cc >> My name is Craig
Christianson. I'm director of licensing at
Wisconsin Alumni Research Foundation, or WARF.
The Gilson Series was launched in 2004, following a gift from
the late Dr. Warren Gilson. Warren Gilson played a strong
role in the Madison business community and the UW campus.
As a UW Medical School alum and faculty member, he was a
prolific inventor of medical electronics and instruments.
Dr. Gilson was also an entrepreneur.
He founded a company that grew into today's Gilson, Inc.,
a leading manufacturer of analytical instruments located
in Middleton. In 2002, Dr. Gilson left WARF a
significant gift intended to promote the exchange of ideas
between the university and Wisconsin businesses.
He often recollected that as a young entrepreneur, he valued
the regular and informal interactions that he had in the
cafeteria of UW Hospital. He was able to have a wide range
of discussions with colleagues within the university community
and the business community, as they looked to solve problems
together. It is in this spirit of
creating connections in dialogue between the university and the
business community that WARF hosts these sessions
to encourage entrepreneurship and interdisciplinary
collaborations. I'd like to welcome and thank a
very special guest, Dr. Gilson's son, Bob, who is joining us this
evening. Thanks, Bob.
He often attends these events. We hope that your father
would've enjoyed and appreciated these events named in his honor.
In case you're wondering about the cameras and my formal
remarks, even though we're a nice group of friends here in
this room, we're being filmed tonight.
This program is being filmed by Wisconsin Public Television.
Tonight, we host Dean Paul DeLuca.
And now, it'll become even more apparent why I'm reading.
Paul received a BS in Physics and Math and a PhD in
Nuclearphysics from the University of Notre Dame.
That same year, he joined the University of Wisconsin as a
research associate. And in 1975, he was appointed to
the faculty of the Department of Radiology.
Following the creation of the Department of Medical Physics in
1981, he served as chair from 1987 through 1998.
He holds and appointment as professor in the departments of
Medical Physics, Radiology, Human Oncology, Engineering
Physics, and Physics. In 1999, DeLuca assumed the
role of Associate Dean for Research, and Graduate Studies
in the UW School of Medicine and Public Health.
And his administrative role was expanded in 2001 with his
appointment as Vice-Dean. Dean DeLuca is an
internationally recognized expert in high-energy particle
radiation effects on humans. He is a member of the
international commission on radiation units and
measurements, and currently serves as vice chairman.
He is also a member and chair of the non-proliferation and
international security division of U-Committee at Los Alamos.
Other national and international associations and professional
society affiliations include the American Association of
Physicists in Medicine, American Physical Society,
Health Physic Society, National Council on Radiation Protection
and Measurements, Council on Ionizing Radiation Measurements
and Standards and Institute of Physics.
Please join me in welcoming Dean Paul DeLuca.
( applause ) >> Thank you.
Craig could have been much more succinct by merely saying this
guy's older than dirt, and he's a resident geek.
( laughter ) I'm also a little bit
startled by the membership of the audience.
I had anticipated that this would be more of the general
community, as opposed to people that are deeply experienced in
clinical trial research. So I hope those of you that are
very familiar with it ignore half the remarks.
Secondly, I'd kind of like to spend a little time, and you'll
notice it right away. I'll give you my personal
opinion and interpretation of things, not necessarily, in some
cases, what the standard policy is.
And what you'll see right away is that I tend to be a strict
constitutionalist with respect to this kind of activity.
I'm here tonight to talk about conflict of interest in clinical
trials. And what I'm going to try and do
is give you a little bit of a national perspective on this,
and where it's going. Then I'm going to try and bore
in on local perspective as to how this is managed.
And then I'm going to talk specifically about a typical
case example. We'll try and protect the
innocent as best we can in that case.
So I was not alone in my efforts to do this tonight.
I had some very distinct help from Steve Harsy, who's sitting
in the audience, and from Tracy Cabot.
Two of the people who work in my shop.
Steve, in particular, works right at the interface between
faculty and conflict of interest and conflict of interest
committee, and probably spends 20% or 30% of his time on that.
So let's get down to it. This is a quote taken from a
recent American Association of Medical College report on a task
force on financial conflict of interest in clinical research.
Now the interesting thing, that's now available in draft
form that's available on the Web, and one of the principal
authors of that is the current dean of the Medical School,
Robert Golden, who in fact drafted a fair piece of this
thing. If you kind of read this over,
the first few points become clear, "opportunities to profit
from research may affect, or appear to affect, a researcher's
judgments about what subjects to enroll, the clinical care
provided to subjects, even the proper use of subjects."
