Rolf Weitkunat’s research while affiliated with Université de Fribourg and other places

How nicotine is administered has evolved from cigarettes to various delivery systems. Assessing perceived dependence on nicotine-containing products now requires accounting for product specificity while allowing comparisons across products and users. This study aims to develop a new self-report measure to assess perceived dependence on tobacco and nicotine products (TNPs) among exclusive and poly-TNP users. A draft version of the new measure, the ABOUT-Dependence, was constructed based on literature review, qualitative research, and expert opinion. Data for scale formation and psychometric assessment was obtained through a US-based web survey (n = 2334) that included additional dependence measures for convergent validity assessment. Qualitative research confirmed a preliminary conceptual framework with seven sub-concepts. Following a cognitive debriefing, 19 items were considered to best represent the different sub-concepts. Psychometric findings supported a three-domain structure [i.e., behavioral impact (five items), signs and symptoms (five items), and extent/timing of use (two items)] and an overall total composite score. The data confirmed convergent and known-group validity, as well as test–retest reliability. The ABOUT-Dependence is a 12-item, psychometrically sound, self-report measure that may be used as a tool for research and further understanding of perceived dependence across the spectrum of TNP and TNP users.

Background: This was a pre-market, observational, actual use study with the Tobacco Heating System (THS), a candidate modified risk tobacco product. The main goal of the study was to describe THS adoption within current adult daily smokers by replicating the usage of THS in real-world conditions with participants being able to consume cigarettes, THS, and any other nicotine-containing products (e.g., e-cigarettes, cigars, etc.) ad libitum . Methods: This study assessed self-reported stick-by-stick consumption of THS compared with the use of commercial cigarettes over six weeks. The aim of the analysis was to identify potential predictors for adoption of THS using stepwise logistic regression analysis. Results: By the end of the observational period (in Week 6), 14.6% of participants (n=965) had adopted THS meaning that THS formed 70% or more of their total tobacco consumption. The main predictors of adoption were the liking of the smell, taste, aftertaste, and ease of use of THS. The proportion of adoption was higher in participants aged 44 years and older and in Hispanic or Latino adult smokers. Additionally, adoption of THS was more likely in participants who had never attempted to quit smoking and in participants who smoked up to 10 cigarettes per day. Finally, the adoption of THS was higher in participants who consumed both regular and menthol THS compared with those who consumed only one THS variant. Conclusions: The findings suggest that the introduction of THS in the U.S. has the potential to result in adoption by current adult smokers who would otherwise continue to smoke cigarettes, and that the adoption of THS is unlikely to result in an increase of tobacco consumption. Post-marketing studies will provide further insights on THS adoption and THS use patterns to allow assessment of the impact of the THS at the individual and the overall population level.

Measurement in the social sciences has been characterized by deficient justification and underdeveloped conceptual theories. Instruments supposed to measure the same measurand typically do not provide comparable measurements. From the perspective of metrological traceability, the state of affairs has thus been unsatisfactory. Today, better instruments can be developed as psychometrics provides tools for invariant measurement (Rasch measurement theory), where measurements are justifiable, linear, and sample-independent. Different instruments can be linked to a common metric of the measurand by means of co-calibration of item parameters. Such linkages, referred to as crosswalks, are an important and practically useful contribution to traceability, when common references have not been developed, yet. The measurement of dependence on tobacco and/or nicotine-containing products through self-report instruments illustrates the limitations of traditional measurement, how they can be overcome by new instrument development, and how a network of crosswalks with existing legacy instruments can be established.

Introduction: Various approaches have been used to estimate the population health impact of introducing a Modified Risk Tobacco Product (MRTP). Aims and methods: We aimed to compare and contrast aspects of models considering effects on mortality that were known to experts attending a meeting on models in 2018. Results: Thirteen models are described, some focussing on e-cigarettes, others more general. Most models are cohort-based, comparing results with or without MRTP introduction. They typically start with a population with known smoking habits and then use transition probabilities either to update smoking habits in the "null scenario" or joint smoking and MRTP habits in an "alternative scenario". The models vary in the tobacco groups and transition probabilities considered. Based on aspects of the tobacco history developed, the models compare mortality risks, and sometimes life-years lost and health costs, between scenarios. Estimating effects on population health depends on frequency of use of the MRTP and smoking, and the extent to which the products expose users to harmful constituents. Strengths and weaknesses of the approaches are summarized. Conclusions: Despite methodological differences, most modellers have assumed the increase in risk of mortality from MRTP use, relative to that from cigarette smoking, to be very low and have concluded that MRTP introduction is likely to have a beneficial impact. Further model development, supplemented by preliminary results from well-designed epidemiological studies, should enable more precise prediction of the anticipated effects of MRTP introduction. Implications: There is a need to estimate the population health impact of introducing modified risk nicotine-containing products for smokers unwilling or unable to quit. This paper reviews a variety of modeling methodologies proposed to do this, and discusses the implications of the different approaches. It should assist modelers in refining and improving their models, and help toward providing authorities with more reliable estimates.

