Infante 2015.

Study characteristics
Methods	Trial design: phase 3 RCT  Duration of follow‐up: median 8.5 years Number of trial locations: 3
Participants	Baseline characteristics Number of participants: LDCT arm (N = 1264); control arm (N = 1186) Age: mean age for both groups 65 years old Sex: 100% male Smoking status: LDCT arm (714 active smokers); control (681 active smokers)  Performance status: not reported Ethnicity/race: not reported  Environmental exposures: LDCT arm (391 participants had occupational exposures including chemical industry, insulation, construction, metallurgy, agriculture, mining); control arm (402 participants had occupational exposures including chemical industry, insulation, construction, metallurgy, agriculture, mining) Inclusion criteria Age 60‐74 years old  Smokers ≥ 20 pack years (current or quit < 10 years prior to accrual  Male Exclusion criteria Severe comorbidity, life expectancy < 5 years Severe heart failure  Chronic respiratory insufficiency  Oxygen saturation levels < 94% at rest  Renal dialysis  Uncontrolled hypertension  Severe vascular disease in active smoker  Uncompensated diabetes  Other severe metabolic disturbances  Inability to comply with the follow‐up protocol  Dementia  Drug or alcohol addiction  Schizophrenia or other severe psychiatric conditions  Conditions carrying severe disability  Previous malignancy (except non‐melanoma skin cancer) ‐ any organ site, if treated < 10 years prior to accrual, early squamous cancer of the larynx/oral cavity < 5 years Preintervention investigations Baseline CXR and sputum cytology with clinical examination in both arms
Interventions	Intervention characteristics Frequency of scanning: annual  LDCT setting: 140 kvp, 40 mA Duration of screening: 5 years  Interpretation of scans Volumetric or size criteria: size criteria Use of volumetry software: no  Criteria for significance: abnormalities suggestive of malignancy, such as non‐calcified pulmonary nodules ≥ 10 mm in diameter or smaller but showing spiculated margins, or non‐nodular lesions such as a hilar mass, focal ground glass opacities, major atelectasis, endobronchial lesions, mediastinal adenopathy, pleural effusion or pleural masses  Prespecified protocol for nodule follow‐up: yes Comparison Description: no screening other than yearly clinical examination
Outcomes	Primary outcomes Lung cancer morality All‐cause mortality Secondary outcomes Lung cancer incidence Stage at detection Resectability rates
Identification	Sponsorship source: Italian Association for the fight against cancer Country: Italy Setting: hospital  Trial start date: March 2001  Completion of follow‐up: May 2013 Trial registration number: NCT00420862 Corresponding author's name: Maurizio Infante Institution: Instituto Clinico Humanitas, Rozzano, Milano, Italy Email: maurizio.infante@cancercenter.humanitas.it
Notes	Conflicts of interest: nil declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block randomisation of four
Allocation concealment (selection bias)	Low risk	Allocation stratified by centre according to computer‐generated lists supplied by the data centre
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants were not blinded.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Assessors were not blinded to cause of death nor to subjects' allocation. Cause of death was determined by death certificates which were cross‐checked with available medical records. A death review panel blinded to allocation arm was only consulted when there were several competing causes of death. Only 78% of death certificates were cross‐checked, 91% of lung cancer‐related deaths and 80% of non‐pulmonary cancer‐related deaths and 76% of non‐cancer‐related deaths. Active follow‐up was terminated in February 2012, with information regarding death being obtained from registries subsequently.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Final report was revised due to discovery of 20 duplicate registrations and 2 test records (2015 AJRCC). Compliance data‐ 1223 (97%) of participants had ≥ 3 CTs, 1184 (94%) had 5 CT scans.  Used intention‐to‐treat analysis
Selective reporting (reporting bias)	Low risk	All prespecified outcomes were reported.
Other bias	High risk	Inappropriate inclusion of 10 participants (kept in trial) with a history of malignancy treated < 10 years before accrual (4 with superficial bladder cancer, 2 with prostate cancer, 1 with chronic lymphocytic leukaemia, 1 with aggressive fibromatosis, 1 with renal cancer and 1 with head and neck cancer). All male participants. Unbalanced baseline between arms with more respiratory comorbidities 35.28% (intervention) versus 31.20% (control) P = 0.032.