Table 2. Meta-analyses on influenza vaccines for healthy adults.
| Villari13 | Jefferson2 | Osterholm9 | |
|---|---|---|---|
| |
|
|
|
| End date of the search (mm/yy) |
12/2002 |
06/2010 |
02/2011 |
| Participant’s age-range (years) |
15–65 |
16–65 |
All ages § |
| Included study designs |
RCTs |
RCTs |
RCTs (Obs.) § |
| Funding source |
Public institutions |
None |
Not-for-profit foundation |
| |
|
|
|
|
Laboratory-confirmed cases |
|
|
|
| - Overall ψ |
|
|
|
| N. data sets (sample) |
25 (18,920) |
23 (37,748) γ |
11 (35,215) § |
| Vaccine efficacy, % (95% CI) |
63 (13; 71) |
61 (52; 69) |
49 (16; 69) § |
| |
|
|
|
| - Live-Attenuated (LAV) |
|
|
|
| N. data sets (sample) |
7 (6661) Ω |
6 (8524) |
3 (3054) § |
| Vaccine efficacy, % (95% CI) |
53 (35; 66) |
62 (45; 73) |
32 (-2; 55) § |
| |
|
|
|
| - Parenteral Inactivated (PIV) |
|
|
|
| N. data sets (sample) |
18 (12,259) Ω |
17 (31,265) γ |
8 (32,161) § |
| Vaccine efficacy, % (95% CI) |
67 (55; 76) |
61 (48; 70) |
59 (51; 67) § |
| |
|
|
|
| - Aerosol Inactivated (AIV) |
|
|
|
| N. data sets (sample) |
0 (0) |
0 (0) |
0 (0) |
| Vaccine efficacy, % (95% CI) |
– |
– |
– |
| |
|
|
|
|
Clinically-confirmed cases |
|
|
|
| - Overall ψ |
|
|
|
| N. data sets (sample) |
49 (46,022) |
35 (34,898) γ |
NA |
| Vaccine efficacy, % (95% CI) |
22 (16; 28) |
19 (6; 30) |
NA |
| |
|
|
|
| - Live-Attenuated |
|
|
|
| N. data sets (sample) |
8 (13,964) Ω |
6 (12,688) |
NA |
| Vaccine efficacy, % (95% CI) |
15 (8; 23) |
10 (6; 16) |
NA |
| |
|
|
|
| - Parenteral Inactivated |
|
|
|
| N. data sets (sample) |
35 (30,121) Ω |
25 (25,065) |
NA |
| Vaccine efficacy, % (95% CI) |
23 (15; 30) |
20 (11; 29) |
NA |
| |
|
|
|
| - Aerosol Inactivated |
|
|
|
| N. data sets (sample) |
6 (1937) Ω |
4 (1674) |
NA |
| Vaccine efficacy, % (95% CI) |
55 (27; 72) |
42 (17; 60) |
NA |
| |
|
|
|
|
Mild/moderate adverse events |
|
|
|
| - Local harm* |
|
|
|
| N. data sets (sample) |
NA |
LAV: 3 (4921); PIV: 14 (6833); AIV: 3 (565) |
NA |
| Increase in Risk, % (95% CI) |
NA |
LAV: 56 (31; 87); PIV: 211 (108; 366); AIV: 15 (-12; 50) |
NA |
| |
|
|
|
| - Fever |
|
|
|
| N. data sets (sample) |
NA |
LAV: 3 (713); PIV: 8 (2775); AIV: 0 (0) |
NA |
| Increase in Risk, % (95% CI) |
NA |
LAV: 28 (-57; 279); PIV: 17 (-20; 72); AIV:– |
NA |
| |
|
|
|
| -Systemic, any |
|
|
|
| N. data sets (sample) |
NA |
LAV: 5 (1018); PIV: 8 (2603); AIV: 3 (565) |
NA |
| Increase in Risk, % (95% CI) |
NA |
LAV: 40 (-18; 138); PIV: 29 (1; 64); AIV: -17 (-46; 27) |
NA |
| |
|
|
|
|
Serious adverse events |
|
|
|
| N. studies (sample) |
NA |
NR** |
NA |
| Increase in Risk, % (95% CI) | NA | – | NA |
RCT, Randomized clinical trial; Obs., Observational studies; CI,Confidence Interval; NA,Not assessed; ψ Some meta-analyses only reported separated estimates for PIV or LAV. In these cases, the overall estimate of efficacy was derived combining PIV and LAV summary estimates using a generic inverse variance approach, with a random-effect method. * The outcome “Local harm” includes: local soreness (for PIV); local - any or highest symptom (for LAV and AIV). Ω Villari et al. included both PIV and LAV into a single meta-analysis. Thus, to avoid placebo data replication, they had to split several placebo arms that were in common for both PIV and LAV arms into the same study. If PIV and LAV would have been separately meta-analyzed, as in Jefferson et al. and Osterholm et al. studies, splitting placebo data was unneeded, and the overall totals would have been the followings: LCC-LAV n = 8761; LCC-PIV n = 14,359; CCC-LAV n = 16,064; CCC-PIV n = 32,433; AIV-CCC n = 2149). γ The total sample for PIV was recomputed due to an error (60 subjects missed into a placebo arm61) in PIV data extraction, and because several placebo arms had to split to avoid data replication (see the above point and the Table S2 for more details). ** Not reported: narrative review. § Observational studies on adults were searched but not found. Authors included only studies on vaccines licensed in USA, assessing RT-PCR or culture-confirmed influenza cases. Estimates on LAV from RCTs were re-elaborated from Table 3. All estimates reported in the table are referred to adults only.