Webinar presentation: Nicotine vaping products, the UK smoking cessation experience, 20 October 2021

John Skerritt

Good evening, everyone. I'm delighted to introduce the second of two webinars that the TGA has organised, with tremendous collaboration and cooperation from our international partners. A week ago, we had a webinar learning about the New Zealand experience. And we had three eminent New Zealand healthcare professionals talking about their experience, in a very practical sense, in the role of nicotine vaping products in assisting with smoking cessation.

And that's the focus of these webinars. It's really to learn about the practical experience of countries that have had access to nicotine vaping products in a smoking cessation context for a longer period of time than we have. Tonight, I am delighted to open the second of two webinars. In this case, we're learning from our UK colleagues. We Australians say, there's not much we can learn from UK colleagues when it comes to cricket, when it comes to rugby and when it comes to alcohol, warm, flat beer.

However, we do know that the UK has had a very active, successful and dynamic programme in smoking cessation. And nicotine vaping products are part of that. They're not all of that, but they're part of that. And we're absolutely delighted that three or four colleagues have given up their time this morning for them, tonight for us, to talk about their experience. With that, I'd like to head over to the head of tobacco control from Public Health England.

Public Health England has recently been absorbed into the main Department of Health and Social Care. But Martin Dockrell, who heads tobacco control from the UK, is my co-host tonight. Over to you, Martin.

Martin Dockrell

Thanks, John. I was thinking, as you were speaking, that I got my public health teeth in the 1980s in the AIDS pandemic. And, boy, that was a situation where it was very clear that in the UK, we were learning heaps from the Australians on HIV prevention and the response to the crisis. And interestingly, also, that's where I learnt most of my stuff about harm reduction. And that's what I brought with me to tobacco control.

It's basically all the Australians' fault. But I'm really delighted that we're doing this. We're often pictured as having oppositional positions. I don't think that's true and I don't think that's helpful. John and I were discussing the other day how we're both trying to maximise the opportunities and manage the risks. And we're doing this in different ways and they're going to yield different results. And we just got to watch and learn from each other.

I'm delighted to have three colleagues who are much more expert than I am on these issues. We have my colleague, Julia Robson, who's fairly recently, a little over a year ago, joined my team at Public Health England. But she came from managing a local Stop Smoking Service in England, one of the first really to embrace helping smokers use e-cigarettes in order to quit smoking. Paul Aveyard has been a colleague of mine for 15 or 20 years.

He used to chair the Cancer Research UK Tobacco Advisory Group that I was a member of. And it was always fascinating to hear him and his really insightful critiques of the proposals that were brought before the group. Paul is a GP, but he's also one of the country's leading tobacco control researchers at the University of Oxford. Jamie is a colleague of Paul's. And Jamie, again, is somebody who I've really enjoyed working with over the last decade.

They're part of the Cochrane collaboration tobacco group and they've been doing… I remember Jamie coming to me with the idea of a living review, she had to explain to me what a living review was, of e-cigarettes and smoking cessation. And I encouraged her in that. And that's been extremely productive. All three are really very experts in their fields, but also we've chosen them because we think they're really very good communicators. I'm going to leave it there and I think we'll go straight to Julia. Julia, if you're ready?

Julia Robson

Yes. Good evening, everyone. And thank you, John and Martin, for that introduction. Let's get started with looking at e-cigarettes and the English Stop Smoking experience. Here we go, talking about the English Stop Smoking Service experience of e-cigarettes from 2013, talking about advice for first-time e-cig users and touching on nicotine and flavours. Next slide, please. 2013, e-cigarettes just almost overnight, 12 months, became the most popular quit smoking aid in England.

And this graph is from the smoking in England data. It's not just about Stop Smoking Services. It's across England. And look at the pink line which just rocketed in 2013. Thank you, Martin. Next slide, sorry. As a Stop Smoking Service manager back in 2013, seen the sales of e-cigarettes rocketing. And what we were seeing in the services, the smokers were not there. Footfall was really falling. And when I walked down the high street, they were queuing outside the vaping shops.

The independent vape shops that were popping up very rapidly on the high street. I was fortunate at that time that PHE developed, opened their doors and I had greater access to evidence on e-cigarettes through the vaping in England report. People like John Britton, Ann McNeil and the evidence was growing. I also sought out vapers through the vape forums. And I'll come back to some of their experiences they shared with me in a minute.

But we managed to bring together local independent retailers, vapers, the expert evidence from PHE. And through stakeholder engagement, we're able to train staff to be far better informed to support smokers who brought their own e-cigarette to the service. And by 2016, we're able to offer access to e-cigarettes from non-tobacco industry services through the service itself.

Which significantly increased the number of smokers who were able to access e-cigarettes to quit, with the benefit of the behavioural support from the Stop Smoking Service advisors. Next slide, please, Martin. Listening to vapers, this was really game-changing for me. I spent a few weeks talking to e-cigarette users vaping outside coffee shops. And I remember particularly a gentleman in his late 60s whose son had bought him one from a stopover in Hong Kong.

This gentleman had tried everything. He'd been to the Stop Smoking Services. He'd tried everything. And he tried this e-cigarette to please his son. Couple of days later, he'd quit. And then he was waving at me his lung function test that his GP had supplied him because he was feeling so great. His GP was delighted. And that really was the stories that I was given by the other vapers. That in the main, they tried a lot of things to quit and nothing that worked.

