Table 2.

 Examples of discrepancy between results and conclusions

Study	Summary of results	Author’s conclusions and reviewer comments
Wongsurakiat 200431 (randomised placebo controlled trial in 125 adults and older people with COPD)	Significant reduction shown for total acute respiratory infections (ARI) with laboratory confirmation of influenza (RR 0.24, 95% CI 0.06 to 0.7; P=0.005) and influenza like illness (ILI) (0.34, 0.1 to 0.99, P=0.03). For acute exacerbations, difference not significant (0.92, 0.67 to 1.3, P=0.6). In this category 13/21 confirmed cases of influenza isolated, so, as for total ARI episodes (124 in vaccinated and 145 in placebo group), there was no difference between two intervention groups. This applies also to “probability of not being admitted to hospital related to ARI (P=0.2 by log rank test) and probability of not receiving mechanical ventilation related to ARI (P=0.4 by log rank test)”	Study was conducted over one year. Conclusions support recommendation of annual vaccination (one dose is sufficient in adults, as strong response has been observed). Authors note that vaccine effectiveness has been shown, even if it was possibly administered too late (in region where study was carried out peak incidence of influenza occurs usually in May). Comment: though authors state that effectiveness is shown for influenza related ARI only, and not influenza, they recommend vaccination for patients with COPD. This means recommending vaccine though it is not effective against influenza and acute exacerbations. In addition, lack of comment on community viral circulation and vaccine content and matching make verification of effectiveness against ARI impossible
Wilde 199932 (randomised trials on 264 healthy healthcare workers, three consecutive seasons)	Influenza infection (fourfold increase in haemagglutination inhibiting antibody against virus A or B between serum sample after immunisation and after epidemic). Efficacy against A (H3N2) virus estimated as 88% (47% to 97%, P=0.001); against B virus as 89% (14% to 99%, P=0.02). Authors’ conclusions about efficacy derived from cumulative data only. They apply effect measure and significance test (χ2) to cumulative data only. When applied to single comparisons, significance reached only for influenza A in 1992-3 (P=0.026). Days with respiratory illness (52 v 73 days; P=0.57; mean 0.29 (SD 0.68) days v 0.41 (SD 1.0) days, and absence due to illness (18 v 38 days; P=0.41, mean 0.1 (SD 0.35) days v 0.21 (SD 0.75) days no different among vaccinated and control group (three seasons’ cumulative data)	“In conclusion, influenza vaccine is effective in preventing serologically proven influenza infection in young, healthy hospital-based healthcare professionals and may reduce cumulative days of illness and absence. These data suggest that a policy of annual immunization with influenza vaccine in healthcare professionals will reduce influenza infections and can reduce associated illness.” Comment: influenza vaccination is recommended though outcomes are exclusively serological (surrogates) calculated in aggregate over three years (180 in intervention arms and 179 in three different control arms). Clinical outcomes are not significantly affected by vaccination
Carman 200033 (block randomised trial, 20 long term care hospitals)	All cause mortality less common in long term care where vaccination was offered (vaccination rate 13.6%; 102/749) than in those where it was not (vaccination rate 22.4%; 154/688). Crude OR 0.58, 0.40 to 0.84, P=0.014). Significance disappears after adjustment for degree of disability by Barthel scale, age, sex, vaccination of patients (0.61, 0.36 to 1.04, P=0.092). Virological surveillance (routine, from some symptomatic subjects, from some samples taken at death) did not show different frequency of viruses A or B isolates between two groups (culture and PCR)	“Vaccination of health-care workers was associated with a substantial decrease in mortality [for all causes] among patients. However, virological surveillance showed no associated decrease in non-fatal influenza infection in patients.” Comment: implausible conclusion with use of all cause mortality an outcome lacking specificity. Long list of confounders: biased reporting of autopsy sampling, trenchant conclusion despite apparent lack of effect on viral circulation, brief description of vaccine content or matching (in discussion), attrition in serology follow-up, possible selection bias of healthcare workers and patients, higher Barthel score in vaccinated arm. Once data were adjusted for Barthel score, age, and sex no effect was observed

RCT=randomised controlled trial, COPD=chronic obstructive pulmonary disease, RR=relative risk, OR=odds ratio, PCR=polymerase chain reaction.