NV16871.

Methods	Randomised, double‐blinded, placebo‐controlled, parallel‐group trial of the effect of treatment with oseltamivir on improving rate of recovery from influenza‐mediated asthma symptoms and exacerbations in children (6 to 17 years) with asthma Location, number of centres: 50 centres in 10 countries mostly in Eastern Europe
Participants	A total of 329 randomised of whom 28.6% (i.e. less than estimated rate of 50%) had laboratory‐confirmed influenza; ITTI population had 51 placebo and 43 oseltamivir patients
Interventions	Oseltamivir by weight dosing bid for 5 days or placebo
Outcomes	Primary efficacy outcome was % change in FEV1 from days 1 to 2 to day 6 measured by spirometry. Study stratified for asthma severity at baseline (mild or moderate/severe) and time from influenza symptoms onset to first study drug dose (< 24 hours or ≥ 24 hours)
Notes	There was no significant difference in outcomes between the 2 groups, though a trend in favour of oseltamivir was reported. Secondary outcomes based on diary symptoms appeared to show faster recovery, reduced rate of complications and reduced use of antibiotics in the oseltamivir group. In terms of safety the overall incidence of adverse events was higher in the oseltamivir group than the placebo group (24% versus 21%). This was mainly due to a higher incidence of gastrointestinal events (10% versus 6%), of which vomiting (8% versus 2%) was most significant The definition of the M2 Module itself was not clear in the 614 page PDF reviewed and despite page by page review some things, e.g. the certificates of analysis, were not found and protocol amendments or statistical analysis plan amendments were also not reported. No additional information from M2 changes the original summary and risk of bias
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation list shows random sequence and centralised phone‐driven system was used
Allocation concealment (selection bias)	Low risk	Centralised phone system
Incomplete outcome data (attrition bias) Symptoms	High risk	In the absence of IPD and CRFs we cannot account for all participants
Incomplete outcome data (attrition bias) Complications of influenza	High risk	Unclear how complications of influenza were defined clinically
Incomplete outcome data (attrition bias) Safety data	High risk	Adverse events could be classified either as symptoms of influenza, complications of influenza or adverse events. Reporting is inconsistent and some trials reported the same outcome in the same participant in different categories
Selective reporting (reporting bias)	High risk	SAP and certificates of analysis and amendments are missing. GCP infringements noted in 2 centres
Other bias	High risk	Placebo content unclear
Blinding of participants and personnel (performance bias) All outcomes	High risk	Placebo colour and taste not clear
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Centrally randomised scheme