They'd probably picked up one intending to cut down, but then found that they'd quit. It just worked. Some people needed a bit of practice, but then admitted that they practised a bit with smoking. They remember that cigarette that they had where they coughed and spluttered. They got advice and support from other vapers. They joined the vaping club. But really, it gave them everything that they needed. It was the hand to mouth.

It was the hit to the back of the throat. And it was managing the nicotine withdrawal. And they were able to cut down on their nicotine. And many have progressed to nicotine-free e-cigarettes. Thank you, Martin. Next slide. Coming into 2021, in the Stop Smoking Services, we have now nearly 6% of clients in the Stop Smoking Services using an e-cigarette as part of their quit attempts. That's concurrently, consecutively with other pharmacotherapy or as a single product.

Across the services, quite a significant variation still, we have some who have hardly any e-cigarette users in their service, to some with 34%. But certainly seen a growing number reaching 20% of users with e-cigarettes. Those are the ones that have been able to develop a service with voucher schemes or direct supply in the main. Thank you, Martin. Next slide. And this is a current slide showing the pharmacotherapy success rates.

Looking at the red bars, you can see at 68%, we have licenced medications and e-cigarettes concurrently, 68% quit rate. Consecutively, 67%. On their own, 61%. And that is significantly higher than combination NRT. This is where quitters are getting the most popular quit aid and the behavioural support from experts in smoking cessation. Why is concurrently better? I'd probably go for the fact that you've got an expert advisor who's really listening to the client and really supporting client choice, client control in their quit journey.

Thank you. Next slide. Moving on to supporting first-time users and a little bit more on nicotine on the next slide, thank you. Certainly the advice from vapers was to start simple. Try a closed system, one that is probably disposable. One that clicks together. That there's no messing with anything. There's no fiddling with liquids or anything else. It is just pick it up and go and straightforward and easy to use. Certainly looking at trying to titrate the more dependent smokers, you've taken their history.

How dependent are they on tobacco? Looking then for a higher nicotine level. And we'll talk a wee bit more about nicotine in a moment. Encouraging them to contact other vapers. Looking at independent forums, community networks, maybe setting up a buddy scheme. And I understand you have vape shops around, although they're not using nicotine. Certainly a contact there for people to understand other devices.

Practice. Remember that first cigarette where they coughed and spluttered? It's worth suggesting that there are lots of new models around. If they tried perhaps an e-cigarette many years ago and thought never again, it could well have been that Cigalike. That they really weren't as effective as new products are now. Different inhalation styles, different devices, maybe looking at the vegetable glycerine, propylene glycol mix.

But really just practising and talking to other vapers, because vapers are experts by experience definitely. Next slide, please. A little bit more about nicotine levels. How much perhaps to prescribe? We all know that smokers can self-titrate very easily with how often they smoke. Vapers do the same. There are some other factors that affect how the nicotine levels are in their body, how much they're absorbing.

We started out with freebase nicotine. We've now added in nicotine salts into the products. And salts give a smoother, faster nicotine hit. If you look at the resistance level in the atomiser, a lower resistance, greater vapour, greater throat hit. The power of the device. Higher power, greater throat hit, greater nicotine levels, greater intake. And with the technique, there's a mouth to lung, direct to lung… I've never vaped.

This is where getting the experience from vapers, they will talk somebody through how to do that. As we said, looking at higher nicotine dependency, higher nicotine milligrammes per mil to manage that withdrawal. And just a word of caution… And I refer you to the Dawkins research. If a low nicotine level is prescribed, this could result in that compensatory heavier vaping, as we talked about smokers and vapers self-titrating to manage that nicotine withdrawal.

If somebody's vaping heavily to get the level of nicotine they need to manage those withdrawal symptoms, they're likely to get that increase in the expedience. Something that perhaps would be better to avoid. Thank you, Martin. Next one. And just finishing here with a few words about flavours. Many clients in my experience have switched initially to tobacco flavour. They're looking for something as similar as possible to their tobacco cigarette.

Then they've moved on to other flavours. And leaving that tobacco flavour behind completely is often seen as part of that new identity, an ex-smoker, and seem to really support relapse prevention. As is experimenting with flavours, it's part of the quitting process, we found. I will leave you with that. And then we've got the panel conversation at the end of the presentation. Thank you very much. You're on mute, Martin.

Martin Dockrell

Thanks, Julia. That was really useful. And I should have explained to our Australian colleagues, for the last 20 years, every local authority in England has had a specialist Stop Smoking Service led by people like you with a squad of skilled Stop Smoking professionals, who give the expert behavioural support to support pharmacotherapy. And we know that that's the most effective way of supporting smoking cessation.

Talking of effective ways of supporting smoking cessation, Jamie, are you about ready to present? Think we're going.

Jamie Hartmann-Boyce

I am.

Martin Dockrell

I've introduced you already, Jamie. I won't hold you back. But we really should plug your... What do they call the…? Weblogs? Blogs on this issue at some point. Anyway, carry on.

