Pastorino 2012.

Study characteristics
Methods	Trial design: phase 3 RCT  Duration of follow‐up: 10 years  Number of trial locations: 1
Participants	Baseline characteristics Number of participants: biennial LDCT arm (1186); annual LDCT arm (1190); control arm (1723) Age Biennial LDCT arm: < 55 years old (379), 55‐59 years old (363), 60‐64 years old (261), 65‐69 years old (143), ≥ 70 years old (40) Annual LDCT arm: < 55 years old (394), 55‐59 years old (338), 60‐64 years old (274), 65‐69 years old (134), ≥ 70 years old (50) Control arm: < 55 years old (656), 55‐59 years old (478), 60‐64 years old (359), 65‐69 years old (174), ≥ 70 years old (56) Sex: biennial LDCT arm (813 males, 373 females); annual LDCT arm (814 males, 376 females); control arm (1090 males, 633 females) Smoking status: biennial LDCT arm (810 current, 376 former); annual LDCT arm (820 current, 370 former); control arm (1546 current, 177 former) Performance status: not published Ethnicity/race: not published  Environmental exposures: not published Inclusion criteria Age ≥ 49 years Current or former smokers (having quit within 10 years of recruitment) with at least 20 pack years of smoking No history of cancer within previous 5 years Adequate performance status (assessed on the basis of the patient's eligibility to undergo thoracic surgery) Exclusion criteria History of malignant disease in the previous years  Not adequate performance status (assessed on the basis of the patient's eligibility to undergo thoracic surgery) Preintervention investigations Nil
Interventions	Intervention characteristics Frequency of scanning: biennial and annual arms LDCT setting: 120 kV, 30 mAs Duration of screening: 10 years (median 4 scans in biennial arm, 7 scans in annual arm) Interpretation of scans Volumetric or size criteria: volumetric Use of volumetry software: yes Criteria for significance: non‐calcified nodules with a volume ≥ 60 mm3 or findings such as non‐calcified hilar or mediastinal lymphadenopathy, atelectasis, consolidation or pleural findings Prespecified protocol for nodule follow‐up: yes Comparison Description: no screening
Outcomes	Primary outcome Lung cancer 10‐year mortality Secondary outcomes  All‐cause mortality  Lung cancer diagnosis Smoking cessation ‐ evaluate the impact on smoking cessation of early lung cancer detection through LDCT at annual or biennial intervals versus no screening Molecular risk profile through assessing the value of circulating DNA in blood samples Molecular risk profile through assessing the value of microRNA in blood and tissue samples
Identification	Sponsorship source: Italian Ministry of Health, Italian Association for Cancer Research, Fondazione Cariplo, National Cancer Institute Country: Italy  Setting: hospital Trial start date: September 2005 Completion of follow‐up: June 2018  Trial registration number: NCT02837809 Corresponding author's name: Ugo Pastorino Institution: IRCCS Istituto Nazionale dei Tumori, Milan, Italy  Email: ugo.pastorino@isitutotumori.mi.it
Notes	Conflicts of interest: nil declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation via centralised stratified randomisation using blocks of variable size. Stratification based on reference centre, age (up to 65 years or older), duration of smoking (more or less than 40 years)
Allocation concealment (selection bias)	Low risk	Allocation concealment via centralised system
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants were not blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors were blinded for the primary outcome of lung cancer‐related mortality. It should be noted there was no review panel for lung cancer‐related mortality.
Incomplete outcome data (attrition bias) All outcomes	Low risk	216 participants withdrew from intervention arms. Cause of death was missing in 3 cases (1 annual arm, 2 biennial arm), intention‐to‐treat analysis was applied
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	High risk	Initial recruitment commenced in September 2005 with only two arms, annual and biennial screwing with LDCT. 653 participants were recruited to these arms prior to approval in December 2005 and commencement of a control no‐screening arm. 90% in the control were current smokers compared with 69% in the intervention group