The phase 4 trial will follow guidelines set out in the FDA guidance document discussing non-inferiority immunogenicity studies.

As additional methods to assess immunogenicity, an assessment of anti-NA by performing NA inhibition assays (NAI) and SVN assays will be added.

A recent trial supported the use of NAI and SVN assays as a correlate for protection in a trial of geriatric subjects. A healthy human challenge model showed that NAI is more predictive of protection and reduced disease than HAI

Fluad is an adjuvanted vaccine that has been shown to have a more broad-based or heterologous immunity than SD vaccine that is not adjuvanted. HD is also not adjuvanted.

Broad-based immunity is especially desirable for A/H3N2 immunity as that has had 4 different circulating strains in the last 5 years while circulating A/H1N1 has been the same for 5 years; i.e., vaccine mismatch is more likely with the A/H3N2 circulating strain. A/H3N2 is associated with the majority of influenza hospitalizations and death among the elderly.