Jamie Hartmann-Boyce

Thanks, Martin. I'm just going to talk to you briefly about our Cochrane review of e-cigarettes for smoking cessation. To put out there, I don't have any conflicts of interest to declare. And this work is supported by Cancer Research UK, as well as the National Institute for Health Research here in the UK. The work is supported by a huge author team, some whose faces you might recognise. We're really grateful to all of them.

For anyone unfamiliar with Cochrane, we're a global non-profit. And we exist really to present what we hope are very robust, systematic reviews. We aim for transparency and a really strong emphasis on quality assessment. And generally, Cochrane methods are considered gold standards. And we do this to help people who are making healthcare decisions, whether those be people who smoke, in this case, researchers, funders, policymakers and clinicians, make those decisions with the best available evidence.

To hand in a full understanding of the strengths and weaknesses of that evidence base. And I've been reviewing the evidence on e-cigarettes for smoking cessation, along with my co-authors, since 2014. This is now a living systematic review. And what that means is that every month, a team of us search for new evidence around the use of e-cigarettes to help people quit smoking. We publish the links to any new evidence we've found monthly.

And we update the review whenever anything emerges that really might significantly change the conclusions of that review. As part of this process, just to put out there, we do have various briefing documents available online. We also have a podcast for anyone who really wants to keep up to date with e-cigarette literature. And the results I'm going to be presenting for the rest of my session today are those from a review update that published last month.

And that incorporates evidence up to May 2021. To start with, currently now, when I first started this review, we had fewer than ten studies, I believe. And now we have 61 studies in adults who smoke who were given some e-cigarette intervention. And we include both randomised controlled trials here, as well as uncontrolled intervention studies. 34 of these studies are randomised controlled trials.

And we have data from just under 17,000 participants. Cochrane reviews, for anyone who hasn't read one, are extremely long documents. They are very thorough, which can be a real benefit, but also means that I cannot possibly present everything from it today. What I'm going to focus on is the evidence on our primary comparison. That includes comparisons between nicotine e-cigarettes and nicotine replacement therapy, behavioural support only or no support and nicotine e-cigarettes compared to non-nicotine e-cigarettes.

Which sometimes are also referred to as placebo e-cigarettes in the literature. In terms of outcomes, I'll focus on our primary outcomes today. Those are cessation. How many people have successfully quit smoking at six months or longer, using the strictest available measure? Adverse events and serious adverse events at a week or longer as defined in a standard way by the study authors. We also, in the full review, look at changes in relevant biomarkers.

Those include things like lung function, various toxins. And one of the nice things about this being a living systematic review is that not only can we update it frequently when new evidence emerges, but we can also put in new outcomes or information as requested. And in this most recent update, we'd had quite a few people from around the world, policymakers mainly, get in touch and ask about how many people were still using nicotine e-cigarettes or the medication they'd been prescribed as part of the study at six months or longer.

We now include that as an outcome as well. Getting on to our primary outcomes from our primary comparisons, first of all, looking at the comparison between nicotine e-cigarettes and nicotine replacement therapy. And we really consider here head-to-head comparisons, for example, with an active pharmacotherapy like NRT, as the most important and meaningful comparison here. Because if someone is coming in and trying to quit smoking, chances are they're going to be offered something.

And when we look at comparing nicotine e-cigarettes to nicotine replacement therapy, we find that more people quit with nicotine e-cigarettes than with nicotine replacement therapy at six months or longer. As I mentioned in Cochrane, we're not just talking about what the evidence shows, we're also thinking about how much we trust it. And here, our certainty in the evidence is moderate. The reason it's not high certainty evidence is simply that we need more trials.

And in those trials we have, they're not that big. Not that many people are quitting smoking overall. And that really means we're underpowered still. If we find more studies and they find the same thing, then we might move to having high certainty evidence in this area. When we look at adverse events at one week or longer, again, we have moderate certainty evidence here of no difference in the number of participants experiencing adverse events.

And again, the issue here being that we don't have that many studies. And with serious adverse events, again, no evidence of a difference in serious adverse events, but very, very few studies contributing data here. One of the good things about these trials is that serious adverse events are relatively rare in both the e-cigarette and comparator arms. But that means that it's really difficult to tell if there's any difference in serious adverse events between groups.

Moving on, when we compare nicotine e-cigarettes to non-nicotine e-cigarettes, again, we have evidence that nicotine e-cigarettes are leading to higher quit rates at six months or longer. And again, here, there's a moderate certainty just because we don't have that many studies. And of those we do have, none of them are particularly large. We need more data still to strengthen our conclusions there. But the evidence we do have suggests that they help more people quit smoking.

We have low certainty evidence, again, of no difference in adverse events. Again here, just an issue with very few studies reporting this data. And low certainty evidence of no difference in serious adverse events. Again, very few studies reported this data. Of the studies reporting it, only two of them actually had any serious adverse events occurring in either arm. It makes this very difficult to tell if there's a difference between groups.

And then finally, comparing to behavioural support only or no support, just to clarify what I mean by this comparison. I don't mean one arm is given nicotine e-cigarettes and nothing else and the other arm is given behavioural counselling. What I mean is that all arms are given the same amount of behavioural support, whether that be simply a leaflet or intensive counselling. And one arm is also given nicotine e-cigarettes in addition to that.

