Carrier 2015

Methods	Study design: multicentre, open‐label, randomised controlled trial. Source of funding: Heart and Stroke Foundation of Canada.
Participants	Country: Canada. Setting: hospital. Number of centres: 9. Number of participants: 854. Age (mean (SD)): screening + CT group: 53.4 (14.2) years; screening only group: 53.7 (13.8). Sex: screening + CT group: 299 M/124 F; screening only group: 277 M/154 F. Inclusion criteria: people with new diagnosis of first unprovoked VTE (proximal lower‐limb deep vein thrombosis, pulmonary embolism, or both). Unprovoked VTE defined as VTE in absence of known overt active cancer, current pregnancy, thrombophilia (hereditary or acquired), previous unprovoked VTE or a temporary predisposing factor in the previous 3 months, including paralysis, paresis or plaster immobilisation of the legs, confinement to bed for ≥ 3 days or major surgery. Exclusion criteria: aged < 18 years, refusal or inability to provide informed consent, allergy to contrast media, creatinine clearance < 60 mL per minute, claustrophobia or agoraphobia, weight > 130 kg, ulcerative colitis or glaucoma.
Interventions	Screening procedure: complete history and physical examination, measurement of complete blood counts and serum electrolyte and creatinine levels, liver‐function testing and chest radiography. Sex‐specific screening conducted if it had not been performed in previous year. Breast examination, mammography, or both performed in women > 50 years of age and Pap testing and a pelvic examination performed in women 18‐70 years of age who had never been sexually active. Prostate examination, PSA test, or both performed in men aged > 40 years. Also comprehensive CT of abdomen and pelvis (virtual colonoscopy and gastroscopy, biphasic enhanced CT of liver, parenchymal pancreatography, and uniphasic enhanced CT of distended bladder). Control: complete history and physical examination, measurement of complete blood counts and serum electrolyte and creatinine levels, liver‐function testing and chest radiography. Sex‐specific screening conducted if it had not been performed in previous year. Breast examination, mammography, or both performed in women > 50 years of age and Pap testing and a pelvic examination performed in women 18‐70 years of age who had ever been sexually active. Prostate examination, PSA test, or both performed in men aged > 40 years. Duration: 1 year follow‐up.
Outcomes	Primary outcomes: newly diagnosed cancer during the follow‐up period in people who had a negative screening result for occult cancer. Secondary outcomes: total number of occult cancers diagnosed and total number of early cancers (T1‐2, N0, M0 according to the World Health Organization TNM classification system) diagnosed by occult‐cancer screening and during subsequent 1‐year follow‐up, 1‐year cancer‐related mortality, 1‐year overall mortality, time to cancer diagnosis and incidence of recurrent VTE.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The trial statistician generated the randomisation list using random‐number tables."
Allocation concealment (selection bias)	Low risk	Quote: "A central Web‐based randomisation system ensured assignment concealment."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: blinding of participants and study personnel not done but review authors judged that outcome and outcome measurement not likely to be influenced by lack of blinding.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "A central adjudication committee whose members were unaware of the study‐group assignments reviewed all suspected outcome events." Comment: outcome assessors blinded to study allocation.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: all losses to follow‐up accounted for.
Selective reporting (reporting bias)	Low risk	Comment: primary and secondary outcomes clearly prespecified and reported.
Other bias	Low risk	Comment: study appeared free from other sources of bias.