Welcome to edit HTML viral season 3, a podcast, exploring the science behind Global and public health.

I'm Amy Thomas.

I'm carlberg.

I'm Naomi Stewart, and every Fortnight will explore the latest developments in the covid-19 pandemic and take a deep dive into vaccines and vaccinations.

Nearly 700 million covid-19 vaccine doses have been administered so far, yet billions more are required and vaccine Equity remains a major challenge.

Without doubt, the world faces, the greatest vaccine production and distribution challenge in our history today, marks the start of the modern era covid-19, vaccine roll outs in the UK, so far more than 30 1.6 million people in the UK have had their first vaccine.

Ice and 5.4 million people have received their second.

The UK medicines regulator, the mhra says, under 30 should, now be offered an alternative covid-19, jab to the AstraZeneca vaccine, based on the current evidence on Associated blood clots.

Chief exec.

June rain says, well, the clinical trials of vaccines allow us to assess relatively common effects.

Very rare effects are only detected when a vaccine is used at scale on a large enough number of people.

And that is why the UK As careful monitoring systems in place.

And these monitoring systems are now detecting, a potential side, effect of the covid-19 vaccine Astra eneca in an extremely small.

Number of people Jonathan van Tom explains strangers in preference for vaccines are business as usual.

And this is a course correction in season 3 of Ls.

HTM viral, we have explained how vaccines Scenes will help curb the spread of covid-19 delves deep into the history of vaccines and discovered what they are made from next.

We are exploring the crucial yet contentious stages.

Clinical trials and testing vaccines.

How do clinical trials account for different demographics.

And how do we know vaccines are safe for everyone?

We'll also explore the differences in vaccine protection covid-19 variants, and the very popular vaccine tracker developed by the London School of hygiene and tropical medicine as vaccine Center.

I'm joined today by dr.

Ed Parker research fellow at the London School of hygiene and tropical medicine and a member of the vaccine Center.

Dr.

Ed Parker develops and maintains and Sh t a vaccine tracker, which details all the vaccines currently in Development Across the world.

Ed also researchers vaccine safety in different countries vaccine clinical trials and testing and different populations.

So Ed.

Why do we need clinical trials?

I think in essence, clinical trials, answer.

Two key questions about a treatment or a vaccine.

So number one.

Is it safe.

Number two, does it work and the fairest most reliable way to answer.

Both of these questions is to take a group of people?

Give some of them the vaccine and some of them are control, for example, like a placebo and you compare how they They feel how their immune system reacts and in the case of a larger phase 3 efficacy trial, whether or not they're protected against covid, can really think of clinical trials, as being perhaps one of the great Innovations of scientific history, but it's also one of the simplest, you know, there's something completely intuitive about this basic idea.

You've come up with a new treatment, you want to see if it works.

So you give it to some people not to others and you see what happens next.

One of the earliest recorded can Trials is actually in the Old Testament.

So the king of Babylon was trying to work out whether to offer a diet of meat and wine are a diet of vegetables.

So they did attend a nutritional canonical trial and I could guess in today's terms.

We'd call it a non-randomized open-label, controlled study the end of ten days.

Vegetables came out better off.

So that's the kind of, you know, one of the first records of something like this happening.

If we then To jump ahead to Thousand Years.

Clinical trials, started to become really a Cornerstone of public health research in the 18th century.

So for example, clinical trials were used to show the benefits of citrus fruits, to ward off scurvy.

And I think it's fair to say that things have become more rigorous over time.

So, today a good clinical trial will generally have a few key attributes.

So, firstly, the trial should have a control group who don't get the treatment and this provides that kind of Benchmark for I think the impact of your treatment or vaccine.

So, then, secondly, the trial should be randomized.

And this helps to avoid any bias in who receives a treatment and who receives a control.

And, finally, the trial should be blinded, which means you don't know if you're in the trial, whether you received the treatment or the control, and I think this makes you know, intuitive sense.

If you're in a vaccine trial and, you know, you've received a placebo, you're going to act much more cautiously and that could skew the results.

So then if you look at the Covid, vaccine trials.

These three key features, randomization control groups, and blinding have been really carefully followed throughout.

So I think this can give us a lot of confidence that the results are as reliable as possible.

And they're certainly, you know, a lot more rigorous than their nutritional study being done in the Old Testament.

As really, really interesting.

Thanks so much advocate for going into that detail.

And how do we know that the covid vaccine will be safe for all people when it's not?

Listed on all types of race, gender health conditions and ages.

When a vaccine candidate first moves into clinical testing in humans.

The test population is quite narrow.

So a Phase 1 trial will typically involve between 10 and 100 healthy adults with no underlying health conditions, but then as the candidate progresses into phase 2 and phase 3 trials, The, the trials, become bigger and much more buried.