Introduction: Tobacco Heating System (THS) 2.2, a candidate modified-risk tobacco product, aims at offering an alternative to cigarettes for smokers while substantially reducing the exposure to harmful and potentially harmful constituents found in cigarette smoke. Methods: One hundred and sixty healthy adult US smokers participated in this randomized, three-arm parallel group, controlled clinical study. Subjects were randomized in a 2:1:1 ratio to menthol Tobacco Heating System 2.2 (mTHS), menthol cigarette, or smoking abstinence for 5 days in confinement and 86 subsequent ambulatory days. Endpoints included biomarkers of exposure to harmful and potentially harmful constituents (reported in our co-publication, Part 1) and biomarkers of potential harm (BOPH). Results: Compliance (protocol and allocated product exposure) was 51% and 18% in the mTHS and smoking abstinence arms, respectively, on day 90. Nonetheless, favorable changes in BOPHs of lipid metabolism (total cholesterol and high- and low-density cholesterol), endothelial dysfunction (soluble intercellular adhesion molecule-1), oxidative stress (8-epi-prostaglandin F2α), and cardiovascular risk factors (eg, high-sensitivity C-reactive protein) were observed in the mTHS group. Favorable effects in other BOPHs, including ones related to platelet activation (11-dehydrothromboxane B2) and metabolic syndrome (glucose), were more pronounced in normal weight subjects. Conclusions: The results suggest that the reduced exposure demonstrated when switching to mTHS is associated with overall improvements in BOPHs, which are indicative of pathomechanistic pathways underlying the development of smoking-related diseases, with some stronger effects in normal weight subjects. Implications: Switching to mTHS was associated with favorable changes for some BOPHs indicative of biological pathway alterations (eg, oxidative stress and endothelial dysfunction). The results suggest that switching to mTHS has the potential to reduce the adverse health effects of smoking and ultimately the risk of smoking-related diseases. Switching to mTHS for 90 days led to reductions in a number of biomarkers of exposure in smokers, relative to those who continued smoking cigarettes, which were close to those observed when stopping smoking (reported in our co-publication, Part 1). Initial findings suggest reduced levels of 8-epi-prostaglandin F2α and intercellular adhesion molecule 1, when switching to mTHS for 90 days. These changes are comparable to what is observed upon smoking cessation. In normal weight subjects, additional favorable changes were seen in 11-dehydrothromboxane B2, fibrinogen, homocysteine, hs-CRP, percentage of predicted forced expiratory volume in 1 second, systolic blood pressure, diastolic blood pressure, glucose, high-density lipoprotein, apolipoprotein A1, and triglycerides. Trial registration: NCT01989156.

Introduction: The Tobacco Heating System (THS) is a "heat-not-burn" tobacco product designed to generate significantly lower levels of harmful and potentially harmful constituents (HPHCs) and present lower risk of harm than cigarettes. This study assessed the exposure reduction to selected HPHCs in smokers switching to menthol Tobacco Heating System (mTHS) 2.2 compared with smokers continuing smoking menthol cigarettes (mCCs) and smoking abstinence (SA) for 5 days in a confined setting, followed by an 86-day ambulatory period. Methods: A total of 160 healthy adult US smokers participated in this randomized, three-arm parallel group, controlled clinical study. Biomarkers of exposure to 16 HPHCs were measured in blood and 24-hour urine. Safety was monitored throughout the study. Information was also gathered on product evaluation, product use, subjective effects, and clinical risk markers (co-publication Part 2). Results: Nicotine uptake was comparable in both exposure groups (mTHS:mCC ratio of 96% on day 90). On day 5, biomarker of exposure levels to other HPHCs were reduced by 51%-96% in the mTHS group compared with the mCC group, and these reductions were sustained for most biomarkers of exposure over ambulatory period. After 90 days of use, the level of satisfaction with mTHS and suppression of urge to smoke were comparable to mCC. Conclusion: Switching from mCCs to mTHS significantly reduced the exposure to HPHCs to levels approaching those observed in subjects who abstained from smoking for the duration of the study. Implications: This study compared the impact of switching to mTHS on biomarkers of exposure, relative to continued smoking or SA. Clinical significance: Trial registration: NCT01989156 (ClinicalTrials.gov).

Meta-analyses often combine covariate-adjusted effect estimates (odds ratios or relative risks) and confidence intervals relating a specified endpoint to a given exposure. Standard techniques are available to do this where the exposure is a simple presence/absence variable, or can be expressed in defined units. However, where the definition of exposure is qualitative and may vary between studies, meta-analysis is less straightforward. We introduce a new “Uniform Scale” approach allowing expression of effect estimates in a consistent manner, comparing individuals with the most and least possible exposure. In 2008, we presented methodology and made available software to obtain estimates for specific pairwise comparisons of exposure, such as any versus none, where the source paper provides estimates for multiple exposure categories, expressed relative to a common reference group. This methodology takes account of the correlation between the effect estimates for the different levels. We have now extended our software, available in Excel, SAS and R, to obtain effect estimates per unit of exposure, whether the exposure is defined or is to be expressed in the “Uniform Scale”. Examples of its use are presented.

