If basking young mate down the pub about FAPE in hands, one, they probably say.
No one agrees if it's safer on nuts, so you might as well smoke anyway.
Now, watch your mate needs is a Cochrane review, all the facts have been checked at least twice.
Think, find there's a lot that the experts agree on.
I'd give you a. I'm Jamie, and I'm Nicola.
Welcome to the first episode of our new podcast. Let's talk E-cigarettes.
So back in 2013, Nicola and I applied to Cancer Research UK for funding to support our work on e-cigarettes.
It was 2018. The world was in lockdown and everything felt like it was full of possibilities.
So as part of that grant application, we proposed doing a podcast for people interested in e-cigarettes research.
Now, here we are two years later in a slightly different setting than perhaps we'd originally imagined, but still trying to make this podcast work.
So I'm talking to you from my kitchen in Oxford when a sleeping black Labrador.
My feet. Still only a puppy. Not always the best behaved.
So fingers crossed, he'll stay asleep for our first episode.
And I'm speaking to you from my living room with a fluffy little cockapoo at my feet who is wide awake.
So we're hoping that there's not going to be much barking involved in this first episode.
The cockapoo seems to respond particularly to my voice. So there may well be a little bit of barking going on.
So really what this podcast is here for is to tell you a bit about e-cigarettes.
And the reason that we're doing this is because Nicholai both the research on e-cigarettes at the University of Oxford,
and we do this as part of the coffee and tobacco addiction group.
So just to give you a bit of background, Cochrane is a global non-profit organisation that exists to help people make health care decisions.
And we do this by carrying out systematic reviews of the research literature.
That means we identify and bring together all relevant studies is an area to find out how well something works,
whether it causes any harms and how certain we can be if the findings. So Cochrane reviews are enormous documents and quite large undertakings,
and they often feel like they're never finished because we update them relatively frequently.
So we actually first published our Cochrane Review of Electronic Cigarettes for quitting smoking back in 2014,
and we published an update this October. So in this October's update, we found 50 studies and I'll quickly let you know what we found.
Just to give some context. So in our October update,
we found evidence the nicotine e-cigarettes probably do help people to stop smoking for at least six months and not to do this.
They probably work better than nicotine replacement therapy and nicotine free e-cigarettes.
We also found they may work better than no support or behavioural support alone and that they may not be associated with serious unwanted effects.
However, it was really clear, and this is a common refrain you hear in e-cigarettes research,
that we need more reliable evidence in order to be confident about the effects of e-cigarettes.
And that is particularly the case for the effects of newer types of e-cigarettes
that have better nicotine delivery and also in terms of their long term effects.
So for that reason, for the next couple of years, we're gonna be searching for new studies for this review monthly and updating
the review whenever we find new studies that might change our conclusions. And we're doing this with support from Cancer Research UK.
This kind of continually updated review is a lot of work, and it's called a living systematic review.
So we chose to do a live in systematic review on this subject,
in particular because of ongoing controversy about the public health impact to be cigarettes.
And it's really important that decision makers have the most up to date evidence to hand in our review.
We look at the use of e-cigarettes to help people who smoke to stop using cigarettes.
And in this podcast will first quickly summarise the new studies that we found in our most recent monthly searches.
And then what? We'll then pick an important new study to look into in more detail.
So a deep dive into that study, as it were.
So first off, we'll summarise the new studies we found in our searches this month, which were carried out on the 1st of December.
We'll do this briefly.
So you might say in a notch, say this month we found eleven ongoing studies, which are studies being carried out that don't have results yet.
We found nine new papers reporting on studies that are already included in our review said these were studies that we already knew about.
And we also found three brand new included studies. And we'll incorporate those studies in the next update of our review.
So Jamie and I are now going to give some information on each of these.
And you can also find links to these studies in the description of this month's podcast.
So amazing naglaa. Just first off to say how excited it is to see eleven new ongoing studies.
I've obviously been looking at the research in this field for quite a while.
And by contrast, between 2014 and 2016, we only saw 14 new included studies.
Now we're seeing 11 over a period of 10 months.
So that's great and suggests that we are going to be getting more research in this area to put into our view, which is exactly what we need.
