Schmitt 2014.

Study characteristics
Methods	Randomised, placebo‐controlled, phase 3 trial with 2 arms comparison of aprepitant + granisetron + dexamethasone vs matching placebo + granisetron + dexamethasone Recruitment period: July 2005 to January 2012 609 patients screened 246 patients excluded (131 declined participation, 30 with high‐dose therapy other than melphalan, 59 with contraindications, 4 with previous participation in same trial, 12 with participation in other trial, 10 with other reasons) 363 patients randomly assigned 362 patients were available for efficacy analysis per‐protocol set thus comprised 145 and 135 patients in aprepitant and placebo arms, respectively Masking: double‐blind Baseline patient characteristics: n.r. Follow‐up: Days 5 to 7
Participants	Inclusion criteria ≥ 18 years of age with multiple myeloma undergoing autologous transplantation after high‐dose melphalan conditioning Exclusion criteria nausea or vomiting within 12 h before planned high‐dose chemotherapy any antiemetic treatment within 24 h before planned high‐dose chemotherapy intake of corticosteroids known hypersensitivity to investigational product Median age (range), years: 58.3 (27 to 72) in aprepitant arm, 57.9 (35 to 72) in placebo arm Gender: male + female Tumour/cancer type: multiple myeloma Chemotherapy regimen: high‐dose melphalan therapy Country: Heidelberg University Hospital, Heidelberg, Germany (single centre)
Interventions	Experimental: arm A: aprepitant Day 1: aprepitant 125 mg + granisetron 2 mg + dexamethasone 4 mg Days 2 to 3: aprepitant 80 mg + granisetron 2 mg + dexamethasone 2 mg Day 4: aprepitant 80 mg + granisetron 2 mg Experimental: arm B: placebo Day 1: placebo 125 mg + granisetron 2 mg + dexamethasone 8 mg Days 2 to 3: placebo 80 mg + granisetron 2 mg + dexamethasone 4 mg Day 4: placebo 80 mg + granisetron 2 mg
Outcomes	Primary endpoint overall complete response (no emesis and no rescue therapy within 120 h of melphalan administration) Secondary endpoint complete response (no emesis and no rescue therapy in acute (0 to 24 hours) or delayed (25 to 120 hours) phase) rates of emesis no nausea and no significant nausea total control number of adverse events impact on quality of daily life, as assessed by modified Functional Living Index‐Emesis score
Notes	NCT00571168 conflicts of interest: "employment or leadership position: none; consultant or advisory role: Hartmut Goldschmidt, Janssen Pharmaceuticals (C), Celgene (C), Novartis (C), Onyx Pharmaceuticals (C), Millennium Pharmaceuticals (C); Markus Thalheimer, Merck Sharp & Dohme (C); Gerlinde Egerer, Merck Sharp & Dohme (C); stock ownership: none; honoraria: Hartmut Goldschmidt, Janssen Pharmaceuticals, Celgene, Novartis, Chugai Pharmaceutical, Onyx Pharmaceuticals, Millennium Pharmaceuticals; Markus Thalheimer, Merck Sharp & Dohme; Gerd Mikus, Merck Sharp & Dohme; Jürgen Burhenne, Merck Sharp & Dohme; Gerlinde Egerer, Merck Sharp & Dohme; research funding: Hartmut Goldschmidt, Janssen Pharmaceuticals, Celgene, Novartis, Chugai Pharmaceutical; Jürgen Burhenne, Merck Sharp & Dohme; Gerlinde Egerer, Merck Sharp & Dohme; expert testimony: none; patents, royalties, and licenses: none; other remuneration: Thomas Schmitt, Merck Sharp & Dohme" sponsor: Heidelberg University; collaborator: Merck Sharp & Dohme Corp.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "... computer‐generated randomization list ..."
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
Incomplete outcome data (attrition bias) Subjective outcomes (Patient reported outcomes)	Low risk	Quote: "362 patients underwent ITT analysis out of 363 randomly assigned patients"
Incomplete outcome data (attrition bias) Objective outcomes (including mortality and safety data)	Low risk	Comment: ITT data set used for safety analysis
Selective reporting (reporting bias)	Low risk	Comment: all outcome measures were reported in the results section
Other bias	Low risk	Comment: no information to suggest other sources of bias