones viruses like RSV really detrimental to the ones.
We send a lot of those children into hospital.
But this virus, 75% of the deaths were in over 75 and those under 75 were actually those with co-morbidities.
And in subsequent, the data came out about 90, 95%, either in two categories.
Well, that's operating much more like a seasonal pathogen.
And that's one of the key elements that we're due to direct your interventions to.
Who do you have to look after? What should you do? And these are the important questions that emerge very quickly.
But early on, there was much more of a need to inform the public, the media and the policy.
And so in the first 6 to 8 weeks, I remember I came back to work.
I had about two weeks of feeling unwell until about another two weeks,
and I was back in action by the fall towards the end of April and within a month.
What had happened is by the time I go back to urgent care, it was like it was completely different.
The plan, it got into place, but it took about a month to get into place.
But what was interesting was the the the difference between I call it in my back garden, I've got this COVID where I work from home.
And while everybody's in lockdown, if you go back end of April, May,
it was incredibly nice weather in that period of time and there was a sense of everybody was in lockdown and there was information being produced.
Much of it was not just uncertain.
Some of it was taking viewpoints about worst case scenario or and we were just saying, look, the job here is to try and be really objective.
And interesting, when I went back to work, it was quite it was quite therapeutic to go into work, to be honest.
And but what was really interesting is how quiet was in the world.
And actually it was what was what concerned me at that point is it was also very quiet in urgent care in a way that I've never seen before.
Because we had that message protect the NHS and I think people were taking that too far because they were fearful.
And we've had this problem with people with ongoing issues where they started to present late and where it was worth,
where it's normally present much earlier. And I think that's one of the big issues in terms of we jumped into this lockdown,
never been tried, never been tested, and all of those considered was something that wasn't viable.
And I think there's going to be ongoing debate for the next hundred years about what the values are of lockdowns and restrictions.
And there's going to be people on either side continue to make arguments about what was the right thing to do.
But I spent about six or eight weeks, got very quickly drawn into it.
We have a lot of connections in the media and actually spent about eight weeks and did a weekly seminar for about 40 to 50 journalists,
just about what the old figures mean, how to interpret them.
And so they come out on Tuesday and at 1:00 Science Media Centre would have a briefing and we present the data and said,
Here's what you might want to think about and look out. And so it was an exercise of working with the media to try and inform.
What was going on and how you might interpret the data.
So what was going on with lots of older people dying and a lot of them in care homes?
Yeah. So that was, you know, and pointing that out. So for instance, we went into the lockdown and what was interesting,
if you look at the data is the outbreaks in care homes continue to go up for about another two weeks and about 30% of the deaths were in care homes.
And so generally, if you if you look at that, you think, well, that's where we should be put in 30% of resources.
That's still a big issue for us to argue and point out what I call the Department of the obvious.
There's a problem here and that there isn't much high quality evidence to inform what happens in care home.
But there is a lot of observational data. For instance, the number of staffing reduces the mortality.
Those homes that have clinical examinations on a daily basis have lower mortality.
The size of the home can make a difference. And in America they have these green have homes where there are only about ten or 12 people and but they
have better staff ratios and they don't have this problem where you've got these super sized care homes.
So if they have an outbreak, they can't manage it. There are there was an interest in issues with the elderly, which we've looked into,
because one of the problems when you're elderly, if you get this concept called immunofluorescence.
That basically your immune system starts to slowly wear down.
So it just doesn't become as reactive. And we've noticed this for some time because one of the key things about the very elderly is, for instance,
if they have a urinary tract infection, while a young person will just say, I've got burning, stinging and a fever and a manual.
But actually, if you look at the evidence in elderly people,
they may prevent with something like of legs, confusion, they don't have the tradition over.
Yeah. Falling over. And that's because they may have had the infection on board for a week or two.
And actually they're getting seriously on well, but they don't make the same immune response, which is the fever.
And that's the same probably in the care home population that actually when you go in there,
you see that actually you can end up with a lot of really unwell people, but no one's actually noticed it yet.
And then you've got staff going from one to the other, so it's practically impossible to manage that outbreak.
With the current systems we have in place. And today we've still not sorted out that care home issue.
And we're not sorted out social care. It's a big issue.
And as the population ages, you basically have more of a problem with respiratory pathogens.
And so I see people go, well, this is not the common cold and the common cold is not a problem.
And I go, Yeah, that's correct. But actually, if you take a virus like rhinovirus and put it in a care home, it's devastating.
So in the wrong population. Yeah, but in the wrong population with immunosuppressants, poor health, you are vulnerable.
It can be devastating in that environment and I don't think we've learned how
to consider this issue of risk and a lot of it's got lost in the pandemic,
but I think that's a good example of what we did.
One of the things we did early on as well with a lot of statisticians.
I'm a clinical epidemiologist and we just love looking at the data.
And we all had a lot of spare time because we're stuck in a cabin and home and we can talk to each other and know what's going on.
And very early on, it was very apparent, for instance, the way the data was reported was being I don't think it was people doing on purpose.
I just think they didn't understand what the data was.
So what happens is the way the data gets reported through NHS England and Public Health England on a Tuesday, they always dump in a lot of data,
but the data would come in from care home, from hospital and they'd say there've been 1600 deaths today,
but that was the date of reporting of death, not the day they actually occurred.
So we did the simple things and actually NHS England were the first to come on this.
And so these distribute back about two weeks and they actually look much more like a normal
distribution then you thing deaths have gone up fourfold today and we're going know they're actually
coming down and and so we had this out where we was making statements going that's the coming
down and the media report they're going up four fold and people were latching onto that.
And so we were just trying to clearly correct the data so you could inform the decisions.
And we've continued to do that throughout, and I think that's been helpful.
But the idea that you produce data is is incredibly important, that it's accurate.
Now it's a bit like throwing darts at a board.
There's a bull's eye. An accuracy means you're near the bull's eye.
But what we get with a lot of data is it's precise.
So the darts might be very near together to each other, but it might be some way from the bull's eye.
So this concept of accuracy versus precision, and we get lots of precision in the modern world because we get load the data, big data.
But often accuracy is missing. In the job is to hone in on that information and try and go right.
What's happening in care homes. And and the second area, for instance, where there were lots of problems and still are hospital acquired infections.
And that's been an interesting area and I think we've looked into that.
So we continue to look in areas.
But one of the things we also did early on, which is develop the Oxford COVID evidence, is to just put this information out.
And how do you how did that operate? Well, we have a website, the CBN website, and actually I established in help established in 1995,
I mean, I'd only just about started turning the Internet on it those days.
And I remember we populated a website with evidence and facts and how to do it.
And I've been involved in developing ever since. And we've always I've always had this.
Job. Of all part,
my job is to communicate what the evidence is and what it means and actually were just look for gaps in the evidence based like nobody had.
What's the evidence for social distancing? What's the evidence for masking what?
What's the impact of temperature and humidity? What is case fatality rate mean?
What's the infection fatality rate? The term that would be bandied around for the first time.
And and what was different with this time is normally when that happens, it might be one article, but the whole papers were full of it.
One. And there are just lots of misinterpretations.