So of those three new studies we found, the first one was a study was published in the journal Nicotine and Tobacco Research,
and it was a study led by Chorley and colleagues truly spelt C, z, o l i.
It was a Canadian study with 48 participants, and it was funded by the Ontario Ministry of Health.
And also by the Canadian Institutes of Health Research. So basically by government agencies.
And that's important. We always want to look and see where studies are funded from.
And we tend to trust those funded by the government or health care organisations more than we might trust those funded by,
for example, the tobacco industry or the cigarette industry. So this Canadian study had 48 participants and it looked at relatively short outcomes.
It was primarily interested in the phenomenon of dual use, which means smoking and using an e-cigarettes.
At the same time, they used a overdesign. So that means rather than like in a randomised controlled trial, having, let's say,
two groups of people and assigning them to e-cigarettes or not to e-cigarettes, all participants experienced each of the conditions in the study.
So all participants spent a week using both e-cigarettes and smoking Duell, using, as it were,
a week using just e-cigarettes, a week just smoking and a week using neither device.
And in this study, they measured product use.
So how many e-cigarettes people used, how many cigarettes people smoked during these periods and also what they called biomarkers of exposure?
So those basically measure exposure to things that aren't very good for you.
And in this case, that includes carbon monoxide and various other toxins.
And you'll have to bear with me as I try to pronounce some of these toxins.
Would I tell you about what they found?
So they found that levels of biomarkers of exposure to toxicants, including carbon monoxide, one hydroxide, PIJ rain and four methyl nitro semino.
One three paradiddle. One butanol, which is snappy.
Your name is an NHL, were significantly lower when participants exclusively vaped compared to when they were dual use in.
So when they were vaping and using cigarettes and as you would expect,
they also found that toxin levels were lower in people who weren't vaping or smoking compared to people vaping and smoking at the same time.
Now, interestingly,
they also found that levels of toxins were higher when people were only using cigarettes compared to when they were smoking and using e-cigarettes.
So compared to DOOL using. And the reason why that's interesting is it doesn't really support some commonly voiced concerns.
We hear about possible harms of dual use, increasing toxin exposure compared to just smoking.
Great. Thank you, Jamie. And were all poor listeners are missing out on is how Jamie's eyebrows,
why up and down when she tries to get the name of those biomarkers, which I'm very much enjoying?
Laughter I'm glad you are of to think of a video for my next summer.
So the new included study that I had a look at is called the Quick Nicks Study and was also published in the Journal of Nicotine and Tobacco Research.
It was carried out by researchers at the University of Newcastle in Australia and led by Professor Billy BNF Escape.
And it was funded by the Victorian Health Promotion Foundation, which receives its funding from the government.
So this one was actually a feasibility trial.
So the aim is a feasibility trial is generally to test whether the trial or the treatments given in the trial can be carried out on a practical level.
And to see whether it will actually be possible to carry out a larger trial.
And the reason for this is that it can avoid wasting a lot of time and resource,
which might happen if you immediately carry out a larger trial and you find that things don't work out as you expected.
Therefore, these trials often have sure to follow ups unless participants in full scale trials.
And this means we do need to be a bit more careful about how we draw conclusions from them than larger long term trials, said the Quit.
Nick trial included one hundred people who smoked,
who were recruited from a residential drug and alcohol withdrawal service where the average length of stays eight days.
The sign is a smoke free site and all the clients are offered. Nicotine replacement therapy is standard jeering this day.
The 100 people who were taking. In this study were randomly assigned to two treatment groups.
One of the groups were given twelve weeks worth of nicotine replacement therapy,
including patches and oral forms of nicotine replacement therapy, such as gum.
Following discharge from the clinic and the second group were provided with an electronic cigarettes starter kit,
which included the inner skin Indira T 22 device, which has a one point five Omma atomiser and a 4.5 millilitre tank.
And they were also provided with a 12 week supply of one flavoured nicotine equipped.
And then both of the groups actually received Talison based Quitline support.
So their 12 week follow up. They didn't find a significant difference in quit rates between the two groups.
However, we do need to be very careful about how we interpret this result due to the small number of participants.
