DEVA.

Methods	Randomised controlled trial with partial 2 × 2 factorial design Multi‐centre (36 centres in 5 European countries) Randomisation with computer‐generated permuted blocks. Stratified according to institution and intention‐to‐treat with tamoxifen Accrual August 1997 to December 2005 Baseline patient and tumour characteristics well balanced Randomised 1:1
Participants	Female, postmenopausal Complete tumour excision with clear surgical margins Axillary node positive: 100% Exclusion of metastatic disease HR positive: 77% to 78% in each treatment arm
Interventions	ARM 1 (EPI) EPI × 6 28‐day cycles (epirubicin 50 mg/m² days 1 and 8) ARM 2 (EPI‐Doc) EPI × 3 28‐day cycles (epirubicin 50 mg/m² days 1 and 8) followed by Doc × 3 21‐day cycles (docetaxel 100 mg/m² on day 1) Tamoxifen 20 mg/d for 5 years given to women with ER‐ and/or PR‐positive tumours; some centres randomising to administer concurrently or sequential to chemotherapy Use of prophylactic G‐CSFs and antibiotics recommended in the case of febrile neutropenia
Outcomes	Primary endpoint: Disease‐free survival Secondary endpoints: Overall survival Breast cancer‐free survival Metastasis‐free survival Quality of life
Notes	Intention‐to‐treat analysis Median follow‐up 64.7 months Clinical Trial Identifier: ISRCTN89772270 (see isrctn.com/ISRCTN89772270) Supported by unrestricted educational trials from Pfizer and Sanofi‐Aventis, and docetaxel provided by Sanofi‐Aventis For the review update, O‐E and V for OS and DFS derived using Method 3 (Tierney 2007)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "computer generated permuted blocks were used"
Allocation concealment (selection bias)	Low risk	Central allocation Quote: "independent random assignment was by telephone/fax to the International Collaborative Cancer Group Data centre, London, England"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Open‐label
Blinding of outcome assessment ‐ OS (detection bias)	Low risk	Assessment of overall survival unlikely to be influenced by no or incomplete blinding
Blinding of outcome assessment ‐ DFS & Toxicity (detection bias)	Unclear risk	Toxicity assessed according to NCI CTC version 2. Assessed after each chemotherapy cycle, with follow‐up every 3 months for first year, every 4 months for second year, every 6 months for years 3 and 4, and annually thereafter until minimum 10 years. No other information on outcome assessment included in the report Comment: no apparent involvement of an independent adjudication committee; therefore this domain assessed as having 'unclear' risk
Blinding of outcome assessment ‐ QoL (detection bias)	High risk	Measured by QLQ‐C30 and QLQ‐BR23. Assessed at baseline and at 9 months, 2 years, and 5 years after random assignment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "only one patient withdrew consent for additional treatment and follow‐up (in the EPI‐DOC arm) and approximately 3% were classified as lost to follow‐up; all patients were included in the intention‐to‐treat analyses"
Selective reporting (reporting bias)	Low risk	Outcomes specified in the methods section and reported in the results section consistent. Primary and secondary outcomes not provided at time of registration on ISRCTN
Other bias	Low risk	Quote: "baseline clinicopathologic characteristics of patients were evenly balanced between treatment groups"