I say people taking the information and running with it and going, Oh, you know, we might be talking about the case fatality rate verses.
Know, what you're really interested in is some other measure and using data from China which doesn't match what we're seeing here.
And I think we just felt that actually we should produce and write and put our information in evidence to just inform the debate.
And actually had a huge traction really early on because it was just it also amalgamate other people's studies.
So is it all your own work on that? No, no, no. So we our job is one of the keys within systematic reviews is they can take six months to a year.
Or if I said use clinical study report, you're talking four years.
But actually we have skills of rapid review where what we do is restrict some bit from the methods so we can speed up the process and the bit.
Three Restrict don't add in too much bias. And if we do that, we can produce reviews in about 5 to 7 days.
And so that's our rapid review methodology. And I think over time, people are looking to automate that process.
But I think the next ten, 20 years will see more of an appetite for this is the evidence.
How do we summarise it and then provide you with the latest update?
And so we used all of our skills to produce rapid reviews.
And the people I work with are probably some of the best in the world at doing this, and I think it's probably in Oxford.
We actually do have this long tradition of epidemiology going right back to Richard Dole's age to send over
IBM Cochrane and evolving methods for how do you apply health care information and evidence to decisions.
And that's where we are now. We're still working on how do you get this optimised way of getting evidence to inform decisions?
And it's difficult because there's lots of evidence out there that can be contradicting or harmful.
And there were papers that were being retracted. There were all sorts of drugs being bandied around.
You should use these drugs and you're going, well, we don't we don't do it the speed and pace.
And we're going back to the days of opinion overriding the evidence.
And I think that was hugely challenging early on.
I mean, in terms of the the kinds of restrictions that, you know, lockdown and mask and all that kind of thing.
I mean, do you think it was would be fair to say that that things had to be decided so fast that there
simply wasn't time to reach the standard of evidence that you would that would have been desirable?
Yeah. You know, if you spoke to me 20 years ago as a clinician, I'd say when I went into a moment of health care crisis in decision,
I'd say you've got to make decisions really quick and efficiently and fast.
And as a wise a physician, I'll go into many situations now where it looks really quite ominous for the individual.
And now I tend to take a step back and just slow down my thinking, my analysis.
And all the trainees want to act really quickly and say, Oh my God, the person's going to die.
Well, we've got more time than you think. I think I think you always have a bit more time than you think.
Apart from a few odd situations. And I think in those situations, I think it's so obvious to everybody, isn't it?
I mean, you know, there are times when someone is bleeding to death.
You've got to work really quick. But actually, in many situations, you've got much more time than anything.
Someone has had a cardiac arrest. Minutes matter, you know, I mean, in this instance, when.
So in in March. Transmissions seem to be pretty fast.
Yeah. So I think I think having here's where we're going to get the division of people.
I think there was a problem with preparedness. Oh, clearly.
Oh, yeah. And so that problem of preparedness, lack of preparedness, meant that it almost made the decision inevitable.
Yeah. So you could say in a perfect world, if the NHS had been totally prepared,
had got all the PPE and had you in and got a plan, then you could have acted differently.
But given that they didn't. Yeah. So I think that's the issue. So first time round you would go.
But you know, actually what happened is certain countries like Sweden decided to take a different tact.
Now, obviously, there was a big domino effect of countries taking this viewpoint.
So I think it was incredibly hard for anybody to go go against that in the first lockdown.
But Sweden did. And it's interesting, if you if you look at the first lockdown,
when you start to analyse the data is people that are already modifying their behaviour quite considerably.
You can go on Google and they can tell you about the activity on transport people in the workplace and actually dropped off a stone already.
And in fact, if you look at the data,
the deaths peaked on about April the eighth and we tracked back is the infections peaked about a week before we went into lockdown.
And I think people have learnt over time is to watch the bell shaped curve.
There's a chap called William Farr that you can go back in history and look up Falls Law.
Firth You know, basically infections roughly rise and fall in a symmetrical pattern.
And so you get this bell shaped curve. And that's exactly what we continue to see.
Now, we're actually just about on the cusp of the bell shape right now.
And what happens when you get to the top of the bell shape, everybody starts to panic.
But I think the fact that the biggest one for me with not even having a stockpile of PPE, you just can't go.
You can't carry on because you're not aware of at that moment in time what's the predominant mode
of transmission and how is it going to be affected in that with number one major problem for me?
Just one. Well, if you haven't got that in place, you have to actually say press pause on the bottom.
So I think that's why I think and I think why that happens is is I think, you know,
is influenza has been on the government register for the last two decades.
It's thought they were climate change might even say to both climate change given the potential catastrophe it can cause.
But somehow what happens is probably in in about ten years time, as we filter along, everything starts to get pushed in the fore and disappears.
And it doesn't quite become a predominant issue. And so we this is a major issue about institutional knowledge and losing these all perspectives.
And somebody said, well, why are we spending 250 million on something we never use?
And you go, Yeah, because one day we might need the shelf.
And I think and then second with that is simple things like this is just economically.
I can't fathom why some of this stuff is not on shored.
So we were having to buy it from around the world. So the price was going through the roof.
We spent huge amounts of money and now we're paying the consequences of that,
that actually people didn't realise that actually you need a facility to be able to.
If you're not going to stockpile it, you have to have a facility that can go up and down very quickly.
And I still don't think that message has got through. I call that health security.
You have to be able to maintain the levels of sustainable PPE in a pandemic like this.
You can't buy in at the cost we pay. And you could see the widespread panic that the restriction in fact, I was talking about it yesterday.
Shelves bare of toilet roll, pasta disappearing, all of the flour disappearing.
And I'm like, that must be a big stockpile of this somewhere in people's houses.
But that there was a real sort of panic and anxiety across wider society that probably lasted for a couple of months.
But some people still is still there today.
So I think I think the interesting issue is where are we nearly now thinking of restrictions and lockdowns?
And I think it's interesting where we are, and I think people will look back for many decades to analyse was it a good or bad thing?
But what you've got is a natural control experiment in Sweden where they didn't restrict what they relied on.
They did have. So they have access. I don't have the figures. Yeah.
Yeah. So, yeah. So yeah. So they did. Yeah.
But what they didn't do is have so what happened is with the modelling is it predicted to be half a million deaths in an unmitigated scenario here in.
Yeah. And basically said you have to go for suppression and you'll get that down to 20,000 people.
Well that was wrong as well because what the models don't count for is people, individual behaviour change.
And what the difference is in Sweden is people modify their behaviour according to the risk.
I actually think people are really good at modifying their behaviour.
The question is do you need the government to regulate it or can individuals be informed and then say actually if you look at the size of an outbreak,
it's about eight weeks where you get excess death. And that happened March, April, and it happened in January, February 2021.
So it did happen again. I mean, yeah, but it was only about six or eight weeks.
Now, the key is is is this is the key discussion going forward is what happened in 2020 was the belief that actually the model with the Chinese model.
That actually you could follow a model of depression,
that you could basically take your virus and get it down to below about a thousand to keep it there with things like effective test and trace.
And for many of the people who are epidemiologists, virus experts will just go, we don't quite understand that.
