Our initial clinical investigations (correlation studies) into smoke exposure from conventional cigarettes showed that we have tools available to assess smokers’ exposure to specific smoke toxicants. A clinical study (the RTP1 study) was therefore conducted to assess the reduction in smoke toxicant exposure achieved when smokers switched from a conventional cigarette to an RTP.
Promising results from this prompted a second clinical study (the RTP2 study) to determine whether other RTP cigarette designs would also show exposure reduction over a longer period and as a consequence give rise to a reduction in biomarkers of biological effect.
The RTP1 clinical study (ISRCTN trial registration: ISRCTN72157335) was approved by an independent ethics committee and conducted in the same German clinic as the correlation study. Several RTP technologies were tested at more than one ISO tar yield. A total of 250 smokers of 6mg and 1mg ISO tar yield cigarettes were recruited into the study, along with a group of 50 non-smokers. For two weeks, all smokers smoked a conventional cigarette with their usual ISO tar yield, after which half of them switched to an RTP for four weeks. The study design included short periods of clinical confinement at two, four and six weeks where cigarette filters were collected from smokers and urine and saliva samples collected from all subjects.
Filter analysis and biomarkers of exposure (BoE) were used to estimate the smokers’ exposure to a wide range of smoke constituents at baseline (whilst smoking the conventional cigarette) and then again after two and four weeks of smoking the RTP. Cigarette consumption, sensory impression and behavioural data were also recorded.
The data from this study demonstrated that switching to an RTP resulted in a reduction in exposure to some smoke toxicants, and in some cases these reductions were 80% or more.
The RTP2 clinical study (ISRCTN trial Registration: ISRCTN81286286) is investigating the next generation of RTP product. It uses a similar study design to RTP1, but it has been extended to six months duration. This longer period is required to examine whether the reduced toxicant exposure seen in RTP1 is also seen for the RTP2 product, whether it is maintained for a longer period and also whether an extended reduction in exposure results in a reduction in biological response, as determined using biomarkers of biological effect (BoBE).
Recruited smokers began by smoking a commercial (control) product for two weeks at the end of which samples were collected for baseline exposure and effect measures. Half of the smokers were then switched to an RTP while the remainder continued to smoke the control cigarette. Throughout the following six months there were regular visits to the clinic for further sampling, and the results for these and the final visit were compared to the baseline measures. Samples collected from non-smokers (ex- and never-smokers) provided background levels of biomarkers of exposure and biological effect.
This study is the next step in our understanding of how a potential MRTP could be evaluated.
Ethical approval for the study was obtained in December 2011, the clinical phase of the study was conducted and completed in 2012, and the data became available for analysis in 2013. A series of manuscripts are under consideration with various peer reviewed journals, and will be updated as they become accepted. The RTP protocol was published in July 2013.
As in the RTP1 study, large reductions were seen in BoE levels, indicating a reduction in exposure, and these reductions were maintained throughout the 6-month study. However, most smokers increased their daily cigarette consumption, which partially undermined the potential benefit of this reduction. A questionnaire administered during the study suggested that consumption increase was mainly due to provision of free cigarettes, but also due to a perceived reduction in sensory properties and a belief that the supplied cigarettes were reduced-risk products.
Generally, the biomarkers of biological effect did not show any marked changes as a result of the switch to the RTP. This may have been due, in part to the increased consumption, but also down to the utility of the biomarkers used in this study; many showed no differences between smokers and non-smokers, and so wouldn’t be expected to change on switching to the RTP. However, the levels of some BoBE were different in smokers and non-smokers, and the fact that changes were not detected suggest that either we had not been able to reduce toxicants substantially enough, or longer periods of switching might be needed before detectable changes in these biomarkers are seen.