aa Rudenko 1988

Methods	Apparently cluster randomised controlled trial of schoolchildren in the Kalinigrad area of East Prussia (USSR at the time) in 1984‐85. The text appears to suggest that children were randomised by class. The participants underwent daily clinical examination for 7 working days after inoculation ‐ recorded temperature, complaints, inspection of skin, mucous from eyes and condition of nasopharynx. Morbidity due to influenza and acute respiratory illness recorded during epidemic period (28/1 to 3/3/85) Antigenic activity determined by inhibition of hemagglutinin by 'standard methods' Daily clinical examination of all children carried out for 7 working days after inoculation Examination recorded temperature and recording of complaints, inspection of skin, recording mucous from eyes and condition of nasopharynx Hematological and biochemical tests and analysis of urine carried out to evaluate safety of vaccine, samples taken before vaccination, 3 days after and 1 month after each dose of vaccine Hematological tests included full blood analysis, thrombocyte count and lymphocyte index Biochemical test included determination of C‐reactive protein, protein fraction, neuraminic acid, transaminase alanine‐aminotransferase and urea Antigenic activity carried out on subgroup of 240 children Samples taken from 22 children who received vaccine and 18 who received placebo for re‐isolation of vaccine Genetic stability of vaccine evaluated from swabs taken from nasopharynx after 1, 2, 3, 7, and 8 days. 3 criteria used ‐ retention of antigenic specificity, temperature sensitive‐phenotype, localisation of temperature sensitive‐mutations in individual genes of re‐isolates Statistical analysis of morbidity carried out using EVM using the criteria of the 'reliability of parameter differences of the binomial distribution' Influenza epidemic from 28/1 to 3/3/85, peak from 11/2 to 17/2/85. Epidemic caused by A(H3N2) (i.e. vaccine did not match circulating strain"
Participants	Children aged 3 to 15 years from nursery schools and schools Participants not inoculated against influenza in previous 3 years
Interventions	Live influenza A(H1N1) vaccine administered intranasally, 2 doses 28 to 30 days apart administered using Smirnov apparatus. An influenza epidemic took place from 28/1 to 3/3/85, peaking from 11/2 to 17/2/85. The epidemic was caused by A(H3N2) (i.e. vaccine did not match circulating strain)
Outcomes	Serological Antigenic activity was determined by HAI, haematological tests included full blood analysis and biochemical tests were also carried out Three serum samples were taken from 240 children to test seroconversion. The basis for the sampling is not described Effectiveness "Morbidity due to influenza and acute respiratory illness during epidemic period (28/1 to 3/3/85) Morbidity of other illnesses (excluding influenza and ARI) (data not extracted here) Temperature reactions after 7 working days after inoculation Seroconversion, HAI response to virus re‐isolates, temperature sensitivity of re‐isolates, temperature sensitive‐mutations (data not extracted for any of these outcomes)" Safety Reactogenicity was studied in a sample of 596 children after the first dose and in 164 children after the second dose. It is unclear on what basis the children in the samples were selected. The only outcome reported by arm was fever of various degrees but no definition is given
Funding Source	Unclear
Notes	The authors conclude that the vaccine did not affect morbidity because of mismatch between vaccine and circulating viruses. The vaccine also proved to be stable and not very reactogenic. No description of the vaccine content and unclear randomisation and attrition/sampling make the interpretation of the results very difficult
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient descriptions; cluster randomised trial
Allocation concealment (selection bias)	High risk	Not used
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No description
Summary assessments	High risk	No description of the vaccine content and unclear randomisation and attrition/sampling make the interpretation of the results very difficult