IBCSG 2006.

Methods	Randomised controlled trial Stratified by menopausal status, hormone receptor status, institution Number of dropouts pre‐randomisation: None mentioned Number of women randomised: 344 (173 high dose, 171 standard dose) Number of women analysed: 344 Number of women not analysed: None Number of breaches of protocol/failure to receive prescribed treatment: None stated Intention‐to‐treat analysis: Yes Number of centres: 17 Source of funding: Grants plus industry support Years: 1995 ‐ 2000 Countries: Australia, New Zealand, Italy, Switzerland, Hong Kong, Slovenia
Participants	INCLUDED: Women with stage 2 or stage 3 breast cancer, having at least 10 positive nodes OR at least 5 positive nodes and oestrogen receptor‐negative OR at least 5 positive nodes and an operable T3 tumour
Interventions	HDC arm had 3 cycles of epirubicin 200 mg/m² and cyclophosphamide 4 gm/m² with PBPC support CDC arm had 3 cycles of doxorubicin 60 mg/m² or epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² then 3 cycles of cyclophosphamide 100 mg/m², fluorouracil 600 mg/m² and methotrexate 40 mg/m² After completing chemotherapy all women had tamoxifen 20 mg daily for 5 years
Outcomes	Event‐free survival Overall survival Treatment‐related death Toxicity
Notes	Data immature: 8‐year data in our tables based on 8‐year estimates reported by trialists at median follow‐up 8.3 years
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was conducted centrally (at the coordinating centres in Bern, Switzerland, and Sydney, Australia). A permuted blocks randomization schedule was produced by use of pseudorandom numbers generated by a congruence method."
Allocation concealment (selection bias)	Low risk	Carried out by central data centre
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Blinding not mentioned; however this appears unlikely to influence primary review outcomes
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomised women analysed
Selective reporting (reporting bias)	Low risk	All expected outcomes reported
Other bias	Low risk	No other potential bias identified