Chapman 2015.

Methods	Double‐blind, placebo‐controlled
Participants	180 ex‐smokers from Australia, Canada, Czech Republic, Denmark, Estonia, Finland, Germany, Ireland, Poland, Romania, Russia, Sweden, The Netherlands and the US with alpha‐1 antitrypsin deficiency of the ZZ phenotype (168 participants) and moderate emphysema (FEV1 between 35% and 70% of the predicted normal value)
Interventions	Treated for 2 years Treatment: weekly infusions of alpha‐1 antitrypsin 60 mg/kg Placebo: weekly infusions of a lyophilised preparation
Outcomes	Primary: lung density measured by CT scan Secondary: number of exacerbations, exacerbation duration and severity, FEV1, diffusion capacity, baseline and achieved A1PI concentrations (functional and antigenic assays), incremental shuttle walk test results, health status established with the SGRQ
Notes	Trial sponsored by the manufacturer, CSL Behring. There were no data reported in the published paper for several of the secondary outcomes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised pseudo random number generator
Allocation concealment (selection bias)	Unclear risk	Masked study treatments were supplied to each site in blocks of 4 containing sequential participant numbers. It is not clear whether this procedure could prevent selection bias: "To achieve treatment concealment, A1PI and placebo were packaged identically as lyophilised preparations and individual packages were identified only by patient number. Study drug material was suspended in sterile water for injection and placed in an intravenous bag that was covered with an opaque sleeve by a designated study nurse or pharmacist who did not interact with the patients. Clinical trial associates monitored compliance with the masking procedure throughout the trial". There was no information about the actual compliance with the procedures
Blinding (performance bias and detection bias) All outcomes	Unclear risk	See 'Allocation concealment (selection bias)' above
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Data on surrogate outcomes were available for 187 of the 190 randomised participants. Not clear whether data were missing for the other outcomes
Selective reporting (reporting bias)	High risk	Data on several secondary outcomes were entirely missing, and there were no explanations for this
Other bias	High risk	The trial was industry supported, and the academic authors had numerous financial conflicts of interest. The sponsor collected the data and 3 employees of the company participated in data analysis and writing of the report