There's a reason you call it going viral. The incredibly difficult to manage.
You know, you can do it in the short term, but over the long term.
What's the mechanism and what do you push and what are the consequences of all the strategies is no.
But I think what and this is an important aspect within the concept to BBM and aware of this discussion, everybody's looking for the silver bullet.
There's a simple way to manage this and there's a simple way to prevent this and the simple treatment.
And actually, everyone is much more complex and much more uncertain about what's going to happen next.
So let's talk let's talk about transmission, because that's one of the things you say.
There was a lot of uncertainty about how the virus was transmitted early on.
So what what studies did you do? So, again, again, a transmission.
Incredibly interesting issue. And I think what was interesting, if you go in the history of the UK,
you had a lot of really high quality research until about the nineties in terms of respiratory pathogens.
We used to have a monthly common cold unit in the UK.
Oh yes. They used to give you a young man. Yeah, yeah, yeah, we called you.
But yeah. Human challenge to these two young AMI people and see what happened next.
And then actually probably what ended much of that was the sort of AIDS HIV because
a lot of the focus shifted and that's what happens in research priorities shift,
in the money shift. And then the predominant strategy was vaccination because the predominant mode was influenza.
But the first thing to say is to say how many respiratory pathogens are out there?
Well, when I'm a GP there's about 40. I know of that.
I could say these affect individuals who come through the door, but about 40% of what people have got, we've no idea what they are.
And it could be hundreds more that have not been discovered yet.
So I think the firstly so there's a lot of different respiratory pathogens at any one time.
They're all interacting all the time and that is really interesting.
So, so this idea of influenza morphed into there's only one virus that really matters, but actually there are still all these other ones out there.
And now we know there are like coronaviruses and we knew about it.
We knew there were corona, but there were other. Yeah, yeah, yeah.
So, you know, there are four common ones that been circulating.
Then you've got the ones like sa one and uh so you got them in the background.
But we've had four common ones that basically affect children, infect adults,
and everybody who's basically probably over the age of about two or three had probably had a circulating common corona virus already.
But actually transmission is about ultimately understanding.
Transmission then helps you inform how you might intervene because that's ultimately you want to know how these transmitted.
So for instance, you go back to the common cold. So for instance, in something like rhinovirus,
they did things like put it on people's hands and actually get them to shake hands with
each other and then see if the other person and then split them into barracks and said,
did they get infected? And they showed it was direct contact. Now we can't do them.
We've sort of lost that human challenge to the although they have done the human challenge studies within the vaccine development.
So, you know, actually, although it sounds on ethical human challenges, studies are at the top of pyramid to understand transmission.
We do it with malaria. Yeah. However, we got asked by the World Health Organisation,
it was about September of 2020 and said they'd done a thought, a review and said This is where we are.
But there was so much evidence emerging in a way that never emerged before for a respiratory pathogen.
With about 2000 studies a week being published on Corona virus,
it was incredibly hard to keep up to date with what was going on and emerging and what was happening.
Everything was getting picked up that said, Oh, it's airborne, it's fomite is this?
It's in the sewage, it's everywhere, you know? And it's like, how do you make sense of the.
So we started to do systematic reviews on the mode of transmission.
And we're still in the midst of doing that, and I still think we will get to some certainty.
Oral faecal close contact. Vertical transmission.
Mother to the foetus. Airborne of a third fomite.
We've looked at asymptomatic transmission. We've looked at transmission in immunosuppressed people.
And we've just done our latest update. We've looked at included 591 studies in Across Them review.
So it's been a huge effort. Look at some of your papers and maybe you did make the observation at the beginning
of a couple of them that in general the quality of the studies was poor,
very poor. So if you put a lot of poor studies together, how do you get a good answer?
You don't, you don't. You don't. And I think early on there was a rush.
It was like a gold rush for to produce evidence on on COVID.
And so, for instance, one of the simple things we said, so, for instance,
if you're going to do a study that claims airborne transmission, then you should do some airborne sampling.
And there are studies that say we didn't do any sampling, but it's transmitted through the air.
And you're like, Well, okay, so we've got to create some quality measures.
What defines a good quality study and is that. Yes.
So, yeah, I read those papers as well. I mean, there are those who argue that.
Sampling virus from the air is an incredibly difficult thing to do in any kind of reliable way.
And there are other kinds of evidence. Yeah, I guess more circumstantial kinds of evidence.
Yeah. Yeah. Airborne transmission look likely.
Yeah. So, you know, actually. But there are 27 studies now that have tried to do it.
So actually early on we said there's only four or five.
But actually what we found in at the back end of of this is actually people are starting to do better,
higher quality studies because they get the more serious scientists thinking about this.
But you're right, it it it reminds me of a lot of the problems that occurred early on in beam in randomised trials.
They said there's no way, no reporting standards. So people like Doug Goldman, who is a famous statistician in Oxford,
started movements like consort and Equator and said, We're going to bring reporting standards.
How do you report this stuff?
Because you can't pull it together if it's not reported in a similar way because people would just miss outcomes because they didn't like the answer.
So you're right, there's been a huge problem, but we've been working to create standards for how to determine, uh, transmission.
And we've just published it an update, and it's only peer review now.
We presented it via conferences. We've got a network around the world of people who look at this, and it's clear to us,
if you want to make a transmission claim, there are a couple of things you do have to do.
You do have to have viral culture.
And that means you can say, for instance, if I shake your hand and then we go into your hand and then swipe your hand,
we're going to take that and put it into what's called very thick cells and try and grow that and see if we can get an actual virus.
We can also then do genomic sequencing to make sure it's the same sequence, and then you go,
Yeah, actually we've established transmission, and that's probably the best way to do it.
Now there are surrogate laborious and time consuming.
Yeah, but yeah, but that's like saying recovery trial of 20,000 people.
Why didn't you just do a trial of ten people and say, well, dexamethasone works.
Hmm. Can you imagine what that you know.
Sorry, that's the I think that's all you're doing is giving them some medicine and finding out what the answer is.
It's all this. You know, the individuals will be the collecting of the data.
Yeah, but this is incredibly important. If you want to make a definitive statement, X is transmitted through Y with certainty.
You need to have high quality evidence to be able to make that statement.
You only need to do it about twice. You need to do it once and then replicate it and say, Look, this is what we're looking for.
And I think this is goes to the core of the difference in evidence based approach.
Anybody down here can say, I've got a bit of information, here's how I interpret it.
And, you know, and that's okay. But what's happening is that become statement of fact because of the way it's treated in the media.
Our job is to say, if you're going to say something this way, then actually here's the type of evidence that informed that decision.
And I think this is crucial to the whole debate because that science and science requires I'm building something that is a hypothesis that you tested.
And only only when you can't you can't refute that null hypothesis.
Do you say this is transmitted in this way? So sorry.
How do looking at all the studies you look back so far, what do you think the likeliest form of transmission is?
Yeah, I still think we're in a situation where it's a combination of contact, droplet close contact, but.
But it also means we can't refute anything because of the quality.
And in certain situations like in this room, if we shut the windows and the doors,
there's more likely in a closed environment it'll permeate a bit further.
