M. D. Anderson Cancer Center
Date: February - April, 2008
Duration: 0 / 26:55
All right at this point again it's my very much...big pleasure
introducing Michael Rosenblum. He has a very, very long
title. He works here at M. D. Anderson and out of that long title
just remember one word it says Chair, so he's an important
person. Mike and I go back we had a start-up company in fact
together, right?
Right.
And he owns the
Beach Isle and the water that goes to that beach so we're okay you know
so we have a past year and we think back a lot. Mike is the
incoming chair of the Conflict of Interest Committee here at M. D.
Anderson and so he has as well a start-up company himself and where are
you, phase 2 trials right now?
Just getting ready to sort phase 1.
Okay. So, phase 1 trial so he knows all the whole gamete.
He's an inventor. His patent is hanging in his office and he is a
start-up guy raised the money. We golfed and team together and
his company is still in California.
California, that's right.
Okay. So here we have one that really has done it from A-Z and
now is even the incoming chair of the Conflict of Interest
Committee. So, with that, please the last 25 minutes of today
we'll see what we can do, what we're allowed to do and what we're not
allowed to do. The only one word I wanna say before I let him go,
we just heard, the only start-up opportunities is a 100 million and
bigger. I personally don't believe that so if you have start-up
companies there. He's got but he knows. We have an open
discussion on that so if you have another opportunity you still want to
so your start-up and you think its only 10 million or five million, please
come to us. We'll talk about it because that's how start-up
start. What we call start-ups. Okay. So, just I have
said that.
Thanks Oli. I appreciate the opportunity to talk to you guys
today. A lot of the new rules and regulations were in place when
I first started doing this and so hearing about all of this is a little
terrifying, at least to me you know, hearing it all in one Bell's roof
I mean who's scared you know hearing all these stuff. I mean it's
a little intimidating yeah. So Oli he asked me to present
today issues of conflict of interest and the reason that I was asked to
do that is to prevent that "oh, boy moment" that Elizabeth talked about
from turning to an "oh no" moment because there are lot of issues
regarding conflict of interest in academic research today. It's
become a major buzz word and as you know there have been some egregious
problems with conflict of interest. Our job in the conflict of
interest committee is to prevent you from falling into some of the
traps and some of the problems and the best way to do that is by
educating you as to what we can and can't do and why. So a lot of
this information is available on our web site but good luck in trying
to find something on our web site. I will, at the end, provide
you contact information somebody to contact you know, can we do
this? Can we do that? You know, e-mails were fine. No
problem. As Oli I said I'm the incoming vice-chair or I'm the
vice-chair and the chair-elect of the M. D. Anderson Conflict of
Interest Committee. This is a faculty committee. It's
composed of faculty. We have a lot of institutional members who
help staff it but this is a committee run by the faculty itself.
One of the issues regarding conflict of interest, I don't know if you
remember this, this was about eight years ago. There was a doctor who
absolutely insisted in a publication that zinc lozenges would speed the
recovery from colds. Now, what they didn't disclose and what the
New York Times found out was that this guy had stock in the company and
that was before this paper was published. So the question is,
knowing this now, are you sure of the objectivity of this data?
Wouldn't you have rather seen the information in the study that he
owned part of, you know, that he had a financial interest in
this. And so our job again is to help you...is to help prevent
the New York Times from publishing about investigators at M. D.
Anderson or something like this. And so I'm gonna throw in some
quotes. This is a presentation that conflict of interest group
actually will come around and make two various departments. If
you ask, they'll come out and present. So one of the issues about
conflict of interest is that it's the perception that one's judgment
can be influenced by personal interest and that ended up itself
interferes with that person's judgment. It's the perception that
becomes a reality. So that's something that's very, very
important in terms of conflict of interest and that's something that we
really need to be careful about. There was a med analysis done in
JAMA, in 37 studies of conflict of interest. About a quarter of
the investigators had industry affiliations. No that's not
necessarily a bad thing and as you'll see in a minute industry
affiliations are, you know, a lot of people do it and why? That's
where the money is, right? It's not at the NIH anymore it's
within industry. Two-thirds of the institutions involved in this
conflict of interest analysis had equity interest in start-ups and I
will tell you that institutional conflict of interest not just your
conflict of interest. Not from a personal standpoint but
institutional conflict of interest is starting to get front and center
press in a lot of newspapers and magazines and the lay public is very
worried about that and so should we all been. There has been a
correlation between industry sponsorship and pro-industry conclusions
and that's something that really worries us. Industry restricts
publication and data sharing. As you know, if you have a
materials transfer agreement with industry, there will be likely a
clause in that MTA that says you are not likely able to publish
something for 30 or 60 days until the company has an opportunity to
review your publication for likely patentability or conflicts within
their own research so there will be restriction. In fact, it may
be a permanent restriction for new publishing and I urged you not to
try to include those kinds of documents if you can avoid them that
restrict your right to publish documents. This can be seen in a
vacuum. This is an important aspect we understand that here at M.