Well, probably the key word is that parenthetical phrase, "or
appear to affect," because I think everyone at this
institution, and they wouldn't be here very long otherwise, who
accepts the first premise, namely that they intend to
profit from the research, isn't going to be able to do that for
very long. So in many cases, the entire
problem reduces to the appearance of these activities,
and the perception of those appearance of activities.
That doesn't remove us from having to deal with those
issues, but it does change the emphasis somewhat.
The other point to keep in mind is that this is not dramatically
different than you would have if you were doing NIH research, for
example, not involving human subjects.
All right? Faculty compete very hard
for these grants. They're very successful
in pursuing those grants. It advances their career.
They get promoted. They get salary increases.
Their prestige in the field increases.
So they're not free of conflict of interest.
It's a personal conflict of interest, but it's not obvious
that it's any less of a conflict of interest than in for example,
doing human subjects research. The difference is human subjects
are involved. That's why we have a special
attention to this particular problem.
Here's another quote from that same report.
"Financial interests also threaten scientific integrity
when they foster real or apparent biases in study design,
data collection and analysis, adverse event reporting, or the
presentation or publication of research findings."
This is another example, which is somewhat distinct from the
first statement. I'm going to elaborate on this
point in just a minute or two. Also, I call your attention, we
have this again, the "apparent biases," okay.
So again, we have this perception of reality issue that
we have to deal with. The NIH sponsors vast amounts
of clinical trials. Why are they seemingly less
subjective to difficulties, with respect to financial conflict of
interest? It's largely because there's no
financial relationship, other than the grant or contract
between the agency and the faculty member.
It's when it's this distinct relationship between a drug
company, or even more complicated, when the faculty is
directly involved in it that we run into a conflict of interest
that's directly involved. Now, this statement, which is
toward the end of the introduction of that particular
report, "At the same time, a principled partnership between
industry and academia is essential if we are to preserve
medical progress..." If you kind of wind the
clock back and look at the principal discoveries that have
taken place in care of patients, and in the diagnosis of
diseases, invariably, private companies were involved in that.
And their relationship, very often with the faculty founders
or with the institution, had a very positive benefit on their
research. For example, here at Wisconsin,
I'm deeply familiar with several of these.
One example, a prime example, is digital subtraction
angiography. That was entirely created by one
or two faculty members in the medical school.
And working very closely with General Electric Medical Systems
Division and Phillips, for example, to fully flesh that
out, make that as comprehensive as it is, and then promulgate
that throughout the industry. So it is the standard of care in
cardiovascular diagnosis. Even today, DSA is still the
standard of care. So there was a very distinct
relationship between several of our faculty and several major
companies. And certainly those faculty
individuals had a potential conflict of interest between
those things. Yet, had we not done that, it's
not clear how long it would've been before DSA became popular.
Another example, bone densitometry.
Bone densitometry is one of the most common screening exams done
for example nowadays. The degradation and bone loss is
a severe complication. In fact, most of the vitamin D
work that we see on campus is focused on rectifying some of
these problems. Well, the medical imaging that
was involved in that bone densitometry created a
corporation, Luna Radiation, which was subsequently bought
wholly by General Electric. Faculty were deeply involved in
that process. And not having them involved in
that process very likely could've resulted in bone
densitometry being delayed or otherwise put off for who knows
how long, certainly potentially decades.
So there's a great benefit to this.
The more recent example I think is tomotherapy.
That is, you may not be wildly familiar with the impact of
tomotherapy. I'm sure you've heard of the
company. But in fact, that company and
that device is virtually revolutionizing the field of
radiation oncology. The penetration of that
instrument into the treatment market has gone from essentially
zero five years ago, to probably 20% to 30% in the United States,
but much higher penetration in, if you will, lesser developed
countries, because when they buy new here, they buy the latest
gear. So they're essentially ramping
up their clinical care programs. And they're doing that on the
back of this technology. This was developed as a tight
relationship between one or two faculty members and what
ultimately became a company, Tomotherapy.
So society is benefiting greatly from these kind of
activities. The problem is how do we manage
these activities in a principled way.
There's lots of people who have their finger in the pie.
These are just some of the agencies and organizations which
are really deeply involved in the whole business of clinical
trials and conflicts of interest.
