Physician Awareness and Perception
of Clinical Trials
Community-based Clinical
Trials
Funding Issues
Managed
Care and Clinical Trials
GREG BERK, MD: Hi, my name
is Dr. Greg Berk from the New York Hospital, Cornell Medical Center. I'm
pleased to have Dr. Anne Mohrbacher, Assistant Professor of Medicine in
the Division of Hematology at University of Southern California here today
to address the issue of physician barriers to patient recruitment in clinical
trials. Welcome, Dr. Mohrbacher.
ANN MOHRBACHER, MD: Good morning.
GREG BERK, MD: Dr. Mohrbacher,
I'd like to maybe open this discussion up with a general sense from you
as to how you feel physician awareness and oncology awareness is directly
toward the involvement of patients in clinical trials.
ANN MOHRBACHER, MD: I think there is quite a disparity
between university-based centers and the community that I think is now
coming to a point where we now have to cross barriers and bring those two
systems closer together. I think the community oncologist tends to think
of trials as something they did when they were back in fellowship and sort
of remain in the university arena. I think we're approaching an era now
where clinical trials really have to be out there and in the community.
Perhaps the university will be the coordinating center, but not the only
place where a patient can go for their treatment trials. I think our goal
for this millennium is to involve the community physician in the clinical
trials process.
GREG BERK, MD: That's very
helpful. Dr. Mohrbacher, there is perception amongst both university-based
as well as community-based oncologists that putting patients on clinical
trials creates a whole new tier or work level, much more work, not just
for the physician directly, but his staff. Can you address that perception?
ANN MOHRBACHER, MD: I do think that's true and again
that's a correct perception. I think for community physicians, really the
only practical way at the present time to enroll a patient on trial is
to send them off to a cancer center and sort of give up control over that
patient's case. Because the HMO and the private practice group and so doesn't
have the infrastructure to run a trial. No physician can sit and
do the detail work that's necessary on a trial. Although it's quite simple
work to do, it's time consuming. That includes needing to check eligibility
lists, read through the protocol, make sure an up-to-date version of the
protocol is approved, schedule quite a variety of tests, and follow-up
on the results of the test and make sure they are in charts. That really
requires having a data manager and usually in addition, a research nurse,
which is beyond the scope of most private practice groups. Even HMOs have
been sort of slow about committing to that kind of personnel.
In reality when I enroll patients on trials, my main work
is thinking in the first place of whether the patient should consider a
trial. I then discuss the trial with them, offer them the time to read
the informed consent and then go over with them whether they feel it would
be appropriate to participate in that trial. After that, I turn the workload
over to the data manager and research nurse, so there is actually no additional
work for me. That wouldn't be the case out in the community center. That's
where we need to think a little more creatively about how we're going to
bridge that gap.
I feel personally the only way to do this is to have data
managers and RNs who are linked to a central study site, such as a university
or academic cancer center. They will be doing outreach to the community
groups or working for an HMO in close affiliation with the university to
basically do that footwork for the trial. It is unrealistic to expect a
physician to pursue those details for a study outside of the immediate
university and even in the university setting. We don't do it ourselves.
We have our support personnel do it.
GREG BERK, MD: There are
many community-based oncologists both in small groups and in large groups
who are really, truly interested in getting involved with clinical trials.
As you know, there are many good studies carried out primarily by the pharmaceutical
companies, that are taking place in the community setting.
ANN MOHRBACHER, MD: I'm always impressed, for example,
by how cardiology studies get done out there in the community, compared
to oncology trials, which traditionally have been almost exclusively based
at academic centers. It's probably just a matter of rethinking how we do
things. They tend to have centralized data collection sites, computer access,
and phone access so the physician really has to do only the most minimal
paperwork or detail work on the study before it's turned over to a central
sight that follows up on it. That is a very helpful model that I think
we need to start thinking about in an oncology setting.
GREG BERK, MD: I think
the physician in the community settings that are interested in doing, many
of them are already aware of this. But some are not. Many of these pharmaceutical-sponsored
studies, much more so than the cooperative-group studies, may very well,
in the budget of these protocols, have the budget built in for additional
data managers, research nurses, etc.
I've seen in the New York area,
more and more sort of community practices pop up doing studies, which is
impressive to me, actually.
ANN MOHRBACHER, MD: Yes. There is still a little
bit of a logistical problem in that. An experienced data manager and research
nurse is—there is no course in college that produces someone ready to go
for you that you can just hire with an ad. It usually is someone who is
self-trained in a system. They got into the area and learned by doing trials
under the apprenticeship system. That is not that easy if you have trials
that have intermittent enrollment. I think that's where my argument for
a bit of centralization of those personnel comes in. Then the money would
help fund those individuals.
