Tandon 2010.

Methods	4‐month double‐blind, placebo‐controlled RCT carried out in winter in 4 centres in Western Australia
Participants	People with severe COPD defined by FEV1 < 50% or > 2 acute exacerbations per year for 2 consecutive years Mean age of participants in the vaccine arm was 69.5 and in the placebo arm was 67.3
Interventions	HI‐1640V: each tablet contained 45 mg approximately 10 bacteria of formalin‐inactivated NTHi provided as enteric‐coated tablets Control: enteric‐coated placebo tablets containing excipients only Duration: protocol stated that participants took 3 courses of 2 tablets in the morning for 3 consecutive days with courses repeated at 28 and 56 days
Outcomes	Number and severity of acute episodes (increase in volume and purulence of sputum) Antibiotic courses Sputum bacteriology and immune markers Hospitalisations Adverse effects
Notes	Multicentre trial. Most authors disclosed contributions from Hunter Immunology Ltd.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Participants were reportedly randomised, although the method of randomisation was not discussed. Baseline characteristics suggest that randomisation was successful
Allocation concealment (selection bias)	Unclear risk	No information was provided about the procedure for protecting the randomisation process so that the treatment to be allocated was not known before the patient was entered into the study
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind trial
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Primary outcome was measured using a respiratory questionnaire. These subjective data are prone to recall bias. Secondary outcomes were objectively measured using bacterial colonisations and antibody titres
Incomplete outcome data (attrition bias) All outcomes	Low risk	Participants were followed up for 4 months after completing the 3 courses. No participants were lost to follow‐up. Data surrounding withdrawal and discontinuation from the study were well described
Selective reporting (reporting bias)	Low risk	The published report includes all expected outcomes
Other bias	Low risk	No other sources of biases were identified

ATS‐DLD‐78: American Thoracic Society Division of Lung Disease questionnaire
 COAD: chronic obstructive airways disease
 COPD: chronic obstructive pulmonary disease
 FEV₁: forced expiratory volume in one second
 ITT: intention‐to‐treat
 NTHi: non‐typeable Haemophilus influenzae
 PNG: Papua New Guinea
 RCT: randomised controlled trial
 RTI: respiratory tract infection
 VAS: visual analogue scale