The Public Health Service, the AAMC, the Anerican Medical
Association, the state of Wisconsin.
But probably what should be at the top is public perception.
Our management of public perception, and our ability to
articulate publicly how carefully this kind of work is
being done is seminal to any success.
If we're not able to do that, we're not going to have much
success. Every time we have failed to do
this properly, even if there has been no adverse problem, when
that perception is available to the public it's not completely
above board, we run into severe perception problems that can be
really extremely negative. And we have, unfortunately,
several examples of that on campus.
Let me talk a little about research misconduct and conflict
of interest. Conflict of interest arises when
we have two activities that interact such that the
professional judgment in one may or may seem to be influenced by
the other. That's what we mean by a
conflict of interest situation. You could have this situation
arise in several different contexts.
One that I'm not going to talk about is the clinical practice
conflict of interest, because in our institution, that's governed
entirely by the University of Wisconsin Medical Foundation and
the hospital. There's another conflict of
interest that we have yet to wrap our arms around.
That's the institutional conflict of interest.
That's the relationship between the institution and external
agencies that could put the institution in a conflicted
opinion. An example of that is we have a
very deep relationship with General Electric Medical Systems
Division. Management of that in an above
board public way is really an institutional management of it.
It does not get down to individuals.
It's not an individual or trial related conflict of interest,
but is rather an institutional conflict of interest.
The university's policies in this area are just evolving.
We haven't put anything in place, but we're going to have
to put something in place fairly quickly.
So then we get into research conflict of interest, which is
really governed by UW Policy. This is something that the
university has dealt with in a very comprehensive and proactive
way. And I'm going to spend, as we go
along here, a few minutes talking about that.
In any case, let's diverge a little bit and talk about
research misconduct and the relationship between that and
conflict of interest. Research misconduct, and this
is a quote I've actually taken from the Harvard Medical
School's Web site, which I think has got some really important
material on this. They define research misconduct
as a "fabrication, falsification, plagiarism, or
other practices that seriously deviate from those that are
commonly accepted within the scholarly community for
proposing, conducting or reporting research."
This is exclusive of --. Well, to a certain extent, you
might argue that if someone behaves in a manner that's free
of research misconduct, why do they have any conflict of
interest, okay. And in many ways, a clinical
conflict reduces to an accusation that the faculty
member is either committing misconduct or is committing
malpractice. You really have to accept the
fact that if someone is not committing any form of research
misconduct, and is not committing malpractice, they may
in fact be very well managing their conflict of interest.
It's really a question of how deeply does the institution
reach into that area. That is the crux of the matter,
at least for me. Now, we've had some tragic
forms of research misconduct. We had one about a year and a
half or two years ago at the institution, which resulted from
outright fabrication of scientific information that was
published in the peer review literature, and was subsequently
used to pursue further and more NIH funding, which was obtained.
That constituted absolute fabrication of results, and was
a core violation of research misconduct principles.
And it resulted in the dismissal of that particular faculty
member. If you looked at that case in
detail, you're actually stunned that anything would get that far
along. And quite frankly, if it hadn't
been for the students in that laboratory, that might have
persisted for yet another five or ten years, all right.
That was an example of research misconduct.
Now, in my experience seemingly intermable at the institution,
I've only run into two instances of research misconduct since
1972, that I've been aware of or engaged in.
The probability of this occurring is extraordinarily
rare. It could be argued that the
conflict of interest in a clinical environment is even
rarer. You have very, very few
instances of where we've had any difficulties.
"Medical malpractice occurs when a negligent act or omission
by a doctor or other medical professional results in damage
or harm to a patient." That statement raises the bar
quite a bit above conflict of interest.
In essence, to commit malpractice, the physician has
to behave in such a way that it results in the damage or harm to
a patient because of that misbehavior.
You could easily avoid that in the context of a clinical trial,
but have a significant conflict of interest.
So we need to make a real clear distinction between medical
malpractice, which fortunately, is relatively rare, and conflict
of interest situations in a clinical trial, which are
relatively common. And I'll give you some examples
of that as we go along. "Conflict of interest in
patient care occurs when a medical professional makes
recommendations to patients based on outside influences
rather than on standards of care."
That's really the crux of the matter in clinical conflict.
I have a clinical trial I'm doing over here and you really
don't need this, you really need to participate in that.
