Mark Struthers, I don't particularly like Cochrane Reviews because
they fetishize the prospective double-blind placebo controlled clinical
trial (PDBPCCT) to the point of methodolatry. PDBPCCT are good, and
necessary, but are not capable of demonstrating that a treatment is
useless, as for example homeopathy and are not ethical when the
intervention being tested is of known positive benefit, as for example flu
vaccine.
Healthy adults are the group at least risk from flu, yet the Cochrane
Review does show positive health effects from vaccination. Groups at
higher risk, such as the elderly show even greater benefits, with a 27%
reduction in hospitalizations and a 50% reduction in mortality. [1] I
would say these results on are nothing to sneeze at because they represent
713,872 person-seasons of intervention.
A trial such as this can not be done in a prospective blinded
fashion. It would be completely unethical to subject placebo recipients
to serious risks of harm and death from flu. Not surprisingly, when the
Cochrane Review looked at the issue of flu vaccination in the elderly they
reject all non-PDBPCCT and so they end up looking at only a total of 1,348
participants.[2] Not surprisingly this number is insufficient and the
Cochrane Review calls for trials which cannot be ethically done.
There are problems with non-PDBPCCTs for determining efficacy, there
may be unknown issues that bias the results.[3] That is why looking at
the science behind the intervention (as in Science Based Medicine) is more
important than blindly following the PDBPCCT mantra and throwing up our
hands when such data is not available. Clinicians who desire to treat
their patients ethically and responsibly have to make recommendations
without perfect knowledge. This is where understanding science is
important to the practice of medicine. Less then perfect knowledge does
not justify inaction, or worse, exploiting patients with made-up fantasy
treatments with no credible mechanism or prior plausibility.
We know what causes flu; the influenza virus. We know what prevents
people from getting illness when exposed to the influenza virus;
sufficient immune response to suppress viral replication. We know how to
trigger an immune response to flu virus antigens; vaccinate with viral
antigens. We have a reasonable understanding of how the immune system
works, and when good protection is observed in some groups, a level of
protection can be inferred in other groups. The Cochrane Review on flu
vaccination in children shows good protection.[4] We know that flu
spreads by human-human contacts. Children congregate in schools during
flu season. Children are a probable link between unrelated adults.
Vaccinating children for flu (which is effective) will likely reduce
transmission of flu to other groups. Are there PDBPCCT demonstrating
reduced transmission of flu to unrelated adults when children are
vaccinated? No, there are not and there will not be any because such
trials would be unethical, so ethical researchers won't run them, ethical
funding agencies won't fund them and ethical journals won't publish them.
Ethical clinicians will still vaccinate for flu because there is good (not
perfect) evidence that it does more good than harm.
What is the "theory" behind oscillococcinum and flu? A homeopath
imagined he saw the causal agent of flu, oscillating bacteria, in the
blood of flu victims (influenza virus is too small for his equipment to
have resolved), then later imagined he saw the same oscillating bacteria
spontaneously generate at high levels in duck heart and liver and reasoned
(???) that if he diluted this duck heart/liver by a factor of 10e200 (i.e.
1 gram in a sphere of water 1.3e49 light years in diameter (yes some
1.3e38 times the estimated diameter of the observable Universe)), and then
put drops of this magic water on sugar pills, that he would have something
that would magically cure flu.[5] I say magic because there is nothing in
physics, chemistry, physiology or derived through a rational thought
process that suggests a mechanism other than magic.
A recent review, somewhat more extensive than the Cochrane Review
does not support an increase of 1 chance per million for Guillain-Barr?
syndrome following flu vaccination. Background rates are somewhat less
than that and they say "[t]he evidence is inadequate to accept or reject a
causal relationship between influenza vaccine and GBS. [6]
As safe as you believe oscillococcinum to be, it can't be safer than
doing nothing. If there are no trials that demonstrate harm, there are
also no trials that demonstrate benefit and no trials that demonstrate
lack of harm. If you use science to determine oscillococcinum presents
with zero risk (because it is nothing but water), you have to also
conclude it has zero benefit (because it is nothing but water).
With zero expected benefit, other harms, although small, become
important. In the US there is about 1 traffic fatality per 100,000,000 km
driven. If 20 million customers each drive 5 km to obtain their
oscillococcinum, then likely one person will be killed. At $15 per
treatment, 20 million customers will spend $300 million. At $20/hr that
is ~94 lifetimes of work at 2,000 hours per year and 80 years of work.