So if we take an example of the Pfizer vaccine, we saw the phase 3 trial results published in December and this trial involved over 40,000 adults.

It had study sites in the USA, Argentina Brazil and South Africa.

It involved, young and older adults across a range of different ethnic groups and included individuals, with underlying health conditions, including obesity, diabetes, cancer and HIV.

And the vaccine was shown to be not only safe, but incredibly effective across this diverse study population and the picture is pretty similar.

If we look at the phase 3 trials for other vaccines such as the AstraZeneca moderna vaccine.

So when you look at these trials, I think it's clear that a lot of effort has been made to ensure that the populations are as representative as possible of the broader population.

And I think this can give us a lot of confidence about the safety and effectiveness of the back.

Things that have been approved.

Now, that being said, there are a few notable gaps, where particular groups have been underrepresented in the trials.

So we're now seeing specific follow-up studies to address these gaps.

For example, we're seeing trials involving pregnant, women children, immunocompromised, individuals, and several other groups.

So in these specific cases, will have more data over the coming months.

So there were around 40,000 people involved in their Pfizer clinical trial.

Is that a typical number?

I mean, these are huge trials.

So those are the sorts of numbers that were needed to see enough cases in your vaccine and control groups to give you that, that power to show that these vaccines are effective and safe, is really important to acknowledge the volunteers that have helped make all this happen.

So, if you add up all the different vaccine, trials, including the fires are and And the other trials we've mentioned, we're looking at over 800,000 people across the globe who have stepped up to volunteer for these trials.

And so without these volunteers we wouldn't have that crucial safety and efficacy data that we have today.

What about effects that could happen later on in somebody's life.

How do we test for that?

You can call trials the clinical trials that they're sort of phase 1.

And two trials of people will stay enrolled for you know, up to A year or more.

I'm actually involved in a Phase 1 trial and I've been going for one of the RNA vaccines and I've been going back to the monthly just for kind of blood tests and so forth and will be for 12 months.

The clinical trial started and around spring last year, March April, they're the first advisor and and Oxford vaccine trials.

Started the first people, receiving their covid, vaccines in these trials about a year ago.

So we're starting to get that longer follow-up data from those first.

First trial in Rollies, but it's also worth mentioning that the vast majority of side effects after vaccine happen very soon afterwards.

So the pain in your arm, the kind of maybe nausea or fever those happen in the sort of the first three to five days in quickly, resolved after that.

So it's really those first few days after a vaccine where most of the issues happen.

Going back to this idea of different populations and how we can you know, make sure that the vaccine translates into different groups.

Can we easily translate clinical trials in two different populations, you know, all their safety issues that need to be considered when applying vaccines producing different countries and rolling out to different countries because there's a lot of that happening at the moment.

This is another really interesting question.

I think.

So, let's start with this issue of safety.

And there are a few instances where a safety issue has cropped up only in a specific Geographic setting.

So, for example, the the 2009 H1N1, pandemic, flu vaccine pandemics was linked with cases of narcolepsy and several Scandinavian countries, but this trend wasn't seeing in other countries that were using exactly the same vaccine.

So it's not 100%.

Exactly what was going on here, but there appears to have been at least some genetic component to this.

So we certainly need to be really Vigilant as covid.

Vaccines are rolled out across the globe, but it's worth mentioning that population specific differences in safety.

Is a really rare scenario when you look at vaccines as a whole.

So now if we shift from safety to thinking about vaccine Effectiveness, there are examples of vaccines that work, much better in some populations than others.

So the oral polio vaccine is a good example of this where performance is impaired and children from low-income tropical countries.

And this may be shaped by array of factors, including pathogen exposure, the gut microbiome and a few other factors, but in the case of covid-19, the early signs are really encouraging.

So vaccine tracker includes a living review of every published vaccine trial and we update this week.

So, these now include studies from across the globe using A range of different vaccine types and all signs point to covid.

Vaccines offering a really robust immune response in different Geographic settings.

But there's one final aspect to this question that relates to the nature of the virus that you're exposed to after vaccination.

So we've seen a lot of recent headlines about viral variance and the frequency of different variants will vary depending on where you are in the world.

So it may be that two people receive the same vaccine mount a very similar immune response, but then exposed to different viruses later on and this might impact the level of Detection that they have.

So this is going to be something that is monitored really carefully.

By vaccine research, is over the coming months and it may be that we need to adapt the vaccines to keep up with the SARS virus as it evolved much in the way that we do for seasonal flu, but I do want to emphasize a really important Point here that imperfect protection is not the same as ero protection and this is something that I think often gets lost in media headlines.

So, in other words, even if a vaccinated persons In can be infected by a new variant.

It may well be that their immunity is strong enough to stop them from getting severe disease and at the end of the day that's what vaccination for covid is all about.