That is the crux of the matter for clinical conflict of
interest. Let me keep up with where I'm
going here. Now, this is kind of a flow
diagram of the university's process for managing conflict of
interest. The key to the management of
conflict of interest, and you should really say financial
conflict of interest, because there can be an academic
conflict of interest. I'll get into that in a minute.
But the financial conflict of interest starts the process by
the faculty member disclosing completely and thoroughly any
aspect of their financial situation that could bear upon a
potential conflict of interest. That's done annually by
virtually every member of the faculty and staff.
It is reviewed comprehensively at the unit level.
That unit level is usually the Dean's office.
Our Dean's office, Steve personally reviews every
conflict of interest. There's a subset of those that
he pulls out of his stack that are particularly dangerous.
And then we, together, review those in detail.
So this is done periodically on an annualized basis.
If a faculty member's financial status changes after filling out
that conflict of interest form, we revisit that situation.
This is an ongoing, centralized process.
This occurs in virtually every Dean's office on campus.
That subsequently gets referred to the so-called conflict of
interest committee, which is a broad campus appointed
committee. I'll show you some of the people
on that in a minute. There may be some in this room.
That typically may result in an interview process.
The results of that may result in a management plan.
The management plan may be very trivial.
You can't do it. So your management plan is no,
you can't participate in any clinical trials associated with
that particular company or entity.
On the other hand, there are circumstances where this is
permitted. I'm going to try and talk about
those in a little detail as we move along.
Let me give you a flavor of the review criteria.
If you go out and look on the Web, and you say, okay, DeLuca,
that's the review criteria of Wisconsin.
What is it at the University of Chicago?
What is it at Harvard? What is it at Johns Hopkins?
You will find different criteria depending on the
institutions. Where do our criteria lie in the
spectrum? I'd say more or less in the
middle. The extreme ones are quite
distinct. As far as I know, for example,
Harvard is extraordinarily restrictive on any kind of
financial conflict of interest. Ours breaks out to something
like this. There's four columns.
Three to the right, No Review or No Management; Limited
Management; Full Management. What we're talking about is
whether or not the process is allowed to go forward.
If it's allowed to go forward, all right, the proposed research
clinical trial is allowed to go forward, it's going to fall into
one of those three categories. One, that there's really no
particular issue that we have to deal with, so it moves forward.
Another, where we have a circle of middle ground, a limited
management plan. And then finally, a so-called
full management plan. These criteria are arranged,
probably by order of precedent. So compensation, if it's less
than $10,000 a year, there's no review or management;
$10,000-$20,000; greater than $20,000 a year relationship.
Notice the issue with respect to ownership interest in a
publicly traded company. That's an "and" statement in the
mathematical sentence. You have to receive less than
$10,000 AND that must not constitute more than five
percent equity. If you happen to have $5,000,
and that's more than five percent equity, then you fall
outside the AND, okay. So it's really the product of
those two terms. Notice all the way over to the
right, it's $20,000 OR five percent equity.
So the AND switches to an OR statement.
Either one will trip the discriminator in that particular
venue. Ownership interest, basically
you either do or you don't. If you do, you're automatically
don't pass go, don't collect $200.
You're immediately into at least a management plan, if at
all. No ownership interest, then
there's no particular problem. Leadership position, board of
directors, external advisors, some other capacity.
Doesn't have to be paid, just has to be involved.
These can trigger various review processes.
Here's a chart that kind of breaks out the disposition of
what the conflict of interest committee review might entail.
Focus on the extreme right column, the Full Management
plan. Under the full management plan,
what the heck is going on here? What's going on is, under
special circumstances, the faculty member may be allowed to
participate in a clinical trial. But all of these criteria and
activities have to be included in that participation.
And it's very intrusive, if you look at this a little bit.
For the faculty person to participate, there's a lot of
intrusion by the management plan into their day-to-day
activities, a high level of scrutiny.
An institution wants to be in a position of not only are they
comfortable with this research going forward, they're
comfortable with every aspect of how that research process is
being managed, and that that research project absolutely
minimizes the amount of potential for conflict of
interest or even perception of conflict of interest.
These can be quite intrusive. If you go down to the bottom,
you're talking about monitoring by the chair and the Dean's
office. So we will actively get involved
in faculty, much to their disgust, in day-to-day
activities, with respect to this, even going so far as to
what are they buying, and how are they buying it, and who are
they buying it from, for example, gets dragged into the
discussion. Annual report and review with
the department chair. We take a very proactive.