D. Anderson, we cannot avoid conflict of interest. The issue is
how do we manage it? Number one is transparency and number two is
disclosure. Those are two major ways that we manage conflict of
interest but this has to be seen in a complete environment in which
there are decreasing revenues to academic medical centers. We all
know that that's happening. Managed Cares made major in-roads but
there is a big change in the Paramex, a decrease medicare
reimbursement. There are a lot of uninsured that come in.
The Byh-Dole Act has actually increased the interaction between
industry and academia through a great extent. The rise of
technology transfer--that's mainly a good thing but it can create some
conflicts for you and for the institution. The issue is how do we
manage that? Also, everybody's got a company. I think
that's kind of cute if they put that in but everybody's got a
company. I have a company. Oli has a company and several of
us. Dr. Metha has a company, several companies. He's a
serial entrepreneur. There's also a demand for science that
benefits men and women rather than mankind. And the last but not
the least, in fact, this should be first is greed--both personal and
institutional level because of all the other issues that are
above. So, we have a major issue in erosion of the public state
in the reliability of scientific findings that may be one of the
greatest harms that result from the strengthening of the ties between
industry and academia and I believe that Dr. Harrington was absolutely
correct when he published this. So this is a major problem that
we have to address. So, what are the final interactions that we
have as faculty members here at M. D. Anderson? Well, one is
research support. We all have the opportunity of having research
support from commercial groups. You can be a consultant.
You can serve on an advisory board. You can serve on a speaker
bureau. You can get royalties and licenses. You can
actually go straight if you really want. You can have a promotion
at sponsored symposiums. You can have your way paid. Go to
Merck-based presentation. There are a number of gifts and trips
that are available and equity and options that you can get from
industry. Few more facts, 70 percent of the money from clinical
trials in the US now comes from industry. Big money, big bucks
involved. Community physicians' officers are replacing academic
medical centers. This is a true fact as the site of choice.
This threatens the revenue stream for academia. Now, I don't
think we have a problem at M. D. Anderson than choosing M. D. Anderson
or a smaller doctor's office versus M. D. Anderson, that's really not
an issue. It's mostly for smaller medical centers but this is a
choice that some groups are making in terms of evaluating particular
drugs. Academic medical centers, offices of sponsored programs
and IRBs take time. There are months and months and months of
delays at our IRB and that's why there are now four, count them, four
IRBs, five, five? Five, five IRBs? Okay. It's the
other date. I was wrong. There are now five IRBs that try
to take a load of. I remember back in the day there was only one
IRB. It took like six months to get stuff through trials.
And everyday of delay can cost the company a million bucks or so.
Contract research organizations are playing a much larger role in
industry sponsored trials. What do industry sponsors do to
influence study outcomes? We'll they can opt not to do a post
approval study and we've seen that in some of the major problems, some
of the major drugs that have been recalled because there have not been
post large post approval studies. They fear that the results
could negatively impact drug sales. Particularly for something
that has been approved. Study designs could favor sponsors
product. Use of the younger population that is targeted for the
drug or the dose of the competitor's comparison drug is too low.
So these are a number of the things that industry can do to change the
competitor and make sure that their drug comes out on top. Use of
a surrogate endpoint. This is a hot button item right now.
Some of these surrogate endpoints may not be reasonable--that is they
may not correlate with meaningful clinical results and actually the
agency of the NCI and the FDA are struggling with issues regarding
surrogate endpoints. Another thing that industry-sponsors do to
control study outcomes, they control the data. Participants don't
get to examine all the results. Some phase 1, phase 2, and phase
3 studies are multi-institutional. The companies serve as the
clearing outs for all of the study participants. So all of the
data goes to one central source and that is the company. They
also control publications including the order of authorships, I mean,
who want to be stuck as 24th author in a 50-author publication. I
mean, you know, where do you get the benefit there? Sometimes
results don't get published at all. We've actually seen that,
right? There have been some high profile studies that were done
but never published or published in some obscure journal that nobody
reads. And lastly, which I have to giggle about is, some
publications are ghostwritten by company authors and in fact sometimes
we see people making presentations, faculty members, not necessarily
from this faculty but other faculties making presentations for major
company which the company supplies not only the slides but the analysis
of the data and gives you sort of a list of things that they want you
to say about these particular slides. So ghostwriting, not only
publications for presentations, really influences study outcomes.