But actually that's airborne. Well, that would be but that would be in a specific premotor environment.
So I think, again, the term airborne is not helpful because I think the term airborne is is collates with it's everywhere.
So airborne means it's open air in the in the atmosphere.
It doesn't it's everywhere when you're out, find it. So I think the terms are not helpful.
And I think people should be if the science is very careful about making generic statements about it's airborne.
Because I think what we need to do is be very clear in this situation, in this circumstance, this is how it might be transmitted.
What it. Yes. So what you've got to do in terms of having a policy, what you need to know is how far apart people need to be not to catch it.
Yeah, but like say for instance, ultimately, even irrespective of how it's transmitted, that should inform the interventions you will do.
And then you should formally test those interventions and you should touch them with randomised controlled trials.
But for somehow we get that for drugs and vaccines,
but we don't get it for non-pharmaceutical interventions there's been only two randomised controlled trials of masks.
That being proper?
So far I'm aware of a third one that's testing FFP, maths versus surgical math in a clinical population in Canada, and that will report sometime soon.
What for me is a failure of this of this pandemic.
There are lots of questions we could have tried to answer. With that situation.
And bingo. Well, well, well, well.
Equipoise means you're uncertain about whether it works or not.
If you don't have equipoise, you don't need a randomised trial. You're very clear.
Now here's a key learning point. When you find people who disagree about what to do next, it's generally a failure of the evidence base.
There isn't a high quality to inform what's going to happen next.
Therefore, we can have an opinion either side of the argument make it political and keep disagreeing, and we will keep disagreeing generally.
The answer for me in that situation is as a clinician is to is to reduce the uncertainty.
Now, this is an interesting point in evidence based practice.
I suspect within 2 to 3 decades we'll have done what we've done for drugs and vaccines with non-pharmaceutical interventions will get it.
We have to test these things. We just can't go on spending billions of pounds for interventions where there is uncertainty.
And I think and I think that will be an interesting area for history to look back on and go look
at all the failings we've made when we thought we understood what was the right thing to do.
And it's I mean, if I were to say precautionary principle, would that make you go off?
Well, what I think is interesting, what does the cautionary principle mean is, again,
it's been one of those things people have taken away and wrong with what the precautionary principle generally refers to.
If there's a known exposure in the environment,
that may be harmful and the precautionary principle says remove that from the environment until you can prove it safe.
So there may be some toxin or some fertiliser there.
It doesn't mean you go and intervene in some way.
There are very few areas where we actually mandate an intervention.
And that's why I think if they're also like seatbelts generally,
that they're about removing things, smoking from the environment, smoking in workplaces.
But all of them have a very good exposure for home.
Very rarely do we intervene. And the only good example I can think of is seatbelts, crash helmets in, crash helmets in motorbike.
So we make people do certain things.
But to be honest, the precautionary principle is they never get on the motorbike in the first place because it's so harmful.
It's light way up there in terms of the harmful events.
But we let people take that risk, don't we? But actually, when we decide to do that, there has to be very clear evidence of harm and with seatbelts.
It was actually quite some time to build up the evidence base to actually say, actually, we've got to make this mandatory.
And it's interesting. Before that, we had all this advertising marketing campaigns simply about every trip and all that.
The people that are older in the room remember the. And I think when you decide to intervene, you have to.
It's not precautionary principle. We have very clear evidence of harm that will be negated.
And a seatbelt is actually an all or nothing event. If you do not get ejected from the car with a seatbelt.
And also the homes are virtually zero.
So I think precautionary principle has been used in a sort of way that doesn't make sense to me.
And again, this is there are two things that are radically different about this pandemic.
One is the use of PCR, which we've done work in that area as well.
And social media. And I think the social media 24 hour news bubble has created a sort of these ways of coalescing of the were
doing it because of the precautionary principle and then what we lacked is critical thinking in that moment.
Oh, yeah, that's why we do it. And then we suddenly sort of say, well, when do we intervene?
And we say, yes, they do have a safety valve, but actually it's about generally removing known exposure to precautionary principle.
Which makes sense, doesn't it? You know, you might have I've got a certain type of drink.
It might have one of the carcinogens we've got remove it. Because actually until you can prove it safe, we're not having it in society.
So the coaching principle is about removal and not exposing people to known home.
No about intervening when you go into further into. So you just.
You just threw in PCR. Yeah. So. Well, again, anything.
Yeah. So going back, you see, in May 2009, it was very interested in the 2009 pandemic.
There was a bit of PCR testing, but not a lot.
And also many of the trials were starting to use PCR testing, but then we use an antibody tested and then suddenly overnight.
Just clarify that. So. PCR testing tells you that the virus there and antibody testing tells you that has been the virus.
Yeah, correct. Correct. So generally, if you have an antibody rise, you say if you had a fourfold antibody rise, you'd say you'd have the infection.
And that was generally the way of establishing the group that had the infection.
So you do a trial and say, how many people have had a fourfold antibody, right?
But then what came along with PCR testing and that used to be a slow so it wasn't helpful.
But then they had this real time PCR that suddenly could produce results in hours.
And then subsequent to that, we've had lateral flow testing, which was in a minute, but we'll come up with the real time PCR.
And what was interesting about this. Is one of the things we do a lot of and I do a lot of it in my career is when I have knowledge deficit,
I start to teach myself about some of these issues and then I realise it's not just me with the knowledge deficit,
there are a huge amount of people out there really don't import this fruit.
And actually we was interested again in the relationship of PCR testing.
What does it mean when you take in virus that may be 30,000 pages long and you
take it down to a little fragment of about 20 base pairs in the test for that.
And you then say you're positive. Yes. No.
Now, both clinical tests work in a way of saying yes no.
But actually underpinning that is a threshold for like take your blood pressure, you get to a certain point, and above that you're hypertensive.
And below that, you know, therapy, an inflammatory marker above a certain level, it's abnormal.
Below that it's normal. But with this test, it was yes, no. So that's the first thing that interested us.
But that actually there's an amplification cycle called the cycle threshold.
So what you can take is one little bit of one little bit of paper and you can have that in a sample and you start amplifying it.
And the left that is in the original sample. The heart of the test has to work, and so it has to do more cycles because it's doubling.
And so basically, you can go to this cycle threshold, about 45,
which will pick up about one copy per mill on an individual that is beyond the needle in the haystack.
But in some people, it will get to about 20 and they'll say, well, you've got a billion copies per mill.
Well, that's a huge difference. But we treated them exactly the same.
And we had this service where we were just trying to look at this evidence.
And we noticed there were a number of studies coming out on the relationship of PCR testing to viral culture,
and actually these studies had no problem doing the viral culture.
It's really interesting. But actually we started to build this relationship that actually the more virus you had on the left a lot onboard,
the more likely you were to be infectious and the less virus you have them, the less likely to be infectious.
And that still is something police policy. WIV We're interested in becoming clearer because I'm where clinicians now use the test in this way.
A cycle threshold below further means the probability of being infectious is much higher.
