Warr 2005.

Study characteristics
Methods	Randomised, parallel‐group, placebo‐controlled, phase 3 trial with 2 arms comparison of aprepitant + ondansetron + dexamethasone vs placebo + ondansetron + dexamethasone Recruitment period: October 2002 to December 2003 866 patients included Masking: double‐blind Baseline patient characteristics: reported Follow‐up: n.r.
Participants	Inclusion criteria ≥ 18 years old naïve to emetogenic chemotherapy (Hesketh Level 3 or higher) diagnosed breast carcinoma predicted life expectancy ≥ 4 months Karnofsky score ≥ 60 Exclusion criteria symptomatic CNS malignancy received radiation therapy to abdomen or pelvis in the week before treatment had vomited in the 24 h before treatment Day 1 active infection, active systemic fungal infection, or any severe concurrent illness except for malignancy abnormal laboratory values taking systemic corticosteroid therapy at any dose Mean age (range), years: 53.1 (aprepitant regimen), 52.1 (control regimen) Gender: male (2) + female (864) Tumour/cancer type: breast cancer Chemotherapy regimen: anthracycline plus cyclophosphamide‐based chemotherapy regimen (the following agents were administered alone or in combination: i.v. cyclophosphamide 750 to 1500 mg/m² (± 5%); i.v. cyclophosphamide 500 to 1500 mg/m² (± 5%) and i.v. doxorubicin ≤ 60 mg/m² (± 5%); i.v. cyclophosphamide 500 to 1500 mg/m² (± 5%) and i.v. epirubicin ≤ 100 mg/m² (± 5%). Other chemotherapeutic agents, Hesketh level 2 or lower, could be added to the above chemotherapeutic regimens) Country: 95 centres in the United States, Germany, Austria, Canada, Hong Kong, Hungary, Spain, United Kingdom, Italy, Australia, and Greece
Interventions	Experimental: arm A: aprepitant 125/80 mg Day 1: p.o. aprepitant 125 mg + p.o. ondansetron 8 mg (30 to 60 min before chemotherapy and again 8 h after chemotherapy) + p.o. dexamethasone 12 mg Days 2 to 3: p.o. aprepitant 80 mg Control: arm B: placebo Day 1: placebo + p.o. ondansetron 8 mg (30 to 60 min before chemotherapy and again 8 h after chemotherapy) + p.o. dexamethasone 20 mg Days 2 to 3: placebo + p.o. ondansetron 8 mg
Outcomes	Primary endpoint complete response (no emetic episodes and no rescue therapy) in the overall 5‐day study period
Notes	matching placebos given to maintain blinding "the studies described in this paper were funded by Merck Research Laboratories, manufacturers of aprepitant" conflicts of interest: "Drs. Carides, Evans, and Horgan are employees of Merck Research Laboratories. Drs. Warr, Grunberg, Gralla, Hesketh, Roila, and de Wit have received funding from Merck Research Laboratories for the conduct of clinical studies of aprepitant"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "... using a computer‐generated allocation schedule with a block size of four"
Allocation concealment (selection bias)	Unclear risk	Comment: allocation concealment not reported
Blinding of participants and personnel (performance bias) Blinding of participants	Low risk	Quote: "... double‐blind ..."
Blinding of participants and personnel (performance bias) Blinding of personnel	Low risk	Quote: "... double‐blind ..."
Blinding of outcome assessment (detection bias) Subjective outcomes (Patient reported outcomes)	Low risk	Comment: both patients and personnel were blinded towards the intervention and thus had no influence on outcome assessment
Blinding of outcome assessment (detection bias) Objective outcomes (including mortality and safety)	Low risk	Comment: both patients and personnel were blinded towards the intervention and thus had no influence on outcome assessment (e.g. hiccups)
Incomplete outcome data (attrition bias) Subjective outcomes (Patient reported outcomes)	Low risk	Quote: "... modified intent‐to‐treat analysis was conducted, including all patients who received chemotherapy, took the study drug, and had at least one post‐treatment assessment"
Incomplete outcome data (attrition bias) Objective outcomes (including mortality and safety data)	Low risk	Comment: all patients were included in the safety analysis
Selective reporting (reporting bias)	Low risk	Comment: outcome measure was reported in the results section
Other bias	Low risk	Comment: no information to suggest other sources of bias