Clinical studies

      Clinical studies on smoke-free products

      Clinical research is a cornerstone of our smoke-free product assessment program. Once a product has been demonstrated to release lower levels of harmful chemicals compared with cigarette smoke, and after it has also been demonstrated to be less toxic in laboratory studies, we can begin clinical studies. 

      Clinical studies are a cornerstone of smoke-free product assessment

      Our clinical studies touch on several areas of research involving human study participants. They are conducted by contract research organizations according to strict guidelines and ethics standards. Clinical studies help us understand how quickly nicotine is absorbed into the body, to know whether the product is acceptable to current adult smokers, and they can also provide information about the potential risk reduction on an individual level as a result of switching. Importantly, these products contain nicotine, which is addictive, and they are not risk free.

      Check the list of our clinical studies, including those studies that are in progress and may not yet have results available. Learn more about how our team of clinical scientists run these studies. All our clinical studies are registered on www.clinicaltrials.gov.

      We consistently find that our clinical studies demonstrate the reduced-risk potential of smoke-free products compared with cigarettes, in line with our aerosol and toxicology study results. Still, understanding the relative risk to an individual who switches to a smoke-free product is only half of the equation considering the likely impact on population health. Learn more about our research on consumer perception and behavior. Quitting is the best choice. And for those adult smokers who don’t quit, choosing a scientifically substantiated better product can reduce their risk of developing smoking-related diseases. This is the impact we expect to see in our long-term assessments. 

      You can find a summary of our entire product assessment program in the PMI Science Booklet, and our publications, most of which are open-access, can be found via the publications library.

      Jump to a specific result from our clinical studies on  the Tobacco Heating System (THS):

      • Potentially reduced disease risk

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      • Lower level of exposure

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      • Nicotine uptake comparable to cigarettes

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      Clinical findings provide evidence on the potential of the Tobacco Heating System to reduce the risk of developing CVD, COPD, and cancer compared with continued cigarette smoking

      We conducted a 1-year exposure response study, which involved a 6-month study followed by a 6-month extension study focusing on smoking-related diseases, specifically cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), and cancer. Eight biomarkers of potential harm (BoPH) were measured. Changes in these biomarkers can indicate changes to certain series of chemical processes (physiological pathways) that happen inside the body, and ultimately can signal potential harm to the body as a result. The BoPH that were selected are known to represent pathways that can be altered by cigarette smoking, and they are known to improve within 6 months of smoking cessation. We aimed to demonstrate favorable changes in all eight BoPH when smokers switch to THS versus continued smoking. To compare the effect of switching to THS with that of smoking cessation, we also conducted a 1-year smoking cessation study evaluating the same core set of eight BoPH. 

      Our studies showed that smokers who switched from cigarettes to THS for 12 months had favorable changes in all eight BoPH, in the same direction as smoking cessation. Among THS users who mostly used THS but also smoked cigarettes or used other products, the less cigarette smoking they did, the greater were the favorable effects on their BoPH. Considering all but the most intense cigarette use, THS users saw 67% of the effect of smoking cessation for seven of the eight BoPH. 

      Recent findings from a cross-sectional risk marker study further substantiate the benefits of switching to THS, showing favorable differences in nine BoPH after at least 2 years of use. This study, conducted across 37 healthcare institutions in Asia and Europe, strengthens findings from previous studies and provides real-life data on THS users who chose to switch without intervention. It shows the importance of completely replacing smoking with THS use, as the magnitudes of changes were larger than those observed in the exposure response study where concomitant use of cigarettes occurred. This study is not yet published.

