Kardos 2007.

Methods	Design: Randomized, double‐blind, parallel‐group study Duration: 10 months (+ 4 week run‐in) Location: 95 respiratory centres in Germany
Participants	Population: 994 participants were randomised to salmeterol (487) and salmeterol/fluticasone combination (507) Baseline characteristics Age (mean years): salm 64.0, salm/flut 63.8 % Male: salm 77.6, salm/flut 74.0 % FEV1 predicted: salm 40.3, salm/flut 40.4 Pack‐years (mean): salm 37.0, salm/flut 36.8 Inclusion criteria: Outpatients with post‐bronchodilator FEV1 < 50% predicted., FEV1/FVC of 70% predicted or less, age of 40 yr or more, smoking history of 10 pack‐years or more, and a documented history of two or more moderate to severe exacerbations in the last year before the study. Exclusion criteria: Patients with COPD exacerbations, hospital admissions, or change in COPD therapy during the 4 wk before Visit 1 or during the 4‐wk run‐in period were excluded. Patients with asthma, significant lung diseases other than COPD, and need for long‐term oxygen therapy or chronic systemic steroid use were also excluded
Interventions	1. Salmeterol 50 bid (LABA) 2. Salmeterol/fluticasone 50/500 bid (LABA/ICS) Inhaler device: Diskus dry powder Allowed co‐medications: Inhaled salbutamol was used as reliever medication, and regular treatment with short‐acting bronchodilators, antioxidants/mucolytics, short‐acting oral beta2 agonists, and theophylline was permitted
Outcomes	Number of exacerbations, pre‐bronchodilator PEF, post‐bronchodilator FEV1, SGRQ, symptoms and breathlessness, diary card data
Notes	Funding: GlaxoSmithKline Identifier(s): unknown
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Consecutive numbers were assigned to patients that determined the blinded treatment based on a centrally generated list with blocks of six
Allocation concealment (selection bias)	Low risk	Randomisation list was centrally generated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Described as double‐blind treatment [presumed participants and personnel/investigators]
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	Similar withdrawal rates in each group. ITT included 99.6% of the randomised population (4 patients were excluded due to a randomisation error)
Selective reporting (reporting bias)	Unclear risk	Unable to locate prospective trial registration to check that all outcomes were reported. Author contacted who forwarded request to GSK ‐ no data were provided in time for publication.