Lüdicke 2018.

Study characteristics
Methods	Design: RCT Study dates: August 2013 to July 2014 Recruitment: clinical database and advertisements Location: Tokyo, Japan Setting: 5 days in clinic, and 85 days in an ambulatory setting
Participants	Number randomised: 160 Characteristics: 42.5% women; mean age 37.2 years; 52.5% smoked 10–19 cigarettes per day, 47.5% smoked > 19 cigarettes per day; mean FTND score of 4.4 Specialist population: aged 22–65 years; Japanese; menthol cigarette smoker Inclusion criteria Healthy Currently smoke ≥ 10 menthol cigarettes per day Smoked menthol cigarettes for at past ≥ 3 years Aged 22–65 years No plan to quit smoking within next 3 months Exclusion criteria Medical conditions that were a safety concern or would interfere with study BMI < 18.5 or > 32.0 kg/m2 Use of nicotine‐containing products other than menthol cigarettes in 4 weeks prior to screening Use drugs likely to interfere with study Current or past alcohol problems Positive urine drug test Gave or received blood in past 3 months Pregnant or breastfeeding People of childbearing potential who do not agree to use contraception Current or past employee of tobacco industry (or their close relatives)
Interventions	Randomised (2:1:1 ratio) to use an electronic HTP, continue smoking cigarettes, or become abstinent Heated tobacco arm Device heating method: electronic Device name: menthol THS 2.2, brand name IQOS Device manufacturer: PMI Other instructions and details: provided with menthol tobacco sticks Behavioural support: 5 days in a clinic setting, where product use was monitored. Record use of nicotine and tobacco products in electronic diary. Carbon monoxide breath tests were used to assess compliance Instructions for smoking cessation/switching: switch entirely to menthol THS 2.2 for study period Cigarette smoking arm Behavioural support: record use of nicotine and tobacco products in electronic diary Instructions for smoking cessation/switching: not advised to stop smoking Abstinence arm Behavioural support: record use of nicotine and tobacco products in electronic diary. Carbon monoxide breath tests used to assess compliance. Nicotine replacement therapy was allowed, but not provided Instructions for smoking cessation/switching: do not smoke cigarettes during study period
Outcomes	Follow‐up time points: 4, 9, and 13 weeks Abstinence outcomes: N/A  Safety outcomes: biomarkers of toxicant and carcinogen exposure; biomarkers of harm; adverse events; serious adverse events Prevalence/sales outcomes: N/A
Notes	Funding source Tobacco industry funded: quote: "The study was funded by Philip Morris Products S.A.". Author conflicts of interest Quote: "All authors are employees of Philip Morris Products S.A.".
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details on random sequence generation.
Allocation concealment (selection bias)	Unclear risk	Randomised was performed using an interactive voice response system.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All outcomes were biological.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low attrition reported across all groups, with 97% of participants who were randomised the heated tobacco, 98% to cigarette smoking, and 95% to abstinence arms completing the final follow‐up.
Selective reporting (reporting bias)	High risk	Did not report FVC outcomes, which were preregistered.