We're primarily concerned just sort of bringing it back to us is a
conflict of interest--that is, a set of conditions in which
professional judgment concerning primary interest that is patient's
welfare or the validity of research tends to be unduly influenced by a
secondary influence and that is financial gain. And what are the
kinds of things that we're concerned about? Gifts, hospitality
subsidies offered by physicians and non-physicians, by the
pharmaceutical industry should not be accepted if acceptance might
influence or appear to others to influence the objectivity of clinical
judgment. I don't know if you know it or not but UT Health
Science Center in San Antonio now has a zero-policy for acceptance of
anything from industry--that is you can't walk around with a Merck pen
or an M-gen part of paper of any value. So there are groups that
are really going overboard I think in terms of accepting gifts from
industry such that the appearance of impropriety is completely
ablated. We are trying to avoid that. So this discusses how
could conflict of interests influence the oversight of human subject's
research, inadequate disclosure of risks to patients, exaggeration of
benefits, enrolling ineligible subjects. We don't really have
that problem here because we have an IRB which is very, very on top of
things. Failure to report adverse events and data manipulation,
we really don't see that happening in these kinds of trials but it
certainly is possible. Failure to suspend or terminate a trial;
actually our IRB is outstanding in terms of that. Once you have
reached enrollment number of patients there they jealously guard that
number that you put in that you say that you're going to use. So,
in 2003, September 1, M. D. Anderson launched a new fairly inclusive
and moderately restrictive policy. This was a policy that was
about eight months in the making but this was a policy that was, for the
most part, driven by the faculty. So, to a great extent, the
faculty here at M. D. Anderson rewrote at the urging of others
non-faculty members that we rewrote the entire conflict of interest
policy. The purpose, the number one purpose is to protect
patient's safety and to safeguard the institutional reputation and
integrity, that's the number one purpose. We require disclosure
of all potential conflicts, that is a disclosure from you of all
potential conflicts and we will permit relationships with poor profit
companies as long as it furthers the M. D. Anderson mission,
okay. So, this is a very important aspect. Disclosure
number 1C is probably the top number one thing that people are gonna
get in trouble about, not disclosing. The conflict of interest
committee was then set up. It was always in place but the COIC
became responsible for assessing compliance that is looking at the
compliance across the institution and reviewing conflict of interest
management plans for people who were doing a sponsored research with
companies to which they have an equity ownership and I will get into
that in a minute. Full time faculty member trainee or
institutional decision maker, their primary employment responsibility
is to the M. D. Anderson and that is one of the driving factors that
cause the change the conflict interest policy. You cannot serve, as a
member of the Board of Directors or officer of poor profit company or
the competitor of the M. D. Anderson Cancer Center. Now, as Tom
Lee mentioned, if you really need to serve on the Board of Directors of
start-up for instance, with presidential approval, you can request
that. It's not always granted, it is frequently granted.
But you have to have a darn good reason for it. M. D. Anderson
conflict management policy has set limits on the amount of consulting
that you can do. Fifty percent of your base salary in 12 months
from all sources of consulting--that is if you make 10,000 dollars a
year, only 5,000 dollars you can get from outside sources and only 25
percent of your base salary can come from any one source and that's
because we don't want a major pharma or something having all of
your...having you beholding to one major company for all of your
consulting opportunities. State resources such as M. D. Anderson
property can't be used for any aspect of your consultancy or employment
with an entity other than M. D. Anderson and the same is true with the M. D.
Anderson name. You can't use M. D.
Anderson name
inappropriately. No research is permitted in which payment
depends on specific outcome. It sounds silly but believe me we've
seen it. Extramural leave, there's a 30-day limit on an outside
interest. This is using your extramural leave. Outside of
the 30 days you have to use your vacation time. Additional time
for extra mural leave could be granted by the president of your
activities for which you are receiving no professional financial
gain. Financial relationships, full disclosure is required with
the conflict of interest and that includes unfortunately families,
spouses, dependent children, family trust or corporations or other
known relationships. Obviously, you can't disclose relationship
if it's not known to you but all the known relationships of financial
nature. You need to do full disclosure and publications and oral
presentations. Almost all of us have now slides which say, you
know, you're gonna hear some information on company X and by the way
I'm a consultant for company X and I own, you know, stocks in company
X. So you really need to do that and in publications as
well. And in fact, many of the publications will ask those
specific questions anymore and those will appear in your
publications. Another aspect, if you would have been asked to be
an expert witness or medical consultant that money for that activity
goes to physician's referral service by contract. If you're
involved in negotiations, you cannot negotiate with an outside entity
when you're here at M. D.
