. 2018 Feb 1;2018(2):CD001269. doi: 10.1002/14651858.CD001269.pub6

1. Studies included in the various versions of this review and their impact on our conclusions.

Review version (searches date)	Number of included trials (RCTs/CCTs)	Number of included observational studies	Estimates of effect (RCTs/CCTs only)	Conclusions (1‐2 lines from abstract)
Version 1 Demicheli 1999 (6 July 1999)	20	0	Clinical influenza TIV = 24% (95% CI 15% to 32%) LAIV = 13% (95% CI 5% to 20%) IAV = 40% (95% CI 13% to 59%) Laboratory‐confirmed influenza TIV = 68% (95% CI 49% to 79%) LAIV = 48% (95% CI 24% to 64%) IAV = no evidence	Influenza vaccines are effective in reducing serologically confirmed cases of influenza A. However, they are not as effective in reducing cases of clinical influenza. The use of WHO recommended vaccines appears to enhance their effectiveness in practice.
Version 2  Demicheli 2004 (24 May 2004)	25	0	Clinical influenza TIV = 25% (95% CI 13% to 35%) LAIV = 15% (95% CI 8% to 21%) IAV = 40% (95% CI 13% to 59%) Laboratory‐confirmed influenza TIV = 70% (95% CI 56% to 80%) LAIV = 48% (95% CI 24% to 64%) IAV = no evidence	Influenza vaccines are effective in reducing serologically confirmed cases of influenza. However, they are not as effective in reducing cases of clinical influenza and number of working days lost. Universal immunisation of healthy adults is not supported by the results of this review.
Version 3  Jefferson 2007 (16 February 2007)	38	10 (for harms only)	ILI TIV = 30% (95% CI 17% to 41%) LAIV = n.s. IAV = n.s. Influenza TIV = 80% (95% CI 56% to 81%) LAIV = 56% (95% CI 19% to 76%) IAV = no evidence	Influenza vaccines are effective in reducing cases of influenza, especially when the content accurately predicts circulating types and circulation is high. However, they are less effective in reducing cases of influenza‐like illness and have a modest impact on working days lost. There is insufficient evidence to assess their impact on complications. Whole‐virion monovalent vaccines may perform best in a pandemic.
Version 4  Jefferson 2010 (15 June 2010)	40	10 (for harms only)	ILI TIV = 30% (95% CI 17% to 41%) LAIV = n.s. IAV = n.s. Influenza TIV = 73% (95% CI 54% to 84%) LAIV = 56% (95% CI 19% to 76%) IAV = no evidence	Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.
Version 5  Jefferson 2014 (4 March 2014)	48	42	ILI TIV = 17% (95% CI 11% to 23%) LAIV = n.s. IAV = n.s. Influenza TIV = 63% (95% CI 55% to 69%) LAIV = 45% (95% CI 18% to 63%) IAV = n.s.	Influenza vaccines have a very modest effect in reducing influenza symptoms and working days lost in the general population, including pregnant women. No evidence of association between influenza vaccination and serious adverse events was found in the comparative studies considered in the review.

CCT: controlled clinical trial  CI: confidence interval  IAV: inactivated aerosol vaccines  ILI: influenza‐like illness  LAIV: live attenuated vaccines  n.s.: not statistically significant  RCT: randomised controlled trial  TIV: trivalent inactivated vaccines  WHO: World Health Organization    Versions 1 and 2

Effect estimates are from Comparison 02 (At least one vaccine recommended for that year versus placebo or other vaccine).

A clinically defined case was assumed as any case definition based on symptoms without further specification.

A clinically defined case (specific definition) was defined as:

'flu‐like illness' according to a predefined list of symptoms (including the Centers for Disease Control and Prevention case definition for surveillance);
'upper respiratory illness' according to a predefined list of symptoms.

When more than one definition was given for the same trial, data related to the more specific definition were included.

In Analysis 2.1 from versions 1 and 2, studies with both definitions are included.

Evidence about effectiveness of aerosol inactivated vaccine comes only from studies carried out during the 1968‐69 pandemic. From version 3 onwards, specific comparisons have been added.

Versions 3, 4, 5

Recommended vaccine matching circulating strains.

Version 5

Out of the 42 included observational studies, 8 assessed efficacy or effectiveness of vaccine, or both, when administered during pregnancy (6 cohort and 2 case‐control studies).

Version 6 (current)

In two new RCTs included in this version, vaccination was performed during pregnancy.

Regarding efficacy/effectiveness of TIV administered in general population, estimates assessed by applying random‐effects model were 16% (95% CI 9% to 23%) against ILI and 62% (95% CI 52% to 69%) against influenza, respectively.

In a previous interim unpublished update before the decision to stabilise the review was made, a further 16 observational studies were included: 3 case‐control and 2 cohort studies assessing the safety of influenza vaccine administration in general population, 10 cohort studies assessing the safety of influenza vaccine administration during pregnancy, and one cohort study assessing efficacy/effectiveness of the vaccine administration during pregnancy. In this 2016 updated review, we included a total of 160 studies (137 data sets), while we no longer updated searches for observational comparative studies.