ab Steinhoff 1990

Methods	Randomised, double‐blind, placebo‐controlled trials of intranasal avian‐human and cold‐adapted vaccines. Conducted separately in a step‐wise, dose‐escalating fashion
Participants	63 seronegative (HAI no more than 1:8 to H3N2) children aged 6 to 48 months
Interventions	Cold‐adapted (ca) (H3N2) intranasal reassortant virus vaccine A/Ann Arbor/6/60 x A/Bethesda/1/85 (H3N2) Avian‐human (ah) (H3N2) intranasal reassortant virus vaccine A/Mallard/New York/6750/78 x A/Bethesda/1/85 (H3N2) Both vaccines diluted in L‐15 medium (Whitaker Bioproducts, Walkersville, MD) Placebo was L‐15 medium
Outcomes	Serological Paired sera, duration of viral nasal shedding, production of mucosal antibodies Effectiveness N/A Safety "Fever: temperature at least 38.1°C, within 7 days of vaccination Influenza‐like illness: fever, upper respiratory tract illness or lower respiratory tract illness on 2 or more consecutive days, within 7 days of vaccination Upper respiratory tract illness: rhinorrhoea, pharyngitis or both, within 7 days of vaccination Otitis media: loss of normal tympanic membrane landmarks and decreased mobility determined by 2 independent examiners, within 7 days of vaccination Illness attributable to influenza A virus ‐ laboratory‐confirmation of influenza A infection, within 7 days of vaccination Influenza infection from vaccine (data not extracted) Serum antibody response (data not extracted) Nasal wash antibody response (data not extracted) Isolation of vaccine virus (data not extracted)"
Funding Source	Government
Notes	The authors conclude that the vaccines are safe and induce immunity, protecting participants from challenge with homologous virus A viral challenge study was also carried out (data not extracted) Sensitivity analysis by vaccine concentration (data not extracted)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Double‐blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses to follow‐up
Summary assessments	Unclear risk	Insufficient information to assess study design