Lanier 2009.

Methods	Randomised, multi‐centre, double‐blind, parallel‐group, placebo‐controlled study
Participants	Treatment group: 421 (352 completed). Age: 8.7 ± 1.7.  Males: 287 (68.2%). Baseline lung function: mean % predicted FEV1 (SD): 86.0 (17.8) Control group: 206 (175 completed). Age: 8.4 ± 1.7. Males: 138 (66.7%). Baseline lung function: mean % predicted FEV1 (SD): 87.2 (18.4) Inclusion criteria stated as: Parent or legal guardian was informed of the study procedures and medications and gave written informed consent. Outpatient males and females aged 6 to less than 12 years on study entry, with body weight between 20 and 150 kg. Total serum IgE level ≥ 30 to ≤ 1300 IU. Diagnosis of allergic asthma ≥ one year's duration, according to American Thoracic Society (ATS) criteria, and a screening history consistent with clinical features of moderate or severe persistent asthma according to National Heart Lung and Blood Institute (NHLBI) guidelines. Positive prick skin test to at least one perennial allergen, documented within the past two years or taken at screening. A radioallergosorbent test (RAST) could have been performed for participants with a borderline skin prick test result after consultation with Novartis clinical personnel. Patients with ≥ 12% increase in forced expiratory volume in one second (FEV1) over starting value within 30 minutes of taking up to four puffs (4 × 100 µg) salbutamol (albuterol) or nebulised salbutamol up to 5 mg (or equivalent of alternative β2‐agonist) documented within the past year, at screening, during the run‐in period or before randomisation. Patients were not to take their long‐acting β2‐agonist (LABA) medication within 12 hours of reversibility testing. Clinical features of moderate or severe persistent asthma (at least step three) despite therapy at step three or four (at least medium‐dose inhaled corticosteroid (ICS) fluticasone dry powder inhaler (DPI) ≥ 200 mg/d or equivalent with or without other controller medications) Documented history of experiencing asthma exacerbations and demonstrated inadequate symptom control during the past four weeks of run‐in despite receiving an equivalent dose of fluticasone DPI ≥ 200 mg/d total daily ex‐valve dose Exclusion criteria stated as: patients who received systemic corticosteroids for reasons other than asthma, beta‐adrenergic antagonists by any route, anticholinergics within 24 hours of screening, methotrexate, gold salts, cyclosporin or troleandomycin, or had received desensitisation therapy with less than three months of stable maintenance doses before screening. Patients with a history of food‐ or drug‐related severe anaphylactoid or anaphylactic reaction, a history of allergy to antibiotics, with aspirin‐ or other non‐steroidal anti‐inflammatory drug (NSAID)‐related asthma (unless the NSAID could be avoided), with active lung disease or acute sinusitis/chest infection, elevated serum IgE levels for other reasons, presence/history of a clinically significant uncontrolled systemic disease, cancer, abnormal electrocardiogram (ECG) in the previous month, or platelets ≤ 100 × 109/L or clinically significant laboratory abnormalities at screening Location(s): 87 centres in seven countries: Argentina (eight), Brazil (three), Canada (six), Colombia (five), Poland (six), USA (58) and South Africa (one)
Interventions	Stated as: Participants received omalizumab administered by subcutaneous injection every two or four weeks for a duration of 52 weeks. Omalizumab dose was based on participant's body weight and total serum IgE level at screening. The first 24 weeks of the treatment period was a fixed steroid phase, where the steroid dose was maintained constant; in the following 28 weeks, the steroid dose was adjustable, depending on the participant's condition. Following the 52‐week treatment period, participants were followed up for an additional 16 weeks Placebo was administered by subcutaneous injection every two or four weeks, depending on the dosing schedule in the protocol for a total of 52 weeks. The first 24 weeks of the treatment period was a fixed steroid phase, where the steroid dose was maintained constant; in the following 28 weeks, the steroid dose was adjustable, depending on the participant's condition. Following the 52‐week treatment period, participants were followed up for an additional 16 weeks Matched vials of placebo supplied as sterile powder in a 5‐mL vial designed to deliver 150 mg of placebo for s/c administration upon reconstitution with 1.4 mL sterile water Backgound inhaled corticosteroid dose: at least 200 mg/d fluticasone propionate via dry powder inhaler or equivalent, mean ICS dose 515.1 ± 285.4 mcg/d (fluticasone propionate equivalent) Participants using maintenance oral steroids at baseline = 8 (1.3%)
Outcomes	Primary outcome measures stated as: rate of clinically significant asthma exacerbations per participant in the 24‐week fixed‐dose steroid treatment period (time frame: baseline to end of the fixed‐dose steroid treatment period (week 24). Percentage of participants with at least one adverse event (time frame: baseline to end of the study (week 68))   Secondary outcome measures stated as: change in mean nocturnal asthma symptom score from baseline to the end (last four weeks) of the 24‐week fixed‐dose steroid treatment period (time frame: baseline to the end (last four weeks) of the 24‐week fixed‐dose steroid treatment period). Rate of clinically significant asthma exacerbations per participant in the 52‐week treatment period (time frame: baseline to end of treatment period (week 52)). Change in mean daily number of puffs of asthma rescue medication from baseline to end (last four weeks) of 24‐week fixed‐dose steroid treatment period (time frame: baseline to the end (last four weeks) of 24‐week fixed‐dose steroid treatment period). Change in Pediatric Asthma Quality of Life Questionnaire (Standardised) (PAQLQ(S)) scores from baseline to end of 24‐week fixed‐dose steroid treatment period (week 24) (time frame: baseline to end of 24‐week fixed‐dose steroid treatment period (week 24))
Notes	One‐year trial Co‐medication: inhaled corticosteroids 24‐week fixed‐dose and 28‐week adjustable‐dose
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomly assigned (two:one) to receive omalizumab or placebo by a randomisation card system
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment unclear
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Double‐blind
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Details of 101 participants who did not complete the trial are reported
Selective reporting (reporting bias)	Unclear risk	No apparent indication of reporting bias