cc
End of Evidence-Based Medicine." >> The title of the talk is "The
I actually mean it. AIt's difficult for me to givere
this talk every time, because I'm an advocate of
evidence-based medicine.
I've been teaching
evidence-based medicine conversation is problematic
for me. But it turns out that it also is
something that's interesting to people.
If I had said evidence-based
years, or has reached maturity, or anything like that, we'd have
half the crowd today. People like to go to funerals.
So that explains why you're all here.
There's no way in any of this research to have any sort of
financial disclosure, it would
to disclose. be nice but there is nothing
that there are two principles *Tof evidence-based medicine.s
The first one is that the better
the decision. theSo that's one fundamentaldent
principle of evidence-based medicine.
It turns out that if you ask
of evidence-based medicine, pthey may say this, and thenk
they will stop. They will think that this is the
only principle of evidence-based
and this is one of them. medicine, but there are two,
a problem with this one. And I presume nobody has
And the second principle of evidence-based medicine is that*
the evidence alone is never sufficient to completely inform
a clinical decision.
aspects of the complexity of the But one has to incorporate other
the context of the patient's human experience, like
and preferences of the experience, and the values
with a decision that actually informed makes sense.oming up
In other words, if you were to train monkeys to analyze
and critically appraise the literature and apply every
randomized trial in a strict
major harm. waAnd the monkeys will beuse
evidence-based. *So there's something to
expertise that needs to be
a graph here, in order to make incorporated as well, this is
decisions, there's got to be good high quality clinical
to incorporate what we know from some expertise required
with the patient and what the tpatient's goals for life and
health are. This expertise will vary across
clinicians. And hopefully in our teaching
programs, as we're training clinicians to become
more effective, we're paying
*Now, I'm going to tell you attention to those issues.
about evidence-based medicine since we are in a funeral,
it is appropriate to talk about the life of the dead individual.
And we tend to do in funerals,
and the beautiful things. is wSo I'm going to do that.ves
Anybody know who this guy is? Feinstein, very good.
Feinstein is a very controversial figure in the
history of research,
and we can argue about whether but the major contribution,
for the tobacco industry, hibut I think his majorwas
contribution was that he
epidemiology, and the idea that devyou can use quantitativecal
methodology and apply it
That you can quantify tinferences, that you can.
quantify diagnostic criteria. And the idea of Clinimetrics.
He was very good with words and he always created words
to describe what he was saying. *Now, I want to stop at this
point, because it's really funny
myself bounce on the back end, for me, from here, to listen to
distance conversation swith my parents in Peru.
It's exactly the same sound.
microphone in any way, Are you bothered by my
Okay, so I just have to cope or is it working okay for you?
*So this is Feinstein, and arguably, he's one of the people
that starts laying out the
evidence-based medicine. foundation for what became
Guess? Who's this guy?
And David Sackett is a guy David Sackett.
scientist, nephrologist, that went from being a basic
to then being one of the a public health officer,
epidemiology department at youngest chairs of a clinical
and a big advocate of the use of evidence-based medicine in,
clinical practice, particularly starting from randomized trials,
which ended up being a source of discrepancy between these
two.
that randomized trials could Feinstein quickly went to think
for clinical practice. actually be quite useful
Tom Chalmers. >> Yes, Tom Chalmers.
Tom Chalmers, from Harvard, a big advocate, again, of using
randomized trials.
coined the expression that if you have a new technology,
you want to randomize the first patient exposed to it,
and then move on until you learn
works or not. And also a big proponent
of systemic reviews and meta analysis.
( hums "Jeopardy" theme ) So, Ian Chalmers, no relation
to Tom Chalmers, is an
heard the call from Archie Cochrane, traditional
epidemiologist from the UK, to summarize what we know
about research and created
which then evolved into the Cochrane Collaboration,
which is a large, multinational volunteer organization
that summarizes what we know
and more recently about in observations, tests, andls,
diagnostic studies. *So you can see the evolution
of knowledge being summarized and synthesized.
Yes, Brian Haynes.
You know people. You guys get out, that's good.
