Haldar 2009

Methods	Randomised, double‐blind, placebo‐controlled, parallel‐group trial
Participants	61 participants had refractory eosinophilic asthma and a history of recurrent severe exacerbations. Main inclusion/exclusion criteria: ≥ 3% sputum eosinophils on at least 1 occasion in previous 2 years despite high‐dose corticosteroid treatment ≥ 2 exacerbations in previous 12 months maintenance treatment with high‐dose ICS Age: mepolizumab, mean 48 (range from 21‐63); placebo, mean 50 (range from 24‐72) Males: mepolizumab, 14; placebo, 18 Baseline mean (SD) FEV1, % predicted after bronchodilator use: mepolizumab, 78.1% (± 20.9%); placebo, 77.6% (± 24.1%) Baseline mean (SD) FEV1/FVC ratio: mepolizumab, 72.2% (± 9.6%), placebo, 67.7% (± 13.5%) 29 allocated to receive mepolizumab 750 mg, 32 to receive placebo
Interventions	Intravenous mepolizumab (750 mg) versus matched placebo (150 mL of 0.9% saline) at monthly intervals for 1 year
Outcomes	Reported as: "[P]rimary outcome measure was the number of severe exacerbations per participant during the 50‐week treatment phase. Secondary outcomes included a change in asthma symptoms, scores on the Asthma Quality of Life Questionnaire (AQLQ, in which scores range from 1 to 7, with lower values indicating more severe impairment and a change of 0.5 unit considered to be clinically important), forced expiratory volume in 1 second (FEV1) after use of a bronchodilator, airway hyperresponsiveness, and eosinophil counts in the blood and sputum."
Notes	Single centre trial conducted at Institute for Lung Health, Leicester, UK Supported by GlaxoSmithKline
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Reported as: "Stratified randomisation with use of the minimisation method, which was performed by an independent clinician. Participants were randomly assigned with the use of the minimisation method to receive 12 infusions of either 750 mg of mepolizumab delivered intravenously or matched placebo (150 mL of 0.9% saline) at monthly intervals between visits 3 and 14. The criteria used for minimisation were the frequency of exacerbations in the previous 12 months, the baseline eosinophil count in the sputum and the number of participants taking oral corticosteroids."
Allocation concealment (selection bias)	Unclear risk	Details not reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Reported as double blind
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Reported as double blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	Reported as: "A total of 61 of the 63 participants ( one required and operation and one withdrew consent) who were screened started treatment and constituted the modified intention‐to‐treat population. Thirty‐two participants were randomly assigned to receive placebo. Overall, 94.9% of treatment visits were completed. Participants who withdrew completed a mean of 4.6 treatment visits (38.3%)."
Selective reporting (reporting bias)	Low risk	No apparent indication of reporting bias