ab Steinhoff 1991.

Methods	RCT to compare characteristics of 2 live reassortant vaccines: cold‐adapted (ca) and avian‐human (ah) Vaccines were manufactured by isolating wild‐type A/Kawasaki/9/86 (H1N1) in tissue culture and 4 times passage in tissue culture and once in eggs. These were crossed with donor strains to produce reassortant vaccines. Each vaccine was diluted in L‐15 medium (Whitaker Bioproducts) to achieve desired number of infectious units. Vaccines were evaluated in 1987 and 1988 during periods when no influenza viruses were circulating. Vaccines initially tested in young adults (data not extracted) before continuing with children's study.
Participants	122 children aged 6 to 24 months seronegative to A/Kawasaki/86 (H1N1) were randomised to receive a first dose of either ah (40 children), ca (39), or placebo (43).
Interventions	Avian‐human (ah) reassortant vaccine A/Kawasaki/9/86 (H1N1) x A/Mallard/New York/6750/78 (H2N2) Cold‐adapted (ca) reassortant vaccine A/Kawasaki/9/86 (H1N1) x A/Ann Arbor/6/60 (H2N2) Vaccines were administered in dose‐escalating fashion; after each dose was shown to be safe, 10‐fold higher dose administered until dose of 106 TCID50 was reached. Each child received 1 0.5 mL dose (0.25 mL per nostril). Children were observed for 1 to 2 hours daily for 3 days before inoculation; 7 to 9 days after each dose was shown to be safe, 10‐fold higher dose was administered until dose of 106 TCID50 was reached.
Outcomes	Serological Isolation and identification (by HAI assay) of virus from vaccine (data not extracted) Antibodies in sera and nasal washes (or nasopharyngeal swabs) by HAI assay and ELISA (data not extracted) Effectiveness N/A Safety Fever (rectal temperature at least 38.1 °C) Fever (rectal temperature at least 39.4 °C) Upper respiratory tract illness (rhinorrhoea, pharyngitis or both) Lower respiratory tract illness (persistent wheezing or cough) for at least 2 consecutive days Otitis media Children were observed for 1 to 2 hours daily for 3 days before inoculation and 7 to 9 days after.
Funding Source	Government
Notes	The authors conclude that the ca A/Ann Arbor/6/60 donor virus reliably confers attenuation characteristics to a variety of H1N1 and H3N2 influenza A viruses. No description of randomisation, allocation, attrition, or placebo. Data on adults were not extracted. Data by TCID not extracted separately. Data on ILI with or without infection were extracted, as these are responses to viral challenge.
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	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses to follow‐up
Summary assessments	Unclear risk	Insufficient information to assess study design