Lahn 2004.

Methods	A prospective, randomised, double blinded, placebo‐controlled clinical trial Comparison of single dose of IM methylprednisolone versus oral methylprednisolone Randomisation was accomplished using computer‐generated random set of numbers (20 blocks). Allocation concealment was maintained by research pharmacist using computer generated set of numbers to package medications in balanced blocks (20). Intramuscular injection (methylprednisolone and placebo) with similar appearances and covered content were prepared and administered by a nurse who was not involved in the study. Oral methylprednisolone and placebo were identical in appearance and were given in identical containers.
Participants	Patients diagnosed with asthma (based on the American Thoracic Society Guidelines (1962), PEF ≤ 70% predicted during the ED visit with a minimum PEF ≥ 40% predicted, and included both clinical symptoms and physical examination findings), who presented with an asthma exacerbation and were expected to be discharged after the ED treatment Exacerbation severity not discussed. Exacerbation severity estimated as mild/moderate based on baseline PEF Ages: enrolled patients 18 to 45 years. Mean age of IM corticosteroid group: 33 years (SD: 8). Mean age of oral corticosteroid group: 33 years (SD: 8) Patients who received systemic corticosteroids (within 1 month prior to the study), theophylline or inhaled anticholinergic agents were excluded from study. Set in United States Sex: 56 men, 131 women
Interventions	Interventions: single IM dose of methylprednisolone (160 mg) followed by 8‐day supply of tapering oral placebo versus oral methylprednisolone (8‐day tapering dose: day 1, 32 mg; day 2, 32 mg; day 3, 24 mg; day 4, 24 mg; day 5, 16 mg; day 6, 16 mg; day 7, 8 mg; day 8, 8 mg) in addition to a IM placebo injection Co‐interventions in the ED: nebulized beta₂‐agonist agents and IV injection of 1 mg/kg methylprednisolone Co‐interventions at discharge: albuterol MDI Patients were permitted to use ICS post‐discharge if patients had been using them previously Patients were instructed to continue all other medications without further clarification
Outcomes	Primary end point: relapse within 10 days of discharge (defined as the need to seek unscheduled care at the doctor’s office, a clinic, or ED for symptoms of persistent or worsening asthma, determined by phone contact) Secondary end point: relapse between 11 and 21 days Self‐reported pain of IM injection and the development of bruising, swelling, or continued pain for more than 7 days at the site of injection were reported and discussed Intention‐to‐treat and sensitivity analysis were reported and discussed
Notes	Authors were contacted, but were unable to provide protocol No registered protocol was identified
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation completed via block randomised computer generated numbers. Quote (p. 363): "The medication was prepared and block‐randomised by a research pharmacist who used a computer‐generated set of random numbers to package the medications in balanced blocks of 20 (i.e., each block of 20 medication packets contained 10 packets of oral methylprednisolone plus an IM placebo and 10 packets of IM methylprednisolone plus oral placebo."
Allocation concealment (selection bias)	Low risk	Pharmacy‐controlled central allocation. Quote (p. 363): "The randomisation code was held by the pharmacist and was not broken during the course of the study." "To the best of our knowledge, allocation concealment was maintained."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blinded study. Corticosteroids administered to patients via a study nurse not involved with the patient. Intramuscular injection was administered in a private setting with no one else present. Nurse instructed not to provide patients or staff information on contents of the syringe. Nurse covered the syringe so that other staff or patients could not see what was in the syringe. Oral placebo and corticosteroids was identical in appearance. Quote (p. 363): "The injection was reconstituted and administered by an ED nurse who was not blinded to the treatment but who had no involvement in any aspect of the study. This individual was instructed not to provide the patient, physician, or study personnel with any information about the contents of the syringe. Although the placebo and methylprednisolone injections were similar in appearance, the nurse also was instructed not to allow anyone to see the contents of the syringe. The injection was administered in a private setting with no one else present. The oral methylprednisolone and oral placebo were identical in appearance and were given to patients in identical containers. To the best of our knowledge, allocation concealment was maintained."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information provided on blinding of outcome assessment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Detailed information on study attrition provided in flow diagram provided (p. 364). Excluded patients balanced between groups. Quote (p. 364): "One hundred ninety patients were entered into the study over a 60‐month period from November 1997 to November 2002. As shown in the diagram of the Consolidated Standards of Reporting trials, three patients (all in the oral methylprednisolone/IM placebo group) were removed after study entry due to protocol violations. One patient’s asthma was too severe to be discharged safely from the ED, a second patient did not receive a ‐agonist prescription at ED discharge, and a third patient was instructed by the primary physician to discontinue the study medication at day 5. Seven patients (IM administration group, three patients; oral administration group, four patients) were lost to follow‐up and were excluded from the primary efficacy analysis. The remaining 180 patients, 92 of whom received IM methylprednisolone plus oral placebo, and 88 of whom received oral methylprednisolone plus IM placebo, completed the protocol and were available for follow‐up at 10 days. All patients reached for follow‐up at 10 days were successfully contacted again for follow‐up at 21 days. No patients who were lost to follow‐up at 10 days were available for follow‐up at 21 days."
Selective reporting (reporting bias)	Unclear risk	No protocol available.
Other bias	Low risk	Study funded by pharmaceutical company. Authors state that pharmaceutical company just provided financial support, and was not involved in the design, execution, data analysis, or manuscript preparation. Quote (p. 362): "This research was funded in part by an unrestricted grant from Pharmacia & Upjohn (currently, Pfizer), who, other than providing financial support, were not involved in any way with the design, execution, data analysis, or manuscript preparation."