Smoke-free alternatives to cigarettes play an important role in tobacco harm reduction, and THS is our leading smoke-free alternative. To date, our assessment program has demonstrated that THS reduces the risk of harm for smokers who switch to it compared to those who continue smoking cigarettes. THS produces an average of 90-95% lower levels of harmful chemicals compared to cigarettes. It has also showed 90–95% reduced toxicity in the laboratory and reduced exposure to harmful chemicals among clinical study participants who switched to it compared to those who continued to smoke.
The latest major step in our assessment of THS is our Exposure Response Study (ERS), published in Cancer Epidemiology, Biomarkers & Prevention. This study was designed to answer questions about THS as it is actually used by healthy adult smokers who switch to it. What changes do we see in the first six months after people switch to THS? For example, do we see changes that are relevant to respiratory disease, cardiovascular disease, or cancer? Our ability to answer these questions brings us one step closer to achieving risk reduction.
The THS exposure response study, sometimes abbreviated ERS, was published online early in July 2019.
In this study, we evaluated changes in biomarkers of potential harm in healthy adult smokers who either switched to THS or continued to smoke their own brand of cigarettes. The results of this study further support the findings of our previous studies, which indicate that switching to THS reduces the risk of harm compared to continuing to smoke cigarettes.
Most changes in our health – changes for the better or for the worse – can be measured and quantified, but only if we know what signs to look for. Biomarkers are those signs. They’re usually (though not always) molecules that are found in blood, other bodily fluids, or tissues, and they’re produced as a result or as part of processes in the body. Other measurements can be biomarkers as well, like a measurement of how much air a person can forcefully exhale in one second.
Similar to clinical studies conducted for the pharmaceutical industry, we selected eight biomarkers to be our primary focus for the study. Collectively, these eight biomarkers made up the primary clinical endpoint of the study. They were selected because they indicate potential harm to the body (which is why we call them biomarkers of potential harm) and because they’re known for improving within six months after smoking cessation. The publication also presented additional results on the effects of switching to THS on many other biomarkers, which you can learn more about by reading the paper.
Results from the ERS show that eight out of eight biomarkers of potential harm that were measured showed improvement as a result of switching from cigarettes to THS. Asterisks refer to the five out of eight biomarkers that showed statistically significant changes, indicating that THS caused the improvements with 95% confidence.
All eight biomarkers of potential harm in this study showed favorable changes in the same direction as with smoking cessation, even though the THS group were still allowed up to 30% continued use of cigarettes. On average, replacing some cigarette use with THS provided some improvement, while those who replaced more of their cigarette use with THS achieved greater improvements than those who continued to smoke cigarettes. Completely switching to THS significantly reduces harm compared to continued smoking.
While all eight biomarkers of potential harm showed favorable changes, five out of the eight were statistically significant at six months after switching to THS compared to continued smoking. In this case, statistical significance indicates that switching to THS is what caused the improvements, with around 95% confidence. A lack of statistical significance in three of the biomarkers of potential harm means that we can’t conclude that switching to THS caused these favorable changes, though it’s still possible that it did. Overall, the results of this study confirm THS as an acceptable alternative to cigarettes for adult smokers, and based on the positive biological effects, that switching to THS presents less risk of harm than continued smoking.
The ERS was managed by multiple independent contract research organizations in clinical study sites across the United States. Recruitment started in March 2015, and the last subject completed the study in September 2016. Each clinical study site recruited their own participants after they received approval from an Independent Review Board.
This study included participants who had smoked at least 10 cigarettes a day for the past year, had been smoking for at least 10 years, and were not motivated to quit smoking within the six months of the study. Participants were randomly assigned to either continue smoking their own brand of cigarette (496 people) or to switch to THS (488 people) for the duration of the study.
Participants who were assigned to switch to THS were provided the product and told to use the product exclusively, but also to honestly record all tobacco products they used. The cigarette smoking group was asked to continue purchasing their preferred brand of cigarettes as usual. About half of the participants assigned to THS reported that they predominantly relied on the product for at least 70% of their tobacco use, which is termed “THS use” for this study.
These results were submitted to the U.S. Food and Drug Administration on June 8, 2018, to add to the extensive body of evidence already presented to the agency in support of our applications. The Agency has authorized the sale of THS in the United States, while our Modified Risk Tobacco Product application for THS is still under review.
The results of this study are now available as an open access peer-reviewed publication in the journal Cancer Epidemiology, Biomarkers & Prevention under the title “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.” Check out the publication here.
The protocol for this research was published in 2018 in the journal JMIR Research Protocols: “Evaluation of biological and functional changes in healthy smokers switching to the Tobacco Heating System 2.2 versus continued tobacco smoking: Protocol for a randomized, controlled, multicenter study.”
 Testing relied on a 3R4F reference cigarette as comparison.