      Learn more about these clinical studies:

      A 26-week Extension of the ZRHR-ERS-09-US Study Evaluating Biological and Functional Changes in Healthy Smokers After Switching to THS 2.2
      A Smoking Cessation Study to Understand the Biological and Functional Changes After One Year of Smoking Cessation (RIBESC)
      Effects of switching to a heat-not-burn tobacco product on biologically relevant biomarkers to assess a candidate Modified Risk Tobacco Product: A randomized trial
      Biological and functional changes in healthy adult smokers who are continuously abstinent from smoking for one year: Protocol for a prospective, observational, multicenter cohort study
      Biological and functional changes in healthy adult smokers who are continuously abstinent from smoking for one year: Protocol for a prospective, observational, multicenter cohort study
      Reduction of Exposure, Inflammation, and Oxidative Stress Following at Least 2 Years of Switching to THS Use Compared to Cigarette Smoking
      Reduction of Exposure, Inflammation, and Oxidative Stress Following at Least 2 Years of Switching to THS Use Compared to Cigarette Smoking
      Differences in biomarkers of potential harm after 2+ years of tobacco heating system use compared to cigarette smoking
      Differences in Biomarkers of Potential Harm After 2+ Years of Tobacco Heating System Use Compared to Cigarette Smoking.
      Assessing the Effects of Switching from Cigarettes to the Tobacco Heating System Relative to Smoking Cessation on Biomarkers of Potential Harm – Additional Evidence on the Potential to Reduce the Risk of Smoking-related Diseases
      Assessing the Effects of Switching from Cigarettes to the Tobacco Heating System Relative to Smoking Cessation on Biomarkers of Potential Harm – Additional Evidence on the Potential to Reduce the Risk of Smoking-related Diseases
      Impact of switching from cigarette smoking to tobacco heating system use on biomarkers of potential harm in a randomized trial
      Impact of switching from cigarette smoking to tobacco heating system use on biomarkers of potential harm in a randomized trial

      Smokers switching completely to the Tobacco Heating System were exposed to lower levels of harmful chemicals compared with those who continued smoking

      In our 5-day and 90-day clinical reduced exposure studies, we measured biomarkers representing exposure to selected harmful chemicals in the blood and urine of study participants. We found that levels of 15 biomarkers of exposure in participants switching completely to THS were comparable to the levels of those who quit smoking for the duration of the study. For both the THS group and the cessation group, the levels of these biomarkers of exposure remained significantly below those observed in subjects who continued smoking during the study.

      Examine the clinical studies that support these conclusions:

      Reduction in exposure to selected harmful and potentially harmful constituents approaching those observed upon smoking abstinence in smokers switching to the menthol Tobacco Heating System 2.2 for three months (Part 1)
      Biomarker of exposure level data set in smokers switching from conventional cigarettes to Tobacco Heating System 2.2, continuing smoking or abstaining from smoking for 5 days
      Evaluation of the Tobacco Heating System 2.2. Part 8: 5-Day randomized reduced exposure clinical study in Poland
      Effects of switching to the Tobacco Heating System 2.2 menthol, smoking abstinence, or continued cigarette smoking on biomarkers of exposure: A randomized, controlled, open-label, multicenter study in sequential confinement and ambulatory settings
      Effects of switching to the Tobacco Heating System 2.2 menthol, smoking abstinence, or continued cigarette smoking on biomarkers of exposure: A randomized, controlled, open-label, multicenter study in sequential confinement and ambulatory settings (Part 1)
      Assessment of the reduction in levels of exposure to harmful and potentially harmful constituents in Japanese subjects using a novel tobacco heating system compared with conventional cigarettes and smoking abstinence
      Assessment of the reduction in levels of exposure to harmful and potentially harmful constituents in Japanese subjects using a novel tobacco heating system compared with conventional cigarettes and smoking abstinence: A randomized controlled study in confinement

      When switching to the Tobacco Heating System, the nicotine uptake and urge-to-smoke scores were comparable to those measured in subjects who continued smoking

      We have shown that the level of nicotine and the timing of its peak concentration in the blood were comparable for smokers and for subjects who switched to THS. Furthermore, the urge-to-smoke scores were similar for smokers and switchers. This suggests that switchers do not seek to use THS more frequently than smokers seek to use cigarettes, and that switchers can find THS acceptable and satisfying.

      Read the research on this topic:

      Reduced exposure to harmful and potentially harmful smoke constituents with the Tobacco Heating System 2.1
      Comparison of the pharmacokinetics of nicotine following single and ad libitum use of a Tobacco Heating System or combustible cigarettes
      Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes and nicotine gum in Japanese smokers
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      Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.