Re: Challenge: Where is the Evidence in Evidence-based Medicine?

On Jun 21, 7:19 pm, "Peter Moran" <pmo...@xxxxxxxxxxxxxxxx> wrote:
"PeterB" <p...@xxxxxxxxxxxxxxx> wrote in message

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On Jun 21, 4:00 am, "Peter Moran" <pmo...@xxxxxxxxxxxxxxxx> wrote:

"PeterB" <p...@xxxxxxxxxxxxxxx> wrote in message

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And there are several thousand deaths attributed to use of aspirin
each year, as one example. The point is that all marketing claims
regarding the cardiovascular benefit of that particular drug are not
supported by risk-adjusted data. In other words, there is no
epidemiology showing how many life years are gained against how many
life years are lost to the use of this drug for that purpose. Isn't
that correct?

PM No, unless we accept your blatant shifting of the goal-posts further
away
from what is reasonable and practical.

It is a yes or no question.  The challenge clearly requests this
data.  Either there is epidemiology showing how many life years are
gained against how many life years are lost to the use of this drug
for that purpose, or there is not.  Since you cannot provide such
data, you want to accuse me of moving the "goal posts," but that is
patently false.

PM You lie.  Your original request was "whether any controlled studies exist
to show that the drug in question saves more lives than it takes".  

Let's read the entire sentence, Dr. Doolittle. "If you choose to
respond, you should state the number of deaths per 1000 (or fraction
thereof) associated with each drug, whether any controlled studies
exist to show that the drug in question saves more lives than it
takes, *AND*, if the drug is not marketed as a "cure" for a life
threatening disease, which is typically the case, the justification
for its use in management of symptoms relative to such mortality and/
or morbidity risk BY STATING THE *DOCUMENTED* POPULATION LEVEL
BENEFIT."

While I did not use the term "life years" in the above quote, one
cannot state the *documented* population level benefit without doing
so.

I point out
that there are very numerous prospective controlled trials showing that for
many drugs, but you now want the same outcome expressed in "life years
gained or lost".   That is not only shifting the goal posts -- it is doing
so pointlessly and obstructively, simply to save face.

In other words, you cannot respond to the challenge by posting the
data asked for. But that isn't news. Again, to demonstrate a
population level benefit you would need to show such relative gains
compared to what happens without intervention. By stalling and
sputtering, all you have accomplished is to prove that the data
requested does not exist. Too bad you aren't honest enough to admit
it.

<Snipped by Dr. Doolittle -- something he couldn't respond to>

But
if you like, nominate the common use of drug for a particular purpose that
you think is non-evidence-based, and I will be happy to consider that with
you.

Aspirin for reduction of mortality risk from heart attack is a good
place to start.

PM OK The most recent and exhaustive  is the recent Lancet study --a
metaanalysis of the resuilts of 22 trials of aspirin use in 95000  persons
having either high risk ir low risk of vascular events including myocardial
infarction and stroke and followed up for a total of 700,000 person years..
The evidence of benefit in primary prevention is equivocal, but there is
evidence of fewer strokes and coronary events when aspirin is used as
secondary prevention.

This is not data consistent with what is requested in the challenge.

Quote --
 Aspirin in the primary and secondary prevention of vascular disease:
collaborative meta-analysis of individual participant data from randomised
trials.
Antithrombotic Trialists' (ATT) Collaboration, Baigent C, Blackwell L,
Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P,
Meade T, Patrono C, Roncaglioni MC, Zanchetti A.
Collaborators (39)
Collins R, Peto R, Hennekens C, Doll R, Bubes V, Buring J, Dushkesas R,
Gaziano M, Hennekens C, Brennan P, Meade T, Rudnicka A, Hansson L, Warnold
I, Zanchetti A, Avanzini F, Roncaglioni MC, Tognoni G, Buring J, Chown M,
Gaziano M, Hennekens C, Baigent C, Barton I, Baxter A, Bhala N, Blackwell L,
Boreham J, Bowman L, Buck G, Collins R, Emberson J, Godwin J, Halls H,
Holland L, Kearney P, Peto R, Reith C, Wilson K.