The so-called threshold above further probability you being in fact you see virtually zero
apart from a couple of situations if you're immunosuppressed or in the very short window when
you're about to start being infected but actually meet that test it costly or laborious to
do now because what you want to do is establish the principles and then you can use PCR,
which we consider is a high quality test, but actually most tests will allow you.
So I wouldn't give you the answer. Yeah, in particular because what I'm saying to you is if you've got the if you establish thresholds.
So what I'm saying is if you have a yes no, you can't tell you who's infectious or not.
But if you put a threshold in like a cycle threshold of 30, you've got a much better chance of being infectious.
Yeah, I understand that. But in order to set the test for the cycle threshold is not the same as the PCR test.
Just gives you the. Yes, no. Well, it depends. You see, some do and some don't.
This is where we keep asking questions.
So some give a qualitative answer where they'll just get to the end and they'll say a limited detection is 45 and positive.
But many of the tests. Do give you a cycle threshold and can provide that quantitative result.
And some countries in the world, like Belgium,
are now standardising their reference laboratories and starting to provide that quite the focal threshold.
And what this is, is the movement from analytical accuracy, what happens in the lab to developing clinical accuracy.
Basically, Eben, how do you actually use this test in clinical practice?
So we've rolled out speed. Now we have to think smarter about what does it mean.
Now, our evidence suggests when we've looked at it and we've asked for the information, we've got the evidence.
And in the countries around the UK that about 40% of people when they test positive vs know when they're a yes are not infectious.
And there are two reasons that you actually might got the test and you've cleared it.
And the irony fragments can keep being played for up to 6 to 8 weeks.
In fact, we've got somebody at 180 days. Remember the Florence three that was Latin, stuck in Florence for about seven or eight weeks,
got married because they were only going to be let free if they tested negative.
And every week they get tested and they were positive. But we're completely.
Well, that's contamination. They've cleared the virus, but they still testing positive.
This is basic. Even that actually has to be brought to the fore of the myth down.
And if you do that, it helps you think smarter about.
So when you say there are 10,000 people in hospital,
what you really want to know is how many of them are actually infectious and how many are not infectious.
And that can help you make a better decision, not worry as much,
because if that number go to 20,000, people start to panic and then instigate policies.
So these are just create accurate information. The whole of Ibadan relies on accurate information.
You cannot make a good decision without accurate information.
And I think over time, over the 30 years I've been involved in it,
the idea that people have opinions about what's the right thing to do and produce poor quality data is pervaded.
Poor quality decision making. And so we've done the systematic review.
We've looked 84 times. It's been published in clinical infectious diseases.
It's been highly cited, highly accessed and started to have an impact on decision making and how people are going to think going forward.
And so I think we'll see changes over time. The thing with evidence based best practice is we get there in the end.
It just takes a long time. Yes. Yes, that's that that's the point.
It takes a long time.
But the political decision making has or the policy decision it took about 14 years to get from smoking is bad to changing the policy,
and that's the biggest harm. Obviously, we'll get there in the end.
Our job is to just keep putting out the information. Now, that can be controversial when you're in the midst of, well, who's going to get to that?
And you talked about political views earlier. Yeah.
I mean, a lot of the statements that you've made have been picked up by ostensibly political groups who simply object to the well,
you could call them libertarian groups who object to government control of any of any kind.
I mean, how do you feel about that?
Well, I guess I guess the first thing is to say my views have been right at the heart of government, because in September 2020, it was right.
The Cabinet Office helping them inform the decisions in the debate.
I continue to work widely with policy people on political levels and inform the debate.
And interestingly, evidence based medicine has always been controversial.
And and and one of the things I'm very careful to do is to not tell people what to do is
to inform the debate and say this is generally how you would respond in this situation.
We can all have opinions from, you know, a political viewpoint.
And I think there has been a sense that there's a sort of right and left or right and wrong.
And I think we live in that world at the moment. And I think that's what the social media divide is creating.
Come out of Brexit, come out from this, and it's very polarised.
There's a lockdown around Anti-lockdown group and and there's been a,
a group of people in Oxford that includes myself and people like to actually walk through
it who is incredibly smart person probably theoretical epidemiologists know more about.
I talk to her yeah viruses and and incredibly interesting and I talk to her more or less every week for the pandemic.
Cause I'm just interested in the knowledge and understanding what's going on.
There are things we did that I didn't understand, and I think it's my job is to point out when there's uncertainties and point out and go,
well, look, if we're going to do that, here's what's the answer.
So, for instance, zero COVID is a very good what's the end game?
What do you consider is this is not like a path where you just turn off the top and actually everything will just empirically disappear.
Actually, what the problem is, is you may be storing up huge problems for the future.
And hey, Preston, what's happening? You push it into winter, you push more and more problems.
And so we still going to have the fallout for years to come.
We still haven't thought the care home issue. So all of these strategies don't sort out count.
They don't fall to hospital acquired infections.
There's huge problems like right now with excess deaths in the home that are not covered that we're not talking about.
So I think I think it's been interesting, the groups of people where they are and I think there's been over time a shift,
if that's fair to say, in the dynamic of people thinking. A lot of people have been scared.
And I think most people have been on a journey to think differently because I think early on and a lot of the media were very much like,
oh, by November 2020, we'll be back to normal.
And I would sit with people and we'd have a meeting with the cabinet and say that you've no chance of that.
It's just it's not going to happen. You need to prepare for the winter.
What's the plan for care homes, for instance? What's the plan for the low quality infections?
What you're going to do with schools?
You know, and I'm simple policies to them and said, well, you know, actually school holidays provide a natural social distance event.
You could try in areas, not do it, just pilot ones.
If you increase the Christmas holiday period, how does that buy you more time?
What does it do? But you would pilot these things and try and we'd learn.
But but actually we had very clear views of zero care.
Then we were going to have certain interventions that were going to change the nature of it.
So we're going to have MPI rules that fix all of these things, square boxes in schools where the kids would stay in social bubbles and all this.
And I just looked at them and thought, you know, none of these have an evidence base.
And actually many of the people out there would look at it and go, they don't even feel like common sense to me.
The idea that after 10:00 viruses leave the pub or something just doesn't make sense.
And so. I would put forward questions.
A lot of the media come for me. About 80% of the work I do with the media never gets out there or gets published.
I just help them think through the stories or what they may think or write.
And so over time, I've created a relationship with the media and with policy that I hope people come to me because they go,
Well, it's going to present a sort of fair opinion about where we are.
I do not believe that any clinician's job is to overstate or overemphasise when they think, well, actually we'll just present a worst case scenario.
I still don't quite understand how that helps anybody. And I mean,
one of the things statements that you've made and you and Senator have made and
the bank part of this is about the harms of the non-pharmaceutical interventions.
Yeah, I do. Those homes have an evidence base. I think that evidence base is continuing to emerge, isn't it?
And it will continue.
So, for instance, when you start to say, for instance, now you're starting to see you restrict and close schools and keep children off schools,
and then you starting to see the burden of a mental health anxiety.
But then you start to see things like language development. And particularly I think we'll find certain age groups are more effective than others.
And that's a huge problem.
I think we've still seen many of the collateral damage and I think we're seeing accumulating in terms of co-morbidities and increasing alcohol,
obesity, poor management of diseases.