On the other hand, $300 million could purchase enough gasoline to drive
several billion km, so ~40 drivers who purchase oscillococcinum instead
of gasoline will be saved from highway fatalities through impoverishment.
Since reading about oscillococcinum will deliver exactly the same
dose of duck heart/liver as ingesting it (that would be zero), people who
wish to get equivalent benefit from oscillococcinum with even less risk,
could simply purchase a subscription to BMJ and read this story online.
Since a subscription to BMJ costs $158, purchasing a single BMJ
subscription instead of oscillococcinum will save ~10 times more lives
through reduced highway fatalities. Some might consider it unseemly for
BMJ to promote subscriptions this way (Saves 10x more lives than
Oscillococcinum!!!), even though it is completely accurate. But surely
saving 10x more lives is more important than such sensibilities.
The major benefit from reading BMJ is lives saved through better
medical practices. The 'M' in BMJ does not stand for "Magic", it stands
for "Medical."
1. Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E.
Effectiveness of influenza vaccine in the community-dwelling elderly. N
Engl J Med. 2007 Oct 4;357(14):1373-81.
2. Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning
S, Thomas RE. Vaccines for preventing influenza in the elderly. Cochrane
Database Syst Rev. 2010 Feb 17;(2):CD004876.
3. Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA.
Mortality benefits of influenza vaccination in elderly people: an ongoing
controversy. Lancet Infect Dis. 2007 Oct;7(10):658-66.
4. Jefferson T, Rivetti A, Harnden A, Di Pietrantonj C, Demicheli V.
Vaccines for preventing influenza in healthy children. Cochrane Database
Syst Rev. 2008 Apr 16;(2):CD004879.
6. IOM (Institute of Medicine). 2011. Adverse Effects of Vaccines:
Evidence and Causality. Washington, DC: The National Academies Press. http://www.nap.edu/catalog.php?record_id=13164 (accessed 082611)
Competing interests:
None, but hope to get a commission on sales of BMJ subscriptions to prevent flu. ;)
Rapid Response:
Re:Re:Re:Yes exactly, Let us focus on the facts
Mark Struthers, I don't particularly like Cochrane Reviews because
they fetishize the prospective double-blind placebo controlled clinical
trial (PDBPCCT) to the point of methodolatry. PDBPCCT are good, and
necessary, but are not capable of demonstrating that a treatment is
useless, as for example homeopathy and are not ethical when the
intervention being tested is of known positive benefit, as for example flu
vaccine.
Healthy adults are the group at least risk from flu, yet the Cochrane
Review does show positive health effects from vaccination. Groups at
higher risk, such as the elderly show even greater benefits, with a 27%
reduction in hospitalizations and a 50% reduction in mortality. [1] I
would say these results on are nothing to sneeze at because they represent
713,872 person-seasons of intervention.
A trial such as this can not be done in a prospective blinded
fashion. It would be completely unethical to subject placebo recipients
to serious risks of harm and death from flu. Not surprisingly, when the
Cochrane Review looked at the issue of flu vaccination in the elderly they
reject all non-PDBPCCT and so they end up looking at only a total of 1,348
participants.[2] Not surprisingly this number is insufficient and the
Cochrane Review calls for trials which cannot be ethically done.
There are problems with non-PDBPCCTs for determining efficacy, there
may be unknown issues that bias the results.[3] That is why looking at
the science behind the intervention (as in Science Based Medicine) is more
important than blindly following the PDBPCCT mantra and throwing up our
hands when such data is not available. Clinicians who desire to treat
their patients ethically and responsibly have to make recommendations
without perfect knowledge. This is where understanding science is
important to the practice of medicine. Less then perfect knowledge does
not justify inaction, or worse, exploiting patients with made-up fantasy
treatments with no credible mechanism or prior plausibility.
We know what causes flu; the influenza virus. We know what prevents
people from getting illness when exposed to the influenza virus;
sufficient immune response to suppress viral replication. We know how to
trigger an immune response to flu virus antigens; vaccinate with viral
antigens. We have a reasonable understanding of how the immune system
works, and when good protection is observed in some groups, a level of
protection can be inferred in other groups. The Cochrane Review on flu
vaccination in children shows good protection.[4] We know that flu
spreads by human-human contacts. Children congregate in schools during
flu season. Children are a probable link between unrelated adults.