Steve will arrange for he and I to meet with either department
heads or section heads. These are generally clinical
departments. And sit down and have thorough
discussion about how this management plan is going
forward, and what the difficulties are associated with
it. Now, I'll keep track
of where I am here. One of the key things to keep in
mind is that if it's decided to allow this to go forward, and
there's a management plan put in place, and that, even in a very
intrusive state, it can be very restrictive.
I'll give you one example. But this gives you a flavor of
how restrictive it can be. You cannot serve as PI.
You cannot serve as Co-PI. You cannot be key personnel in
this particular research. This can be very hard for a
faculty member to accept, to not be key personnel.
Let me give you a list of what key personnel do.
Key personnel are people who do one or more of these particular
activities, designing of research.
So what you're really saying to this faculty member, is because
of your financial conflict of interest, you cannot be involved
in the designing of research associated with this.
This was, for example, an extremely troublesome problem.
I used the case of Tomotherapy. The faculty member was 100%
responsible for that entire product.
So when you say you want to pursue that research on campus,
and you can't in any way get involved in designing the
research, that is a real challenge.
The faculty members are not thrilled to have that particular
process put upon them. Making eligibility decisions
about human subjects. That's obvious and that's not a
particularly compliance related thing.
We do that very easily. Analyzing or reporting the data
for publication. Submitting manuscripts.
All of these things could be restricted, curtailed or
otherwise affected by conflict of interest management plan.
So it's a significant intrusion into the faculty member's life.
I frankly, as an aside, have to tell you, I really struggle with
that sometimes. You know, the risk benefit ratio
that's involved, we tend to err tremendously on the risk side
and don't look very carefully, necessarily, at the benefit
side. It's a huge advantage, in many
cases, to have our faculty participate in this thing.
They very often can get pushed off that because of the concern
about the perception of this. So the general central campus
policy is to err on the side of caution rather than to look
necessarily at the benefits. I personally am more willing to
accept a little higher level of risk.
Exceptions to a full management plan limitation.
There can be exceptions. However, they really require
some very compelling circumstances to implement those
exceptions. Namely, that the greater good
would be restricted by not implementing those compelling
circumstances. Without those, for example,
maybe the work can't be done. Or without those, maybe the
results will not be interpreted correctly.
Without that participation, maybe that research won't go in
the correct direction at all, and we'll waste a lot of time,
energy and money and miss an opportunity.
There really needs to be some compelling reasons to do this.
If the risk is greater than minimal, and I mean minimal is
close to the accident rate for driving your car to work, which
is about one part in 10,000 or something like that.
This is generally not granted as a probable.
Compelling circumstances. Nature of the clinical research;
nature of the significant financial interests.
There may be significant financial interest, but if they
are sufficiently isolated, they may be significant, but if
they're sufficiently isolated and at arm's length, maybe
that's a reason for allowing this to go forward.
How closely do the financial interests relate to the
research? If they're really well uncoupled
or mildly related, maybe that's compelling.
Potential for bias. Unique qualifications of the PI,
and I'll give you an example of this.
In many cases, all of these activities are compelling
circumstances that could result in a conflict of interest
committee taking a more open policy with respect to granting
an exception. But this last point is probably
the most important to keep in mind.
Full disclosure is the essence of reality.
In any kind of conflict of interest situation, failure to
provide full disclosure is absolutely lethal.
In realty, it's location, location, location.
In this kind of instance, it's disclosure, disclosure,
disclosure. The more you disclose, the more
comprehensive it is, the less difficulty you have.
This is the committee. And I show you this largely
because how broad it is. You wouldn't necessarily
recognize all the names. You might recognize some of
them. This is a very broad swath of
faculty. These faculty tend to be very
deeply experienced, not just in research, but in clinical
research. They're also experienced in
commercialization, technology transfer.
They have a very good knowledge of what the institutional
mentality and history is. They tend to execute on those.
It's chaired by Brian Fox. And the fact that they can get
Brian to spend that much time on it is quite shocking, because
this committee spends a lot of time on these issues.
They represent physicians, scientists, basic scientists,
social scientists. There's a broad swath of faculty
expertise on this committee. Almost as important as the
faculty members on this committee are the ex-officio and
consultants. Some of those are in this room
right now. So for example, amongst the
consultants, you have individuals from Letters and
Science who are responsible for tech transfer, and the Medical
School, CALS. You have representation from the
institutional and human subjects IRB, Michele Cobb and Carol
Pech. You have Kathy Irwin from legal
services. So the infrastructure
associated with all human subjects research is heavily
represented on this particular committee.
