ab Vasil'eva 1988b.

Methods	Randomised, placebo‐controlled trial carried out during 1983 to 1984 in the area of Rostov‐on‐Don in the former USSR. The study was conducted to assess efficacy, effectiveness, safety and immunogenicity of 2 types of bivalent vaccine versus placebo. These were administered by injection and needleless injector, although the data are presented by what the translator calls "chromatographic", "centrifugal", and "adsorptive" types of vaccines, whereas elsewhere they are reported as whole virion vs split. Randomisation is described only as that older children ("adolescents") were drawn individually into the randomisation sequence, whereas children aged 11 to 14 were selected on the basis of their class. It is unclear whether this means cluster randomisation, although denominators are roughly on a 3:1 basis. There was a B virus epidemic in January 1984, and then a H1N1 epidemic reported in Rostov‐on‐Don.
Participants	13,355 children aged 11 to 14 and "teenagers" observed, 9962 of whom took part in the vaccine evaluation (explanation not given). 6596 children were randomised to vaccines and 3393 to placebo. However, there are several inconsistencies in the text (see outcomes). The participants were recruited from schools, professional technical establishments, and technical colleges in Rostov‐on‐Don, Taganrog, and Novocherkassk.
Interventions	Bivalent vaccine whole virion or split ("formed from the influenza virus strains A/Leningrad/385/80 (H3N2) and A/Kiev/79 (HINI): chromatographic, centrifugal and adsorbitive(?) chemical influenza vaccines") or placebo ("sterile apirogenic solution of sodium chloride, using a syringe or intravenous injector (as for the vaccine) in volumes of 0.2 ml to 0.5 ml")
Outcomes	Serological Paired sera taken from 198 children who developed ILI symptoms during the season to confirm an influenza diagnosis. "Antigenic activity" (presumably immunogenicity) was tested on 655 children with paired sera taken 1 month apart. Effectiveness "Considering the mixed nature of the 1984 influenza epidemic and the fact that the tested preparations did not contain component B, it is interesting to analyse the rate of illness in children in the second half of the epidemic. At this time, the intensive circulation of the influenza virus type A (HINI) amongst children was confirmed by serological methods. A subsequent analysis showed that according to data from clinical diagnostics, 14.4% of children aged 11 to 14 years inoculated with the chromatographic preparation contracted influenza and acute respiratory illnesses in February to March 1984. For those inoculated with the centrifugal preparation the figure was 13.0% and for those who received placebo the figure was 12.6%. According to data from the serological correction of diagnoses, influenza A (HINI) was confirmed in 18.2% of those inoculated with the chromatographic preparation, 24.2% of those inoculated with the centrifugal preparation and 37.9% of children in the control groups. Figures for the corrected rate of illnesses were 2.6 and 3.1, as opposed to 4.8 in the control group. The indices of efficacy were 1.9 and 1.6 respectively. The differences in the figures given are statistically reliable (P < 0.001 and 0.01)". Safety "Reactogenicity was assessed on a sample of 866 school children aged 11 to 14 years. Paediatricians carried out a daily clinical examination of the children for 5 days after immunisation. This included the compulsory measuring temperatures, noting complaints of general reactions (feeling unwell, headaches, disturbed sleep etc.) and local reactions (reddening of skin, development of infiltrates, presence of illness at place of preparations’ administration" The basis for the sampling is unclear, and it is not at all clear whether this is a random sample (DATA NOT EXTRACTED). Earlier in the report, the text reports "When the groups were formed, with the aim of evaluating the preparations’ reactogenic properties and antigenic activity, the units of selection were individuals" ??? Data for the 866 children include several measures of induration and fever (Table 1). Elsewhere the text reports: "In order to evaluate the safety of the inactivated influenza vaccine, a comparative analysis was carried out of requests for emergency medical attention amongst those children who were inoculated and those who received placebo, for the 30 days after immunisation. The total figures for such requests amongst children aged 11 to 14 years and teenagers were 0.1% to 0.3% and 0.7% in the analogous group of children who had received placebo. The frequency of hospitalisation for inoculated children and those who had received placebo also did not reliably differ and did not exceed 0.04% to 0.06%". The outcomes reported in this analysis (Table 3) are very unusual (allergies, bronchitis, neuralgia, carbuncles, stomach ulcers, etc.), and there are gross imbalances and inconsistencies in the denominators of the arms (centrifugal 6625, adsorptive 491, chromatographic 4655, placebo 3493 = 15264).
Funding Source	Unclear
Notes	The authors conclude the following. "The safety, low reactogenicity and high antigenic activity of the Soviet whole‐virion inactivated influenza vaccine has been established, when administered once subcutaneously in a dose of 7.0 μg of haemagglutinin to school children aged 11 to 14 years and to teenagers In view of the discovery of the residual reactogenicity of the adsorbitive(?) influenza chemical vaccine, it is recommended that further work should be carried out on the preparation, aiming to ensure the possibility of an intravenous method of administration The clear prophylactic efficacy of the whole‐virion vaccine during the mixed epidemic period of influenza B+A (HINI) was noted: the indices of efficacy, from the calculation of the serological correction of clinical diagnoses, were 1.6 and 1.9 The safety, high inoculation activity and prophylactic efficacy allow the inactivated influenza whole‐virion vaccines to be recommended to be introduced as part of the practical prevention of health of children aged 11 years and older" We are not happy about the large number of inconsistencies in the text and non‐random (or at least unexplained) sampling carried out. Terrible reporting leading to loss of data. We have tried extracting data for influenza from the effectiveness text assuming a denominator of 6596 for all vaccinees and 3393 for placebo, converting percentages from the text as follows for influenza A (H1N1) 18.2% of those inoculated with the chromatographic preparation (4655, i.e. 847), 24.2% of those inoculated with the centrifugal preparation (6625), and 37.9% (i.e. 1603) of children in the control groups (3393, not 3493 as it says in Table 3, i.e. 1286). The summed numerators exceeded the denominator reported. However, these numerators do not match even remotely the 198 paired sera taken for influenza diagnosis. Too many inconsistencies
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	Unclear risk	Not described
Summary assessments	High risk	Insufficient information to assess study design