And actually we won't be including this in our meta analysis of smoking cessation results,
because in amateur analysis, we only included results that results from a six month or more follow up.
And because this was a short Herland study, we weren't including it.
And we're hoping to maybe in a future podcast at Splaine a bit about our
reasoning behind that in terms of potential harmful effects of the treatments.
That is something that we'll be looking at in our review. And what this study found was that there were no adverse events or serious adverse events
which were classified as probably or definitely caused by any of the study products,
said that was both the nicotine replacement therapy and the electronic cigarettes.
Great. Thanks, Nicola. I am looking forward to incorporate in that study into our main review and
also hopefully to see in that study progressed to a full trial at some point.
And now we mentioned there are three studies. You've heard about two of them.
But for the third one, you'll have to hang on until the next section to hear about it.
So you'll have to hang on until our deep dive. This bit was pre-recorded at an earlier date.
So as we mentioned earlier, each episode,
we are going to select at least one study from the illegible studies identified from the most recent literature searches to take a closer look at,
say, for this month's deep dive. We've chosen to focus on a new randomised controlled trial led by Professor Mark
Eisenberg at McGill University in Canada and published in JAMA in November.
So I was lucky enough to speak to Professor Mark Eisenberg lead of this trial about this earlier this month.
It was the first time I'd ever been the interviewer on a podcast as opposed to the person being interviewed.
So it was a new experience and I am super grateful to Professor Eisenberg who gave us such useful insights.
So to start off with, will that Professor Eisenberg tell you a bit about his background and how he came to lead this trial?
My name is Mark Eisenberg.
I'm a professor of medicine at McGill University, Montreal, Quebec, Canada, also a cardiologist at the Jewish General Hospital at McGill.
So this Emma and I'm a cardiologist and I'm an interventional cardiologist,
so I do angioplasty to open up arteries for people that are having heart attacks.
And I noticed two years ago that a lot of the patients that they had heart attacks.
Now we give them a routine set of medications.
We give them aspirin, we give them a statin for the cholesterol, get beta blocker and his inhibitor, and we give them an antiplatelet agent.
And I thought, you know, a lot of my patients, least a quarter of them are active smokers.
And if I can give them a pill at the same time when they came in hospital, that would give them to stop smoking,
I would do as much good as, you know, giving them an aspirin or a cholesterol medication.
So I started getting interested in smoking cessation.
I did a series of trials in patients that had heart attacks, starting them with the medication in hospital to see if I could get them to stop smoking.
So I did a trial with would be appropriate in the trial of Varenicline.
And then, you know, during the vertical trial, that's when the e-cigarettes started to come out.
I thought, wow, this is a potential sea change for smoking cessation because they had a number of patients came to me and said,
you know, I've tried everything for smoking cessation. Nothing worked. And then I picked up any cigarette and I never smoked again.
So I said, you know, I think this would be something that we should study for smoking cessation.
Does it work? Is it safe? And so we put in a grant application to the Canadian Institutes of Health research years ago.
And when we first sent it in. It got rejected. They said, what's in e-cigarettes?
Nobody smokes anymore. This is not important. What is this?
And then you cigarettes were in the newspaper and the media, you know, every day for a year we resubmitted our application.
I think it came in first amongst 663 applications because, you know,
the importance of it was recognised because everybody was using them and nothing was really known about them.
So that was the background for a trial. So I hope you enjoy that.
I love hearing about how people got involved in this line of research.
Yeah. And I think what Professor Eisenberg is saying is something that we hear a lot from people,
that the drive for doing research in this area often comes from people who have switched from smoking to using e-cigarettes.
And that's that's spurring researchers in the community to pursue that as an area of study.
You're absolutely right. That's one of the reasons why I really like doing research in this area, feels quite different from research.
And pharmacotherapy is where often it's driven by a company here.
Actually, what we're seeing as a whole research movement, that's in quite a considerable way being driven by the people who the research that effects.
So when I was talking to Professor Eisenbach, he went on to talk a bit about the design of a study and what he found and what he thought were
the most important take home messages from that summit to let him tell you about that as well.
Well, first of all, this study, as it was its previous studies, was done in and not in patients.
They were just regular smokers in the community and they were recruited by word of mouth, by social media, by flyers.
