Lucchiari 2020.

Study characteristics
Methods	Design: Randomized parallel‐assignment double‐blind trial Recruitment: Participants enrolled in lung cancer‐screening programme Setting: Early lung cancer detection programme (Cosmos II) at European Institute of Oncology, Italy Study start date: September 2014; Study end date: January 2016
Participants	Total N: 210 N per arm: 70 participants per arm Inclusion criteria: Participants are involved in the COSMOS II study Participants are 55 years or more and have smoked at least 10 cigarettes a day for the past 10 years Participants wish to reduce tobacco smoking (motivational score higher than 10) who are not treated at a smoking centre Signed informed consent Exclusion criteria: Symptomatic cardiovascular disease Symptomatic severe respiratory disease Regular psychotropic medication use Current or past history of alcohol abuse Use of smokeless tobacco or NRT Participation in another anti‐smoking programme in the current year Inclusion based on specific population characteristic: 55 years of age or older 37% women; mean age 62.8; mean cpd 19.38; mean FTND 4.37 Motivated to quit: yes E‐cigarette use at baseline: Excluded people who smoke who had ever regularly used e‐cigarettes for more than 1 week alone or in combination with tobacco cigarettes
Interventions	EC: Cig‐a‐like Both arms received “low intensity counseling” – phone at week 1, 4, 8 and 12, approx. 10 mins each Nicotine EC arm: e‐cigarette kit and 12 10‐mL liquid cartridges (8 mg/mL nicotine concentration). During the first week, participants could use the e‐cigarette ad libitum. At the end of the first week, asked to use only EC for the next 11 weeks Nicotine‐free EC (placebo) arm: Nicotine‐free EC – same as above but with nicotine‐free EC
Outcomes	Months 3, 6 and 12 (but only 3‐ and 6‐month data available) Cessation: Continuous abstinence for previous month, CO ≤ 7 ppm Adverse events and biomarkers: FOR EC ARMS ONLY: Exhaled CO Leicester Cough Questionnaire (LCQ) Respiratory symptoms (self‐report) Side effects using checklist Other outcomes measured: Motivational questionnaire HADS EC use
Study funding	This study was supported by a grant from Fondazione Umberto Veronesi (FUV)
Author declarations	The authors declare no conflicts of interest
Notes	Listed as ongoing study Lucchiari 2016 (NCT02422914) in 2016 review; new for 2020 update
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “A randomization list using a permuted block design (40 blocks of 6 subjects randomly assigned to 1 of the 3 treatment arms) had been previously prepared by independent personnel.”
Allocation concealment (selection bias)	Low risk	Double‐blind, active and placebo e‐cigarettes labelled by independent personnel, researcher and participants blind
Blinding of participants and personnel (performance bias) All outcomes	Low risk	“double blind” for nicotine vs no nicotine EC but limited info given; however, as similar levels of support across arms performance bias judged unlikely
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Biochemical validation used
Incomplete outcome data (attrition bias) All outcomes	Low risk	Approx. 73% followed up in each group at 6 months, very little difference between groups
Selective reporting (reporting bias)	High risk	Paper states data also collected at 12 m but this is not presented and unclear why. Paper states CO collected but data not presented