You are a member of the London, School of hygiene, and tropical medicine vaccine Center, have been heavily involved in producing a vaccine tracker for covid-19.

Vaccines.

Can you tell us a bit more about this?

It's been almost a year to the day since we first launched the vaccine tracker and at the beginning of the pandemic, you know, early 2020.

It became clear that vaccine researchers were mobilizing incredibly quickly.

Lee and the vaccine Center at London.

School wasn't involved in any particular effort, but we started to get an increasing number of media requests, trying to make sense of things.

So our aim with the tracker was it was pretty simple.

We wanted to collect data on the various vaccine development, efforts, present it in a clear and intuitive way.

And then try to keep things up to date as a situation evolved.

So when we launched the tracker in April last year, there were about 60 different candidates in development and a small handful was starting to move into the early stages of clinical testing in humans, and we've been keeping the tracker updated weekly ever since then.

So if we fast forward to the present day that the progress has been really incredible a year ago, we knew about 60 and then if we look at the tracker today, we are aware of over 300 vaccine.

It's in some stage of development.

So these include RNA vaccines like the Pfizer and moderna vaccines DNA.

Vaccines vectored, vaccines like the Jansen and AstraZeneca vaccines and several other different types of vaccines.

So then of these, 300 vaccines 86 are undergoing, clinical trials in humans, and there are 25 of these that are being tested in large, phase 3, efficacy trials.

So these are the Big Percy bow controlled trials involving Since the volunteers, they help to show whether the vaccines are safe and protect against covid-19.

And then alongside all this testing.

We're also, of course, seeing the rollout of vaccines outside of clinical trials.

So as we record this, there are, there are 13 vaccines have been given some form of approval for using the general population.

So some of these are being used very widely, like the Pfizer and AstraZeneca vaccines are some of it being used in a more restricted way.

And so, overall as of today, there are around 500 million doses of vaccine have been given a cost 150 different countries.

How do you feel about the scientific development?

That's gone behind?

Such a large number of vaccines?

Right, from the start of covid, people were really aware that individuals, react, very differently to this virus.

And it's going to be the same to some extent for the vaccines.

We're all very different.

We all have very different immune systems.

But one thing that's really exciting about covid is it's coming at a time when we're able to kind of Probe the Human immune system with more Precision than ever before.

So you can take some samples from blood and from stool to look at the gut microbiome and you know look, The genes that are activated after vaccination, all of these studies, you know, are going to be done for these covid vaccine.

So we kind of got the big banner headlines of does it give you antibodies, does it protect against disease, but there's going to be a really exciting years of research.

For this field.

Using this vaccine in this huge vaccine development effort, to understand vaccine responses and our immune system, how it responds, and how it differs between different people with more Precision than ever before.

So, I think it's going to To be an exciting time for the field.

What would you say to someone who was feeling uncertain about about clinical trials, in general?

And, you know, potentially there being a mistake made and that having an impact on them or their family.

I'd say a couple of things.

So firstly, I think people were a bit worried about the speed with which everything happened.

So, you know, a year into the pandemic, we've already got licensed vaccines.

But if one of the, I think things that becomes clear.

If you if you spend a bit of time, looking at the tracker is that although things happen quickly every day.

Due diligence was done at every stage.

If the phase 1 trials in a small group of people to bigger Phase 2, and then those large phase 3.

He's checking for safety and effect, efficacy, and thousands of people.

And it's just because of the huge amount of funds and Regulatory impetus, put behind it and this amazing sort of efforts of all of these volunteers who step forward really quickly to get involved in these trials, we managed to do, what would have taken 10 years?

Usually in the course of 12 months, but all of those key steps were done along the way to make sure that these are safe.

And effective.

So I think it's just knowing that, you know, this happened quickly, but everything was done, right and you can have confidence in that.

And so, I think there's a lot of reassurance to know that all of the careful steps followed along the way, having that reassurance about, you know, the rigor and just the amount of resources been put into this is is quite amazing.

So, yeah, well, that's that's great.

Thank you so much and I really We really enjoyed that.

Thank you again for joining us on the podcast.

It's been a pleasure.

So if that discussion has inspired you to learn about clinical trials, you can find the fundamental principles of randomized, clinical trials as an online course on our website.

So go and check that out.

It's called Essentials of clinical trials and it's running this summer.

As always, please share and subscribe to the podcast, share it with your friends.

Your colleagues, your family's, anyone who you think could be interested in this area.

If you can leave us a rating on Apple podcast star rating, that will be great.

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What you like about the show.

Remember you can ask us your vaccine questions and queries by emailing qualms at lfhe M.A.

C2k.

That's Co double m/s.

At L sh t m dot ac.uk until next time.