CTSU, Oxford University, Oxford, UK. colin.baig...@xxxxxxxxxxxxx

BACKGROUND: Low-dose aspirin is of definite and substantial net benefit for
many people who already have occlusive vascular disease. We have assessed
the benefits and risks in primary prevention. METHODS: We undertook
meta-analyses of serious vascular events (myocardial infarction, stroke, or
vascular death) and major bleeds in six primary prevention trials (95,000
individuals at low average risk, 660,000 person-years, 3554 serious vascular
events) and 16 secondary prevention trials (17,000 individuals at high
average risk, 43,000 person-years, 3306 serious vascular events) that
compared long-term aspirin versus control. We report intention-to-treat
analyses of first events during the scheduled treatment period. FINDINGS: In
the primary prevention trials, aspirin allocation yielded a 12% proportional
reduction in serious vascular events (0.51% aspirin vs 0.57% control per
year, p=0.0001), due mainly to a reduction of about a fifth in non-fatal
myocardial infarction (0.18%vs 0.23% per year, p<0.0001). The net effect on
stroke was not significant (0.20%vs 0.21% per year, p=0.4: haemorrhagic
stroke 0.04%vs 0.03%, p=0.05; other stroke 0.16%vs 0.18% per year, p=0.08).
Vascular mortality did not differ significantly (0.19%vs 0.19% per year,
p=0.7). Aspirin allocation increased major gastrointestinal and extracranial
bleeds (0.10%vs 0.07% per year, p<0.0001), and the main risk factors for
coronary disease were also risk factors for bleeding. In the secondary
prevention trials, aspirin allocation yielded a greater absolute reduction
in serious vascular events (6.7%vs 8.2% per year, p<0.0001), with a
non-significant increase in haemorrhagic stroke but reductions of about a
fifth in total stroke (2.08%vs 2.54% per year, p=0.002) and in coronary
events (4.3%vs 5.3% per year, p<0.0001). In both primary and secondary
prevention trials, the proportional reductions in the aggregate of all
serious vascular events seemed similar for men and women. INTERPRETATION: In
primary prevention without previous disease, aspirin is of uncertain net
value as the reduction in occlusive events needs to be weighed against any
increase in major bleeds. Further trials are in progress. FUNDING: UK
Medical Research Council, British Heart Foundation, Cancer Research UK, and
the European Community Biomed Programme.

So this contradicts earlier metananalyses such as this one, which showed
greater benefits.

1: Heart. 2001 Mar;85(3):265-71.

Aspirin for primary prevention of coronary heart disease: safety and
absolute benefit related to coronary risk derived from meta-analysis of
randomised trials.
Sanmuganathan PS, Ghahramani P, Jackson PR, Wallis EJ, Ramsay LE.
Clinical Pharmacology and Therapeutics, Royal Hallamshire Hospital, Glossop
Road, Sheffield S10 2JF, UK.

