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Analysis And Comment Public health

Influenza vaccination: policy versus evidence

BMJ 2006; 333 doi: (Published 26 October 2006) Cite this as: BMJ 2006;333:912

Rapid Response:

Evidence hunters versus public health workers

Though there is little new in this review article (much is
reiterating previous publications by the same author [1-3]) and there are
significant gaps in the data he presents [4] the views of the author
require careful consideration. This is especially the case since the
article appeared at a time when flu vaccination campaigns are at their
peak in most European countries and the paper was interpreted by the media
in some countries as meaning that immunisation of the recognised risk
groups (the elderly, those with chronic diseases and health care workers)
was of no value.
We are really concerned about the conflicting views that sometimes exist
between "evidence hunters" and public health workers, even though we are
sure that a serene scientific discussion at the proper time can benefit
prevention policies.

The author considers two issues which we wish to comment on:

Effectiveness. "The heavy reliance on non-randomised studies (chiefly
cohort studies) especially in the elderly" ... "Either the absence of
evidence or the absence of convincing evidence on most of the effects at
the centre of campaign objectives". Placebo controlled randomised
controlled trials (RCTs) are one gold standard, but in fact RCT data are
available both on efficacy and effectiveness of flu inactivated vaccines,
including in the elderly and these indicate a protective effect. [2,4-6].
Nevertheless they are few trials as performing RCTs is difficult,
especially among particular higher risk populations. Even in the face of
incomplete knowledge, many people would consider it unethical to allow
high risk population groups to miss this opportunity of protecting
themselves in order to generate RCT data. [4] Observational studies may be
affected by bias and confounding but dealing with this is a large part of
the science of epidemiological research and many studies have attempted to
allow for it and still found protective effect. The bias also operates in
both directions with tendencies for better off groups to be immunised
counterbalanced by people with more severe underlying conditions being
immunised preferentially.[4] While unknown sources of bias and
confounding can never be absolutely ruled out, the large body of evidence
points to immunisation is protective against influenza or influenza like
illness). Even if it’s incomplete, the list provided by the Author in his
table 2 shows a majority of studies having positive (protective) outcomes,
especially regarding the efficacy/effectiveness in the elderly who remain
the principle target of the vaccination campaign in EU countries.
Estimated point efficacy range from 23% to 95% in this age group,
depending on the considered outcome and the study design. [1]

Safety. "The small and heterogeneous dataset on the safety of
inactivated vaccines" – Inactivated influenza vaccines are widely used
worldwide from decades and data on safety are available from routine
adverse event surveillance systems and focused studies. These sufficient
to assert that the current used inactivated vaccines are generally very
safe and are among the safest vaccines used in the targeted population
groups. The only serious enduring adverse effect being an increase of
Guillan-Barre syndrome in older recipients at a rate of around one per
million vaccine recipients. [7]

Hence it is important to underline that vaccination is the most
effective available measure to lessen the burden of seasonal influenza.
The current vaccination policy carried out in EU countries (mainly centred
on the selective vaccination of high risk groups such as elderly people
and persons with underlying chronic disease) is based on strong scientific
evidence. Even if such evidence does not fit the gold standard placebo-
controlled, double-blinded-RCT criteria “Lack of evidence” doesn’t
necessarily mean “evidence of lack of efficacy”. Not every scientific
question can be answered only by RCTs [8].

Nevertheless, this article shows that there is room for discussion
and further investigation and development in influenza vaccination. Better
and more universal vaccines are needed but presently the field efficacy of
influenza vaccines is not routinely estimated in the European Union. This
is an important gap given that the mix of circulating viruses and the
vaccine combination changes over time.[9] Also there is the issue of the
vaccination children vaccination, where the lack of knowledge is
particularly evident (and that’s the reason why no EU country has started
routine vaccination in children). Producing an expert independent opinion
on childhood vaccination is a priority in ECDC’s current (2006) work-plan
and developing a plan for routine monitoring of vaccine efficacy in the EU
is central in its proposed 2007 work-plan.

1. Jefferson T. Influenza vaccination: policy versus evidence. BMJ
2006; 333:912-5

2. Jefferson T, Rivetti D, Rivetti A, Rudin M, Pietranjoni C,
Demiceli V. Efficacy and effectiveness of influenza vaccines in elderly
person: a systematic review. Lancet 2005; 366: 1165-74

3. Rivetti D, Demicheli V, Di Pietrantonj C, Jefferson TO, Thomas R.
Vaccines for preventing influenza in the elderly. Cochrane Database Syst
Rev 2006; (3):CD004876.

4. Mangtani P, Hall AJ, Armstrong BE. Influenza vaccination: the case
for a gap in the evidence is flawed. BMJ Rapid response (Nov 7 2006)

5. Mazick A, Christiansen AH, Samuelsson S, Mølbak K. Using sentinel
surveillance to monitor effectiveness of influenza vaccine is feasible: A
pilot study in Denmark. Eurosurveillance 2006; 11 (10)

6. Centers for Disease Control and Prevention. Prevention and control
of influenza: recommendations of the Advisor Committee on Vaccination
Practices (ACIP). Morbid Mortal Wkly Rep 2006; 55:1-41.

7. WHO Influenza vaccines (WHO position paper): WER 2005; 80: 279-

8. Gordon C S Smith and Jill P Pell. Parachute use to prevent death
and major trauma related to gravitational challenge: systematic review of
randomised controlled trials. BMJ, 2003; 327: 1459-61.

9. Gerdil C. The annual production cycle for influenza vaccine.
Vaccine 2003; 21: 1776-9.

Competing interests:
None declared

Competing interests: No competing interests

13 November 2006
Angus Nicoll
Seconded National Expert
Pier Luigi Lopalco and Johan Giesecke
European Centre for Disease Prevention and Control