Reference change values in concentrations of urinary and salivary biomarkers of exposure and mouth level exposure in individuals participating in an ambulatory smoking study

BACKGROUND: Modified-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. METHODS: This 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. RESULTS: Greater 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. CONCLUSION: Variability 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.