ca El'shina 2000

Methods	Report of a 2‐phase pilot RCT carried out in 1997 to 1998 among Moscow school children to assess safety of live attenuated trivalent vaccine ("Grippol"). The comparator was standard care. As usually happens in reports from Russia, there is a third study nested in the text. The study of cohort design was school based and assessed effectiveness against ILI. Data on general morbidity (excluding influenza and ARI) collected over entire observation period to determine possible side effects. Efficacy evaluated by comparing morbidity due to influenza and ARI using co‐efficient of efficacy
Participants	In the first study 2 groups (aged 14 to 17 years) were formed by randomisation. Both groups had 30 participants. In the second study 40 children aged 6 to 14 were again randomised to Grippol or standard care. The cohort study was carried out in three schools located near each other with a relatively similar level of morbidity and a comparable number of pupils. The school with a total number of 1835 students was assigned to the intervention group and 2 schools with a total number of 1315 individuals were assigned to the control group. However in the schools which had been assigned to the intervention group, "930 individuals were inoculated in the pre‐epidemical season. The remaining 905 pupils were also practically entirely healthy at the time of the inoculations but remained UV due to temporary medical exclusions. They acted as the so called ‘internal’ control group"
Interventions	"The influenza tri‐valent polymer‐subunit ‘Grippol’ vaccine was created in the State Scientific Centre (the Institute of Immunology, the Ministry of Health for the Russian Federation) (7, 10). The preparation belongs to a new generation of vaccines. It is a sterile preparation, based on highly pure surface proteins of the influenza viruses A and B – hemagglutinins and neuraminidases. They are protective antigens (6). It is also based on synthetic high‐molecular immuno‐stimulator polyoxidonium, which has an adjuvant activity (10). ‘Grippol’ differs from other subunit influenza vaccines in the world because of its antigenic load, which is reduced by 3 times because of the inclusion of an immuno‐stimulator. The inoculation dose of the ‘Grippol’ vaccine contains 5 μg of hemagglutinin of each strain of the influenza virus and 500 μg of polyoxidonium". No mention of matching nor of content is made
Outcomes	Influenza and ARI during period of seasonal rise in cases of influenza and ARI (12/97 to 04/98) Influenza during period of seasonal rise in cases (12/97 to 04/98) only 60.4% serologically confirmed General and local reactions to vaccination >/= 5 days (local reactions excluded as no placebo administered for comparison) Somatic and infectious morbidity (excluding influenza and ARI) during period of seasonal rise in cases (12/97 to 4/98) "From December to April, monthly collections and analysis of data for the morbidity of influenza and acute respiratory illnesses were organised in the working and control groups. Moreover, in order to correct the clinical diagnoses, the selective serological decoding of cases of illness diagnosed as influenza and acute respiratory illnesses was carried out". Table 3 reports ILI for the 930 in the intervention cohort and their 905 controls out of a total of 1835 and 1315 school children respectively. This also includes "serological confirmation in 60.4% of cases"
Funding Source	Government
Notes	The authors conclude that Grippol is safe and effective and recommend immunisation of children. The extensive contradictions between text and figures, unexplained selective serological testing and vaccination make this a high risk of bias study Figure for serologically confirmed is 60.4% of calculated per 1000 figure for number with influenza and ARI. Therefore serological confirmation is an estimate not an absolute figure and it may not be appropriate to include in meta‐analysis of serologically confirmed influenza Tables show period of seasonal rise from 07/97 to 04/98, likely to be mistake. Text refers to period from December 1997 to April 1998
Risk of bias
Bias	Authors' judgement	Support for judgement
PCS/RCS‐Selection Exposed cohort	Unclear risk	Insufficient description
PCS/RCS‐Selection Non Exposed cohort	Unclear risk	Insufficient description
PCS/RCS‐Comparability	Unclear risk	Insufficient description
PCS/RCS‐Assessment of Oucome	High risk	No description
Summary assessments	High risk	Plausible bias that seriously weakens confidence in the results