McMaster University. Brian Haynes also from
he did is he harnessed the value It's interesting, because what
the evolution of Medline of the Internet and
can we now bring this and information that's beingokay
produced at dizzying speeds,
of clinicians. and put it into the fingertips
the journal of evidence-based medicine, services that are now
available, that are now services
up-to-date, are things that byhe has developed, piloted,ns
or has had his hands on at
*I'm going to show you some poone last picture.lopment.
Yes, Gordon Guyatt. And so, Gordon Guyatt
is a guy that in 1990 took over the residency program
at McMaster University, and sent
saying, look, enough of this out a letter to the residents
that I tell you what to do expert-based teaching here
to do scientific medicine. sort of thing, now we're going
And so in everybody being very It got everybody really upset.
better label for this, and then went for evidence-based medicine
and published it for
the ACP Journal Club editorial. *There's debate about whether
this account is true, but I'm sticking to it.
There's a very distinguished
epidemiologist, who claims epidemiologist, an American
And the way I think it has been resolved, although not to this
latter individual's satisfaction
an NHS official, who remembers is through a UK--
in Washington, D.C., being in a taxi cab
told David Sackett, "You know, when Gordon Guyatt
great term for this thing that we've been struggling.
I'm going to call this
It is interesting that perhaps* evidence-based medicine."
proof that Gordon tcame up with it and told Davey
about it is from somebody recalling it from a taxi cab
in Washington.
And this is 17 years ago. ThaSo this funeral is for aen.
teenager. So it's a 17-year-old thing,
so it's been evolving since its inception.
*But where are we now? I would put forward that this is
the end of evidence-based medicine, because the
evidence base, the research evidence that we can use
to guide our clinical decisions is corrupt.
And I'm going to show some
And corruption is of a magnitude examples of such corruption.
evidence-based practice. such that it cannot support
I think another reason But that's not enough.
of evidence-based medicine why it's the end
patient preferences is are being ignored.ly,
We were having a discussion coming here as to why that
might be the case, but
they're being ignored. the fundamental thing is,
it's the end of this thing. Now I could stop at this point,*
and take questions, but I think that would be a little
disappointing, so let's go
of the corruption through of the evidence.e issue
*Most of the effort in evidence-based practice has been
looking at, can we understand where bias is introduced
in clinical research. So of those of you who have
gone through courses
the attention has been, to how do you ascertain bias?ch,
How do you look for bias
So for instance in randomized trials, how is a randomized
sequence generated, where there was allocation concealment,
who was blinded, and to what
of follow-up. exAnd we recently contributedss
to this evidence-base by pointing out clinical trials
stopped early for benefit are likely to produce
an overestimation of the treatment effect.
*So individuals that know
look at the paper and look critical appraisal can sit down,
the extent of bias, or the for these things and say yes,
is significant, or is moderate, potor is small, or is absent.dy
This idea of clinical trial stopped early for benefit
introducing bias has become completely illustrated
more recently with the example
*Here's a trial by published oin the New England Journal of.
Medicine in 1999, in which
between those patients there was an enormous difference
cardiac surgery, that were going to undergo
and were found to be at risk had a stress echocardiogram
a beta blocker. The alternative arm just
received standard of care.
in outcomes with 100% reduction in the risk of nonfatal MI,e
and 80% reduction in the risk of cardiac death.
In other words, perioperative beta blockers cured MI.
( light laughter )
nobody questioned the fact Interestingly enough,
to be a little big. And decided that this will be
a great target
And many institutions, including for quality improvement.
major efforts put forward the Mayto make sure thatave been
every patient at risk that
receive beta blockers is undervery promptly.surgery
*Now we conducted a systematic review of meta analysis of the
evidence, and then we produced
The red line represents the community of evidence in support
of the use of beta blockers,
until the trial, and you can see it's fairly flat
And then it stays essentially fairly flat, or coming down, as
the clinical trials accumulate. Since we conducted that review,
two additional trials were published.