They provide at least some constants here.
Let me talk about a case study. And as I said, I kind of
suppressed some of the science and suppressed the names to
protect the innocent or guilty, depending on your attitude.
Here's an example where we have a faculty person who creates
shall we say a drug. What does that mean?
That means this faculty person developed and created all the
intellectual property associated with this particular
intervention. They did all the animal work,
all the biophysical experiments. They are the world's expert on
this drug. There is no one else who has the
depth and breadth of knowledge about this particular drug,
other than that faculty member. And the faculty member deviates
from reality. He or she goes out and forms a
private company, which licenses the intellectual property back
from the university. The faculty person owns all or
part of the company. The faculty person receives
significant compensation from the company.
The faculty person serves as chairman of the board of this
particular company. So you have the elements of a
perfect storm here. You have the world's expert, the
person who created this intellectual property, and is
fully responsible for it. It's obviously an
extraordinarily attractive property.
They pursue a tech transfer and it's chiseled into Bascom Hall
that we view tech transfer as a good thing.
So they behave by all the good rules.
Formed a company, put their own money into it, stood this whole
thing up. And now we have a massive
conflict of interest. The company wants to pursue a
Phase 1 clinical trial of that drug.
What does that mean? That's the first in humans
study. The purpose of that is generally
to explore toxicity and to a degree, efficacy.
This is a very research interventional trial.
So now we have a perfect financial conflict of interest
storm occurring. Now you have your worst
nightmare with respect to a clinical trial.
So we have lots of faculty issues associated with this.
The faculty person is the world expert in all aspects.
If you ask anyone in North America or Europe, they say
that's the person. They're the world expert.
It's been a major research focus area for the next ten years.
It's quite clear that development of this drug and
related drugs and derivative drugs is going to consume this
faculty person for the next ten years.
So this problem is not going to go away.
It's a problem that's been created that's going persist for
literally, probably, the lifetime of that faculty
person's career at this institution.
Frankly, the work cannot be done without the faculty person's
knowledge. You literally could not do this
particular trial and pursue this first phase of clinical research
without that faculty member being involved.
So I'm building a case here for the strength of the perceptions,
the strength of the needs and the reason why the conflict of
interest committee would make an accommodation on this.
Such a trial poses two conflicts of interest.
One is financial. All right, that's the one we're
talking about. But it also imposes a
non-financial academic conflict of interest.
This is not a peer reviewed federal process.
This is a particular company, a privately owned company that is
pursuing this Phase 1 study. The degree of peer review is
much less than you would get at the NCI or NIH level.
That opens the door for all kinds of potential scientific
misconduct issues associated with it, but are equally as
important as the financial conflict of interest.
These are issues, we know entirely have to be managed from
the first principles. Now what was the school's
response to that? Well, we did a full review and
approval necessary before the conflict of interest committee
review. In other words, this request to
pursue this particular research was thoroughly reviewed at the
dean's level, and resulted in a highly iterative process of
dialogue, probably much to the dislike of the faculty member
that this takes so long to accomplish.
But given the importance of this, this took a lot of
internal review before it even went to the conflict of interest
committee. And what I'm talking about is
what went to the conflict of interest committee was there was
a request to them to make an exception in this case for
participation of a faculty member in this.
Conflict of interest committee responded with a full management
plan. Basically indicating the faculty
cannot participate in this clinical trial without the full
review and approval. The faculty relationship with
the company must have these elements: ongoing management
plan and oversight by the school and the conflict of interest
committee. So this raises the intervention
level fairly dramatically, significantly interfering and
affecting the research output. Study specific provisions are
built into this management plan for the proposed clinical trial.
In other words, the conflict of interest committee reached in
and made particular provisions with respect to how this
clinical trial is going to take place.
And oversight of the future protocol development is clearly
a part of this. So the next stage of this
research is on the table. This interferes with this in a
significant way. For this particular study, what
happened? Well, the faculty person was
limited to preparation of the drug.
This is the world's expert. Sure, eventually other people
will be able to prepare this particular activity.
But in this case, this person is the only person who can
adequately do that. Consultation about dose levels
and timing of administration during the study, because it's
dangerous for the subjects to not have that person comment on
those things. Otherwise, you are at the risk
of misinterpreting the clinical data.
Co-authorship on resulting publications.
Not lead authorship, co-authorship.
It can be a bit of a pill to swallow.
