Critical appraisal of interventional clinical trials assessing heated tobacco products: a systematic review

Abstract

ObjectiveTo critically assess the methodological characteristics and quality of interventional clinical trials investigating the effects of heated tobacco products (HTPs).Data sourcesWeb of Science (Core collection and MEDLINE), Scopus, MedRxiv, ClinicalTrials.gov and ICTRP trial databases and transnational HTP manufacturer online publication libraries were searched for clinical trials on HTPs published between January 2010 and April 2022.Study selectionInterventional clinical trials of any design, in which at least one group of adult participants used a currently marketed HTP, were selected by two reviewers with good or very good agreement.Data extractionData relating to trial characteristics and effects of intervention on primary outcomes were extracted using a predesigned form. Risk of bias was assessed using Cochrane’s Risk of Bias tool v1.Data synthesis40 trials were included, 29 of which were tobacco industry affiliated. Methodological characteristics, such as registration, design, setting, comparator interventions, participants, outcomes and analyses, varied between trials, though there were few significant differences between industry-affiliated and independent trials. Of the 40 trials, 33 were judged to be at high risk of bias and 6 at unclear risk of bias. Trial findings were not significantly associated with either affiliation or risk of bias.ConclusionsThe conduct and reporting of HTP interventional clinical trials were poor in many respects and limited to investigating effects of short-term exposure. These trials fall short of what is needed to determine whether HTPs are beneficial to public health, meaning they may not be a sound basis for tobacco control policy decisions.

Intermittent Nicotine Access is as Effective as Continuous Access in Promoting Nicotine Seeking and Taking in Rats

“…Our IntA procedure may be useful to model intermittent nicotine exposure relevant to humans. Studies of smoking patterns using ecological momentary assessment and related methods suggest that some smokers have peaks and troughs in the number of cigarettes smoked across the day, as well as variation in the number of daily smoking bouts (Braznell et al, 2022; Li et al, 2022; Shiffman et al, 2014). In addition, 20 to 40% of current smokers are estimated to be light and intermittent smokers [i.e., smoking < 10 cigarettes/day and not smoking every day (Reyes-Guzman et al, 2017)].…”

“…Daily smokers can have peaks and troughs in the number of cigarettes they smoke over a day, as well as repeated cigarette smoking in short time windows (Zhai et al, 2022). Non-daily smokers also show variation in smoking rates and in the number of smoking bouts on the days when they do smoke (Braznell et al, 2022; Li et al, 2022; Shiffman et al, 2014). Food, caffeine and alcohol consumption, work, social setting, cigarette availability and mood all contribute to the intermittency of cigarette smoking (Shiffman et al, 2014; Stennett et al, 2018).…”

Seeking to be seen as legitimate members of the scientific community? An analysis of British American Tobacco and Philip Morris International’s involvement in scientific events

“…However, at a time when the tobacco companies are launching new products which are seen as crucial to their future and yet the safety of these products remains uncertain, the industry is again actively engaging in and funding research 24. Companies conduct research internally but also fund others, and in 2017 Philip Morris International (PMI) set up the FSFW with close to US$1 billion funding which claims to "support medical, agricultural and scientific research" 25.…”

“…Furthermore, much of the evidence relating to the health effects and efficacy of newer products is affiliated with the tobacco industry,26 and researchers have raised concerns regarding industry’s research practices: for instance, reporting of tobacco industry-sponsored trials examining e-cigarettes was found to be neither complete nor transparent27 and a strong association was found between authors’ financial conflicts of interests and tobacco and e-cigarette industry-favourable findings 28. Conduct and reporting of interventional clinical trials studying the effects of heated tobacco products, most of which were affiliated with the industry, were assessed as inappropriate for determining the impact of such products on public health 24. Researchers have also strongly challenged the FSFW’s claims of independence and legitimacy 29 30.…”

Assessing and minimizing risk of bias in randomized controlled trials of tobacco cessation interventions: Guidance from the Cochrane Tobacco Addiction Group

“…However, we have also augmented this with specific considerations for randomized controlled trials of tobacco cessation interventions, documented since 2012. This guidance has been available off-line to Cochrane Tobacco Addiction Group authors and has been used in other systematic reviews of tobacco control interventions, as well as Cochrane [5,6].…”