Treasure 2014

Methods	RCT Accrual: 1982 to 1993 Multicentered trial Setting: not stated Follow‐up: not stated
Participants	216 (128 men and 88 women) participants who have had potentially curative resection of colorectal cancer Dukes' A: 10 Dukes' B: 95 Dukes' C: 74 Country: UK Setting: hospital
Interventions	If a CEA rise occurred, the participants were randomised to the "aggressive" arm or "conventional" arm. In the "aggressive" arm, a CEA rise triggered the "second‐look" surgery, with intention to remove any recurrence discovered.
Outcomes	Survival
Notes	All participants had identical clinical follow‐up: every 3 months for the first 2 years, then every 6 months for the next 3 years. CEA was monthly for 3 years, then every 3 months for 2 years.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (page 5): "Patients were randomised equally between the two arms (1:1). Patients whose compliance was between 50% and 70% or whose immediate postoperative sample had not been received within the 4–6‐week guideline were randomised in a separate stratum. Randomisation was also stratified by participating clinician. A block size of two was used in order to maintain as close a balance as possible between the two treatment arms." Comment: while the report did not describe the method of sequence generation, the authors who wrote this publication (not the original investigators) stated that the study was well performed, so we judged this domain to be at low risk of bias.
Allocation concealment (selection bias)	Low risk	Quote (page 4): "The trial was coordinated (initially) from the Cancer Research Campaign Clinical Trials Centre at King’s College Hospital." Comment: while the method of allocation concealment was not described, the study was co‐ordinated remotely, so we judged this domain to be at low risk of bias.
Blinding of participants and personnel	Low risk	Quote (page 6): "By the nature of the trial design, the clinician was blind as to whether such patients had been randomised to the 'Conventional' arm of the trial or had not been randomised because the CEA had failed to denote the presence of recurrent disease." Participants were blinded to treatment allocation. With regard to personnel, clinicians were blinded to which arm their participant had been allocated to; we judged this domain to be at low risk of bias.
Blinding of outcome assessment	Low risk	The study did not mention blinding of outcome assessment. It was most likely not done. but is at little risk of introducing bias because of the blinding of participants and personnel.
Incomplete outcome data (attrition and exclusions)	Unclear risk	Exclusions: not reported Attrition: not reported We judged this domain to be at unclear risk of bias.
Selective reporting (reporting bias)	Low risk	Outcomes stated in the protocol A definitive answer concerning the effectiveness of CEA‐prompted second‐look surgery to improve survival An accurate picture of the 'lead time' produced by CEA compared to clinical pick up of patients with recurrence. Outcomes reported in the paper Deaths Recurrences Second‐look laparotomy and subsequent surgery Lead time for CEA detection of recurrence The third and fourth outcomes were thought to be preplanned subanalyses, but problems with data formatting meant they were not able to be reported. We judged this domain to be at low risk of bias.
Other sources of bias	Low risk	Quote (page 8): "A Data Monitoring Sub‐Committee (DMSC) composed of Working Party members not entering patients into the trial was asked to review the data after the first 100 patients had been randomised, which occurred in January 1988, and again after 200 patients had been randomised in February 1993. At this point it was recommended by the Data Monitoring Committee that the trial be stopped since it was very unlikely that any clinically important advantage would be demonstrated for patients undergoing second‐look surgery." Comment: early stopping occurred; this was recommended by the trial monitoring committee, and was unlikely to have introduced bias.