The widely-held perception
that the influenza vaccination reduces overall mortality risk in the elderly
does not withstand careful scrutiny, according to researchers in Alberta. The vaccine does
confer protection against specific strains of influenza, but its overall benefit
appears to have been exaggerated by a number of observational studies that found
a very large reduction in all-cause mortality among elderly patients who had
been vaccinated.
The results will appear in
the first issue for September of the American Journal of Respiratory
Medicine, a publication of the American Thoracic
Society.
The study included more than 700 matched elderly subjects, half of whom
had taken the vaccine and half of whom had not. After controlling for a wealth
of variables that were largely not considered or simply not available in
previous studies that reported the mortality benefit, the researchers concluded
that any such benefit “if
present at all, was very small and statistically non-significant and may simply be a
healthy-user artifact that they were unable to
identify.”
“While such a reduction in
all-cause mortality would have been impressive, these mortality benefits are
likely implausible. Previous studies were likely measuring a benefit not
directly attributable to the vaccine itself, but something specific to the
individuals who were vaccinated—a healthy-user benefit or frailty bias,” said
Dean T. Eurich,Ph.D. clinical epidemiologist and assistant professor at the
School of Public Health at the University of Alberta. “Over the last two decades in the
United Sates, even while vaccination rates among the elderly have increased from
15 to 65 percent, there has been no commensurate decrease in hospital admissions
or all-cause mortality. Further, only about 10 percent of winter-time deaths in
the United
States are attributable to influenza, thus to
suggest that the vaccine can reduce 50 percent of deaths from all causes is
implausible in our opinion.”
Dr. Eurich and colleagues
hypothesized that if the healthy-user effect was responsible for the mortality
benefit associated with influenza vaccination seen in observational studies,
there should also be a significant mortality benefit present during the
“off-season”.
To determine whether the
observed mortality benefits were actually an effect of the flu vaccine,
therefore, they analyzed clinical data from records of all six hospitals in the
Capital Health region in Alberta. In total, they analyzed data from 704
patients 65 years of age and older who were admitted to the hospital for
community-acquired pneumonia during non-flu season, half of whom had been
vaccinated, and half of whom had not. Each vaccinated patient was matched to a
non-vaccinated patient with similar demographics, medical conditions, functional
status, smoking status and current prescription medications.
In examining in-hospital
mortality, they found that 12 percent of the patients died overall, with a
median length of stay of approximately eight days. While analysis with a model
similar to that employed by past observational studies indeed showed that
patients who were vaccinated were about half as likely to die as unvaccinated
patients, a finding consistent with other studies, they found a striking
difference after adjusting for detailed clinical information, such as the need
for an advanced directive, pneumococcal immunizations, socioeconomic status, as
well as sex, smoking, functional status and severity of disease. Controlling for
those variables reduced the relative risk of death to a statistically
non-significant 19 percent.
Further analyses that
included more than 3,400 patients from the same cohort did not significantly
alter the relative risk. The researchers concluded that there was adifficult to capture healthy-user effect
among vaccinated patients.
“The healthy-user effect is seen in what doctors often refer to as
their ‘good’ patients— patients who are well-informed about their health, who
exercise regularly, do not smoke or have quit, drink only in moderation, watch
what they eat, come in regularly for health maintenance visits and disease
screenings, take their medications exactly as prescribed— and quite religiously
get vaccinated each year so as to stay healthy. Such attributes are almost
impossible to capture in large scale studies using administrative
databases,”
said principal investigator Sumit Majumdar, M.D., M.P.H., associate professor in the Faculty of Medicine & Dentistry
at the University of Alberta.
The finding has broad
implications:
- For
patients: People with chronic respiratory diseases such as
chronic obstructive pulmonary disease, immuno-compromised patients, healthcare
workers, family members or friends who take care of elderly patients and others
with greater exposure or susceptibility to the influenza virus should still be
vaccinated. “But you also need to take care of yourself. Everyone can reduce their risk by taking
simple precautions,” says Dr. Majumdar. “Wash your hands, avoid sick kids and
hospitals during flu season, consider antiviral agents for prophylaxis and tell
your doctor as soon as you feel unwell because there is still a chance to
decrease symptoms and prevent hospitalization if you get sick— because flu
vaccine is not as effective as people have been thinking it is.” - For vaccine developers: Previously reported mortality reductions
are clearly inflated and erroneous–this may have stifled efforts at developing
newer and better vaccines especially for use in the elderly.
- For policy makers: Efforts directed at “improving quality of
care” are better directed at where the evidence is, such as hand-washing,
vaccinating children and vaccinating healthcare workers.
Finally, Dr.
Majumder said, the findings are a reminder to researchers that “the healthy-user
effect is everywhere you don’t want it to be.”
News release from
American Thoracic Society on September 1, 2008.