Hypertension is coming through the system.
I think we'll be living with some of these issues for 5 to 10 years until we start to really get a grip of the whole problem.
But I think when you define to intervene a position of equipoise, there are potential benefits and potential harm.
There are no interventions I know of where they're just all benefit.
Now if someone is going to say they'll probably all, but generally they are you know, maybe the seatbelt is worn, you know.
Actually, even if you have a seat belt, you might have a low impact and duty. So some harm at low impact.
But actually, you have to remember, there's always going to be homes.
And the key is understanding the net benefit to home ratio of any intervention.
And then how do you weigh up? Well, you see what people would do in a five year old's death against a child's health difficulties.
Well, it's interesting, isn't it? Normally what you do is you ask people what they would like to do.
I haven't until you 85 and I know what she wants to do.
She would just say, I want to meet my grandchildren. And then only that's what you do.
And she says, I'm prepared to take the risk because I've only got a couple of years.
I can't put it off to 2024.
So it's an individual risk. Why do we take that risk or benefit away from that?
Basically saying 85,
it's more benefit to me to see my grandchildren and the quality of life that provides than go that so that I might live another six months.
So it's about informing. And each, as I said, each individual can come to different decisions about what they want to do, and that's okay.
But when you decide to mandate on everybody, that's a problem.
But that was the decision to mandate was because of, as you said yourself,
because looking at what's happened in Italy, in the hospitals being overwhelmed.
But I'll give you a good.
So that I think that well, I think I'm completely with you on what you weigh but the worry of the hospitals being unable to cope,
probably because they were under-resourced. Yeah. So that's fine.
That's fine. But I think what happens now is every time you get to near peak infection, that re-emerges.
So we could argue and I could argue and we wrote about this is that England has 100,000.
I don't care. But if it's one of the lowest numbers in Europe and Germany has somewhere like 3 to 4 times as many beds.
So they do have this problem. Although what we have is you could argue that what you need in winter and this
has been a persistent problem for the 20 years I've been in health care. I wrote about this before is the winter crisis.
When I came in 2000, it was it was unbelievable how bad it was.
But generally what you need is for to deal with respiratory pathogens is about a 20% flex in your bed care number.
And so, for instance, if you look at the number of admissions for respiratory diseases pre-COVID,
they doubled between August and December and actually January.
We normally have about 5000 excess deaths in January compared to August.
And so going in, we've always had this problem of people have gone in to see grandma with a respiratory infection in January.
Their deaths go up and that is one of the consequences of the way the winter seasonal effect works.
So we've got a problem. But the problem that the answer is not to look down.
The answer is to say, how do you ensure you've got extra capacity?
Well, everybody goes in a supermarket, will know at Christmas they can deal with the extra capacity,
the higher some seasonal workers, they put on more checkout, they bring in more stock and they prepare for it.
But we go, no, no, no, we're not going to prepare for this natural variation in demand.
We're just going to pretend it's not there. And if it occurs, we'll lockdown.
Now, it's interesting.
Wherever you've been in the world and somebody could do this piece of work, it could look at the media headlines where they've all gone.
We're going to be we and we're going to go beyond capacity.
Our hospitals are going to be completely overwhelmed. What if you come back four weeks later and you go, it didn't happen.
And that's because of the Final Four. You're right in the peak of infections.
And just as soon as you get there, they just drop off as quick as they've come in.
And the explanation for that are just really interesting.
But I do think you've got to trust the law that exist.
But one is on the way up. Everybody panics, and that's why they give rise to these exponential curves.
It's like, I think it's a bit like you're on the motorway and when you're on the motorway,
you've come on the slip road and start speeding up, don't you? And what we watch is the data.
So you start of 2040, you don't blink. But as you get to near the speed limit, you're acceleration slows down, doesn't it?
And you can watch that acceleration. So you go 64, 65, 66, and once that starts happening, you know,
you come into the peak and you're going to get to 70 and then you can flow down in a final way to come off the motorway.
So if you watch the data really carefully, you can see when it's slowing down.
And I've watched that movement multiple times. And that's exactly the point when everybody starts panicking.
What the mathematical models try to say to you is actually there's no speed limit and you've got no brakes.
And therefore this car is so dangerous, you need to do something like pull them.
Right. But actually the river speed limit and you can watch the data very carefully.
And that's what we do. And we did it day to day to watch not what we think it's going to be in a moment.
Just ask a question. What does the acceleration look like?
That's giving us a combination of immunity and behaviour change.
It's a combination of all three. There are some things I think.
Yeah, like now you look at it and you go, well look, the immunity, natural immunity that kicks in is I mean,
the I would say there's been over 50 million people have been infected in England this year.
So at some point your natural immunity kicks in. It doesn't protect you forever.
I mean, with everyone, it seems to be even less. Yeah. But again. But again, you see, this is the bit where everybody's going.
We've got genomic sequencing, we've got variants, and we've got this new scary thing called variants.
But if you go back to the AMC Common Cold Unit, they did these experiments in Human Challenge Studies 25,
30 years ago and showed exactly this with coronaviruses and rhinoviruses.
About 50% of the people got reinfected at one year.
And that's because, yeah, there's a natural variation in these viruses, but there's also a natural waning in your immune system.
And so one of the arguments you've got is the idea that what we really do in societies keep topping up our immunity,
that actually these viruses are all in competition all the time, and that interaction means that we go about our daily lives.
But actually, if you give yourself a big break. That actually that's harmful and deleterious to.
And you can think of that because many viruses are bad for you if you don't get them in childhood and get them another world for the first time,
you get the cytokine storm. Really bad news for you.
So actually what we do in childhood, and I say this as a GP is you start from ground zero.
And I think within a lifetime, you're going to get about 200 viruses.
But first, you know, we don't know. In a bad year, a child might have 5 to 7.
And you as a parent are going to have a bad time, too, because you only get more viruses while your parents.
And by the way, when you're a grandparent, you start to run in trouble again.
But actually, it's really interesting to look at some. I mean, I think we should study these.
There are some natural groups who have probably topped up immunity all the time.
Primary school teachers, my sister's one. She continually gets cold, but she never gets seriously ill.
Well, and she had to have fixed the 70 year I am feeling with weekends and you know and that natural.
So one of the arguments was if you're interfering with if you're starting to create
immune gaps and now the worries are what about the RSV and the influenza coming back?
We've got this increasing susceptible population that actually will create more harm.
Now, at this moment in time, people are watching Australia looking all they've got influenza and COVID autoimmune problems.
That's the worry now going into winter. And I think these are interesting issues to look out to say, can you intervene in that?
Generally, the laws of nature would say, well, if we've grown up in this way,
in this symbiotic relationship, there must be benefits for us and there must be some potential harms.
I agree. The interesting issue for me is I think, is what makes you fit for that viral challenge?
We've got an older population, we've got more multimorbidity than we've ever seen and more obesity.
So actually we've got we stood up and that's where we are in the world.
And we haven't even thought about, well, what does it mean to have an ageing population?
Because in the seventies you wouldn't have had the 75% of death in over 75 because they didn't exist in the same way.
