Schwartzberg 2015.

Study characteristics
Methods	Randomised, parallel‐group, active‐controlled, phase 3 study with 2 arms comparison of rolapitant + granisetron + dexamethasone vs placebo + granisetron + dexamethasone Study period: 5 March to 6 September 2013 1369 patients randomised Masking: double‐blind Baseline patient characteristics: reported Follow‐up: yes
Participants	Inclusion criteria ≥ 18 years of age, of either gender, of any race naïve to moderately or highly emetogenic chemotherapy, and will receive a first course of MEC including ≥ 1 of the following agents: cyclophosphamide i.v. (< 1500 mg/m²), doxorubicin, epirubicin, carboplatin, idarubicin, ifosfamide, irinotecan, daunorubicin, cytarabine i.v. (> 1 g/m²) Karnofsky performance score ≥ 60 predicted life expectancy ≥ 4 months adequate bone marrow, kidney, and liver function Exclusion criteria contraindication to administration of prescribed MEC agent, granisetron, or dexamethasone pregnant or breast‐feeding has taken the following agents within the last 48 h: 5‐HT₃ antagonists, phenothiazines, benzamides, domperidone, cannabinoids, NK₁ antagonist, benzodiazepines scheduled to receive any other chemotherapeutic agent with emetogenicity level ≥ 3 (Hesketh Scale) from Day ‐2 through Day 6, except on Day 1 scheduled to receive any radiation therapy to the abdomen or pelvis from Day ‐5 through Day 6 has received systemic corticosteroids or sedative antihistamines within 72 h of Day 1 of the study, except as pre‐medication for chemotherapy (e.g. taxanes) symptomatic primary or metastatic CNS disease ongoing vomiting, retching, clinically significant nausea caused by any aetiology, or history of anticipatory nausea and vomiting has vomited and/or has had dry heaves/retching within 24 h before the start of MEC on Day 1 in Cycle 1 Median age (range), years: 58 (22 to 86) in rolapitant group, 56 (22 to 88) in active control group Gender: male (265) + female (1067) Tumour/cancer type: malignant solid tumour (breast, colon or rectum, head and neck, lung, ovary, stomach, other tumours) Chemotherapy regimen: MEC including ≥ 1 of the following agents: cyclophosphamide i.v. (< 1500 mg/m²), doxorubicin, epirubicin, carboplatin, idarubicin, ifosfamide, irinotecan, daunorubicin, cytarabine i.v. (> 1 g/m²) Country: 170 cancer centres in 23 countries (multi‐centre)
Interventions	Experimental: arm A: rolapitant Day 1: rolapitant (200 mg p.o.) + granisetron (2 mg p.o.) + dexamethasone (20 mg p.o.) Days 2 to 3: granisetron (2 mg p.o.) administered orally Control: arm B Day 1: placebo + granisetron (2 mg p.o.) + dexamethasone (20 mg p.o.) Days 2 to 3: granisetron (2 mg p.o.) administered orally
Outcomes	Primary outcome no emetic episodes and no rescue medication [Time frame: > 24 to 120 h post chemotherapy] Secondary outcome(s) acute phase response [Time frame: 0 to 24 h] overall response rate [Time frame: 0 to 120 h]
Notes	ClinicalTrials.gov Identifier: NCT01500226 sponsors and collaborators: Tesaro, Inc. sponsor remained unaware of treatment allocation conflicts of interest: "LSS is a consultant for TESARO, Helsinn, and Eisai, outside the submitted work. BLR and IDS are advisory board consultants for TESARO, outside the submitted work. AP is an employee of the funder TESARO. SA has received contracting fees from TESARO to direct statistical analyses during this study and outside the submitted work. All other authors declare no competing interests"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "for randomisation of patients, we used an interactive web‐based randomisation system (IWRS) at cycle 1"
Allocation concealment (selection bias)	Low risk	Quote: "for masking, a double‐blind technique was used. Placebo capsules were identical in appearance to rolapitant capsules. Through out the study, neither the patient nor the investigators and assessors knew which treatment the patient was receiving."; "... an independent group with no further role in study implementation ..."
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. neutropenia, febrile neutropenia)
Incomplete outcome data (attrition bias) Subjective outcomes (Patient reported outcomes)	Low risk	Quote: "therefore, in cycle 1, the modified intention‐to‐treat population comprised 666 patients in each treatment group"
Incomplete outcome data (attrition bias) Objective outcomes (including mortality and safety data)	Low risk	Quote: "the safety population consisted of all patients who received at least one dose of study drug"
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