And here, again, what we find is that more people are quitting smoking at six months or longer when they're given a nicotine e-cigarette. Our certainty here is very low. This is partly due to that imprecision issues. So needing more studies with more data. But also the way that Cochrane assesses risk of bias in studies means that a study like this, which is all the studies contributing to this comparison, by their very nature are unblinded.

And one group is receiving more support than the other and knows that, means that we'd also consider these at high risk of bias. But it's worth saying that if we think about nicotine e-cigarettes compared to nicotine replacement therapy as isolating the behavioural, social, psychological elements of e-cigarettes. And we're seeing that that is effective. And also if we think about nicotine e-cigarettes compared to non-nicotine e-cigarettes as isolating the effect of the nicotine delivered via the e-cigarette…

And both of those are showing more people quit smoking. Then of course, we'd also expect to see more people quit smoking compared to behavioural support only or no support. For adverse events at one week or longer, we have very low certainty evidence of a slight increase in adverse events experienced by people using nicotine e-cigarettes compared to behavioural support only or no support. This is very low certainty due to the exact same issues as with the cessation evidence.

And here, most of the adverse events we're talking about are localised. They're the things that you might see with nicotine replacement therapy. We're talking about oral delivery here. We have some throat and mouth irritation, cough, sometimes headache and nausea. And these tended, in the studies we looked at, to dissipate over time as people became more used to the devices. We had no evidence of a difference in serious adverse events at one week or longer.

But here, again, very low certainty evidence for this comparison and outcome. Also of relevance, what we're getting more and more studies of now are comparisons between nicotine e-cigarettes. This is what we really want to see, is we want to see more studies which are doing head-to-head comparisons, where both arms are given nicotine e-cigarettes and they vary in some way. Because that can help us think about how we prescribe or advise around use of e-cigarettes moving forward.

Three of our trials provided data which compared different doses of nicotine. However, only one of these actually looked at quit rates. And that study found that quit rates were higher in a 36-millilitre arm than an eight-millilitre arm. But this includes no difference in terms of the confidence intervals. It was quite a small study. We definitely need more data on this. And we didn't find any evidence from these studies of any differences in safety outcomes based on nicotine doses.

We have one study which was available only as an unpublished abstract, which compared nicotine salt and freebase nicotine. This was, again, a fairly small study. Quit rates were similar between arms when comparing nicotine salt and freebase nicotine. We didn't have any data on safety outcomes because it was just an abstract. We hope that that will be published in full and we can glean a bit more information from it in due course.

All Cochrane reviews and with implications for research and implications for practice. Because of the audience today, I'm just going to focus on the implications for practice. As you've seen, the evidence that we have suggests that nicotine e-cigarettes can help people quit smoking. And that's consistent across several comparisons. We have low certainty evidence around e-cigarettes and nicotine compared to behavioural support only or no support.

But because we have that moderate certainty evidence about e-cigarettes from nicotine compared to nicotine replacement therapy or compared to placebo e-cigarettes or e-cigarettes without nicotine, that gives us increased certainty that we are really seeing the true effect here. We did have a couple studies looking at the effect of nicotine e-cigarettes when added to nicotine replacement therapy. And then there, it was unclear.

We just didn't have enough data to say anything with certainty. None of our included studies detected any serious adverse events which are considered possibly related to e-cigarette use. But there are, of course, caveats around here. One of those being that the longest follow-up time was two years. They were definitely underpowered to detect differences in serious adverse events. And of course, these are studies of regulated nicotine-containing devices.

Not something that someone might buy on the black market. The most commonly reported adverse events, as I mentioned earlier, were throat and mouth irritation, headache, cough and nausea. And these tended to dissipate over time. And in many of the studies that looked at it, actually, we saw reductions in biomarkers in people who had switched from smoking to vaping that were consistent with people who had stopped smoking and not taken up vaping.

Really promising outcomes there as well. That is it from me. I'd really encourage you to see the full review for more detail on everything that's been presented and also to keep up to date with the evidence if you're interested in it. And I look forward to taking questions later if anyone has them. Thank you.

Martin Dockrell

Jamie, that's great. Thank you very much. I can see lots of or some activity in the chat. There's something that brings your two presentations together. And the chats are about policy issues, which we're not really going to discuss. But I think there's something in the data about different jurisdictions and that e-cigarettes seem to be more effective for smoking cessation in environments in a policy context, which is more positive for e-cigarettes.

I think that's a finding of Ann McNeil's. Is that right? Does that reflect your view, your data?

Julie Robson

That is a great question, Martin. I think what we're limited by, of course, is the fact that most of the studies we have of e-cigarettes, which look at quitting outcomes, are from environments which are policy-favourable. If you're looking at trials, then I think it's very difficult to make those indirect comparisons. But I have seen that data that's based on observational data. I think that does suggest that. And I think it's reasonable to think that that would be the case as well.

There's lots of reasons to think that they might work better in environments where they've been promoted to help people quit smoking.

Martin Dockrell

That's very useful. Thank you very much. It was an insight I got from Australian Professor Gary Dowsett, back in the 80s, 90s, where he said to me, Martin, context is everything. I don't think he was the first person to say that, but he was certainly right. Now we're going to move on to Paul Aveyard, Professor Paul Aveyard, as I should probably call him. And Paul's been a great colleague. And I've been very fortunate with the UK academics who have been extremely patient educating me on tobacco control.

