9UNP0138SD_Paul DeLuca_WordPRess

- 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)