The faculty can not serve as a PI, co-PI or key personnel.
The faculty person cannot recruit patients and subjects.
The faculty person can't make decisions about the
implementation of protocol. The faculty person can't
participate in summary conclusions of the clinical
trial. So the resulting science that
falls out of this, that's fine, but that faculty person can not
participate in any way in those conclusions.
That has to be up to the other investigator involved in this
trial. This is a pretty intrusive
situation. So when we try and put all of
this together, the institution conflict of interest is quite
distinct from and individual conflict of interest.
We haven't addressed the former, and we're trying to address the
latter. I think our management of
individual conflicts of interest is still evolving.
My perception is that how the campus conflict of interest
committee responds is a learning curve.
They're coming to an understanding of what's involved
and what's not involved. I expect that process to evolve
as a function of time. I also expect it to be kind of
bumpy, to tell you the truth. This is right at the crux of the
matter. Institutional conflict of
interest is going to be quite formidable.
It's going to take a while. The University of Wisconsin has
very deep relationships with tech transfer and individual
companies. And avoiding institutional
conflicts of interest is going to be a bit of a challenge.
There's easy stuff to do. I mean, keeping drug companies
out of our enterprise, in terms of buying lunches and putting
pens all over the place, that kind of stuff is really quite
easy to accomplish. I'm much more worried about
where the institution has a potential interest in terms of
licensing intellectual property, and reaches a broad agreement
with a particular entity could be a problem.
A few buzz words that keep cropping up and need to be at
the front. Perception, disclosure, and
oversight and management. I think if I ranked those,
disclosure is absolutely at the top.
The more you disclose, the better off you are.
So where are the faculty on this kind of thing?
Well, there's sort of two perceptions, sort of how the
faculty feel about this process and how society feels about this
process. Just a little bit on how the
faculty feel about the process. ( laughter )
We have the wily fox surrounded by the hounds.
Don't move. Say nothing.
Look straight ahead. They're trying to avoid any
possible difficulty with respect to the conflict of interest
committee. So they would be very cautious.
The perception of how they're behaving by society is quite
different, all right? The crazy clinical rabbits have
been very, very bad again. So the management of these
highly divergent points of view is really a tremendous challenge
institutionally. And unfortunately, I get
dragged in at both ends of the spectrum.
I have to manage the public perception of the problem.
And at the same time, sway the faculty that no, I'm not trying
to put them out of business. I'm not trying to restrict their
research activities. I'm trying to keep things in a
box sufficiently carefully that I don't run into a problem in
terms with perception. I have to tell you there's been
only one, and I won't discuss it, there's only been one
instance where I've had a real problem in the clinical trial
area. It turned out it was not a
situation that would be particularly harmful to the
subjects, but it was a completely abhorrent situation
with respect to clinical trials. There's only been one instance
of that that I've encountered in the ten years that I've been
having to worry about these kinds of things.
So, we're talking about a small slice at the bottom of the pie.
But it's a slice that's pretty important.
So I'll stop babbling. I think I've talked about 45
minutes or so. I'd be happy to not answer any
questions. ( laughter )
Yeah? >> Just in general, does this
affect faculty staying at the university?
Have you heard? >> Yeah, definitely.
If you make it sufficiently difficult for faculty to
rationally pursue their research, they will definitely
find a denominator that works better.
They will find a place where they can pursue their research
in a more fascile manner. No question about it.
I think the biggest troublesome thing for faculty is the delays
this add. This stuff really adds delays.
To get a protocol approved, which is already an exquisitely
painful process, to now add on a conflict of interest issue
attached to that protocol doubles and triples the amount
of time to get something approved.
I know Steve has scars that have been welted on him by faculty
who are just enraged that it's taken this long.
It's not like we're ignoring the problem, it just adds a
significant complexity, which is very frustrating, especially
when, you know, quite frankly, if we're not committing
scientific misconduct, and we're not committing malpractice,
we're mostly worrying about perception.
This leads into my question. That is, are you rooted to the
opportunity costs of taking this very cautious approach to
conflict of interest? Is there some way, have you
started to get some insights on what those opportunity costs
are? You know, delaying in getting
therapies out to help patients. Delays in getting graduate
students their degrees and out to practice.
Because that seems like one of the weapons we have perhaps
available to counteract the poor perception.
Not widely. There are some focal incidents,
you know, it's relatively easy to figure that out.
