Next in our Science Lab sessions, Chloe Rose PhD presents on the importance of properly designed studies and trials to determine the safety and relative risk of nicotine products.
Transcription:
00:06 - 00:33
[Gizelle Baker]
All right, I guess with that we will go to the next presentation, which if you're looking at the agenda is with Chloe Rose, but she is unable to attend today. So we have Marta who will be here to answer the questions and give a little talk about it at the end. But in the meantime, we're going to watch a video on looking at the perceptions of safety of products and the relationship to properly designed clinical trials.
00:34 - 08:10
[Chloe Rose]
Good afternoon, everyone. Today, I'd like to talk about how we can drive trust in nicotine product safety through choosing smart site selection and innovative trial designs. Despite common knowledge that smoking is harmful, the general population continues to smoke. This has resulted in the development of potential reduced risk exposure products. which have been suggested as a way to reduce the risks associated with smoking tobacco. And with that, the result is that nicotine research has evolved rapidly from neurobiological mechanisms to harm reduction strategies. But even the most innovative study can falter if the research site lacks the right infrastructure, population access or regulatory readiness. These validated human clinical trials are instrumental in outlining the risks and potential benefits of these products. And with these trials, the main focus is always the subject safety and the reliability of the data. As demonstrated in recent conferences, there is a key trend of increased emphasis on harm reduction and alternative nicotine delivery systems. These alternative systems reduce the health risks of smoking or using these nicotine associated products. And these can come in all sorts of formats, including chewing gums and cigarettes, pouches or electronic smoking devices. However, in order to bring these to market, they need to be tested via clinical trials to determine their efficacy and safety. As you can see on the right hand side, we have a graph showing traditional cigarette smoking in Poland versus alternative reduced risk products. And combined, you can see actually at this point in time that the majority of the population are actually switching to these reduced risk products. But in order to bring these reduced risk products to market, you need to, of course, first test them. But how do you choose the right research centre for your tobacco related studies? With this, you need to stick to the key pillars to ensure that you partner with someone with expertise, processes and a department that you can trust. With this, you should ask what kind of experience does the research centre have? Do they have experience with nicotine pharmacology, behavioural studies or neuroimaging? Are there established protocols for handling nicotine and related compounds? How do they ensure quality and compliance? Are they familiar with the FDA, EMA or local regulatory frameworks for nicotine and tobacco products? And is the IRB and ethics approval a streamlined process? And lastly, do they actually have access to the right patient population and the equipment? And is there any demographic or behavioural data to support recruitment feasibility that you can look at to ensure that this study will recruit the appropriate number of patients? But why does this matter? Tobacco studies are complex and time sensitive. Only established clinical research units with audit ready infrastructure and trained teams can deliver consistent results under such pressure. With this, five signs to look out for when choosing a clinical trial provider. They need to show you that they've got proven experience across the years. Can you afford a risk to go cheaper with a less experienced SMO? Do they have therapeutic expertise that align with your study goals? Because without the experience in sensitive therapeutic areas, they will be unable to arise to the challenges that happen during the study. Number three, are they recognised for excellence, not just participation? Are they trusted within the research community itself and are they good collaborators? Four, audit tested infrastructure and proactive quality systems. You need to ensure that compliance is embedded, not just improvised, and that mock trials are run on a regular basis to see the flow of patients. And lastly, number five, do they have proven access to diverse, well-characterised patient populations? Always ask for the real recruitment metrics, the screen failure rates and population insights. A responsible site management organisation always balances feasibility with ethical engagement. With that, please find an overview of the different types of nicotine studies that a centre could be asked to run throughout any period of time. You'll see a case study for a phase four double-blind, placebo-controlled study of pharmacodynamic effects of four milligrams of nicotine gum, a study that was conducted in healthy smokers who were willing to quit. With this, Ablibitum intake of tested products were tested. And as you can see, the enrollment time was six weeks, whereby MTZ, our early phase unit at Pratia in Warsaw, Poland, recruited 220 healthy Caucasian adult subjects, both male and female, 19 to 60 years. we have a case study for a one-week controlled randomised open-label single centre confinement study to compare levels of biomarker exposure in smokers of SMAR cigarettes versus smokers smoking their own cigarette brand. In this instance, ad libitum intake of tested products for 112 Caucasian adult subjects where the enrolment period was six weeks, where the subjects needed to be between 23 to 45 years old both male and female and have a daily consumption of 10 to 30 cigarettes to summarize in nicotine research where you conduct your study is just as important as what you study by aligning site selection with scientific regulatory and operational goals we can accelerate discovery and improve public health outcomes At MTZ, we have a large database of readily available subjects and the research centre has a dedicated smoking area for all smoker groups within the clinic premises monitored by study personnel. The centre is experienced in 24 hour urine collection, processing, sampling and shipping. In addition, there are QA procedures in place and performed as planned with risk management policies implemented including study-specific mock training maps to map the patient flow and required procedures for each protocol. Thank you for your time today. If you have any questions, please feel free to reach out to myself, Agnieszka and Marta, who are all available at the conference this year. Thank you.
