CONTROVERSY THAT
EXIST IN VACCINATION AND BENEFITS
Influenza vaccination may not be protecting the elderly
as much as we have thought.
You are listening to ReachMD XM 157, The Channel for
Medical Professionals. Welcome to the Clinicians Roundtable. I am your host,
Dr. Maurice Pickard and joining me today is Dr. Lisa Jackson. Dr. Jackson is
Research Professor of Epidemiology and adjunct research professor of medicine
at the University of Washington School of Public Health. She is also senior
investigator in the Group Health Center for Health Studies in Seattle,
Washington.
DR. MAURICE PICKARD:
Thank you Dr. Jackson for joining us.
DR. LISA JACKSON
Well thank you for having me.
DR. MAURICE PICKARD:
To begin with, could you describe the new findings recently
published on influenza vaccination in lancet.
DR. LISA JACKSON
Well, that study, my colleague, Michael Jackson and I
evaluated whether adults with pneumonia appeared to have been more or less
likely to have received influenza vaccine than adults without pneumonia. So,
the question we were attempting to address is whether influenza vaccine
appeared to reduce the risk of getting pneumonia among seniors and our study
was quite a bit different from studies that have been conducted in the past to
answer this question because we were couple of steps further I would say. For
one thing, we did not rely only on diagnosis codes to document that the seniors
had pneumonia, we actually had it validated by radiograph review or by clinical
chart review. Second, we actually reviewed the medical records for all our
cases of pneumonia and persons without pneumonia in order to determine whether
they had medical conditions such as heart disease and lung disease, and if they
did have severe those conditions whether they had limitations in ability to
walk or bathe themselves or eat, whether they had conditions such as dementia,
etc. Because in previous studies we have identified those factors as being
potentially important. And lastly, we used somewhat novel methodology where we
evaluated persons not only during influenza season, which is our main period of
interest when we are looking at influenza vaccine, but also before influenza
starts and that may seem sort of counterintuitive, but the purpose of looking
at people with pneumonia and those without pneumonia in the period before influenza
starts is to identify whether there are differences in the types of people, who
get vaccination compared to the people who do not get vaccination. Because
those types of differences could create bias and influence the results that we
would then find influenza season.
DR. MAURICE PICKARD:
So, doing this study differently were your results any
different than what most of our audience have kind of come to feel about
influenza vaccination in people over 65.
DR. LISA JACKSON
Yes, we found no evidence that influenza vaccination reduced
the risk of pneumonia, either all pneumonia, we included both outpatient cases
and hospitalized or when we restricted to looking at just hospitalized cases we
did not find any effect of vaccination and so forth. So, our study did not
confirm any benefit of influenza vaccination against pneumonia in this
population of seniors who are also restricted by the way to be persons without
immunocompromising conditions, so without serious cancer, without renal
failure, and things like that. So, it is a population of people that we would
expect to be able to benefit from the vaccine as the vaccine did produce the
benefit.
DR. MAURICE PICKARD:
You mentioned that you study not only during the influenza
season, but also at other times when you might not have the same results as far
as deaths in hospitalization. What happened in the other seasons?
DR. LISA JACKSON
Well, in the period before influenza season, we actually
found that persons who got an influenza vaccine were less likely to get
pneumonia than other persons. So, we know that can’t really be an effect of
the vaccination, because the only way the vaccine works is by preventing
influenza infection. If there is no influenza around, then the vaccine itself
is not doing anything. So, what we are seeing there is a difference in the
health status of people who tend to get vaccine as opposed to the people who
tend to decline vaccine and you know we have seen this kind of healthy user
bias or healthy vaccinee effect type of bias and other evaluations like hormone
replacement therapy and differences between people who take vitamins and those
who don't for example and so forth. So, this type of problem with influenza
vaccine analysis is common to other evaluations are preventive interventions
and therapeutic sensing in population. So, then what we did was we started out
and we had this difference between people that were due to their personal
characteristics of baseline health status and then we incorporated in our model
factors that we identified from the medical record review like lung disease and
severity of lung disease and whether they were on home oxygen for example for their
lung disease, heart disease and severity. These with certain medications and
we were able to adjust and control the difference, so that we eliminated the
differences between vaccine and vaccinated persons before influenza season by
including those factors in the analytic model. We then applied the same
factors to the analytic model during the influenza season and that's where we
found no effect during influenza season.
DR. MAURICE PICKARD:
Is it possible that people with cancer or heart disease go
to their doctors more often, take better care of themselves, more likely to get
vaccination and actually may be despite their comorbidity actually be fitter
and instead of looking at things like we are used to things that appear on our
laboratory chart or an x-ray, we should be looking at people who are frail or
fit. We are beginning to look at people with cardiovascular disease and
wondering why some of them do so well despite all their laboratory evidence to
the opposite and yet they may be fit and we should may be looking at activities
of daily living ADLs like you mentioned as really something that we should be
paying more attention to.
