BackgroundLong-term studies of smokers who switch to lower nicotine yield cigarettes have been identified by the World Health Organization Study Group TobReg and the US Food and Drug Administration as one key area where new knowledge is required to guide science based regulation. The limited number of long-term switching studies have concluded that smokers who switch to lower nicotine yield cigarettes show evidence of partial compensation. Since the European Union tobacco product directive of 2001 introduced tar and nicotine yield ceilings, there has been no long-term observational switching study. To address the limitations of previous studies where smokers were forced switched for relatively short durations, we plan to undertake a long-term study of spontaneous switching which is appropriately powered and includes non-switchers as a control group.Methods/designHealthy adult smokers aged 21–64 years will be enrolled into this 5-year non-residential, multicentre study across 10 cities in Germany. They will be assessed at 10 timepoints with 6 month intervals during which inclusion criteria will be reassessed and spent cigarette filter tips, saliva and 24 h urine samples will be collected. These samples will be used to determine average daily cigarette consumption, estimate mouth-level exposure to tar and nicotine and measure selected biomarkers of exposure, respectively. Spontaneous changes in subjects’ preferred cigarette products and any consequent change in tar or nicotine yield will be monitored. Subjects will be required to complete questionnaires on quality of life, smoking behaviours, smoking-related sensory attributes and recent life changes.DiscussionThe planned study is anticipated to contribute to understanding smokers’ behaviours and their consequent exposure to smoke constituents. It will also allow assessment of compensatory changes in their behaviour following spontaneous switching of cigarette product smoked. Data from this study are expected to provide insights into study design and conduct for non-clinical assessment of smokers’ exposure as part of post marketing surveillance programmes.Trial registrationCurrent Controlled Trials Database reference ISRCTN95019245.

A challenge in investigating the effect of public health policies on cigarette consumption and exposure arises from variation in a smoker's exposure from cigarette to cigarette and the considerable differences between smokers. In addition, limited data are available on the effects of spontaneous product switching on a smoker's cigarette consumption and exposure to smoke constituents. Over 1000 adult smokers of the same commercial 10mg International Organization for Standardization (ISO) tar yield cigarette were recruited into the non-residential, longitudinal study across 10 cities in Germany. Cigarette consumption, mouth level exposure to tar and nicotine and biomarkers of exposure to nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone were measured every 6months over a 3 and a half year period. Cigarette consumption remained stable through the study period and did not vary significantly when smokers spontaneously switched products. Mouth level exposure decreased for smokers (n=111) who switched to cigarettes of 7mg ISO tar yield or lower. In addition, downward trends in mouth level exposure estimates were observed for smokers who did not switch cigarettes. Data from this study illustrate some of the challenges in measuring smokers' long-term exposure to smoke constituents in their everyday environment.

BackgroundModified-risk tobacco products (MRTPs) are being developed that may contribute to tobacco harm reduction. To support reduced exposure or risk claims, a scientific framework needs to be developed to assess the validity of claims and monitor consumers after product launch. We calculated reference change values (RCVs) for biomarker of exposure (BoE): salivary cotinine and hydroxycotinine; and urinary total nicotine equivalents, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and creatinine. Mouth-level exposure (MLE) to nicotine and tar were also recorded in an ambulatory setting to characterise variation among smokers in their everyday environment.MethodsThis non-residential, observational study was conducted over 3.5 years across 10 sites in Germany. Smokers of the same commercial 10 mg ISO tar product were included in the study (N=1011). Urine samples, questionnaires and cigarette filters were collected every 6 months for a total of seven timepoints.ResultsGreater variability in BoEs was observed compared with confined clinical studies. Gaussian distributed data showed 2-sided values over 100%, which are uninformative for decreases. The proportion of significant changes increased slightly among switchers, probably as a result of additional variability due to the range of products used post-switching. Overall proportions of changes remained small, consistent with literature reporting that when switching to a different tar yield cigarette, smokers partially compensate by changing their smoking behaviour.ConclusionVariability estimates and RCVs can be useful for monitoring subjects' BoE and MLE endpoints in longitudinal smoking studies where subjects are followed in their own environment and to aid sample size calculation of studies involving these endpoints.