So you might have had this outbreak and then you've got there's been a funny virus circulating,
so nobody's even thought about the challenges of having that increasing ageing population.
And if it continues to grow, the viruses will continue to present more challenges.
But does that mean you should lock down every time that occurs?
I think there's a growing realisation that now the collateral effects, the economic consequences mean it's sort of off the table.
But I'm not sure it's off the table forever, because I think some people have an appetite for restrictions.
And some people are still in a mode where they think it's the right thing to do.
I will continue to question the. Right.
So I've just got some more questions about what actually know there is.
Yeah, there is the question when you say some people. So I know there are people even within this department who disagree with you.
How difficult is that people to deal with. Science is built on testing hypothesis and and and I actually there are two distinct things.
I welcome people who provide criticism because it makes you think harder, work harder, and try and keep testing your hypothesis.
It won't ultimately be me that says here's what how this is transmitted or here's how to do the test.
It will be the evidence and the quality of the evidence, and that will inform the decision making.
What's been difficult throughout this pandemic, though,
is I think with the social media work and the frenzy and fear and the anxiety is with people up in making things personal.
And that's not to say that this department just out there, this is an issue that that is now a problem in the world.
If I don't like the message, I'm going after the messenger and I am not brought up in that way.
I'm brought up in a family where, you know, is is the most important thing is not so much to say say.
But never make it personal. Make it about the issue. Make it about what it means, the evidence, and how are you going to test it, how you go about it.
But I think we live in very dangerous times because I think social media has created a frenzy and a way of trying to say,
well, what we need to do is paint you into a firm corner, and then that will get rid of you and your viewpoint.
But I think I'm okay with it. I mean I mean, you know, you've still got funding for your research.
You haven't you've not been ostracised.
I suspect there are people who don't want to work me or people in certain places who would not not want to support my work.
But that's okay. It's more about them than me. I personally, the work we do, uh, I build my skill base.
I can do the work. It slows me down on my own. You know, I don't need a team of 30 people,
but I've got some really amazing collaborators and generally we've worked for decades together and these people are so good at
what they do and we've been thinking about these issues for a long time and we'll be thinking for a long time going forward.
There's been a lot of people who dipped in and will now dip out of this pandemic they saw as an opportunity to get involved.
It's it's the only show in town. And they'll disappear and we'll still be publishing the evidence.
And actually, I think what's helpful now is sort of everything's calmed down a bit.
People are less fearful, less anxious, but in the middle of it.
It was a bit like any challenge to the public messaging is not not you know, not acceptable and you need to be silenced.
And we've had that. I've had that. And to be honest here, that was challenging in the middle of that.
Very challenging. But I think I think is I think we'll see a reinvigoration of the need to have academic freedom.
We all don't have to agree. We do have to agree, though, when the evidence is high quality and very clear about what to do next.
And that's the most important thing about informing decisions, not what I think.
What does the evidence tell you about making this decision?
This is an important issue for policy because what I think a lot of people think politicians want to hear and policy makers is.
You tell them what to do. They know that people in their lives is very opinionated.
What they want to do. You say, Can I have a chat with you?
Can you help me understand this? I have former prime ministers, current prime ministers talking to me, asking those questions.
And the and and I think that carried on because I'm very clear about what we do and don't know.
I won't step out of the market and go, I'm going to give you some outlandish to run with.
I just go, this is what we know. Here's what you think about PCR testing, superb quality innovation though this is in this,
but actually we could improve how we did it if we understood how to use PCR to make decisions about these infections and if we understood that better,
we could move forward. You decide what we should do next?
And I think that's because I also think and I think what's happening in this modern era, if people are sort of moving out of science into politics.
And, you know, in evidence based medicine, it's a really clear,
rational approach to the thinking, which is not been unusual for us to be controversial.
I do. I mean, you've been a media commentator before this before all this started.
Yeah, yeah, yeah, yeah. I have.
And people have come to us over time. Probably the first thing we did was the metal hit scandal.
Then we did a lot about in the Olympics about sports products and trans vaginal mesh areas where
there were issues going on and there have been some controversial areas have been involved.
And we did a review on the use of transgender hormone drugs for children, which was, you know, a very controversial area.
And all we tried to say is what does the evidence say about what to do next?
Oh, my gosh, that was so controversial.
And generally we said, you know, in this normal situation, if we're going to use this treatment, we do it in a trial.
So it should be research, no such thing. And that was hugely controversial.
And and interestingly, over the time of the pandemic, I still have lots of relationships now with the media.
In fact, this morning I was doing talk radio this morning TV and did an interview this morning.
Should we be worried? It's a question. You know, right now cases are going up.
Should we be worried?
And it's interesting, a lot of people say to me, well, I wouldn't do the media maybe because message will get distorted or get twisted.
Okay, go. Well, look, if the message is going to get there at whatever you do.
The question is, do you want to be part of helping inform them?
And going forward and I think over time is if it's about building a relationship in trust.
So a lot of them might just come to me and say, can I ask you a question? There's no no benefit for me.
But I think there's a benefit to wider society.
If they put a report out or a publication that says, well, actually, here's what the death certificate data says.
No, not what I think it might do. And I think that's I found that quite rewarding.
But it also means you've got to be on top of your game. You've got to understand what's going on.
You've got to understand the information and the evidence at any one point.
And so if somebody comes to you and says. Are you worried about the data rise in infections?
You have to go. Okay. Well, what would make people worried? Okay.
Well, hospital admissions. Well, what about the intensive care admissions?
If they were going up, that would we worried that we're going up? That would be worrying.
So I look at all the data and I'll go, well, actually, when I look at it, although cases are going up,
actually the death of actually come down and intensive care numbers have gone up.
So actually, I wouldn't be that worried, but actually I'm giving you the information that can help you make a better decision.
And yet and I think working in the media has been quite an interesting challenge.
And you have to be thoughtful about what you say. Cause words in words can be taken out of context really quickly.
But I think there's a lot of benefits to working in the media.
Mm hmm. I mean, presumably you want the public to be informed and that they're not going to read your papers?
Well, ultimately, we've done we've had projects even based in schools, and we've tried to get this off the ground.
It's not quite work to actually work with big. Spanner in the works, if you like.
But ultimately, I think these sorts of issues should be taught in schools and it's increasingly a little bit hidden.
But if you don't do biology often, it's not in there for biology.
Will talk about clinical trials, regulation and what's a drug trial and so forth.
But actually, ultimately, everybody faces health care decisions. They even might have consent even at the age of 13 or 14.
You've got to make decisions about all sorts of things, about HPV vaccination, very young.
You might be thinking about all sorts of treatment. So I ultimately think we should be teaching about risk prevention,
consent and informed decision in school for everybody ready for the world where they'll face these decisions.
Because what happens is one day you wake up. And suddenly you might be 50.
And somebody said, Well, we're going to do your blood pressure. Can you come in and like, well, what's that for?
I'm a you know, now for men and women are probably with the fact that you engage much more with health care than men,
but you get these very difficult questions.
We cardiovascular risk is in the next ten years, it's going to be 8% chance of having a cardiovascular event.
And you mean what's that about?