And we randomised them to three different groups to e-cigarettes with nicotine, identical e-cigarettes without nicotine or to counselling.
All three groups got counselling, but the counselling counselling alone not only had counselling.
And we. The intention was to this is done in 17 sites in Canada, across Canada.
And if the intention was to look at smoking cessation of one year, we give them e-cigarettes only for only for three months or for 12 weeks.
So the idea was short term use of e-cigarettes. Would this lead to smoking cessation at one year?
But we got most of the way through the trial and we had difficulty obtaining a final supply of e-cigarettes.
And ultimately, we had to stop enrolment early. And so in conjunction with the data and Safety Monitoring Board,
we changed the primary endpoint from smoking cessation at one year to smoking cessation rates in 12 weeks.
When you know the just at the time before. Before the participants stop their e-cigarettes.
So what we found was that if you got an easier nicotine, you you little over doubled your quit rate at twelve weeks compared to concern alone.
And that there was there was there was a high rate of quit rates,
even amongst people that got e-cigarettes without nicotine didn't reach statistical significance.
Twelve weeks quit. It was, it was more than counselling alone.
These, you know, these results we just recently reported these results in the journal American Medical Association with a six month follow up.
And the cigarette quit rates were no longer significant in six months.
And surprisingly, the cigarette quit rates without nicotine work were significant at six months.
So I think that, you know, because we started trial early,
we only had about three quarters of the participants that we wanted to know that we really had the power to look at the six month results.
But I think the results show pretty clearly that if you are,
you are smoking a cigarette with nicotine while you're actively using it, you have a higher quit rate than if.
And then if you didn't. And it also showed that if you were still smoking using any cigarette with nicotine,
you substantially reduce the number of cigarettes you were smoking, conventional cigarettes.
OK. Now, I should say that the quit rates amongst those those subjects who got counselling alone or it was
a little under 10 percent and the quit rates amongst those who got e-cigarettes with nicotine,
it's 12 weeks is a little over 20 percent. So a double quit rates, but it's only from about 10 to 20 percent.
And that's somewhat similar to what we see with other therapies like your programme Varenicline.
They double quit rates, but still the vast majority of smokers are still smoking. OK.
So this is not a magic bullet for smoking cessation. On the other hand,
it does appear that the for for certain individuals who have tried other other therapies and have been unsuccessful at smoking smoking cessation,
that e-cigarettes do work should say that I think 90 percent of our participants have previously tried to quit several times,
at least several times, and 80 percent of them had used other smoking cessation therapies before.
These were people that had smoked for, I think, thirty five years on average and was smoking about a pack a day.
You know, on average.
So they were confirmed smokers who had previously tried to quit and we were able to show double quit rates compared to consent alone.
So those were the primary primary results.
That's really great to have those results summed up in that way by the person who actually carried out the study.
And one thing that struck me from what you said is that only 20 percent of people quit in the most successful of the study.
So that's really telling us that e-cigarettes caelum a magic bullet.
So what do you think that really means for people trying to quit?
Jamie? I think that's a really good point, Nick. I think within the field of smoking cessation research, that's a quote, right?
We're kind of excited to see. Right.
But relative to some treatment, there's some other areas of research, it seems like while only 20 percent of people successfully quit.
Surely we can do better. An unfortunate reality is that though most people who smoke do want to quit, it can be really, really hard to do so.
And as Professor Eisenberg mentions, a lot of people make lots of attempts before being successful.
So. And we're looking at the success rates in a study of this type.
What we're looking at is the success rates of one attempt to quit smoking, not whether or not that person will succeed eventually.
And so I think it's important that people who want to quit smoking know that this is the case.
They shouldn't be discouraged. Many people need to try to quit multiple times, but end up being successful.
And even when we look at kind of the main front line smoking cessation medications, such as nicotine replacement therapy or varenicline,
you still got relatively low quit rates, even in populations who are really motivated to quit smoking.
And that doesn't mean these medications don't work. Smoking is uniquely deadly.
It kills one in two regular smokers. So it's super important that anything that increases quit rates is available.
But what these low quit rates mean overall is how much we still need more research on how to best support people in quitting.
