ab Grigor'eva 1994.

Methods	Placebo‐controlled randomised trial of safety and effectiveness of live vaccine carried out in Havana, Cuba (with the collaboration of scientists from the former USSR) during the 1991 to 1992 season. The unit of allocation in schools was 1 child. The trial had 5 arms: 1 ‐ inoculated with A(H1N1) vaccine; 2 ‐ inoculated with A(H3N2) vaccine; 3 ‐ inoculated with B vaccine; 4 ‐ inoculated with trivalent vaccine A(H1N1)+A(H3N2)+B; and 5 ‐ placebo. Morbidity studied during period 1 December to 31 December 1991. The period of epidemic was defined according to serological data and epidemiological curves. Calculation of morbidity based on clinical diagnosis of influenza and ARI.
Participants	3663 children aged 5 to 14 years
Interventions	Live influenza vaccines, industrially produced series: A (H1N1), strain A/47/T (epidemical virus A/Taiwan/1/86, attenuated donor A/Leningrad/134/47/57); A (H3N2), strain A/47/6/2 (epidemical virus A/Zakarpatye/354/89, attenuated donor A/Leningrad/134/47/57); and B strain B/60/32 (epidemical virus B/USSR/3/87, attenuated donor B/USSR/60/69)
Outcomes	Serological Immogenicity ‐ seroconversion ‐ assessed on a sample basis (rule for sample selection not reported) Recombination analysis of genetic stability Effectiveness Morbidity due to influenza and acute respiratory viral infections according to a variety of symptoms and signs (essentially ILI). Only effectiveness of the 2‐dose schedule was analysed. Background viral circulation was also assessed, as well as data from seroconversions. Safety The following outcomes were recorded: temperature, general ill‐health, dysphonia, reddening of the throat, nasal bleeding, conjunctivitis, cough. Safety was assessed on the basis of sampling (rule for sample selection not reported). Clinical examinations were carried out for 4 days after each vaccination to record temperature, examination of integuments, nasopharynx, and eye mucous and any complaints.
Funding Source	Government
Notes	The authors conclude that live attenuated "polyvalent" vaccines are effective but no more than monovalent. Poor reporting (no description of blinding, placebo content and aspect, attrition, etc.) and likely selection bias of safety and immunological samples. However, there is a fairly detailed description of background viral circulation in Havana during January to December 1991 and an attempt at putting the results into this context. The authors show that there was no significant difference in morbidity between mono and polyvalent vaccine arms (49.7% in placebo arm versus 32.04% in arm 1 versus 28.29% in arm 2 versus 31.52% in arm 4 ‐ the trivalent vaccine).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No description
Allocation concealment (selection bias)	Unclear risk	No description
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blinding
Incomplete outcome data (attrition bias) All outcomes	High risk	No description
Summary assessments	Unclear risk	Plausible bias that raises some doubt about the results