Paul, chief amongst them, he brings a wealth of experience, as I say, both clinical experience and academic experience and indeed, research into clinical effectiveness. And he kindly invited me to be among the advisors of a very interesting trial, which I think you might touch on, which was looking at e-cigarettes in primary care. Paul, are you ready?

Paul Aveyard

Yes. All right, then. Thanks, Martin. And hello, everyone. I am going to talk about a trial that Martin talked about, which we called the management of smoking cessation in primary care or MaSC trial. And this was a trial aimed at people who smoked and yet had smoking-related disease. Things like heart disease, various forms of lung disease, serious mental illness as well, as a non-smoking related illness.

But this is a group of people who are targeted by GPs in the UK for special help with their smoking, i.e., at least annual discussion about smoking and offering help to stop smoking. And our trial really aimed to engage people with that effort who said, no, thank you, to the doctors. What we're talking about is a moment in the consultation where the doctor had said, can I offer you some help to stop smoking? And the person says, no, thanks.

And that's when our intervention started. And people were then randomised for the doctor to, or the nurse, depending on the type of consultation, just carry on with the usual consultation about whatever disease they were looking at. Or to say, I've got something else for you. How about using an e-cigarette. That's the context into which we were speaking. And we asked clinicians to talk about switching.

This wasn't about stopping smoking. It was about switching as much as possible, but certainly some switching between smoking and using an e-cigarette. We asked clinicians to give some reason why this might be a useful thing. And then we told them some key techniques that we'd learnt from our studies of consultations about ways to encourage uptake. There's often a thing that clinicians do when they start talking about behavioural issues, is they try to distance themselves from the consultation and say, we believe.

And what we found in these consultations is when doctors meet a little bit of resistance from the patient, if they could just come in with, I think this could really help you, something as simple as that can really unlock the consultation and make it progress in a way that would be helpful. And then questions like, would you be willing? Or are you prepared to give it a go? We asked clinicians to use that. What we did was, in order to refine these insights, we listened into these consultations after they'd taken place.

In this case, there were 72 recordings that we listened to different clinicians talking with different patients, in which they were offering e-cigarettes, trying to find out what it is that we can do to increase their uptake. And we were listening really for interactional trouble. Where does this consultation go wrong? And what do clinicians do in response to that? One of the common things that doctors and nurses did was they offered a choice.

And then when the person said, no, they did one of two things. Either they sighed and said, okay, and clearly presented the choice the person had made to not engage with the e-cigarette as a wrong choice. Or the second thing they did was they just presented more information of, we trained people for this role. We train them in some of the things that Jamie had presented, these things that seem to be effective and they seem to be safer than smoking.

They just gave some more of those information. And neither of those strategies led to problems. Essentially, no patients turned around and said, okay then. What I'd like to show you is a consultation. But what the doctor was doing in this consultation was the doctor described some reasons why this will be helpful. It's safer than smoking and you get the same nicotine hit and there's something to puff on and you don't get those horrible chemicals from the tobacco smoke.

And then he ended with the phrase, have you ever seen people using these vape kits? And the patient says, yes. Actually, I did buy one. And the doctor says, did you? And by ending with those two questions, what the doctor did was elicit the patient's concerns that actually, I did try one and I felt it was way too strong. I was dizzy. I had to pull over by the side of the road. But what the doctor did next was to say, look, two things.

First of all, what I can give you today is some really good equipment. Second of all, it's not by definition stronger. This thing is very adjustable. There's different doses and you'll get some expert help on how to set things up and get the right dose for you. And that was an effective strategy. Eliciting patient's concerns, I suppose it's the essence of good consultation technique, is a very helpful thing when you're trying to discuss smoking with patients.

And in particular, to offer e-cigarettes for which people probably have strong prior beliefs about. The same probably is true for most of the people we're dealing with, many of whom have tried lots of different ways to stop smoking. A useful consultation technique. We had trained clinicians in our trial on some of the evidence that Jamie presented, that these were effective interventions. And we had told them about, for example, organisations like Cancer Research UK, a well-respected charity, says that e-cigarettes are much safer than smoking.

And presented some of the evidence that backs up that assumption. And what we'd hoped was that that was enough. There's a rational case here. Here's something that's safer. Here's something that's effective. Why not use it? But where clinicians really struggled when we asked them afterwards about our trial… And bless them, they carry through our instructions. But they felt unhappy about doing so.

And the reason they felt unhappy was they felt that they were sanctioning second best. They were giving people a product that we think is probably somewhat harmful. We don't really know. But we were, in any case, not overcoming the nicotine addiction. And clinicians felt very uncomfortable with that proposition. And the only exception occurred when it was clinicians who gave other kinds of services for drug misuse.

For example, methadone replacement schemes. They were very comfortable with this way of thinking. But it was at odds with people's concepts of what good clinical practice was. And I started to think of an example where there's something similar in another area of medicine, nothing to do with drugs. And I thought, what about anticoagulants for atrial fibrillation? A very common condition in older people, essentially asymptomatic in many people.

