Ferry 2017.

Methods	Inclusion: Eligible participants met criteria for histologically confirmed NSCLC, PS 0 to 2, life expectancy > 12 weeks, stage IIIB/IV disease, and had a GFR of > 60 mL/minute calculated using the Wright equation. Participant compliance and geographic proximity that allowed adequate follow‐up was required. Exclusion: Patients were ineligible if they had: mixed histologies of small cell lung cancer and NSCLC; clinically apparent brain metastases; had prior chemotherapy, including neoadjuvant or adjuvant chemotherapy; other concurrent cytotoxic chemotherapy; had prior radiotherapy (prior surgical resection for NSCLC allowed); other malignancy that would preclude study treatment or study comparisons; pre‐existing neuropathy grade > 2; psychiatric disorder making reliable informed consent impossible or that might prevent completion of treatment or follow‐up; evidence of severe or uncontrolled systemic disease, significant clinical disorder, or laboratory finding that would preclude study participation.
Participants	Arm I: 456 people Arm II: 454 people Arm III: 453 people
Interventions	Arm I (GC80): gemcitabine (1250 mg/m2) iv over 30 minutes on days 1 and 8 and cisplatin (80 mg/m2) iv over 1 hour on day 1 (total time of infusion: 6 hours), every 3 weeks Arm II (GC50): gemcitabine (1250 mg/m2) iv over 30 minutes on days 1 and 8 and cisplatin (50 mg/m2) iv over 1 hour on day 1 (total time of infusion: 6 hours), every 3 weeks Arm III (GCb): gemcitabine (1250 mg/m2) iv over 30 minutes on days 1 and 8 and carboplatin (AUC 6 mg/mL X minutes) iv over 1 hour on day 1 (total time of infusion: 1.5 hours), every 3 weeks
Outcomes	Primary outcome: overall survival Secondary outcomes: symptom control and QoL as measured by the EORTC QLQ‐C30 and QLQ‐LC13 together with the EQ‐5D treatment response as measured by RECIST criteria dose intensity of chemotherapy ratio of treatment courses given as inpatient vs outpatient toxicity as measured by CTCAE v3.0
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was stratified by PS (0, 1 and 2), stage (IIIB and IV), and centre to ensure balance between treatments within the strata defined by these key prognostic factors.
Allocation concealment (selection bias)	Low risk	Random assignment to treatment was conducted by a computer, based at the BTOG2 study office.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Since times to infusion differed (extra fluid administration in cisplatin arm), participants were not blinded.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information about blinding of the assessor
Incomplete outcome data (attrition bias) All outcomes	High risk	Response rate could not be evaluated in several people (160 people in GC80, 152 people in GC50, and 151 people in GCb), which could have affected the final analysis of this endpoint.
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting bias
Other bias	High risk	It is important to note that the Wright formula was used for calculation of creatinine clearance, which usually results in about 10% higher doses of carboplatin than with use of the Cockcroft‐Gault formula.