Absolutely. And that's why we're really excited to see this trial. Still, though, because of issues with conducting.
It can't give us definitive results on those long term smoking cessation rates.
So it does feel like there are a lot of hurdles to conducting research in this area.
What do you think, Jamie? I think there absolutely are. I mean, it's not easy to set up a trial in any area.
But I think there's some particular challenges when it comes to e-cigarettes. And as I've been reviewing the research in this field for six years now,
I am always struck by essentially how long it takes to get these things off the ground.
But also the evidence is coming. And it's always quite, I suppose, reassuring and exciting to see new trials coming out.
And I wish they could come out a bit quicker. So I asked Professor Eisenbach to talk a bit about this.
And what you'll hear next is that he had quite an interesting take on some of the unique challenges around doing research for these cigarettes.
And I think some of those are driven by geographical contacts.
And as we know, different countries have very different regulatory environments and public health messaging when it comes to e-cigarettes.
So I'll let you guys listen to what he had to say about that.
Oh, you know, look, it's it's shocking, really how little research has been done into e-cigarettes, considering how common use they are, you know,
in North America and Europe across the world in the large part of this is because they're the cigarette companies have not sought approval,
regulatory approval to use them for smoking cessation. And and so individuals picked them up in order to use them for smoking cessation.
But the companies never claimed it for smoking cessation.
They claim that their alternative methods of obtaining your nicotine and there's no reason for them to support research,
either financially or to even provide e-cigarettes for for the research, because they're you know,
they're selling, you know, millions and millions and millions of e-cigarettes.
So it's really very little, you know, incentive for them to do that.
At the same time, I think that the particularly in the US, there's been a reluctance to examine e-cigarettes for smoking cessation.
And so there's been really a dearth of trials in this area when you can when you compare it to, you know, in cardiology,
when you compare it to large cardiology trials that are driven by by pharma, you know, with tens of thousands of subjects.
And there's you know, there's many, many trials coming out all the time.
And you're looking there's only been really a handful of of well conducted clinical trials of these cigarettes.
And and, you know, we have a you know, one of the issues, I think, with e-cigarettes is it's is a device, not just a drug.
And whenever you use these devices are and always criticised saying, well, you used an old model, there's different models.
No generalisable. It's not you know, it's not commercially available or was commercially available.
But now everybody's using jewel. And so, you know, so you're never going to be able, you know,
takes takes years to do these trials from the time that you conceived of the idea to actually get funding, to get regulatory approval to do it.
So the by the by the time you actually publish it, you know, that device is no longer being used and you can be criticised on those grounds.
So I think it's very, very difficult area to do research in.
So the interesting thing is that despite this being such a difficult area in which to do research,
I think there is really wide consensus that it's so important to have more studies and more data.
Absolutely. I mean, I think those familiar with research in this field know that there is a whole lot to disagree about when it comes to e-cigarettes.
But what I think everyone agrees on is that more research is needed.
So even if you read systematic reviews or articles that find opposing things when it comes to e-cigarettes,
they almost all end with directions for further research.
So that actually brings me nicely onto the next question to ask Professor Eisenberg, which is really thinking about,
OK, if these hurdles were in place, if we could do what we wanted around e-cigarettes research.
What research does he think should be done next on the back of his study?
Well, that's a good question. First of all, I think that we need many more studies on e-cigarettes.
You know, my my father was a doctor and or whether I was a medical school and read an article in the New England Journal about some new drug.
And I said, I think you should put all your patients on this drug.
He said, I like to see 10 different studies in 10 different patient populations with long term follow up before they started switching my patients.
And I think it's the same thing with e-cigarettes. I mean,
we really need to have multiple different studies using different devices in different populations for with a longer term follow up close look.
You look at safety, different comparators. I think that, you know,
our study was really very particular and that we we were only giving e-cigarettes
for 12 weeks and then looking to see what the impact on longer terms quit rates.
And I think that's that's probably, you know,
not it's an incomplete snapshot because most individuals who pick up e-cigarettes use them for a long time.
They use them for four years. Some of them never stop, which I, you know, I don't think is a good idea.
