Impact of heated tobacco products on biomarkers of potential harm and adverse events: a systematic review and meta-analysis

Objective:
To systematically review available data on the effects of heated tobacco products (HTPs) on biomarkers of potential harm (BoPH) and adverse events, including comparison to cigarettes, e-cigarettes and smoking abstinence.

Data sources:
Web of Science, Scopus, MedRxiv, ClinicalTrials.gov, ICTRP database and HTP manufacturer libraries were searched from January 2010 to December 2024.

Study selection:
Included studies were interventional clinical trials of any design that measured BoPH or adverse events in adults assigned a marketed HTP and another assigned either cigarettes, e-cigarettes or smoking abstinence.

Data extraction:
Two reviewers independently extracted data into a predesigned form and assessed risk of bias using Cochrane’s Risk of Bias tool version 1.

Data synthesis:
BoPH data were synthesised using effect direction plots. A random-effects model was used to calculate pooled risk ratios for adverse event data. 40 studies (10 independent, 29 industry-affiliated and 1 of unclear affiliation) were included. Only nine studies lasted longer than 5 days. 19 involved using the intervention just once. Risk of bias was high for 32 studies and unclear for 8. Data on 143 BoPH indicated short-term HTP use had mixed effects compared with cigarettes, e-cigarettes and smoking abstinence. The rate of adverse event reporting was not significantly different between HTP and any comparator group.

Conclusions:
Despite a growing evidence base, significant limitations hinder interpretation of the data, which do not yet provide clear indication of harm or benefit, even compared with cigarettes. Longer, better quality studies independent of tobacco industry funding are needed to determine the health impacts of HTPs.