So we have all these features that are thrust upon us and actually the require you to be pretty skilled in terms of risk prediction,
prevention, understanding, impact, bias, all of these features.
And I think what's happened in the Kobe pandemic is they've been forced on you in a way that people have now said,
hold on a minute, I didn't ask for this. What actually is informing need?
And on the bit that's been for me, I've had huge support in the public.
I can't I can't quite say how positive it's been, whether it's I get letters, get emails on occasion, people send me things.
My window cleaner wants to talk to me every time he comes round and said, Can I have 15 minutes of your time?
Want to talk about COVID, please? And I'll give them 50 minutes. You know, and the public has been amazing.
And I think the public has an appetite for understanding interventions, what it means to them.
So you talked about your hut. Mm. So my next bit of question is what was working through the pandemic restrictions like for you?
I mean, how easy was it to carry on doing what you were doing?
I think, um, so I think, yeah. So I've got this hot in my back garden, which has got two computer screens and I plug my laptop in on a daily basis.
And I have to say, I've never been as busy. I was probably working minimum 12 hours a day.
And and that's because a combination of we were doing the review, the evidence service.
But then I get media people saying, can we talk to you? Then we will write an article.
We had a splurge of articles in certain journals which we knew like wrote a whole series in The Spectator,
which had a big policy impact of all the politicians and journalists that had an inverse stop note with it.
Well, you know, what I could find was. Yeah, so we write in spiked at the moment at the moment we move around I tend to move around
will come back to spectator and I think it's just go through cycles with the media.
You know it's not it's not I we we life and work gets in the way.
You know, it's hard work to do everything and publish a piece and then and so, you know, we were having to take a day,
a week out and we sort of work out for the evening on Friday morning and then finish it on a Saturday.
And that was like for about for a month.
And in the background we was also doing for about four months is a statistician here called Jason Oke, who is amazing.
And for about four months we were producing the daily update for the media on the death on the day of reporting.
And we put that out every day so, so never been busier.
And and I think, I mean, combination wise as well is the urgent care setting in general practice is suffering from a lack of doctors as well.
And so they're also calling out for people to come and work all the time.
And so, you know, in the middle of Christmas, we we're in deep trouble.
And so there's lots of shifts that need to cover. So never been busier.
I think, you know, we've had this huge shift to online working we some of it's good.
Some of it is not so good. I think we're more efficient in business meetings, but we're lacking that sort of in the corridor brainstorming moment.
And I think there will be some good stuff.
But I think for me I haven't still even come up for breath in about two and a half years and it's very difficult even.
I was away last week. I'm still with work about 20 hours a week.
Otherwise, I still did a media request and did that and don't know why I do it, but I do because it's just that.
And I think there's still a lot to work through. And I think what you'll probably find with most researchers who are at that level,
you just really can't let go of things because it's an evolving thought process.
You can't go, so I'm going to park it for a month and then come back to it.
You know, it's a thought of passion that you have for these are the issues and and here's here's how you might look at that.
And I found that that's what defines, I think, academics in their own right.
They only tell you, oh, 9:00 at night, I'm talking to work about why and I don't even know why, but we're still interested in these issues.
What about coming back to the office with me where you were involved at all in the departments because of safety precautions and how.
Well, you know, I tended to stay away.
You know, there's you know, there's enough people living in the university to to be able to evolve and put together this sort of department.
So I'm I think, you know, I think it will take time for people to return to normal.
We're not there yet and probably be another year in the in that situation.
I guess the thing we did in the middle is we did that thing where we got a dog as well.
I guess both my girls have left the university and we got the dog and that's making it harder for me to return.
And we've got to find a way of getting them into the department because I think that's been a real plus time interview.
Somebody in her office with a dog. Yeah, not in this department.
Well, I think I'm a big a big I mean, that's the most important learning point.
Wherever you are, if you've got to even stay in the moment, you've still got to look after yourself.
You've got to be out there. So, you know, I'm working long days, but I'm still out.
I walk that out for an hour, I look after myself. And I think you've got to do the things.
Where you just take that bit of time out to keep keep yourself fine, if you will.
I don't know where the future will lie in terms of where we go next,
but I think there will be significant changes as a result because I think more people want to work from home and a hybrid well from this point on.
And I think that will have a significant impact. And that's how you able to behave in a way.
That's one of the key things where we talked about it. Where can you change what happens next with minimal impact on society?
Well, actually, asking people to work from home for a couple of weeks is not a big problem because,
you know, we've just seen it happen with the rail strike. So there's the way you should be thinking about when you do restrictions,
what can you do that actually doesn't really alter the fabric of everybody's life?
We'll get to the bit of effect. So I think slowing down what's going to happen next.
Schools, for instance, could give you an extra week on holiday and get them to do their exams from home.
Well, that wouldn't be a big deal. So are you looking for those little bits that can just subtly gain you a bit of time?
And I think that's where we should be smarter going forward in the future.
Mm. Yeah.
I think I got the last one, so. I think it can be a long answer.
We've got time. Mm hmm. Has the experience of working through COVID changed your attitude to your approach to your work?
And how would you like to see things change in the future?
You know, I think I think having it certainly changed it for me, my position in terms of media profile and out there.
I mean, I couldn't imagine it would have happened in this way and it still happens today.
It's been interesting to me and a lot of people come and go in that media journey and profile and policy journey.
But actually, for me, I'm still there. And I think that I'll stick to the evidence based approach with I'm going to write more.
We took a particular position. You know, I've published enough.
I still published in journals, but actually the days of writing an editorial that have impact, I think have gone.
But actually, if you write a piece in the newspaper and suddenly a million people read it, you can have a significant impact.
And in a way that is radically different to anything I've done in the editorial world.
And I think I've enjoyed the challenge of trying to write to the public or write to a wider audience is not either.
You'll get your people who won't like what you say when you do that, and you have to have your flak jacket on ready.
But actually, that, I think, is where the future lies, is for scientists to be more.
Communicating with the wider public, put their ideas out there and try and justify them.
And if we do that well, I think there'll be a better, healthier society.
And so I'll keep doing that. And I think in terms of the workload,
I think with the team I'm very mindful we're an outcome orientated unit and I think we will be more hybrid in the future.
Are our courses are going more online because we one of the things we didn't talk about is our master's in evidence based healthcare.
We have to completely flip it to an online strategy. 14 days.
That's pretty stressful as well. And but the team did an amazing job.
But now we've used it. We've just got approval from Education Policy Committee to increase the number of
courses that can be taken online so students don't have to come here as much.
And we think that's a sensible strategy in the middle of winter. It will be difficult to travel if you're well.
But also next week, we're all in a summer school for all the students, as about 45 coming next week.
So we're changing the strategy. We think they still want that in the corridor moment and there's a big appetite for that to come to Oxford.
But they may change the nature of when they do and what suits them. So the flip side is, I still think there's a lot of issues to work through.
There's a lot of things to think through in terms of the backlog now of homes, you know,
whether it's cancer care and diagnostics, whether it's mental health, whether it's social care.
We've got huge problems. And I think they're going to require a lot of astute thinking going forward.
Pete. What? Hate.