It's hard unless you have a critical mass of patients
who are going on a trial. This is particularly true of hematology trials
because they tend to be a scattering of low numbers of patients because
the diseases are less common and there are many different things to treat
them with. It hard to have the critical mass of patients to know that you
can sustain a full-time research nurse or a full-time data manager.
To find people who are really good at that is a whole
other project. You'll find that one good very experienced research nurse
and data manager is worth two novices easily. Spreading that expertise
around is sometime the problem and again, I think [it is] an argument for
a little centralization having more experienced people supervise and train
more junior people who are perhaps out there in the community outreach.
I think one of the other big issues about clinical trials
is, even where available, how do the physicians come to know about them?
The current system is very much a patchwork that relies extensively on
the physician's initiative for seeking out those trials. They have a patient
who has gone through two lines of treatment and they're looking for something
else that they can offer that patient. I think that's where the physician's
desire to get involved in these trials comes in.
It's difficult to identify trials that might be appropriate
for patients. They are scattered throughout individual Web sites affiliated
with the centers that offer the trial. You might have to check the National
Cancer Institute site, the Central Watch site, which is a more global listing,
but by no means complete. [Check] individual universities, perhaps in the
area where the patient lives, or pharmaceutical company Web sites to try
to seek out what trials might be out there.
I know other groups such as Hutchinson tried to approach
this by direct mailing with a brief synopsis of eligibility criteria to
physicians in the area to make them aware of new trials that were opening
up and might be available for their patients. Then there are special interest
groups like the Lymphoma Research Foundation, Cure for Lymphoma, or other
disease-oriented special interest groups that will try to maintain their
own listings or make announcements of new clinical trials.
The process is cumbersome. I still find that sometimes
patients are approaching me with information about—they heard of a trial
in such and such place. It becomes incumbent on me to sort of track that
trial down. It's really not a smooth process.
We don't have a global access system to all clinical trials
available everywhere. That would sort of be a very desirable thing to make
it more convenient for physician to consider getting their patients enrolled
in trials and also seeking out trials that they might want to join—if they're
not already part of a large intergroup such as SWOG or ECOG in the case
of oncology trials.
GREG BERK, MD: Anne, I'm
an active member of CALGB. Our institution has been a member of CALGB since
its founding. We have at Cornell, over the years, put much more emphasis—and
in recent years—in a lot of these pharmaceutical-sponsored studies—
ANN MOHRBACHER, MD: So have we.
GREG BERK, MD: —as CALGB
funding has sort of dwindled down. But at the same time, I have heard from
many of the companies involved in clinical trials that the cost of doing
clinical trials in the university setting and in the big cancer centers
continues to escalate. Do you have any handle on...
ANN MOHRBACHER, MD: I was just reading a little
synopsis on this from the Cancer Journal, I believe, about how the
intergroup trials are grossly underfunded relative to the amount of work
it takes in terms of personnel—data managers and research nurses. That
ends up being a motivation to steer away from those trials. The pharmaceutical
companies vary tremendously, but generally offer just an adequate amount
of money. I think it's got to be somewhere in range of being adequate to
cover the personnel, plus a little extra for sort of the time and trouble
factor. But they can't be so highly paid that it becomes a purely
monetary motivation to enroll patients on trials. I think that would sort
of cloud the ethical issues of why we encourage patients to consider trials.
But it really is sort of a question of what is an adequate
amount of money. As in our case, we are expecting that most of the tests,
CT scans, and so on done for the trial are part of routine care for the
patient. We're not expecting the trial to cover those costs. Insurance
companies have certainly been becoming more flexible and open to this idea.
First of all, I think some of them realize that as the
drug, the main agent, is usually provided free in the majority of trials,
and that offsets the fact that they might do 20 percent more tests than
in routine medical care. Most of them are not particularly objecting to
patients going on clinical trials at this point, I'm finding.
But it does sort of raise the question of what the money
is for. My mind is that the sponsor should provide for the mailing of samples
that they need to do any esoteric tests under their own center in a central
lab, rather than, of course, trying to pay that out to individual centers.
Most of the expense of the trial should be focused on the cost of the data
manager's and research nurse's efforts. That is usually paid on a per patient
basis. It really depends on the complexity of the trial once you start
introducing in terms of how many tests have to be interpreted, how much
data has to be entered, how many meetings there have to be to go over the
charts.
But once you start entering issues about what's going
to be covered or not in terms of clinical care, it's impossible to estimate
what a trial should cost. That's very difficult.