*One called POBBLE and the other one called DIPOM,
which were very large trials
And the whole estimate for the in and of themselves.
influence approached null. reduction in cardiovascular
wide enough that still *But the confidences were
Pretty far from being so sure that you have to implement this,
that you would do quality improvement on this measure.
The one trial has since been
We had a chance to participant completed.
8,000 patients randomized to perioperative beta blockers
were the control. And the trial in fact,
confirmed a reduction in
in the order of 30%. the risk of coronary events,
*But also, where it is powered Noenough to be able to show%.
an increase in the risk of death
So you get peri-operative anbeta blockers.e.
Yes, you prevent the chance of peri-operative heart attacks.
But you will be more likely to die or have a stroke.
( light laughter )
at risk of coronary event So makeundergoing surgeryatient
gets their beta blockers, because that would be
a good quality improvement. *So here's an example where we
were misled by a clinical trial,
benefit, and not only overestimated the treatment
effect, but also hid the fact that this intervention
could potentially produce harm. But that's bias.
*And bias is easy because
on the paper. It's there for you to see it.
With the right training,
It's not too difficult. If that was our only problem,
we would be okay. *So what is our next problem?
This is our next problem. Anybody have a problem
with this?
not be objective? People do it, right?
It's because science
Scientists are not objective. isNow why would scientists.
not be objective? I mean, maybe you are
not objective but my science
Right? is pretty objective.
( laughter ) I love my ideas.
In fact, I have to make you Now I nlove my ideas, ideas.
because you may, in fact, be
So I need to have successful in charge of my future, right?
successful ideas, I will have academic success.
I have to not only believe that,
that you believe that. I have to make sure
you understand that my findings I are critically important.at
My research is the only research
It's the only research that matters.
in the New York Times. that should be highlighted
high quality. I'm rigorous as rigorous comes,
and you should believe
Because I need my peer review funding, and you're my peers.
And so I need to make sure that money put on my career
and my research is money well spent.
*So this is enough to push me
the way I present myself, ithe way I present my resultsg
to you, the way I present my results in papers
and publications, because I need you to believe this.
This is what we sometimes call
right? putting your best foot forward,
people to do exactly that. In fact, we may have mentored
This is a survey of almost *Now, issues and problems.
in top journals in 2003, 200 diabetes trials published
And we found that when you look at things that are predictors
of bias, they're infrequently reported, 11% report
allocation concealment, half of them or less reported
blinding of different groups, 71% reported
on loss of follow-up. And then we looked at
which of the trials,
the apparent highest when you read them, have
In other words, all these things are present.
And what we found as
for-profit patient-oriented majparallel trials,re
so those trials funded
have the better quality bwhen you assess themt
on critical appraisal tools when they're published.
*So the ones that are putting
are the ones that are funded their best food forward
Okay? Here's a systematic review.
I participated in this
We looked at both drugs and devices, and we looked to see
association between funding source and the mapping
to the treatment effect.
for-profit funding sources And we found that on average
favoring their product. *Now, there's a numberls
of explanations for this. Maybe for-profit funding sources
are more careful with their money, and they're able to
actually fund trials that they
They've done their homework. think are going to be positive.
But as you know from the bottom is that this is adjusted
for the quality of studies
So they're really, really good and adjusted to sample size.
in some way. at selecting the winners
There may be alternative ones. Well, that's one explanation.
point of evidence. *Let me show you another
for the product, or device, or drug that's being evaluated
in randomized trial.
They looked for a sentence Als-Neilson did this in JAMA.
and conclusion of section like tof the studies,ussion
"The experimental intervention
of choice." So one of these very exuberant,
positive things that you will say in a study, and then look at
the predictors of ending up with a conclusion like that.
And this was from 370 trials
over a 30-year period of time, from 25 Cochrane reviews
And what he found was that 18% in high impact journals.
was associated, I think fairly strongly,
you will agree I hope, with having that sort of sentence.
But I just show you, they got bigger treatment effects.
Why would they not conclude this sort of thing?
Well, except that this
for treatment effect, and the magnitude of the adverse effect.
So this is independent
benefits comparative benefits of of the control group. the
And then, this is now very much* outdated, but this is the best
I can find. There's a major flow,
as you well know. There's a major flow of academic
research from academia
So remember my ideas to industry.
