ab Scheifele 2003.
| Methods | Randomised, double‐blind, placebo‐controlled, cross‐over trial assessing the association between exposure to the vaccine and onset of ORS in healthy adults with no previous history of ORS. The trial took place in 5 centres in Canada in September 2001 and was 1 of the conditions of registration of the vaccine, given the high incidence of ORS in the previous season. Centralised randomisation and allocation of centrally prepared, coded, opaque syringes took place. Cross‐over to either vaccine or placebo took place 5 to 7 days after the initial injection. | |
| Participants | The study included 651 adults with a mean age of 45. 17 participants are unaccounted for. | |
| Interventions | Fluviral (Shire) split trivalent containing A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), B/Victoria/504/2000 with additional splitting with Triton X‐100 splitting agent or saline placebo 0.5 mL. Additional splitting was necessary to test the hypothesis that large clumps of virions were responsible for the ORS seen the previous season. | |
| Outcomes | ORS (bilateral conjunctivitis; facial swelling ‐ lip, lid, or mouth; difficulty in breathing and chest discomfort, including cough, wheeze, dysphagia, or sore throat). Local signs/symptoms (redness, swelling, pain). Follow‐up was by phone interview at 24 hours and 6 days after vaccination. | |
| Notes | The authors conclude that (mild) ORS is significantly associated with split TIV immunisation (attributable risk 2.9%, 0.6 to 5.2). Other adverse effects associated with TIV are hoarseness (1.3%, 0.3 to 1.3) and coughing (1.2%, 0.2 to 1.6). The study is good quality, and the authors' conclusions are robust. It is extraordinary that no one has looked for these symptoms before, but it may be that the relatively young age of participants and the hypothesis contributed to this. Safety‐only study. Government funded |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Block randomisation |
| Allocation concealment (selection bias) | Low risk | Adequate |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Adequate |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Adequate |
| Summary assessment | Low risk | Adequate |