Mandelli 2009.

Methods	Design: RCT with three arms: IDA versus DNR versus MIT Recruitment period: November 1993 to December 1999 Median follow‐up: 67.2 months (range not stated)
Participants	Eligibility criteria: Inclusion criteria: 15 to 60 years untreated primary or secondary non‐M3‐AML identified by the FAB criteria no evidence of severe concurrent cardiac, pulmonary, neurologic, and metabolic diseases or uncontrolled infections adequate liver (serum bilirubin level 2 upper normal limit) and renal (serum creatinine 2 upper normal limit) function tests Exclusion criteria: blast crisis of CML AML supervening after other chronic myeloproliferative diseases and other progressive malignant diseases Patients randomised (n = 2157) IDA arm: n = 717 DNR arm: n = 721 MIT arm: n = 719 Median age: IDA arm: not stated DNR arm: not stated MIT arm: not stated Gender (male, female): IDA arm: n = 373, n = 344 DNR arm: n = 354, n = 367 MIT arm: n = 358, n = 361 Country: Europe, 80 centres
Interventions	IDA arm: IAE regimen, 1 to 2 cycles IDA: 10 mg/m²/d for 5 days, IV Ara‐C: 25 mg/m² IV bolus followed immediately by 100 mg/m²/d for 10 days, continuous IV VP‐16: 100 mg/m²/d for 5 days, IV DNR arm: DAE regimen, 1 to 2 cycles DNR: 50 mg/m²/d for 3 days, IV Ara‐C: 25 mg/m² IV bolus followed immediately by 100 mg/m²/d for 10 days, continuous IV VP‐16: 100 mg/m²/d for 5 days, IV MIT arm: MIE regimen, 1 to 2 cycles MIT: 12 mg/m²/d for 3 days, IV Ara‐C: 25 mg/m² IV bolus followed immediately by 100 mg/m²/d for 10 days, continuous IV VP‐16: 100 mg/m²/d in 0.9% saline for 5 days, IV
Outcomes	Outcomes and time‐points from the study that are considered in the review: reported: OS, DFS, CR, death on induction therapy, AEs not reported: relapse, quality of life
Notes	Published as a journal article Funded by National Cancer Institute, Bethesda, MD, Italian Cancer League and Italian Association Against Leukemias, Lymphoma, and Myeloma The authors declared no potential conflict of interest
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "patients were randomly assigned" Comment: the study probably had an adequate sequence generation
Allocation concealment (selection bias)	Low risk	Quote: "Patients were screened at each centre, and those who fulfilled the eligibility criteria were randomly assigned at the European Organisation for Research and Treatment of Cancer Data Center in Brussels, Belgium"
Blinding (performance bias and detection bias) Overall survival	Low risk	Comment: the review authors judge that the outcome OS is unlikely to be influenced by lack of blinding
Blinding (performance bias and detection bias) All other outcomes	High risk	Comment: blinding was not explicitly stated
Incomplete outcome data (attrition bias) OS and DFS	Low risk	Quote: "All the efficacy analyses were performed according to the intention‐to‐treat‐principle (all patients randomly assigned were included)" Comment: all randomised patients were included in the analyses
Selective reporting (reporting bias)	Unclear risk	Comment: a study protocol is available (clinical.trials.gov: NCT00002549), but it does not provide any information of the pre‐planned primary and secondary outcomes.
Other bias	Unclear risk	No information provided