Anderson. If you have an equity interest
in that company, if you have a consultancy that is paying you greater
than 10, 000 per year or if you serve on a scientific or advisory board
for that particular company; this does not include research
agreements. Without human subjects faculty can hold equity in
companies that sponsor your research. A monitoring plan, a
conflict of interest, a monitoring plan has to be in place to manage
that interaction. There are limits. You can have more than
50% interest in a privately held company. You can have
more than 5% interest in a publicly-traded company and you have
to have less than 20% interest in a private company at the IPO
launch. Trainee participation is voluntary in research programs
if the supervisor, if your supervisor has both equity interest and
receives or search support from that particular sponsor. Any
holdings in consultancy or consultancies have to be disclosed the
entire research team annually. My research team gets a letter
from me, a hardcopy letter which discloses all the consultancies and
equity interest that I hold. They're asked to sign that that has
been disclosed to them and I keep that on file that's required in my
conflict management plan. In terms of human subjects, you can't
be paid for enrolling patients in the trial. In fact, you can't
be the principal investigator or primary physician for a patient on a
trial if, here she has an equity interest in the sponsor or receives
cash greater than 10,000 dollars a year. This is a really
critical issue that maintains the integrity of our clinical trials and
that is the number one thing at the M. D. Anderson that were known for
as our clinical trials and we are really zealous about the guardianship
of this particular aspect. So if you want to run a foul of any of
the rules at M. D. Anderson, please don't run a foul of this one.
Any equity or cash received by non-PI members of research team, as an
executive of the institution itself, should be disclosed in the consent
document that is in the phase 1 or phase 2 or phase 3 consent
documents. The patients have a right to know what equity interest
a physician or managing physician has in a particular study. In
terms of supervisory rule relationships, we've looked at that as
well. The direct supervisor can't oversee approval of another
person's compliance with time commitment limits if the supervisor has
equity or receives greater than 10,000 per year from an outside entity
for which the supervisor has commitment. This is really very
important. A supervisor may hold no equity interest greater than
10,000 dollars in an outside entity sponsoring research which is
directed by a faculty member which reports to that supervisor.
Institutional decision makers--the leadership can't hold equity or
receive cash greater than 10,000 a year from any outside entity
sponsoring him in subject's research when M. D. Anderson faculty member
is the PI. Exception is if the trial is multi-institutional, PI
is elsewhere, the data management is elsewhere and M. D. Anderson
doesn't hold the R and D. What are the types of business
interests that we're talking about; pharmaceutical and medical device,
biotechnology and software, chemicals, firms raised in capital for the
above and M. D.
Anderson competitors. So, we have a lot of these in
the data base. We maintain a fairly sophisticated data base that
cross-checks all conflict with faculty members particularly as they
relate to the clinical IRBs and that probably the number one issue that
we are concerned about is the integrity of clinical trials but we
maintain this data base for faculty and trainees to submit disclosures
and annual certifications. I'm sure all of you, if you've been
here at least a year, you've seen the annual certification that comes
out I think in October. You are asked to certify that you have or
don't have or if you have these are the conflict of interest things
that you do have. We track and report these conflict in interest
issues and circum plans with the federal state and local rules and
believe me, if we don't, somebody else is gonna do it and they're going
to impose rules and guidelines that are much more restrictive than what
we have here at present. It's not a complicated issue when you
are in any doubt you need to disclose. It's confidential and it's
an automated process so please go ahead and disclose. We think
without this, as Cathy De Angelus said that the institutions where
clinical research is based and faculty members who perform this are in
grave danger--grave danger of losing the support and respect of the
public. We cannot lose that. Without the support, trust and
medical discoveries in their applications will not be
forthcoming. Medical research is doomed without this trust.
Matthew Davis and Laura Vincent in the Office of Research
Administration, this is the phone number 792-3220, please give them a
call. You can pin me. I'll be glad to help you if you have
questions and I'll be happy to take any questions you have now.
You've mentioned 50% equity in private companies, is that the
same for start-up companies? Is that what you're pertaining to?
Yeah. Right. That's what we're talking about.
No questions now.
© 2007 The University of Texas M. D. Anderson Cancer Center
1515 Holcombe Blvd, Houston, TX 77030
1-800-392-1611 (USA) / 1-713-792-6161