I think they should be used as a if they're if they're used for smoking cessation, they should be used as a bridge to quitting altogether.
But if we were to look at using e-cigarettes for a year, for example, I think we would expect to see quit rates higher than what we saw.
I'd like to give short term use of cigarettes and then withdraw.
Then we'll look at longer term quit rates is probably not giving them the device a fair shake.
So I would like to see. I would like to see different devices, different and different populations.
But the longer term use perhaps also using using combination therapy.
And we did. We did. We haven't seen this, even though other smoking cessation trials of other Varenicline trials were varenicline versus placebo.
You know, appropriate drug be appropriate versus placebo. Nicotine patch versus placebo.
There are only a handful of trials, one of which, you know, I think was perhaps the best trial.
You know, every demos the Eagles tried really.
They finally did, you know, Verini plan versus B appropriate versus patch versus placebo in a thousand subjects.
So, you know, a head to head trial or head to head to head trial, I think is, you know, is ideal in placebo controlled.
But but, you know, you need, you know, major, major funding to do those kinds of trials.
You have to have buy in from lots of different organisations. And it's very difficult even to get regulatory approval to even to do in Canada.
Do you know, we had to get approval from Health Canada to to to do this trial.
It took almost a year to get approval to do it. So a lot of hurdles.
So basically what he's saying is we need the Eagles trial.
But with e-cigarettes rolled in. But until we get that trial, do you think that smaller studies can tell us anything?
Yes, absolutely. So it can be really hard to run huge studies.
They're incredibly time and resource intensive and smaller studies not only can be useful in their own right, but from our perspective,
as people who bring all the evidence together, getting more studies is super important because it feeds into our meta analysis.
So that's why we combine the results from across studies.
And the more information we have in there, the more studies we have in there, even if individually the studies are small and don't find an effect,
the more they help us understand how certain we can be about the effectiveness and safety of e-cigarettes for helping people quit smoking.
So I think that just leaves it with me to say. Thanks so much, everyone, for listening and follow the link on our podcast page.
Siddall latest on our Clocker view of electronic cigarettes for smoking cessation,
depending on how our dogs, children and the global situation in the world procedes.
Were hoping to post these podcast approximately monthly from here on in.
So please subscribe. If you want to be alerted to the next one.
In the meantime, we'll be incorporating findings from a study into our Cochrane Review and hoping to have an update out this spring.
And we'll leave you with these closing words from Professor Eisenberg.
We don't have long term studies, but most authorities would agree that they are much, much safer than conventional cigarettes.
If you have a choice, your only choice is between smoking conventional cigarette and your cigarette.
Thank you. Much better off smoking in e-cigarettes, but we clearly need large safety studies.
And even those those have not been done right. So so this this area is begging to be studied.
So really, I think, you know, and it's really it's got to be supported by funding agencies like the Canadian Institutes of Health Research or NIH,
because the industry is just not going to do it. They have no incentive to do it in any way, even if you it were to do it there.
They're considered to be tainted. Right. It's like you can't accept money from from a tobacco company to do cigarette research.
Well, these cigarette companies are sort of the same. So we really would prefer to be at arm's length and maybe use their devices.
You know, we purchase we purchased our e-cigarettes when all the funding came from the Canadian government.
So I think that's probably the right way to do it. So thank you for that show.
Going into our first episode of Let's Talk E-cigarettes.
You've been listening to Nicole Anderson and Jamie Hartman Boyce with thanks to our guests this month, Professor Marc Eisenberg.
The music you've heard is performed by Johnny Berlinguer,
and it was co-written by myself and Johnny a couple years ago to perform on the streets of Oxford.
We'd also like to thank Jonathan living some banks for running our monthly searches.
Elsa Butler found it in this podcast and to all of our brilliant copper and co-authors for helping us sift through and interpret the literature,
which is no small task. This podcast was made possible through funding from Cancer Research UK and through core infrastructure
funding to the Corporate Tobacco Addiction Group from the National Institute for Health Research.
The views expressed are those of Nicola and I,
and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care.
Theo. Smidgens of Fabin is safe and sound may help you.
Yeah.
But some mention the findings we have can tell us what happened long term, even though we know in his paper and than smoking remains still buying.