On the other hand, a national intergroup paying say $500
or $1000 per patient and requiring—quite frankly I find usually the intergroup
trials require the most data collection. They add in the most tests, have
the most mailings of special samples, and then pay an inadequate amount
to cover the time that it takes that data manager or research nurse to
participate in the trial. It's somewhere between the two.
I think we are able to make fairly accurate estimates
of what time commitment. A nurse can look at a trial now and say, "This
one is going to take me about as much time as this other one, and I was
able to handle 20 patients a month. My salary is X for a year." You can
pretty much piece it out of the slice of the pie, how much that trial should
be per patient. I think most pharmaceutical trials are paying a reasonable
amount in correlation to the work load of the trial. It's not excessive.
If it were excessive, then that sort of again starts to raise some ethical
concerns.
GREG BERK, MD: Very good.
Anne, I'm wondering if you could comment on what's happening with managed
care's approach to clinical trials in the oncology setting—at least from
your standpoint out in California.
ANN MOHRBACHER, MD: Traditionally they have been
very opposed and everyone has had a global veto line saying, "no experimental
trials." "No experimental therapy will be covered by this insurance."
Many of them, even when they have that clause, have in
fact, been perfectly happy to have patients on trials. I believe that they've
been aware of the fact that we've put their patients on trials. I think
they just want to have a line-item veto to be able to refuse it when they
want to, if an individual trial proposed something extremely expensive,
like a month-long inpatient hospitalization.
In fact, most mainstream insurers including PPO and HMO
plans have been fairly open to this particularly if it's an outpatient
treatment. As long as the tests don't strike them as being wildly out of
line with the routine tests of standard care.
When they start to require inpatient stays, then they
need to compare it against what the patient would otherwise be receiving
at this point in their care. Very often we can justify it on that basis.
We will often end up writing a supportive letter for why
we feel this is reasonable. The drug doesn't cost them money. The inpatient
hospitalization is no more or less than what they would have taken as an
alternative standard treatment at this time. Given the cost of chemotherapeutic
drugs, that ends up being a significant argument. When you pay $5,000 for
Taxol, for example, for a single dose and you're now talking about a one-day
hospitalization with the drug that's free. It doesn't look that expensive
anymore.
What I'd like to see, though, are large institutions like
Kaiser and some of the larger HMOs who clearly have some interest now in
participating in clinical trials. There are some special advantages in
having them participate. They've got a large patient population and relatively
healthy patient population with a central computerized database. That is
a special advantage that you don't have in most other medical centers.
I think they are actually an ideal setting for doing perhaps
some of the late phase II and phase III trials. I don't see them particularly
as a phase I type setting to offer clinical trials in where they have to
deal with unknown toxicities. I think they want to deal with something
that is already a bit of a known entity where the treatment issues have
been simplified, where there aren't dose escalation problems or additional
lab testing.
I think some of the larger HMOs would be the perfect place
to do some of the trials that we look to do in the future. I even have
particular ones in mind, and occasionally can get cooperation, even from
a very traditional HMO, if I have a drug I can offer that's either oral
or has very brief outpatient administration. We have worked out sort of
informal agreements. They will agree to do the blood tests, the CT scans,
the MUGA scan, and the patient will only pay for the drug administration
for the day they come to our hospital—the actual agent. If it's IV, it
usually has to be administered at the site.
That has worked out in a couple of patients cases. But
I'd like to see it done much more systematically. I think the HMOs could
be a very powerful tool for advancing research in cancer medicine. It's
more of a commitment to the idea of perhaps hiring some data managers and
research nurses. It allows some more creative arrangements with research
personnel from another center, interacting with their staff to request
tests and enrollment in trials
GREG BERK, MD: On that
note, I'd like to actually close. I really appreciate your comments on
this important subject.
ANN MOHRBACHER, MD: Well, it’s an important area.
As I've pointed out, with breast cancer, for example, one of our most prevalent
cancers in this country, only three percent of patients participate in
clinical trials. We're going to be stuck at our present cure rate for the
next 10 to 15 years if we don't increase the participation in clinical
trials. It really has to become a routine part of cancer care—whether that
be in an HMO, PPO, or an academic center. I think that should be one of
top priorities in cancer research.
We've got lots of creative ideas that are sitting there
percolating very slowly through the system. We need to get out there and
get enrollment up in these trials. I think there are a lot of safe and
very innovative drugs out there that could be perfectly well-handled in
a variety of settings from the community right on up to the university.
That's one of my big hopes for this decade—that we can
really improve the speed with which we do clinical trials research.
GREG BERK, MD: I think
your comments are really very timely and really helpful in that regard.
And thanks again.
ANN MOHRBACHER, MD: Thank you.