And we give anticoagulants to prevent strokes. And in the UK, at least, we had struggled to get the proportion on anticoagulants up to anywhere near what the trials suggest would be sensible. And that, I think, comes down to the fact that we're giving drugs that we know are harmful to people who are essentially well. It's another thing giving harmful drugs to people with cancer and other life-threatening conditions.

But to essentially give drugs for prevention that will lead to catastrophic bleeding in some people has been a difficult thing for doctors to do. And there is always reasons not to do it. And the same is true of e-cigarettes. We have to get past that mindset and get ourselves into this harm reduction mindset if we're to feel comfortable about doing it. One of the things that happens with e-cigarettes, unlike traditional quitting aids like varenicline or nicotine replacement, is people don't necessarily make a standard quit attempt, as indeed was the case in our trial.

They were just trying to switch. And one of the reasons that we think this will be a helpful thing to do or we believe it's a helpful thing to do is a systematic review. There's a Cochrane review. We produced one earlier in the BMJ which looks at what happens if you give people nicotine, replacement therapy in that case, but nicotine to help people who say they don't want to stop, but want to cut down? And the answer is that in the long run, it leads to double the rate of abstinence.

There's a certain benefit there from this harm reduction approach. There's some, but not very strong evidence, that that might also be beneficial for health if this reduced smoking state can be held for a long time. I don't think it's the main thing we should be shooting for, but it may be helpful. It seems to reduce the risk of cardiovascular disease, at least in observational studies. And there is some reductions in, for example, adverse cell changes in the lungs.

They're precancerous changes in people who've cut down on their smoking. One of the things we did also in our trial was talk to people who were smokers and who were switching onto e-cigarettes. And the thing that united almost every one we interviewed was that they really liked smoking. And that at least was the justification they gave to us for why they continued smoking in the face of these smoking-related diseases.

And what they were looking for in an e-cigarette was something that gave a comparably enjoyable experience. And for them, this all revolved around this coalition of the senses. Taste and smell were important. What people wanted was something that was as similar to their cigarettes as possible. They really liked the tobacco-orientated flavours and not the fruit flavours and this kind of thing. In terms of touch, they really wanted something that felt in the fingers, in the hand, not unlike a cigarette.

They did not want the big, bulky thing in their hands. That it just felt wrong to them. These were new vapers, as I said. In terms of the experience of how it looks, they really did not identify with being a vaper. They were smokers who were switching and they wanted something that did not produce clouds of vapour. We as clinicians often have concerns about dual use. In other words, smoking and using nicotine, won't that lead to overdose?

But we know from prior studies of nicotine replacement that when we give types of nicotine replacement like gum or inhaler that are analogous to using an e-cigarette, in other words, dosable, the total nicotine concentration in people who smoke is no higher. It's similar. Whereas carbon monoxide, a marker of smoke exposure, reduces. And cigarettes per day also reduce. And where smokers are trying to cut down, those reductions have been seen to be larger.

I'm going to stop in a second except to say it is possible to get hardcore smokers who maybe even have no intention to quit smoking, to try smoking reduction with an e-cigarette. For which there is good evidence this will increase abstinence. And early use is promoted by listening to patients' concerns about e-cigarettes and responding to those with information, but also some degree of reassurance. And the sensory experience is key to patients moving to becoming regular vapers.

In other words, not just trying it a few times and giving up. It was feeling comfortable with how that e-cigarette felt. And for us as clinicians, we need to be comfortable with the notion that we're prescribing, I call it, medication that has harms. Because the alternative, which is smoking, is far more harmful. And we need to get ourselves into the position that that feels like something responsible clinicians should be doing, not something which responsible clinicians should be shying away from.

And as some of the evidence Julia presented is that dose of what we prescribe is far less important than you may guess, simply because people are used to altering their dosage of nicotine from cigarettes and will do the same and will learn how to do this with an e-cigarette too. That's all I wanted to say. Thanks very much for listening. And sorry for the absence of slides.

Martin Dockrell

Paul, thank you very much. That was...

Martin Dockrell

Very clear and useful. And thank you for being such a trooper. But that does give us ten minutes for questions. I've got to say, Paul, as a person with atrial fibrillation who's on anticoagulants, I'm looking forward to a dinner party where I can talk to you loads about that, because I know how much doctors like to hear friends talk to them about their symptoms. But let's go to questions. Quick observation from the chat and something you'll have heard from Paul and Jamie and Julia, and you'll hear from me now.

Is that in the UK, we did spend quite a lot of time right at the start just seeking out vapers and listening to them. And I think Australia has been the other way. Vapers have often sought out health professionals to tell their stories. And we found it really useful to listen. And I think that's part of why we've had a much more shared mission in the UK between smokers who're trying to quit with e-cigarettes and health professionals who are trying to help them. John, you're going to identify the ?

John Skerritt

Yes. I've identified some questions that have come up. And I'll ask Martin's assistance in directing them. We've talked mainly about vaping, obviously, in this webinar. But when a naïve patient comes in and they are showing an interest in quitting smoking, as clinicians… And I guess this is directed towards Paul or Julia. What are some of the things you think about, should I encourage this person to explore e-cigarettes or varenicline or patches?

Or indeed, when do you use a combination of those approaches? How do you have the discussion about what approach might be right for the individual person wanting to give up smoking?