OBJECTIVE: To determine the cardiovascular and coronary risk thresholds at
which aspirin for primary prevention of coronary heart disease is safe and
worthwhile. DESIGN: Meta-analysis of four randomised controlled trials of
aspirin for primary prevention. The benefit and harm from aspirin treatment
were examined to determine: (1) the cardiovascular and coronary risk
threshold at which benefit in prevention of myocardial infarction exceeds
harm from significant bleeding; and (2) the absolute benefit expressed as
number needed to treat (NNT) for aspirin net of cerebral haemorrhage and
other bleeding complications at different levels of coronary risk. MAIN
OUTCOME MEASURES: Benefit from aspirin, expressed as reduction in
cardiovascular events, myocardial infarctions, strokes, and total mortality;
harm caused by aspirin in relation to significant bleeds and major
haemorrhages. RESULTS: Aspirin for primary prevention significantly reduced
all cardiovascular events by 15% (95% confidence interval (CI) 6% to 22%)
and myocardial infarctions by 30% (95% CI 21% to 38%), and non-significantly
reduced all deaths by 6% (95% CI -4% to 15%). Aspirin non-significantly
increased strokes by 6% (95% CI -24% to 9%) and significantly increased
bleeding complications by 69% (95% CI 38% to 107%). The risk of major
bleeding balanced the reduction in cardiovascular events when cardiovascular
event risk was 0.22%/year. The upper 95% CI for this estimate suggests that
harm from aspirin is unlikely to outweigh benefit provided the
cardiovascular event risk is 0.8%/year, equivalent to a coronary risk of
0.6%/year. At coronary event risk 1.5%/year, the five year NNT was 44 to
prevent a myocardial infarction, and 77 to prevent a myocardial infarction
net of any important bleeding complication. At coronary event risk 1%/year
the NNT was 67 to prevent a myocardial infarction, and 182 to prevent a
myocardial infarction net of important bleeding. CONCLUSIONS: Aspirin
treatment for primary prevention is safe and worthwhile at coronary event
risk >/= 1.5%/year; safe but of limited value at coronary risk 1%/year; and
unsafe at coronary event risk 0.5%/year. Advice on aspirin for primary
prevention requires formal accurate estimation of absolute coronary event
risk.

PM Other studies are underway, but we can conclude that the taking of
aspirin for primary prevention of cardiac events is neutral in terms of
overall mortality, but it probably does reduce the number of non-fatal
myocardial infarctions.   It seems to be of more definite benefit in
secondary prevention and its use there can be justified pending further
evidence.

These data show that the quality of the evidence is muted, which is
why the challenge requests data that is more meaningful. For
instance, a more broad review of the data by Kauffman showed that even
the benefit noted here is mostly ascribed to the first month following
a heart attack, with a rise in side-effect risk and declining
prospective benefit as time goes on. I could also point out that
these studies did not evaluate the issue of aspirin sensitivity in
those individuals who might be harmed by the drug (25% of patients,
IIRC), nor do they provide the population level benefit in
demographics likely to respond to promotion of aspirin as a preventive
for MI (data asked for in the challenge.) Such additional data would
have been responsive, but that is data you could not provide because
it doesn't exist. If you were honest, you would admit that it
doesn't exist.

Cite the highest quality of evidence available for
the widest demographic.  If you cannot provide data demonstrating life
years gained compared to life years lost, stating the particular
demographic affected, please be honest enough to acknowledge that
fact.

PM Acknowledge what fact?  

Just answer this question, Yes or No. Is it true that people who take
aspirin as a preventive for heart attack may, in fact, be killed by
the drug or have their lives shortened by it?

Medicine has to be conducted according to the
best evidence obtainable at the time.  

No, it doesn't. It has to be "conducted" according to a threshold of
evidence necessary to ensure that intervention is necessary, rather
than simply suggested. Of course, that is exactly what is NOT
happening at the moment, and that's the problem.

If the amount of investigation
available on this subject, with ruthless publication of both favourable and
unfavourable results does not support the idea that convenitonal medicine is
evidence-based to a high level, I don't know what will.  

A focus on population level control of disease using actual health
outcomes as the model for drug approval is the only rational
approach. Your support of ad hoc approvals based on surrrogate
endpoints (marker bending) that lead to use of most drugs on the list
in the challenge (and most drugs approved by FDA) is, based on
iatrogenic studies, a proven disaster.

Or do you wish to
challenge the conclusions that are being drawn becasue they don't meet your
latest conception of what it takes for medicine to be evidence-based?

As I've said often, science is about the *quality* of the evidence, a
distinction obviously lost on you.

PM I also don't think it has yet been common practice to advise aspirin for
primary prevention (i.e. persons without vascular disease), so that medical
practice has been following the evidence..

I have seen marketing for aspirin that is clearly misleading.

I have an idea I offered this once before.

Your talent for evasion must have really impressed me.

PM Want to do another one?  Want to test the evidence base for an
"alternative" claim?

You didn't respond with the data requested for any drug on the list,
or for aspirin, but seem to think you've earned a "star" for your
cap.
.

Relevant Pages

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