DR. LISA JACKSON
Yes, exactly, I mean the whole story is much more complex
than I think we have first appreciated. For one thing, seniors are incredibly
heterogenous group of people. One given 75-year-old can be preparing to climb <_____>
and other is bedridden. One person with heart disease as you say is doing very
well, really keeping up with their health, going to physical therapy and other
is not taking their medications and declining in health. You know it is very
difficult to completely account for such nuances and analysis, which is why we
feel like looking at this before influenza season is very important because
that's a very objective way of getting a handle on how big a problem we have
with these types of differences. The other thing is what we are interested in
is the fact that they are creating problems for us are not only things that are
related to the outcome in this case pneumonia, but also things that are related
to the likelihood of getting vaccine and we have tended to sort of not put as
much emphasis on factors that effect whether people get vaccinated, but you
have to have both of those things in order for the problem to occur on the
study. The factors that you mentioned you know inability to ambulate, may be
lack of cognitive function are clearly related to how likely a person is to
become vaccinated. I mean when you think about it, influenza vaccine is sort
of unusual intervention in that it comes on at certain applicable time, usually
sometimes during October vaccine is first available, 90% of vaccine is given
out within the next 4 weeks just about and so if you are seeing you had to be
certainly on the ball, you have to know when vaccine is coming out, you have to
know where to go to your doctor's office or the drug store whatever to get and
you have to have some motivation to do so. So any factors that both affect
your health and your ability to seek vaccination for yourself can interject a
bias into our evaluation.
DR. MAURICE PICKARD:
You brought up earlier about the immune response to
vaccination, we know the elderly don't respond to any kind of vaccination as
well as younger age groups, do you think we are giving the proper dose. There
has been some evidence that the dose might have to be 4 times as great to
somebody over 70 as it might be for say somebody who is 40.
DR. LISA JACKSON
Well, I think that's definitely an area that should be
pursued and I think you are exactly right. I think it's sort of legacy of the
past that we get the same dose to everyone over 3 years of age when there are
known substantial difference in immune response as persons get older. So, if
the higher dose were more effective, that would be a relative easy way to
improve effectiveness in seniors because we could use the vaccine that we
already have. Now, I would need to do some more evaluation to determine
whether that would in fact be beneficial, but the studies to date showing are
greater you know antibody serologic response to higher doses of vaccines suggest
that could be a promising avenue to pursue.
DR. MAURICE PICKARD:
If the frail don't get vaccinated, should we be looking at
other strategies? Certainly something that comes to mind is the very low rate
of vaccination and healthcare providers, who are taking care of these frail
people. Should there be some response to that? Should there be mandatory
vaccination in the workplace? Of course, with an opportunity for informed declination.
DR. LISA JACKSON
Well, I think that you know increasing the healthcare
provider and vaccine coverage is an area of active pursuit of thorough
professional agencies and the CDC, but to obtain a substantial overall impact
in seniors by reducing their risk of being exposed to influenza, so apart from
the ability to you know vaccinate them and protect then if they should come in
contact with influenza, then other approach is to you know sort of put them in
a bubble and prevent them from having a chance to come in contact with somebody
with influenza. You really need to know a lot more about how this influenza
virus circulate in the population at large, who are predominant spreaders, and
how it gets here from one place to another and what we suspect is that really
children, especially school age children, are one of the primary transmitting
agents of influenza and so that's why you know there are new recommendations
this year to vaccinate all children up to 18 years of age in order to dampen
the transmission in the overall population. It is little unclear what level of
coverage you need to achieve to get that kind of effect and what kind of
decrease if any you will see in the senior age groups as a result of more
widespread vaccination of children.
DR. MAURICE PICKARD:
Archives of internal medicine in 2005 commented on despite
tripling the amount of people, who are vaccinated between 1980 and 2001, the
number of deaths has not changed. Should the CDC step back and change their
recommendations as far as vaccinating the elderly.
DR. LISA JACKSON
Well that was a very nice study done by my colleague
<_____> Simonson and what that is showing is a lot of observational
studies, mini studies that simply compare people, who get vaccine and those who
don't have reported that the vaccinated group was at greatly lower risk of death
from any cause, 50% lower risk of death during the winter from any cause. If
that's true then as we give more and more vaccine to seniors, you would expect
to see a decrease in all cause mortality, which was not seen. The problem is
that those results are not plausible, but those results tell us is that there
is this problem about differences in people, who get the vaccine and those who
don't. So it is not getting the vaccine that reduces the risk of death by
half, is the fact that seniors, who are at much lower risk of death are more
likely to get the vaccine, but the true impact that influenza vaccine could
have on all deaths depends on what proportion of all deaths are caused by
influenza and we believe that although influenza is an important cause of
wintertime mortality, you know there are lots of other causes of mortality that
act throughout the year. So, during the winter, influenza probably causes only
about 5% of all deaths in seniors and that can vary a bit, but that's roughly
the proportion. So, if you had a vaccine that was perfect and prevented all
those deaths, you would expect to see a 5% decrease in all deaths as a result
of preventing the fraction due to influenza. So, really you could have a great
vaccine and you have no detectable change in death overtime, as you increase
vaccination rate because it is a sort of needle in haystack or signal to noise
problem, your true factors are relatively small proportion of the whole pie
that you are looking at would all cause death. So, I don't think the CDC needs
to change the recommendations on the basis of the fact that we haven't seen
notable declines in all cause mortality, but I do think that we need to
recognize that those studies reporting such fantastic effects against all cause
mortality are not due to true vaccine effects, but due to the healthy vaccinee
bias.
DR. MAURICE PICKARD:
You know today we have been talking about the controversy
that exist about the vaccination and its benefits that may be possibly been
overestimated, but certainly no one can deny that being vaccinated has helped
millions of people. I think we should continue as Dr. Jackson suggested to
investigate and to look at all the clinical research in this area as it unfolds
for us. I want to thank Dr. Jackson for being our guest today and we have been
discussing this controversy that exist about influenza vaccination.
I am your host, Dr. Maurice Pickard and you have been
listening to the Clinicians Roundtable on ReachMD, The Channel for Medical
Professionals. To listen to our on-demand library, visit us at reachmd.com.
Thank you for listening.
