A provocation that makes reflection
The article by Tom Jefferson, published in the British Medical Journal
the 28 October (1), is a lucid and intelligent provocation that shakes
the foundations of vaccination strategy against influenza and, at the same
time, suggests methods and solutions.
Jefferson’s analysis covers all aspects of complexity (often
underestimated) connected with the study of continuously mutating viruses such
as influenza viruses, and variable and unforeseeable epidemic. Jefferson
describes all methodological mistakes and inadequacy of studies made up to
now, to investigate similar matter and explains how these weakness can
distort results and lead to incorrect conclusions. From too short times
of observation, lack of randomisation and control groups, to the
unreliability of case definition (influenza like illness or true
The conclusions are that available evidence is weak and that benefits
expected from vaccine are unrealistic. Nevertheless, his call to make
randomized controlled trials as the only tool to assess vaccine efficacy,
raises ethical problems that are not easy to resolve. The vaccination of elderly
people is amply widespread and, even if there is lack of evidence (2), we
can’t exclude that vaccination could protect them from complications or
even save their lives. So, we can’t propose to suspend vaccination and
choose whom to randomize to vaccination to verify the effects on deaths.
A similar study could rather be proposed to assess the vaccination
efficacy in healthy children, because in most places in the world, as
for example in all Europe, children aren’t vaccinated. But hypothesis of
vaccination should rise from knowledge of burden of disease in childhood.
Knowledge that we don’t have in a convincing manner yet. Then there
remains the not insignificant problem of lack of efficacy of vaccines in
children, particularly under 2 years, as shown in a Cochrane review
published in Lancet in 2005 (3).
These results, together with the observation of cases and deaths also in
vaccinated children (4), lead us to believe that we need to make innovative
tools through new technologies which could perhaps derive from research in
progress from several drug industries to face the possible pandemic.
We must not forget that the techniques to make actual influenza vaccine
date back to the first half of the last century and they are unchanged. To
have more effective products is much more important for children and all
persons at increased risk of complications for influenza, apart from the
duty to study their immune response to vaccine stimulation, and strive for
To conclude, among the many stimuli offered by the analysis of Jefferson,
I would like to underline some that I have at heart. Above all, his recall
to rigour of scientific logic and to defend its supremacy as regards on
other logic, including vaccination strategies. Otherwise we risk to act
without possibility of knowing the results of our actions. In the second
place, we need (desperately, he says) to know efficacy of influenza
vaccine with studies more adequate than those that we have now:
studies that produce evidence. For the elderly, for the children and for
all persons at higher risk. In the end, we need to modify radically the
ways and the choices of research and of production of new vaccines.
Public health should not run after, same time breathlessly, the choices
and the decisions already taken by industry. It would be better to
coordinate the timelines of industry with the timelines of public health,
to allow the time and the way to identify priority of intervention in the
delicate matter of prevention and to allow evaluation of health impact and
appropriate use of vaccines in different contexts. Before or at the same
time as availability of new products.
Cultural Paediatrics Association, Italy
1) Jefferson T. Influenza vaccination: policy versus evidence. BMJ
2006; 333: 912-915.
2) Influenza-related mortality in the Italian elderly: no decline
associated with increasing vaccination coverage. Vaccine 2006; 24: 6468-
3) Jefferson T, Smith S, Demicheli V et al. Assessment of the efficacy
and effectiveness of influenza vaccine in healthy children; systematic
review. Lancet 2005; 365: 773-780.
4) Influenza associated deaths among children in the United States, 2003-
2004. N Engl J Med 2005; 353: 2559-2567.
Competing interests: No competing interests