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We were grateful to the presenters this morning who were
fabulous on staying on time.
We wanted to hear all points of view and that is the purpose of
the meeting and we are really getting there.
We appreciate.
That so we think the afternoon will be no exception.
I believe it was 14, I counted them once and I have forgotten.
We have a number of speakers this afternoon.
First are Jeffrey Drazen, Peter Vasilenko, Steven Joffe, David
Foster, David Magnus, Carl D'Angio, Jon Tyson and Michele
Walsh and Shawn Pratt, Sharissa Cook and I know you'll corrected
me if I have pronounced these incorrectly.
No slides?
Great, thank you.
Thank you and good afternoon, everyone.
I'm Jeffrey Drazen.
I view myself primarily as an active physician and secondarily
an editor.
So when you seek medical care, your provider has to make many
decisions.
His diagnostic setting, what test to order, in a therapeutic
setting, it's what treatments to give, and in standard care
settings, it may be something as simple or complex as what
screening tests to do.
And for many of these decisions, we have absolutely no data.
I just finished a brief period working in our intensive care
unit at the Brigham and Women's hospital and I counted every
day, over 50 questions for which the answer could have been given
by a flip of a coin.
We need to do better than that if we are going to improve our
health care system.
There needs to be a way to address things that we commonly
do to determine whether there is one better way that is better
than the other.
And there are lots of settings for this, some of which may seem
surprising.
Consider a study published in the New England Journal of
Medicine, one of my favorite medical rags, that compared two
different preparations used for cleaning the skin before
surgery.
One of them was developed at the Brigham during World War II and
the other was a newcomer, chlorhexidine alcohol.
Before the study was done, these two skin preparations were
considered to be essentially equivalent.
But a study was done and informed consent was attained to
compare the outcomes of having your skin cleaned with each.
Looking at the incidents of surgical site infections,
postoperatively.
And to every one's surprise they thought they would be pretty
much the same.
There were more infections with the propadiene iodine than with
the alcohol.
So as a result of this work, comparing two treatments that
could be considered standard of care.
Now George, I don't want you to worry about this.
Standard of care to me, is easily defined.
When my kids were little, I'd say, the standard of behavior is
standard behavior and I'll know when you're violating it.
Standard of care in a medical setting is the same way.
Doctors who do things that are generally accepted by the
community are a standard of care.
Unfortunately, we don't often keep meticulous records about
what standard of care is, which may lead to many arguments about
it in an expo facto sort of way.
When we are looking at things that are standard of care, I
think most people understand what that means.
Since we have to make decisions every day on which we have very
little data, we do want feels right to us or what we learned
at the time of training.
But we know from the behavioral research, that you're more
likely to do something based on your recent prior experiences.
So imagine you're a surgeon and the last case you did had a skin
infection, and you had cleaned that patient's skin with
alcohol.
So you're next patient, you're going to say, that wasn't good.
Couldn't have been my hands.
I'm going to switch to iodine.
And you probably watch all your patients until you have a couple
of in a row that had a infection with that and then you switch
back.
For this particular case, we have data.
We know.
We go from something we think to something that we know to be
able to make an informed decision.
And that is what this meeting is about.
It's about doing research to improve what we do in many, many
things on a daily basis.
So, this has led, this desire to improve outcomes has led to
research studies that compared diagnostic approaches or
therapeutic regimens or processes of care in which each
intervention is considered to be essentially the same.
One may be more costly, one may have or may hurt a little more,
but have better outcomes in the long run.
We don't know.
In what a physician does when he or she makes decisions in the
process of care, is they try to customize, but I think it was
put most eloquently by Dr. LANTOS earlier, we are just
guessing.
And his grandchildren are the result of those kinds of
guesses.
When we do things that are protocolized, we do better.
It's been shown over and over again.
If you have a roadmap to follow, you're way better off than if
you're wandering around without one.
It's my premise that settings, to determine what is best among
things that are considered standard of care.
The researchers proposing the work need to study the area and
prepare the document outlining the research trial showing what
is known.
Now, for most of the things that we are going to be looking at,
there aren't going to be randomized control trials
looking at A versus B. There may be some observational
data which we know is highly likely to be biased, and there
may also be expert opinion.
But there probably won't be gold standard evidence on which to
base our decisions.
But these people, the people proposing the work, the own us
lies with them to write out what the question is and why they
think clinical equipoise exists.
This is where I think we need to do something different.
Right now that proposal goes to a bunch of different IRBs.
I think that there should be an IRB convened specifically with
expertise to look at the question that is being asked.
And once they have read and said yes, clinical equipoise exists
and the method that you're using to address that question doesn't
contain excess risk for the people in the population, it is
well laid out.
We then say, yes, it has happened.
At this point in time, equipoise exists.
When we look at the support study and we spent a lot of time
arguing about the support study, to me the biggest problem is,
where we can't put ourselves back in 2003.
>> You're seven minutes are up.
>> So to get there, we need to have an IRB that knows why the
study was being done and how it is being done.
Thank you.
>> Thank you.
Now to the panel.
FDA?
>> Your last comment intrigued me, we said that central IRBs
were okay and you didn't need more than one for study.
England sort of giving everybody a central IRB.
But our understanding is, nobody likes them here.
Do you have any particular insight into why that is?
>> So I don't think the local folks like to give up local
control.
So in my idea, there would be a central IRB that would approve
the study design and equipoise exists.
But that the local IRB would be involved with the making sure
the researchers are in fact qualified, and that the informed
consent is appropriate for that community.
When we were doing Asthma studies, the appropriate
informed consent in Harlem was different than it was in San
Francisco.
>> So you could do that now.
Would you have thoughts about how to encourage that behavior?
>> So, the way I would encourage that behavior is for the OHRP to
say, let's use a central IRB to define the question and clinical
equipoise and move forward.
Looking backwards as we have done with the support study, I
think it is just fraught with difficulty.
So we need to go forward, not backwards if we are going to
make progress.
>> NIH?
>> Thank you.
So, your proposal for a specific IRB is not that different from
the recommendation that an IRB results with appropriate
expertise in order to make a determination of whether or not
research within the standard of care does achieve that balance,
does achieve clinical equipoise.
>> I think there are different flavors of the same thing but
not very different flavors.
>> Thank you.
>> OHRP.
>> Thank you Dr. DRAZEN.
I appreciate the comments about central IRBs and more broadly,
the purpose of this meeting is to make sure that everybody
understands what the rules are going forward.
So, in terms of -- let me ask you a question, clinical
equipoise tells you it's a legitimate study.
It doesn't answer the question about informed consent and what
people should be told.
You could have clinical equipoise but there can still be
legitimate reasons why somebody might want to take one arm or
the other arm as their treatment outside of the study and move
back to what should you disclose in terms of if in fact, we
physicians out there is concerned about a particular
risk.
Shouldn't that be disclosed?
>> So, what if the -- if the IRB authorization that clinical
equipoise exists and sometimes it is full equipoise and
sometimes there may be compelling arguments one way or
the other.
One treatment may be more effective but more toxic, the
other treatment may be les toxic but less effective and trying to
see which gives longer life, for example.
But I think that with respect to the issue of what you tell
patients, I think that you should tell them what the
question is and how you're proposing to answer it, rather
than couching this in the language of panel A or
intervention A has this risk and intervention B has that risk.
Lay the question out and then explain how you're proposing to
answer it.
And I think that will get to this issue.
>> Thank you.