But they can easily be quite catastrophic in terms of the
opportunity costs. I mean, for example, one of the
reasons we work so hard on our affiliation agreement with
General Electric was it allowed us to be very agile.
So when it becomes clear that you are agile and you can be
highly responsive when the circumstances are right, that's
a big phenomenon. If that particular research
walked out the door and went someplace else, it would be
literally be millions of dollars a year of a loss.
But you know, you're not in the business necessarily to just get
it that way. >> Protocols are many times
where the faculty PI is in consultation of the company
medical officer or scientific advisor.
In your instance, if the faculty member is founder of the
company. What extent the faculty member
can get involved in the discussion of the clinical
trials, as a member of the company, or as an advisor of the
company? Where the PI is not related to
the company. >> The protocol is developed by
the institution not by the company.
Right, but can he participate in discussion from the company,
as a member of the company, with the PI, who is not a member of
the company, to discuss, the institutional PI.
No, I think that's not a situation that I've ever seen.
In other words, let me repeat what I think I heard.
You have a PI who's formed a company.
No, a faculty member from the company.
And an institutional PI, not associated with the company,
submitted a clinical protocol. >> Right.
How does the faculty member, as a member of the company,
allowed to participate with discussions with the PI who is
submitting the protocol? >> They're usually not at all.
Because then they have the potential to bias and affect the
protocol. >> So if I was not associated
with the university whatsoever, and I worked for a company,
would there be a different standard for faculty who had a
company who's working with another PI on campus that would
be a different standard than say, just a PhD scientist that's
with the company that's the expert with the company and no
association with the university, or would that standard be about
equal? >> Generally, I think it would
be about equal. Because the faculty member's
completely isolated from the particular clinical trial.
They don't have any reason to participate in it.
They're not part of a big acquisition.
They're not on the protocol and what they do privately is what
they do privately. But notice that faculty person
is uninvolved in that clinical trial, completely.
You spoke a great deal about compensation directly to the
investigator faculty member and ownership in the company by the
faculty member. I wonder if you could speak to
us a little bit about support for the faculty member's
laboratory and how that might differ.
Yeah, the laboratory support, generally from the company, has
to come in in the form of some kind of contract, some agreement
to accept those funds. I think what you're talking
about is a situation where the faculty member is involved in
some substantive way with a company, and that company then
wants to support research in that faculty member's
laboratory. And to what degree is that
allowed. Well, that's invariably embodied
in the form of either a contract, or it's just an
outright gift. If it's an outright gift, the
gift comes completely unencumbered.
Remember, that's the definition of a gift.
So if the company says I'm going to give $5 million to support
research in this general area in Dr. Smith's laboratory, but how
you use it is up to you, and we have no claim and there's no
intellectual property. There's no issue.
The issue comes if there's a contract.
A contract embodies some thing, okay.
Maybe that contract embodies something to do with an
additional IP that's generated. Maybe that thing has something
to do with the company's resources.
A very common example is the company, the faculty member may
have a totally unique resource, which the company desperately
wants to take advantage of. And the company says I will
support your research for X amount of dollars, but I would
like you to deliver the following kind of product.
That creates a conflict of interest, absolutely, and
definitely requires discussion. It is not, however, forbidden.
That's a different conflict. The most common problem I see in
that area, and it occurs a lot, is when the company is in
essence, hiring the faculty member, the faculty member's
resource, which the faculty member is involved in the
company, to advance that particular research.
There are instances where we've allowed that to go on.
For example, if a faculty member has a totally unique resource,
that it's unreasonable and irrational to expect the company
to have it at that point in its development, and the company
wants to compensate the university fair market value,
we've allowed that for a limited period of time.
But not in any ongoing way. There has to be some degree of
isolation. Did that get at the question?
Any other questions from the audience?
What happens if members of the laboratory of the PI get
involved with a protocol design, for example?
You can't re-label it by having other people do it.
It has to be clean. >> That's the disclosure part.
You can't play games like that.
And if you do, you're going to attract all the wrong attention,
even if it's completely above board.
Why risk something like that? It's just not worth it.
If the faculty member is a clinician, and will he be
allowed to see patients who are in a clinical trial at that
company, and there are separate means.
The trial is run by a separate PI who is not conflicted with
the company. The faculty member is a
clinician who routinely sees patients.
Will he be allowed to see patients who are in the clinical
trial? >> No.
You can't do that. >> Any other questions.
Well thank you, Dean DeLuca, for your good talk.
A pleasure. ( applause )