Michele Walsh.
>> Thank you for allowing me to present today.
Traditional research is the context in where the common rule
was promulgated where there is a control group, which receives
the standard or in legal ease, standard of care, or
experimental group with new or untested treatment.
However, this traditional paradigm doesn't recognize there
may not be one standard but many standards.
For example, there are currently over 100 drugs licensed for
hypertension by the FDA and each of these is a standard.
Comparative effectiveness research has been promoted
defined by the patient centered outcomes research institute as
evidence designed to inform health care decisions by
providing evidence on effectiveness, benefits and
harms of approved treatments.
There is no experimental group, that is a group receiving a new
or untested treatment.
PCORI, recently had extensive standards silent on the approach
to informed consent in these studies.
I think everyone here has agreed and many have said, that we
recognize that consent is a process, not a form.
Despite ever longer consent forms, comprehension of studies
is imperfect.
There are a number of studies that have explored this,
assessing the effectiveness of a consent process in a
well-regarded adult study randomized trial of two
different cancer treatments.
Within the months after enrollment and accessing
participants understanding, 62% understand the purpose of the
study.
Forty-four% understood the study procedures.
But only 40% could correctly list at least one major risk.
Indeed, OHRP has recognized that in affective informed consent is
a process, not a form.
However, it is obvious that existing informed consent
processes can be improved.
Many studies have been published as investigators have recognized
the need to improve and this systematic review demonstrates
that enhanced discussion and improved consent form show the
most promise for improving the consent process.
Unfortunately, the use of multimedia techniques are
graphic displays to demonstrate risk or benefit do not result in
improved understanding.
Let's look at a hypothetical case.
A competent adult patient undergoing major surgery has
postoperative pain medication selected by the individual
treating physician, Morphine or fentanyl.
Limited evidence of the superiority of either drug
however there is a four-fold difference in price.
Let's walk through this to demonstrate a ethical framework.
Routine medical care does not necessarily fully inform the
patient where the choice of the individual's physician may be
less about the individual patient characteristics but
rather about physician preference often by how they
were trained, institutional habits or pharmaceutical
detailing.
If instead the patient is asked to participate in a
observational study where the treating physician chooses the
pain medication, there is improved disclosure of both
benefits and risks associated with those routine treatments.
If instead, this is the traditional randomized clinical
trial, again, ethical framework is fully met.
Randomization does not change the risk of either treatment.
Participants are carefully monitored and the protocol
provides distinct exit criteria if pain is not adequately
controlled or complication occurs.
Within the context of the trial, care is individualized by the
treating physician not the investigator.
Now what if this is a prospective comparative
effectiveness trial?
The treating physician chooses which drug is assigned, consent
is given, data collected to fully assess the risks and
benefits.
I would argue that there is no compelling evidence than
informed consent in prospective CER of this type should be
handled differently than any other research, especially in
the interest of transparency.
However, comparative effectiveness research, lives at
the interface between randomized control trials and other newer
forms of research called quality improvement learning networks,
yet patients, each in QI learning networks, can be fully
protected by the routine provision of information that
the hospital where the patient resides routinely seeks to
improve care through continuous improvement methods.
As required by the joint commission on hospital
accreditation.
Indeed, if we look tat from a justice standpoint, what patient
would want to seek care in an institution that did not seek to
improve.
So why are going to get informed consent for this hypothetical
case.
What might then consent form look like?
The benefit is clear.
Alleviating postoperative pain but what potential harm should
be disclosed?
The risks here are take ebb from the drug insert for Morphine in
the PDR.
There are additional 22 lines that will not fit on the slide.
However, if instead the consent form presented risks in a
tabular form graded by how frequently potential harms might
occur, understanding would be greatly improved.
Multicenter trials have become the strongest method to evaluate
new treatments or to evaluate existing but unsteady treatments
and they do represent special challenges informed consent.
Respect for persons requires that information on benefits and
risks disclosed participants should be identical between
sites.
Yet individual IRBs exercising their local control frequently
alter model consent forms.
Use of federated IRB mechanisms should be encouraged for
multicenter trials.
In addition, reasonable readability standards, I would
suggest, eighth grade level, should be promulgated and
enforced by the OHRP.
Finally we need guidance on recommendations for informed
consent adds we hurdle headlong into the electronic medical
record era.
In conclusion -- >> You're seven minutes are up.
>> Thank you.
The common federal rule has protected research participants
and guided investigators well over the last decade.
Newer research methods can be addressed within the current
framework.
Thank you.
>> Thank you.
Let me turn first to NIH.
>> Thank you very much.
I had a question and maybe I was spacing out for a second.
In your discussion about quality improvement, I agree that
certainly patients and health care systems are interested in
improving quality, but in terms from a patient's perspective, or
participant's perspective, what's the difference between
some, if you looked at something that was quality improvement and
it was not labeled as quality improvement, could you tell the
difference between quality improvement and comparative
effectiveness and how, the difference in terms of
transparency, consent and those two areas.
What are your thoughts on that?
>> I think you have identified it completely well that there is
no difference in my way of thinking.
And I think that participants are best served through an
informed consent process.
At a minimum, a letter of information notifying them that
this is going on.
In our own context of the statewide collaborative, we had
IRB approval for every QI intervention.
>> Thank you.
>> OHRP?
>> Thank you for the helpful comments.
We were talking about what comparative effectiveness
research was in your slides and you noted there is no
experimental group.
I'm wondering your take on the earlier comments we got in terms
of some of these studies for example where the continuum of
treatment and we are not sure exactly what criteria physicians
are using in terms of assigning you to a particular value.
Is there is some notion of risks related to these tools yet
acknowledging there are other studies where it is much clearer
to say there is nothing experimental.
Do you agree there might be such lines?
>> Yes.
I agree there is such a line.
>> Thank you.
>> FDA?
>> We are aware of one study of two widely available drugs that
used online informed consent.
It was very interactive and people asked questions.
If they didn't get it right, they had to do it again.
For comparative effectiveness or things where the drugs are
involved are not very familiar where it shouldn't be that
complicated, does that seem like a promising avenue?
Current informed consent forms are all too leading far too
often.
>> They are very similar to the FDA product inserts in many
ways.
[ Laughs ] That they have complete
information.
>> Those are directed at the most knowledgeable people in the
world.
>> They have complete information but perhaps not
presented in a way that makes it very informative for the
participant.
I was very disappointed in the estimate I think review I cited
in that I personally hoped that some of the more interactive
multimedia studies would give us a way out to try and be sure
that our participants are more fully understanding what it is
they are agreeing to.
That said, at my own institution, we had pushback
from our IRBs when we had parental agreement to
participate in a study and yet, we concluded at the end of that
process, that they didn't really understand what they had agreed
to.
And we went to the IRB and said, we don't think we can take this
consent.
We don't think it is truly informed.
We were told that would be paternalistic of us to reject
their right they had agreed to be in this study.
So it is really a conundrum for us every day.
>> I'm going to once again take the moderator's prerogative and
recognize the panelists have been terrific.
I know we have seven more speakers.
The afternoon lull, the post lull, I seen a few people maybe
not nod but thinking perhaps with their heads down, let's
take a -- let me again punish you all and will ask for a seven
minute break.
We will start promptly as close to 2:30 as we can.
Restrooms over there.
If you need them, if you don't, feel free to just get up and
stretch a little bit.
We have about two more hours of timed work to do here.
Thank you.