That was because of my own and how much I love them?
and my ability to survive. personal career
of a large company whose future is riding on the results of this
particular research project?
the HDL, the drug that was You may all recall that when
was not found to be associated supposed to elevate HDL
a whole Pfizer plant closed and people lost their jobs.
So it's just not about my career
and how much I love them. This is a real problem
when research results modify the livelihood
of individuals. *So, then, am I saying that
for-profit research is fraudulent?
No. Am I saying that I'm introducing
a mechanism to cause bias?
that's easy to pick up. So what other mechanisms
are present there to actually make things look better?
And I'm going to call that spin.
for some groups, so I'm going to give you an example of spin.*
I'm from Peru!
And in Peru, soccer is big. I'm Soccer is huge.ica.
Now it's actually a problem for Peru that soccer is huge,
because we haven't had a team in the World Cup since 1982.
( laughter )
doesn't deliver, a country So when your biggest sport
That's how I would characterize cour sports situation in Peru..
But this is spin. So we play against, say, Brazil.
And say, Brazil puts in five goals against us.
And the coach goes on TV
of my team. and sayMy team delivered. proud
It was outstanding work." You know, "I'm particularly
proud of my goal keeper.
That's spin, all right? HSo when you know the truth
is over here, and you try to create this alternative
explanation or alternative view of the truth.
So let's see how that plays out* in research.
Here's a trial. It's a high quality RCT.
If do all the assessment for
randomized trial, 1700 patients with hypertensive
diabetic nephropathy. Using-- pain, versus-- blocker.
Almost three years of follow-up.
from the conclusion. This is lifted directly
which is a receptor blocker, Treatment with irbesartan,
of the primary composite it was associated with a risk
than that of the group. I've given you, the P value
has a bunch of zeros, and I'm giving you what that
composite endpoint was. Doubling of the creatinine
level, onset of end stage renal disease,
or death from any cause.
are clinicians here, *Now, how many people
All right, so they tend to be distributed in the back
of the room.
I wonder if any of you Okay.
of how they would explain this would like to give me an example
( laughter ) to Mrs. Jones?
And I may actually go and have ( no responses )
say anything quickly. a( laughter )ou don't
Anybody?
is likely to suffer... >> Only one-quarter of her
I suspect, if you actually ( laughter )
you don't talk to them see patients, that's the thing,
Seriously, what would you say? like that.
Say you talk about research How with your patients.his?
How would you say?
you know, and she happens to Give her a PhD in statistics,
and you're going to explain this have diabetes and hypertension,
What would you say? At this point, she's feeling
very uncomfortable, because you're being silent for awhile.
( laughter )
( inaudible ) >> Four people are going to have
the problem, if I give you
Thank you doctor. Now I understand, it's better.
So what is it I'm going to
Getting bad kidney disease, avor dying.g?
Wow, so this is a drug
That's wonderful. thatAnd so, that's exactlyger.
the intent, right?
a 23% reduction of the risk of dying, or having bad kidneys,
or having a distortion
in the laboratory. in your creatinine level
results, the doubling *But of the creatinine andtual
the end stage renal disease goes with that 23% reduction.
But what about the mortality? It's kind of not going with it.
Right?
You told me I was going to live Soforever, right?n--
And this drug may or may not
on mortality. The point estimate is on
the wrong side of the, right? It's actually going
in the wrong direction. So composite endpoints can
actually hide this important
give you an average difthat doesn't in fact applyt,
to each of the components.
critical if the components *And this is particularly
of patient importance. do not have the same degree
to feel when I die. So I don't know if I feeling
the elevation of creatinine,
not going to feel like dying, mayat least not to my family.t's
So that's kind of weird,
But this is one mechanism by which you get a sense
that this is going to cause a bigger impact
than you think you will.
Of the clinicians in the room, Now this is actually a fun one.*
if somebody comes in with an exacerbation of emphysema
or bronchitis to the emergency room,
would you give them steroids? Pretty much everybody.
