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

Objective: To critically assess the methodological characteristics and quality of interventional clinical trials investigating the effects of heated tobacco products (HTPs). Data sources: Web 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 selection: Interventional 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 extraction: Data 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 synthesis: 40 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. Conclusions: The 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.