Szafranski 2003.

Methods	Design: parallel group Randomisation: yes, method not stated Blinding: double blind, double dummy Withdrawals: stated
Participants	Setting: multicentre study, hospital outpatient clinic Number eligible: 980 Number enrolled: 812 Number in groups: Combined 208, BUD 198, FM 201, placebo 205 Number of withdrawals: Combined 59, BUD 62, FM 64, control 90 Number completing trial: Combined 149, BUD 136, FM 137, control 115 (total 537) Age range: mean 64 yr Sex: 639M, 173F Ethnicity: not stated (multicentre) COPD diagnosis: GOLD guidelines Severity of COPD: mean FEV1 36% predicted Inclusion criteria: outpatients aged >=40 yr, COPD symptoms >=2 yr, smoking history >=10 pack‐yrs, FEV1/VC <=70%, FEV1 <50% predicted, total symptom score >=2/day during at least 7 days of run‐in, use of short‐acting inhaled bronchodilators, >=1 severe COPD exacerbation within 2‐12 months before study Exclusion criteria: asthma, seasonal allergic rhinitis before age 40, relevant cardiovascular disorders, current respiratory tract diseases or disorders, regular oxygen therapy, exacerbation during run‐in, patients in whom it was considered unethical to withdraw inhaled steroids Baseline characteristics of treatment/control groups:
Interventions	budesonide/formoterol 160/4.5 µg, 2 inhalations, 2 times a day (640 µg/d of BUD) BUD 200 µg, 2 inhalations, 2 times a day (800 µg/d) formoterol 4.5 µg, 2 times a day placebo Turbuhaler 12 months
Outcomes	Exacerbations Morning and evening COPD symptoms short‐acting beta‐agonist use PEFR Spirometry SGRQ adverse events
Notes	Trial of combined therapy versus monotherapy versus placebo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method not stated
Allocation concealment (selection bias)	Unclear risk	Method not stated
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Relatively high withdrawal rates
Selective reporting (reporting bias)	Low risk	All outcomes reported