Background: Several instruments are widely used for assessing dependence, craving, withdrawal symptoms, and reinforcing effects in users of tobacco- and nicotine-containing products (TNP), including the Fagerström Test for Nicotine Dependence (FTND), Questionnaire of Smoking Urges, original (QSU) and brief (QSU-b) versions; Minnesota Nicotine Withdrawal Scale, original (MNWS) and revised (MNWS-R) versions; and Cigarette Evaluation Questionnaire, original (CEQ) and modified (mCEQ) versions. Although these instruments have been translated extensively, their translations and corresponding measurement properties have not been systematically assessed. This study aimed to (1) identify the translations of these instruments for which psychometric properties have been published, (2) describe the methods used for translation, and (3) describe the measurement properties and the context in which these translations were evaluated (e.g., target population and TNP used). Methods: Embase and MEDLINE databases were systematically searched. Results: While no information could be found for the CEQ/mCEQ, several translations were available for the remaining instruments: FTND, 25; QSU and QSU-b, 4 each; QSU (12-item version), 1; MNWS, 4; and MNWS-R, 1. Cigarette smokers represented the main target population in which the validation studies were conducted. Information about the translation process was reported for 25 translations. In most cases, the properties of the translations mirrored those of the originals. Differential item functioning was explored in only one case. Conclusions: There are few publications describing the measurement properties of the translations of the FTND, QSU/QSU-b, and MNWS/MNWS-R. None of these translations have been validated for TNPs other than cigarettes, which suggests the need for greater development and validation of instruments in this area.

Measurement in the social sciences is characterised by a multitude of incompatible paradigms, most of which fail to adhere to fundamental principles of measurement explicated in metrology. This has led to a fragmentation of instruments that are hard to interpret and lack a common reference. Rasch measurement theory, the metrological framework of the Rasch model, combined with strong substantive theories of the measurand, has the potential to advance measurement in the social sciences significantly. The Rasch model establishes a reference standard with a common unit of measurement against which different instruments can be calibrated ensuring traceability in social measurement. Uncertainty in the calibration process is addressed by a standard error of measurement for a specific estimate taking into account that precision varies over the continuum of the measurand. A strong substantive theory of the measurand allows for concrete predictions that can be tested empirically with positive evidence supporting accuracy. We exemplify the potential of the Rasch model by developing the ABOUT-Dependence, a new instrument for the measurement of dependence on tobacco- and nicotine-containing products (TNP). The instrument provides comparable measurements of dependence on different TNPs as well as dependence on multiple TNPs used concurrently. A co-calibration of the new instrument and existing, product-specific instruments allows for a conversion of scores of existing instruments into scores on the new instrument, and vice versa, via the established equal-unit reference scale. The score comparability adds to traceability in the measurement of dependence, is likely to facilitate the acceptance of the new instrument, and helps avoid a discontinuity in the research of dependence.

Background: We have developed an approach for modelling the health impact of introducing new smoke-free tobacco products. We wished to compare its estimates with those of alternative approaches, when applied to snus, used in Sweden for many years. Methods: Modelling was restricted to men aged 30-79 years for 1980-2009 and to four smoking-related diseases. Mortality data were extracted for Sweden and other European countries. Published data provided Swedish prevalence estimates for combinations of never/former/current smoking and snus use, and smoking prevalence estimates for other European countries. Approach 1 compares mortality in Sweden and in other countries with a smoking prevalence similar to Sweden's prevalence of combined smoking/snus use. Approaches 2 and 3 compare mortality in Sweden with hypothetical mortality had snus users smoked. Approach 3 uses our health impact model, individuals starting with the tobacco prevalence of Sweden in 1980. Tobacco histories during 30-year follow-up were then estimated using transition probabilities, with risk derived using a negative exponential model. Approach 2 uses annual tobacco prevalence estimates coupled with estimates of relative risk of current and former smokers regardless of history. The main applications of Approaches 2 and 3 assume that only smoking affects mortality, though sensitivity analyses using Approach 3 allow for risk to vary in snus users and dual users. Results: Using Approach 2, estimated mortality increases in Sweden in 1980-2009 had snus not been introduced were: lung cancer 8786; COPD 1781; IHD 10,409; stroke 1720. The main Approach 3 estimates were similar (7931, 1969; 12,501; 1901). They decreased as risk in snus users and dual users increased. Approach 1 estimates differed wildly (77,762, 32,538; 77,438; 76,946), remaining very different following correction for differences between Sweden and the comparison countries in non-smoking-related disease mortality. Conclusions: Approach 1 is unreliable, accounting inadequately for non-tobacco factors affecting mortality. Approaches 2 and 3 provide reasonably similar approximate estimates of the mortality increase had snus not been available, but have differing advantages and disadvantages. Only Approach 3 considers tobacco history, but develops histories using tobacco transition probabilities, which is possibly less reliable than using estimated tobacco prevalences at each follow-up year.