Busse 2011.

Methods	Randomised, double‐blind, parallel‐group trial
Participants	Treatment group: 208. Age: 10.9 ± 3.6. Males: 122 (59%). Baseline lung function: mean % predicted FEV1 (SD): 92.9 ± 18.7 Control group: 211. Age: 10.8 ± 3.4. Males: 120 (57%). Baseline lung function: mean % predicted FEV1 (SD): 92.2 ± 17.6 73% of participants had moderate/severe asthma according to NAEPP guidelines Inclusion criteria stated as: males and females between the ages of 6 and 20 years; both body weight and total serum IgE suitable for omalizumab dosing (more information about this criterion can be found in the protocol); diagnosis of asthma made by a physician more than one year before study entry OR diagnosis of asthma made less than one year before study entry but asthma symptoms for longer than 1 year before study entry; receiving long‐term asthma control therapy OR symptoms consistent with persistent asthma OR evidence of uncontrolled disease; positive prick skin test to at least one perennial allergen (e.g. dust mite, cockroach, mold, cat, dog, rat, mouse); live in a preselected zip code area; able to perform spirometry measurements; willing to sign informed consent or parent or guardian willing to provide informed consent; previously had chicken pox or received varicella (chicken pox) vaccine; some form of healthcare insurance that covers costs of medications Exclusion criteria stated as: if participant meets any of these criteria, not eligible at that time but may be reassessed: systemic prednisolone (or equivalent) during the two weeks before visit two; systemic prednisolone (or equivalent) for more than 30 of the 60 days before study entry; pregnancy or breast‐feeding; acute sinusitis or chest infection requiring antibiotics within one month of study screening; currently participating in another asthma‐related clinical trial or previously participated in an another asthma‐related trial within one month of study entry; does not sleep at least four nights per week in one home; lives with a foster parent; does not have access to a phone; plans to move during the study; previously treated with anti‐IgE therapy within one year of study entry; currently receiving or received hyposensitisation therapy to any allergen in the year before study entry; previously received hyposensitisation therapy to dust mite, Alternaria or cockroach for longer than six months in the three years before study entry. If participant meets any of these criteria, he or she is not eligible for the study and may not be reassessed: significant medical illness. More information on this criterion can be found in the protocol: certain medications within four weeks of study screening. More information on this criterion can be found in the protocol: known hypersensitivity to any ingredients of omalizumab or related drugs; diagnosis of cancer; being investigated for possible cancer, or history of cancer; will not allow study physician to manage asthma; does not primarily speak English (or Spanish at centres with Spanish‐speaking staff); history of severe anaphylactoid or anaphylactic reaction(s) Location(s): eight centres in USA
Interventions	Stated as: Subcutaneous injections of omalizumab will be administered every two or four weeks, along with standardised asthma care for 60 weeks, beginning with the randomisation visit. Dosage is dependent on participant's individual characteristics. Injection dose of omalizumab (75 to 375 mg) was calculated on the basis of individual weight and total serum IgE level to ensure a minimum monthly dose of 0.016 mg per kilogram of body weight per international unit of IgE per mL versus placebo Background inhaled corticosteroid dose: at least 180 μg budesonide once a day
Outcomes	Primary outcome measures stated as: maximum number of asthma symptom days (recorded monthly throughout study) Secondary outcome measures stated as: economic outcomes (recorded monthly throughout study); asthma‐related medical care resource utilisation (recorded monthly throughout study); asthma exacerbations (recorded monthly throughout study); pulmonary function and exhaled nitric oxide (recorded at various visits throughout the study); asthma control test or childhood asthma control test (recorded monthly throughout study); number of missed school/work days (recorded monthly throughout study); asthma‐specific quality of life (QOL) (recorded at various visits throughout study); asthma medication use, rescue beta‐agonist and inhaled corticosteroid (ICS) use (recorded at various visits throughout the study); safety (recorded at every study visit)
Notes	60‐Week trial Co‐medication: oral prednisolone for exacerbations
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details of sequence generation not included in trial report
Allocation concealment (selection bias)	Unclear risk	Details of allocation concealment not included in trial report
Blinding (performance bias and detection bias) All outcomes	Low risk	Reported as double‐blind. Nurses giving Rx aware of Rx allocation; all other staff and participants blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	90% (386) included in primary outcome analysis 272 missed, 25% of Rx visits
Selective reporting (reporting bias)	Unclear risk	No apparent indication of reporting bias