FACS 2014

Methods	RCT (1:1:1:1:1 minimisation algorithm, 2 x 2 randomised trial) Accrual: 2003 to 2009 Stratified for adjuvant chemotherapy, age, and sex Mean follow‐up: 40.8 months Setting: tertiary centres
Participants	1202 participants (736 men and 466 women) treated with curative surgery for primary colorectal cancer Dukes' A: 254 Dukes' B: 553 Dukes' C: 354 Colon primary: 811 Rectal primary: 359 Country: United Kingdom
Interventions	CEA testing every 3 months for 2 years, then every 6 months for 3 years with a single CT scan of the chest/abdomen/pelvis if requested at study entry by clinician CT scan of the chest/abdomen/pelvis every 6 months for 2 years, then annually for 3 years, plus colonoscopy at 2 years CEA and CT follow‐up: both blood and imaging as above, plus colonoscopy at 2 years Minimum follow‐up: no scheduled follow‐up except a single CT scan of the chest/abdomen/pelvis if requested at study entry by a clinician
Outcomes	Recurrence (loco‐regional, distant metastases, interval recurrences) New cancers Surgical salvage Survival DFS Compliance
Notes	Eligible participants were those with no residual disease (confirmed by a CT scan of the chest and liver or a MRI of the liver), microscopically clear margins, and postoperative CEA ≤ 10 μ/L following surgery or completion of adjuvant therapy as indicated. All participants had colonoscopy at trial entry to ensure there was no residual intraluminal disease and were offered an end‐of‐trial colonoscopy.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (page 265): "Randomization to 1 of 4 groups (Figure 1) on a 1:1:1:1 ratio was performed centrally at the Oxford Clinical Trials Unit using a minimization algorithm to balance patient characteristics within each centre based on 3 variables: adjuvant chemotherapy, sex, and age group." Comment: we judged this domain to be at low risk of bias.
Allocation concealment (selection bias)	Low risk	Quote (page 265): "Study nurses contacted the Oxford Clinical Trials Unit by telephone to enter a patient in the trial, reporting the relevant patient characteristics; they were then told the trial group to which the patient had been allocated." Comment: we judged this domain to be at low risk of bias.
Blinding of participants and personnel	Unclear risk	Quote (page 265): "Because this was a pragmatic open trial, it was not possible to conceal the allocation group from either participants or clinicians." Comment: we judged this domain to be at unclear risk of bias.
Blinding of outcome assessment	Low risk	Quote: "However, the research staff who abstracted outcome data from clinical notes were employed by the local National Cancer Research Network teams independent of the investigators. The analysis program was undertaken first using dummy variables for the allocation groups and the code was not broken until the precise procedures for analysis were agreed on." Comment: we judged this domain to be at low risk of bias.
Incomplete outcome data (attrition and exclusions)	Low risk	Quote (page 265): "Exclusions: Intensive arm: 6 exclusions, 1 withdrew consent, 6 had residual disease Minimal arm: 3 excluded (1 entered a conflicting study, 2 had residual disease)" Comment: there was complete information given to explain the exclusions, and they were reported by arm and given the 3:1 randomisation ratio; the numbers were similar in each arm. We therefore judged this domain to be at low risk of bias (figure 1). Attrition was reported; it did not occur.
Selective reporting (reporting bias)	Low risk	Primary outcome measures (recorded on isctrn.org) Current primary outcome measure amended as of 11 February 2009: Number of recurrences in each group treated surgically with curative intent, analysed at study end (5 years) Previous primary outcome measure: Overall survival by intention‐to‐treat analysis Secondary outcome measures Current secondary outcome measures as of 11 February 2009: Overall survival by intention‐to‐treat analysis, reviewed at study end (5 years) Quality of life in survivors, assessed at baseline and then at the end of study years 1 to 5 by the following: 2. 1. EuroQol‐5D (EQ‐5D) 2. 2. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients (EORTC QLQ‐C30) 2. 3. Hospital Anxiety and Depression Scale (HADS) 2. 4. Modified form of a College of Health Questionnaire 2. 5. A small number of items from the 7‐item questionnaire used by Kjeldsen 1997 Cost of NHS services utilised (data collected at the end of study years 1 to 5 for all participants) NHS cost per life‐year saved, assessed at study end (5 years) Outcome measures reported Primary outcome: Surgical treatment of recurrence with curative intent Secondary outcomes: Overall survival Colorectal cancer‐specific survival Time to detection of recurrence Survival after treatment of recurrence with curative intent Recurrences Compliance We assumed that this was the initial publication and that subsequent publications will present the quality of life data, so judged this to be at low risk of bias.
Other sources of bias	Unclear risk	We detected no other bias.