Anybody who would not give steroids to somebody
with COPD exacerbation? Okay, so pretty much everybody.
The fundamental study-- Yes?
( inaudible ) >> Current recommendations are
to use steroids only if you're
They recommend that if you're above a certain level,
that steroids have no benefit.
So, ughh, I'm in bad shape! You're going to give me
some steroids.
bronchial dilaters. >> All right, so we have
a nuanced answer. Other people said do it.
And it's interesting, because the fundamental trial that
started that tendency was published in the New England
Journal of Medicine in 1999.
so they're all on the side These are the results,
And the composite endpoint of benefit.
for mechanical ventilation, a readmission to the hospital
or requiring steroids.
as I'm going to show you, the number of endpoints,
keep in mind that the steroid arm was double the size,
the number of endpoints is actually very small
to drive policy.
and three deaths in the other. You had two deaths in one arm
of evidence. That's not a whole lot
in one arm. ThrThree people in the other.ion
Again, one of the arms
Readmission, six and five. was bigger.
in this trial Sois about requiring steroids.e
In other words, give steroids to the patient,
because if you don't, they are going to need it.
( laughter )
That's what this trial showed. Right?
steroids, just in case So we all started giving
So these composite endpoints they will need it later.
*This is my favorite, because kind of hide this stuff.
So everybody knows that the UKPDS is the largest of each
trial, about 4,000 patients followed for ten years.
And it showed that intensive
the risk of any diabetes-related glycemic control reduces
This is diabetes-related complication.
in the intensive therapy arm complications, and 35%
38% of the conservative arm had these events.
The difference was 3.2%,
So what does that actually mean? P value .029.
had 14 endpoints in them, Well,that included death,oint
and cataract extraction.
So it's a little bit different, right, the experiments there?
Amputation, stroke. That's kind of relevant,
Cataract extraction?
as the trial progressed, And it's interesting because
no difference, no difference, they wno difference.thing,
So they kept adding components
Right? to the composite endpoint.
I said there are 14. And so, you notice there are 13,
a blank spot, because the last component they added wass
photocoagulation of the eye,
where you laser which the back of the eyehe eye
to prevent blindness. And of that difference of 3.2%
between the two arms
photocoagulation after ten years of therapy,
So the last component added to this composite endpoint
captured the majority of the impact of this treatment.
*Now does anybody here treat diabetics so this extent
to prevent photocoagulation?
we're preventing all these No, we all think that
*So we've tried to contribute diabetes complications.
In order to take the spin out of these things,
these are the questions that we ask you to ask.
Is there a big gradient of patient importance,
death in cataracts? Is there a big range of
treatment effects, you know,
of treatment effect like we saw with the nephropathy example?
Is there a gradient of events,
the steroid example? like we saw with
your confidence in the composite And when you see big gradients*
and you should be focusing your attention on the effective
on the components.
that all the components will be so underpowered and imprecise
that you may not be able
from this study, to draw any conclusions
Which begs the question why did we go to composite endpoints
in the first place? And the reason is we needed
a P value less than .05.
fundamentally wrong around how we're doing this.
*Now, the cardiologists
the cardiologists have been arevery good at adoptingause
evidence-based medicine,
of evidence tyranny, where to almost to the point
and the trial has not showed it, if the trial has not occurred
If the trial shows it, I'm not doing it.
Right? I'm doing it.
In their trials, we looked at Ther242 cardiologist trials,on.
112 used composite endpoints, and 86%
failed the first two criteria.
incredibly hard to interpret. SAnd I know cardiologistse
are very smart, but I suspect that they also have difficulty
interpreting. And they either have chosen
to ignore the difficulty
or should be in and jumajor psychotherapy.site,
( laughter )
*This is a large prospective Iblinded international clinical.
trial called the DREAM trial, of diabetes prevention.
Eight milligrams of Rosiglitazone daily, together
with lifestyle recommendations
of diabetes or death by 60% sin individuals at high risksk
for diabetes. This is lifted
from the conclusion.
of diabetes. This medication reduces the risk
sugars went from 124 to 128, The doctors are saying your
and it was 132. You have diabetes.