Vaccinating children for flu (which is effective) will likely reduce
transmission of flu to other groups. Are there PDBPCCT demonstrating
reduced transmission of flu to unrelated adults when children are
vaccinated? No, there are not and there will not be any because such
trials would be unethical, so ethical researchers won't run them, ethical
funding agencies won't fund them and ethical journals won't publish them.
Ethical clinicians will still vaccinate for flu because there is good (not
perfect) evidence that it does more good than harm.
What is the "theory" behind oscillococcinum and flu? A homeopath
imagined he saw the causal agent of flu, oscillating bacteria, in the
blood of flu victims (influenza virus is too small for his equipment to
have resolved), then later imagined he saw the same oscillating bacteria
spontaneously generate at high levels in duck heart and liver and reasoned
(???) that if he diluted this duck heart/liver by a factor of 10e200 (i.e.
1 gram in a sphere of water 1.3e49 light years in diameter (yes some
1.3e38 times the estimated diameter of the observable Universe)), and then
put drops of this magic water on sugar pills, that he would have something
that would magically cure flu.[5] I say magic because there is nothing in
physics, chemistry, physiology or derived through a rational thought
process that suggests a mechanism other than magic.
A recent review, somewhat more extensive than the Cochrane Review
does not support an increase of 1 chance per million for Guillain-Barr?
syndrome following flu vaccination. Background rates are somewhat less
than that and they say "[t]he evidence is inadequate to accept or reject a
causal relationship between influenza vaccine and GBS. [6]
As safe as you believe oscillococcinum to be, it can't be safer than
doing nothing. If there are no trials that demonstrate harm, there are
also no trials that demonstrate benefit and no trials that demonstrate
lack of harm. If you use science to determine oscillococcinum presents
with zero risk (because it is nothing but water), you have to also
conclude it has zero benefit (because it is nothing but water).
With zero expected benefit, other harms, although small, become
important. In the US there is about 1 traffic fatality per 100,000,000 km
driven. If 20 million customers each drive 5 km to obtain their
oscillococcinum, then likely one person will be killed. At $15 per
treatment, 20 million customers will spend $300 million. At $20/hr that
is ~94 lifetimes of work at 2,000 hours per year and 80 years of work.
On the other hand, $300 million could purchase enough gasoline to drive
several billion km, so ~40 drivers who purchase oscillococcinum instead
of gasoline will be saved from highway fatalities through impoverishment.
Since reading about oscillococcinum will deliver exactly the same
dose of duck heart/liver as ingesting it (that would be zero), people who
wish to get equivalent benefit from oscillococcinum with even less risk,
could simply purchase a subscription to BMJ and read this story online.
Since a subscription to BMJ costs $158, purchasing a single BMJ
subscription instead of oscillococcinum will save ~10 times more lives
through reduced highway fatalities. Some might consider it unseemly for
BMJ to promote subscriptions this way (Saves 10x more lives than
Oscillococcinum!!!), even though it is completely accurate. But surely
saving 10x more lives is more important than such sensibilities.
The major benefit from reading BMJ is lives saved through better
medical practices. The 'M' in BMJ does not stand for "Magic", it stands
for "Medical."
1. Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E.
Effectiveness of influenza vaccine in the community-dwelling elderly. N
Engl J Med. 2007 Oct 4;357(14):1373-81.
2. Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning
S, Thomas RE. Vaccines for preventing influenza in the elderly. Cochrane
Database Syst Rev. 2010 Feb 17;(2):CD004876.
3. Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA.
Mortality benefits of influenza vaccination in elderly people: an ongoing
controversy. Lancet Infect Dis. 2007 Oct;7(10):658-66.
4. Jefferson T, Rivetti A, Harnden A, Di Pietrantonj C, Demicheli V.
Vaccines for preventing influenza in healthy children. Cochrane Database
Syst Rev. 2008 Apr 16;(2):CD004879.
5. http://www.sciencebasedmedicine.org/index.php/ososillyococcinum-
and-other-flu-bits/ (accessed 083111)
6. IOM (Institute of Medicine). 2011. Adverse Effects of Vaccines:
Evidence and Causality. Washington, DC: The National Academies Press.
http://www.nap.edu/catalog.php?record_id=13164 (accessed 082611)
Competing interests: None, but hope to get a commission on sales of BMJ subscriptions to prevent flu. ;)