Martin Dockrell

Julia, your service did this pretty much full-time? Why don't you have first crack? And then Paul, if you want to add anything from your clinical experience. How does that sound? Julia.

Julie Robson

For me, it just comes back to listening to the smoker to understand their experience of smoking and what they know about the different products, their particular circumstance. That might be, are they pregnant? How old are they? How long have they been smoking? All of it just to really understand their experience and take it from there. Where is the most? What are they most interested in? Their lifestyle, everything, basically, from that conversation.

It really does come down to the client making the choice. You are facilitating that client making the choice, as long as there's no caveat, say, varenicline in pregnant women in this country. But very much with the client-led, client choice, client control and they're far more likely to quit.

Martin Dockrell

I think also this idea that people might change their mind halfway through and the...

Julie Robson

Absolutely.

Martin Dockrell

Skilful clinician will be ready to respond to that. Paul, anything you want to add?

Paul Aveyard

I was set to say I think there's ways and ways of presenting choice. I remember someone saying their mum went to a cardiac surgeon clinic and the doctor there said, do you want to pick valve or a plastic valve? And there's no way that person can make any useful choice. And guiding that choice is also helpful. There's a role for a skilful combination of guiding and listening.

John Skerritt

When would you encourage people to use a combination of therapies? The New Zealanders at least have done some work on a combination of patches and vaping products. Is that done in the UK?

Julie Robson

Yes, definitely. It comes down to, I think, how they smoke and their lifestyle, their dependency level. Where the more dependent they are, then having a patch as well as an e-cigarette could well be an option. That depends on their feelings about an e-cigarette as well. But certainly, we've given out patches alongside e-cigarettes for some time for the more dependent smokers, as they found that more manageable.

But again, are they working? What's their work situation? Are they able to vape in certain situations or not? You may need to give them something to cover those times when they can't vape either.

John Skerritt

Because I guess there's a lot of places, I assume it's the same in the UK, where you can't vape on public transport or in the office. You may need a patch then.

Julie Robson

You may need an inhalator or some gum or something instead, yes.

John Skerritt

I heard an interesting comment about, in some cases, starting people with tobacco flavour, but then moving them on to a non-tobacco flavour is almost a threshold step, that they're moving from being a smoker to a vaper. I'm interested in people's comments on that observation. We've had a lot of discussion about flavours. There are some who say, really, we shouldn't have flavours at all because they might keep people on vaping forever.

Or they might attract children. But I'm interested in the thoughts of the panel about tobacco and other flavours versus mint and non-traditional flavours in vaping products for adults.

Martin Dockrell

I'm going to pitch in quickly on that, because it also raises the question that Jamie touched on about the now gathering data on people continuing to use e-cigarettes for six months or more. When I used to run quit groups, my big challenge was getting people to use nicotine replacement therapy for long enough. And I was never really worried about them coming off too quickly. Julia, Paul and Jamie, in that order, what are your thoughts on flavours and the general appeal of products? Is that a useful thing or something to worry about?

Julie Robson

I think it's not something to worry about at the moment. It's, again, client choice and what they've heard about it and just talking through any concerns they might have had. But if they want to start with tobacco because it resonates with their use of cigarettes, then fair enough. If they want to jump straight into a fruit flavour or a mint to completely get away from the tobacco, then that works for others. And again, there is even non-flavoured ones as well.

It does come down to customer choice. As much as Paul said, you can guide that choice effectively. But what do they know about ?

Martin Dockrell

The interesting thing about unflavoured vapes, of course, Julia, is often they're bought unflavoured, but rarely used unflavoured.

Julie Robson

Yes, they want to add.

Martin Dockrell

And people add their own flavours, which is something of more concern potentially.

John Skerritt

Another question that is often raised is, I guess the endpoint for people who want to give up smoking is really actually to get them to give up nicotine. Nicotine is still a harmful, addictive substance, although we've heard a lot of evidence that vaping is less harmful than combustible tobacco smoking. Again, what's been the experience for UK of getting people to move the next step, to move away from vaping for a longer period, of nicotine, to move away to nicotine freedom?

Martin Dockrell

Paul, do you want to have first crack at that?

Paul Averyard

I'm really seeing a lot of evidence that it's been much of a policy priority or a practice priority to do that. People have always used NRT for when they've stopped smoking and carried on using it for many years, potentially, as far as one knows, in perpetuity. And a small minority do that. The prevalence of vaping, which has been pretty steady in the UK, even though a high percentage of people are vaping.

And studies show that people don't necessarily vape for life. And where people carry on vaping, they say, as with nicotine use, that they're doing so in order to stave off smoking. For us, I think that's what they say. And at the moment, we don't have a lot of effort in trying to get people off vaping. And it's that sense of, is nicotine addiction harmful? One could argue that we're all pretty much caffeine addicts and we all have coffee every day and so on or other caffeinated drinks.

And we don't worry about it because somehow it's perceived as different. For us… I might be speaking out of turn, Martin. Do jump in. But it hasn't been a priority.

Martin Dockerell

There was a local authority, at least one in the north of England, that rebranded its Stop Smoking Service a Stop Nicotine Service, pretty much in opposition to the drift towards e-cigarette from these services in other parts of the country. And they found three interesting things. First, that there was very little interest. Although clinicians and healthcare professionals were really interested in nicotine cessation, nicotine users weren't.