08:18 - 08:20
[Gizelle Baker]
And with that, we'll hand it to Marta.
08:20 - 10:17
[Marta Zakrzewska]
Hi, everyone. I'm glad that I have opportunity to be with you today and I have opportunity also to sum up this presentation. What I would like to underline as a sum up that the most important is keeping the safe for the subjects. it should be our goal to think about their well-being and also safe. The most important is safe. The crucial also is opinion of Ethic Committee that we have to think about the study design, how to schedule the procedures, how to schedule the study design to not encourage subjects to smoke more than normal. So the first thing is not encourage them to smoke more, they should smoke at least a libidum and also try to achieve only endpoints of the studies and not go further. Right now, I see majority of studies when we only check the single intake of the nicotine-containing products. It is also connected with the not encourage to smoke more and concentrate on the achieving of the endpoints.
10:21 - 10:29
[Gizelle Baker]
Thank you so much, Marta. Do we have any questions from the floor? Jeannie.
10:36 - 11:51
[Jeannie Cameron]
At the beginning of the presentation, there was mention of innovation in products, etc. And then it went on to the trials and clinical trials. Some of the companies that I've recently been sort of involved with, they're very innovative, but they're also very small companies. And I was just thinking to myself, because there's some new, really interesting innovations that they are doing, but they would never have the money You know, every last dollar that they have is spent on their product design and getting everything accurate in order to, you know, come onto the market. And through Europe or the UK, it's a notification system generally. So I just... I was just interested in... I can see the need to do... clinical trials and things for innovative products if you're wishing to go down a medicinal route, but for the consumer route, I was just wondering, like, had you thought of that? Because you had innovation, but these companies, they're so small, they can't, that have really good products, they can't, they would never be able to afford to do clinical trials or anything like that, or like a US sort of PMTA model. So I was just curious. Yeah.
11:51 - 13:19
[Marta Zakrzewska]
Yes, first of all, I observed that tobacco and nicotine industry would like to perform the clinical trials even more strictly than the industry from the medicinal products. They are more looking into details and would like to achieve more than needed purposes and objectives during one studies. In your case, if you are talking about saving money on the research also, I would recommend just to try to concentrate on the endpoints and perform exactly what is needed to prove something of the teeth of this research. And also, it's good to discuss. We have vast experience in clinical trials, in medicinal products and also in the smoking products. And we can discuss with the sponsors, the clients, what we have to perform during this particular research project. and what is not so necessary to them. And it will lead to save money, because we can concentrate only on the most crucial aspects of this project.
13:24 - 13:47
[Thomas Nahde]
Thomas from Imperial Brands. First of all, thanks for the presentation, and I think it's good to see more CROs with the expertise in clinical tobacco and nicotine research in Europe. I have one question to you. First question, was that study that you have shown run and conducted in Poland...
13:48 - 13:48
[Marta Zakrzewska]
Yes.
13:49 - 14:25
[Thomas Nahde]
Okay. In Warsaw. In Warsaw. So you have shown that in Poland there are now more NGP users compared to smokers, right? So how challenging do you find it, actually, to find... participants, smokers, for your studies? Because what we see in more bigger scale observational studies, it's actually really challenging to find enough smokers, obviously often with no intention to quit. How is the situation here in Poland?
14:26 - 16:53
[Marta Zakrzewska]
In the slide, it was shown that we have the different population of the smokers. However, still, we have a lot of smokers in Poland and the users of the nicotine product. From my observation right now, also, it is a tendency to check the dual smokers. And because right now, we have Lot of data about the smokers, about harmless of the smoking. We have lot of data about the users of different ways of the nicotine intake. However, it's mono users. And what I observe, there is several studies, and in one of the study also we are involved right now, is checking the dual smokers and harmless. Of course, all of us assume that if someone smokes normal cigarettes and, for example, e-cigarettes, harmful will be somehow in the middle. But as I, went through the litter and publics, there is no evidence on this. So... Trends is everywhere, probably the same. We have different users of nicotine-contained products. And in my observation, it will be study not, JTI presented the mono users only in your study. It was non-smokers, cigarette smokers, and HR smokers. But the world is changing. People one day using the e-cigarettes during the working days and afternoon at the party they also choose the normal cigarettes. So I think the clinical charts and clinical research will go as the world is changing. I hope I answered a little bit.
16:55 - 17:22
[Gizelle Baker]
I think, are there any more questions? I did have one that was very similar to that, but slightly different. So maybe I'll ask it anyhow, even though I think you answered probably 70% of it with that answer. But in randomized trials, how hard is it to actually get people in a randomized trial that actually use the product that they're randomized to within the trials that you've done?
17:23 - 18:04
[Marta Zakrzewska]
All of PK studies is randomized. However, it's quite different studies. Probably you are talking about the studies you have to choose the right one arm for the long period of the time. It's also doable because, to be honest, we have to remember that during the study people participants will receive from the sponsor the product and also it is for them the cost effectiveness. So they will stick to this arm because they will be provided with this product. I'm ready to say it loudly, but it's true.