aa Ohmit 2006.
| Methods | Multicentre, randomised, placebo‐controlled trial assessing effectiveness of both inactivated and live attenuated vaccines in preventing laboratory‐confirmed influenza in healthy adults aged below 50. | |
| Participants | For enrolment in the first study year (2004 to 2005), participants were recruited at 4 centres (2 university and 2 community sites) in Michigan. Participants were healthy adults between the ages of 18 and 46 years; those for whom influenza vaccination was recommended or contraindicated were excluded. In all 1247 were enrolled. | |
| Interventions | After informed consent was obtained and a first serum sample drawn, enrolled participants were randomly allocated to receive 1 dose of the following:
Identical syringes were filled on site with the inactivated vaccine or matching placebo (physiologic saline) by study nurses who were aware of the intervention assignments. The live attenuated influenza vaccine and matching placebo (physiologic saline) were preloaded in identical nasal spray devices by the manufacturer. Both vaccines were licenced for use in the 2004 to 2005 influenza season. Participants were randomised to vaccine or placebo in ratio of 5:1 using 4 site‐specific randomisation schedules, generated with the use of a random permuted block design with a block size of 12, in order to assign participants sequentially to receive a vaccine or a placebo as they enrolled. Since the trial was double‐blind, the participants and nurses who administered the study vaccine or placebo were unaware of whether the participant was receiving vaccine or placebo but were aware of the route of administration. Further serum samples were drawn 3 to 5 weeks after vaccine administration (as participants returned diary cards for local and systemic reactions, preseason sample) and during April to May 2005 (postseason sample). |
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| Outcomes | Local and systemic reactions within 7 days from immunisation (self filled questionnaires): fever, chills, runny nose or congestion, cough, sore throat, headache, muscle aches, weakness, abdominal pain, trouble breathing, red eyes, arm soreness, arm redness. Laboratory‐confirmed influenza. Active surveillance was maintained between November 2004 and April 2005. Participants were contacted by phone or email twice monthly. Symptomatic influenza was described as the presence of at least 1 respiratory symptom (cough or nasal congestion) and at least 1 systemic symptom (fever, feverishness, chills, body aches) occurring during influenza activity and at least 2 weeks after administration. Participants were instructed to contact study staff when at least 2 respiratory and systemic symptoms were observed. Throat swab specimens were collected from all participants with symptomatic influenza. Swabs were cultured for identification, and all isolates were typed according to strain using the fluorescence antibody assay and evaluated for antigenic relatedness to vaccine strains by the Influenza Branch at the CDC. In addition, all throat‐swab specimens obtained from participants with symptomatic influenza were tested at the University of Michigan by means of real‐time PCR assays using the TaqMan system (Applied Biosystems). All collected serum samples were tested with the haemagglutination‐inhibition assay, with the virus strains present in the vaccines used as antigens and against the circulating type A (H3N2) (A/California/07/2004‐like) virus and the circulating type B (B/Hawaii/33/ 2004‐like) virus (i.e. Victoria lineage not included in the vaccine). For effectiveness the following endpoints were used: On ITT population: laboratory‐confirmed influenza: culture‐positive or real‐time PCR‐positive, or both. On per‐protocol population: laboratory‐confirmed influenza: serologically positive; serologically or culture‐positive. |
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| Notes |
Intention‐to‐treat analysis: includes all enrolled participants who were randomly assigned to a vaccine or placebo group and who received a vaccine or a placebo (TIV = 513; placebo IM = 103; LAIV = 519; placebo IN = 103). Per‐protocol analyses: limited to participants having the postintervention (preseason) blood specimen collected at least 3 weeks after receipt of a vaccine or a placebo and at least 2 weeks before the beginning of local influenza activity (TIV = 367; placebo IM = 73; LAIV = 363; placebo IN = 73). Government funded |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Centralised automated sequence generation |
| Allocation concealment (selection bias) | Unclear risk | Allocation procedure not described |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Blinding apparently successful |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Active surveillance carried out Participants contacted bi monthly |
| Summary assessment | Unclear risk | Unclear |