Okay? That experience,
versus you're dead. ( laughter )
Big difference, right?
in that difference. And so, when you look at
the actual data, it's really
In other words, the rosiglitazone lowered
the glucose enough to actually
the trial, so there will be make enfewer diagnoses.hrough
There was no effect on death. And as we know from the recent
discussion, maybe the opposite
*So this composite endpoint is exactly true.
But it's certainly not is a problem.
Inadequate patients and comparators is another way.
Haliparadol, at 40mg versus a new antipsych--
anticraziness, you know,
Right? antipsychotic drug.
comes reported as having fewer And so, the antipsychotic drug
yeah, right? extra-parametal side effects,
antidepressant Or, I'm going to use a new
And difference? with aDaytime somnolence.a day.
We kind of knew that, right?
the comparative, you may And so when you have
Composite endpoints, actually have the wrong answer.
We've talked about surrogate we have large gradient.
hemoglobin, A1C is a good example of that.
Post hoc changes in outcome definitions, and there's major
literature on that now. Inadequate and abundant subgroup
analysis. It works in this group
and it doesn't work in that group.
We have no idea how many
before that conclusion subgroup analyses were done
And then, the spinning of the discussion and conclusion
section that we discussed.
is small treatment effects. If the treatment effects are
small, you have to compensate.
mom says you have this big heart This is the joke, "Daddy,
What is it that you're to compensate for something.
Right, you know that joke. compensating for?"
small treatment effects, Same thing here, if you have
your conclusions, yyou need to start looking atg
composted endpoints to get a bigger P value.
You start looking at surrogate
looking at small endpoints, because you're
*Now, where in Madison are we treatment effects.
Pretty much everywhere. seeing small Right?ent effects?
We're looking for incremental benefits.
Very small treatment effects. We're not looking for a cure
for rabies, right?
So this is a major problem. So we talk about bias and spin..*
If that was a problem, well we
bias and spin are both present, canthey're both in your face,use
you can look for it,
you can try to infer it. you can potentially see,
and the other enemy *So wis bias reporting.my
So this is a third mechanism
of the evidence. that we can see corruption
by Chan and Altman looking at Danish protocols, followed them
for ten years, so 102 protocols became 122 reports
ten years later.
they were going to measure They compared what they said
measuring in the trial. witThis was randomized trial.ted
So 50% of the outcomes
That is they were not reported were incompletely reported.
just by saying at all, or they were reported
The odds of fully reporting an outcome, were 2:1
if the outcome was significant. So what it means in general,
when you're reading the literature, you're keeping up
with the literature,
over-optimistic view of treatments, because the majority
of what's getting published are positive results
at the full study level.
the outcomes are interesting. But withYes?he study
*So we actually looked at
if we take all these systematic the lreviews and we look at see
the proportion of trials
outcomes, plus a lot of outcome that creporting bias,portant
we'll have bigger treatment effects in summary
than even if most trials
This is what that graph publishelooks like.utcomes.
*If they had 100 trials
only 20 reported on mortality, in the systematic review, but
an overestimation of you can see that there's
than if the majority reported the treaton mortality.n average
And the only way this could be explained is if
the decision to report
of the treatment effect. is related to the magnitude
literature that we have, because So in general, the view of the
is an overestimation of outcome reporting bias
And this again, is not fraud. of thIt's just thatfect.
that's what's interesting.
*And then there's the problem That's what people want to read.
So, perioperative beta blockers positive trial, most people
knew about this study.
about the DIPOM that was Most people didn't know
It had 900, nine times more patients, and people didn't know
about it. The POBBLE trial, the same
number of patients, but had a relative risk increase.
People didn't know about it.
number of patients The MAVS trial, five times the
People didn't know about it. relative risk reduction of 15%.
for diabetes, the CARDS trial In my very positive trial,at is*
30 percent benefit, relative reduction 37%.
A trial with essentially the
essentially started and stopped same about the same time.ial,
Two additional years to get published, and was published
in the subspecialty journal the Lancet,
relative risk reduction of 10%. *So, we have the problem
of bias, spin, bias reporting and then fraud.