John Skerritt

Were not.

Martin Dockerell

There wasn't really much demand for it. For those people who did approach them, they didn't really have anything particularly effective to offer them. That was the second lesson. They could help them cut down, but there was really no particularly good evidence base for that. And the third thing was that there was a risk of unintended consequences, as Paul said. And because our relationship is complex, I accept.

But the thing that's strongly associated with early cessation of nicotine is early relapse to smoking, which is plainly the opposite of what we want. That Nicotine Service changed back to a Stop Smoking Service fairly swiftly and I think wisely.

John Skerritt

A question for... Sorry.

Julie Robson

Sorry, John.

John Skerritt

I was going to go in for a question for Jamie. You mentioned that there's some studies just recently reported on the efficacy of different doses, different levels of nicotine in smoking cessation. Are you aware of other studies underway? Because this broader issue of what level, do people always self-titrate or is it possible to provide advice? And our clinicians are really struggling to say, do I start with a different amount for a two-pack-a-day smoker compared with a social smoker?

I'd be interested to know if you're aware of other studies underway that may be in next year's update of your living review you're about to refer to. And then I'd like to turn to the clinician practitioners about their experiences with different levels of nicotine.

Jamie Hartmann-Boyce

There are studies underway, I'm happy to say. Whether or not they'll be published in time to go in next year is another question. But we hope so. I think it's a real challenge particularly in this area because the amount of nicotine in the e-liquid is only one element of what's determining how much nicotine the end user is receiving. And what we probably need are more sophisticated ways to measure that nicotine delivery, studies which are going up to do that.

And also more studies which are comparing, for example, different device types, different generations of e-cigarettes. As I said before, we had our first study comparing salt versus freebase as well. Though it's tempting to think, all we need to do is compare higher versus lower doses of e-liquids. Actually, we need to do a little bit more than that to get a sense of what optimum delivery of nicotine might be.

John Skerritt

Do the others, the clinicians, want to comment on that?

Julie Robson

As with Jamie, that it's more than just the milligrammes per mil that you're prescribing. It's how they use it. As you know in England, we have a maximum of 20 milligrammes. I would certainly look at giving that to a 20-a-day smoker and maybe also talking about a patch and on top of that with somebody who's very, very dependent, almost chain-smoking. But it very much comes down to the individual.

Paul Averyard

And light smokers rarely seem to present for treatment, it doesn't become an issue, I think.

John Skerritt

And I'm aware we're almost five past the hour. One final question's been submitted. And the final question, I think, comes back to the point that Paul was making around how to frame the discussion with patients, the choice of words and getting feedback on the vaping experience. Again, it's a question for anyone on the panel. In terms of your experience, what sorts of arguments work best for smokers who come to you?

Are people motivated because of safety of alternative approaches to smoking? Are they more motivated by their general health? Or indeed, are they motivated by the need to save money? Because especially in some countries, the taxes are so high now that smoking is a very expensive habit and affects your general lifestyle, just because of a cost. What sorts of ways of framing the discussion have been most effective in your experience, panel members?

Paul Averyard

All of those. And therefore, if you're going to have an efficient consultation, assuming Australia clinicians are as pressed for time as British ones, then you're probably best to raise the topic, say something good about e-cigarettes. Something that you feel… One of the common concerns, for example, is safety. Addressing that in Britain, half the smokers think they're as harmful as cigarettes, which is not true.

And whatever it is, it's less than that. Expressing some certainty about reduced risk and saying, have you ever thought about vaping? Or what are your thoughts about vaping? And then eliciting some responses from your patient will allow you to shorten the consultation by getting their responses and targeting where they want to go. I don't think it's a question of persuading as much as listening and targeting .

Martin Dockerell

I would say it's not a question of persuading so much as… I'm struck by a scheme that was in a Salford housing association, a deprived part of a deprived city, with the most deprived social tenants. A very high smoking prevalence. The social landlord offered vouchers for… They had 1,000 vouchers for e-cigarettes. The condition was that you had to make a quit attempt and get behavioural support in that quit attempt.

And it just went to unmotivated quitters, just their tenants in general. Supplies disappeared very rapidly. The pharmacists providing the behavioural support were complaining that there were queues outside their door. They couldn't keep up with demand for behavioural support. Which is really encouraging. I guess my thought would be… I understand this is a second-line approach. But when you've got patients who have tried quitting before, whether or not they're interested in trying again, you might say, have you ever thought of trying an e-cigarette?

Because I could write you a prescription if you were interested.

John Skerritt

That's probably a very good point to end and thank everyone. It's been tremendous to hear four very diverse experiences. And again, we really want to thank you for sharing your time with us. I also want to thank… I think we hit the peak of 75 participants. And I know many of them are health professionals at eight o'clock at night after at least a 12-hour day. It's now after dark here in East Coast of Australia. We've all had a very long day.

But I know it was certainly something that captured my attention for the full webinar. And again, on behalf of Australia, we want to really thank our British colleagues for your time and for your insights. And I hope that we can continue the dialogue moving forward. Thanks very much, everyone. And thank you .

Martin Dockerell

It was a pleasure, John. Let's keep it up.