I'm not going to talk about fraud, because fraud
is incredibly difficult.
there's a whistle blower, you Somehear about it. it,
But beyond that, there's nothing
*But if you then say this we can do about it.
When people say this is an is corrupting the evidence base.
you should be running in the evidence-based "blank,"
Because it is quite possible exact opposite direction, right?
introduced here is the product that what is being
from research that is corrupt. of inferences drawn
if you have now guidelines *If you have guidelines,
are telling you what to do, that's becoming a little more
problematic, isn't it?
your quality is going to be Ameasured on the basis of these
parameters, this is becoming
isn't it? And if I tell you now that your
pocketbook is going to be hurt
If you're going to have pay for performance, that's
going to be based on evidence-based guidelines,
again, you should be running
You should all be practicing in the opposite direction.
They have a better soccer team. ( laughter )il.
Notice that I chose to say
they call it football. soccer, even though
by saying they have I da better football team.ody
( laughter )
*So this is a major problem. This is a major problem.
And so, this is the point about the evidence being corrupted.
What about the second point?
patient preferences Whatare being ignored?hat
*I'm actually going to skip
to highlight one thing. throuThis is, I think,ickly
a little bit of a video.
clinician at the Mayo Clinic. The clinician is telling
the patient, "I think you should be on statins.
You have diabetes.
I think you should be on Your cholesterol is high.
And what is the first thing on that patient's mind?
That guy. ( laughter )
Yeah, I've seen that guy. He's like the artificial heart
guy, and he's in the canoe. He seems to be taking statins.
He's good.
I want to be like that guy. I wanSo what could behat.
on the physician's mind?
but from an advertisement. Maybe the evidence,
decisions heavily influenced So we have the people making
direct-to-physician advertising by diand detail.sumer,
*But that's not it.
prescribing are these Anoquality measures.ther
You know, this LDL has to be
undetectable cholesterol! less( laughter )ss than 50,
We need to use highest dose of statins that we can
in these people.
present Grand Rounds We just had Scott Grundy
And literally, everybody over athe age of 50 should havey.
their LDL at less than 100. So how do patients respond
to this challenge?
So after two years of therapy, By not being adherent.
are no longer taking the stuff. And if you look at the place
where the curve is separating,
two years. the large clinical trials,
of resources, doesn't it? *When people have been asked
what do you do
15,000 will say, with prescription?
Why? I haven't taken them.
"I don't like the side effects." "I don't think I need them," or
outside the visit. These decisions are happening
The clinicians may or may not They'know about them.home.
And this is consistent poll after poll, patients actually
second guessing why they're getting all these prescriptions,
and deciding to take them only occasionally,
or not taking them at all,
completely unfounded. foSo we have a probleme
with communication. And so if this is the case,
this is really the end
*Now, if I were to stop here, of evidence-based medicine.
one of those European movies. ( laughter )eel like
The boy meets girl. They seem to be
made for each other.
And it's just getting to the end They love each other dearly.
turn around, and they walk away from each other.
And then the credits roll,
( laughter ) and you go, "What the hell?"
I mean, this is just Right?
I won't leave you like that. how you feel.
bit of a sunrise in this. I think wIs there hope?a little
So, this is a Hollywood ending. ( laughter )
Is there hope?
lies right here. And I think the hope
for a completely different I think we need to be advocating
The funding structure we have funis creating this problem.ch.
Is contributing to this state.
for completely different We need to advocate
We need to find a way of funding funding structure.
important research research, for particularly
that don't make the funder in ways that are not dependent
*We need to be looking cafor large evidence.s.
If we're going to be looking
we need large evidence, either by having meta analysis
of small trials that follow the protocol,
or having large trials. But this idea that my trial
of 15 patients will give you
is ridiculous. a P value less than .05
has to be definitive That every trial
That the IRB says that your trial is unethical, because
you don't have enough patients
And what happens is, you start is ridiculous.
effect sizes to justify your trial of 15 patients,
because you only have money for 15 patients.
And so you're creating
able to get your trial through. some aThat is ridiculous.s to be
We need to just basically realize that.
If we have money
we do it on 15 patients. for 15 patients,
And we hope that somebody else We report the results.
and we will contribute to an will get money for another 15,
confidence around the answer. Not thinking that all the trials
that we're going to do
*We need to be asking patients are gimportant questionive.
and getting patient important outcomes.
I do not know how it feels
of my creatinine. I need to have patient
important outcomes to be able to know, and to be able
to educate Mrs. Jones.
Do you feel funny about that Right?
So there must be ways of doing that better.
We need to have methods to enhance validity.
*We need to have routine registration of clinical trials
and protocols so that we can
and make sure nobody's cheating. actually go back
of clinical trial registries. I'm going in there,
it's just amazing how many stuff
the protocol says, is not there, and how many times
is on our Web site," "the rest of our detail
Web site. And you go there and you go to
"Welcome to MERCK..." And then where do you go
from there? You know, where is the data?
And of course, if it lives
I can change it any day. in my Web site,
conduct of research, *We need to have rigorous
reporting of all the outcomes rigoand all the data, open
so we can actually
We need to develop look for these things.
We need to get better at this. more spin detectors.
is we need to have methods *The other thing we need to do
preferences and decision-making. to incorporate patient
we need to talk about statins Thiwith patients in waysthat
that would not, hopefully,
And what we found with this tool introduce bias.
trial was that patients when wereally liked it.inical
It improved their knowledge,
risk estimation. and improved their
decisional conflict. It decreased their
It improved the action It improved their trust.
prescriptions in the lower if you think that 70% fewer
There were some short-term risk category.
of three-fold. adherence improvements
patients and physicians a script they can go through
to understand the patient's risk
associated with the medication. And this was published
in the Archives of Internal Medicine.
So you can do these simple
*I'm going to show you one potential mechanism for this
decision aid that has nothing to do with the content
of the decision aid.
no decision aid. One physician with a patient,
with a decision aid. Same physician
Is that the mechanism of action, Now we're having a conversation.
we're provided information. or iI don't know. that
*We're now doing this
I think it produces for diaba major change. choices.
Watch this. >> Yes, I agree, we need to
make sure your sugars are better controlled.
That means we need
So which aspect of your next a new medication.
do you want to discuss first? d>> Weight change.n
I'll let you review that. >> This is the one I'm on now,
right?
This one looks good to me. >> You're already on medformin.
you lose some weight. What aspect of that medication
would you want to learn about next?
I'd say daily routine.
Oh, so this is injectable. >> Sure.
There are a couple of pens >> Yes, it's actually very easy.
and you inject into your belly. You do that twice a day
before your meals.
You don't want to go with >> I don't tneedles?eally want.
I'd much rather just pills. So, the sulfonylureas?
That's the next best one
That's a daily pill. for you in terms of weight?
a day. You can start with one pill
Yes, usually 30 minutes >> Andbefore breakfast.before?
Would that be okay? The other thing to consider
is that sometimes they can
so we're going to ask you to monitor a little more often
than you're doing right now.
okay. If you were to change your mind
after you go home,
It has the same thing as the I'll give you this pamphlet.
So as you're using the tablet, cards.
you expect, you can review this again and give me a call, andt
we can discuss it again.
Thank you. >> Okay, all right.
day, we can get better at >> detecting bias and spin,he
and bias reporting
the revelation of sophisticated forms of reporting bias
and misconduct. If we are able to promote
patient participation and decision-making,
so that we get the whole idea of evidence-based medicine,
not only the evidence piece,
participation piece. but also the patient
for evidence-based medicine because the way we got to know
that we had the problem we have now, is because we were
following those principles
So if we were to stop, of evidence-based medicine.
if we don't train people if we were to declare defeat,
what will happen is when to be alert of these issues,
our clinicians will not have we all become patients,
be healthy, and to get these tools to help us
that we would like to get. the medication and treatment
of evidence-based medicine. SoBut maybe there'snd
a little bit of hope. And I welcome your questions.
Thank you. ( applause )