VOLUME 25 - No. 3 - MARCH 2001
Mitchell retires but will stay until new CEO is on board
MedRec archival system set for April launch; complements LastWord physician order entry
Dermatology expands outpatient services for skin cancer, aesthetics and rejuvenation services
Books on the desktop: e-Books available through Health Library
Q: What is the purpose of your office.
SIKIC: Our mission is to provide the infrastructure to facilitate new therapies for cancers.
Q: Have community physicians actively supported the CTO and clinical trials at Stanford?
SIKIC: The large majority of physicians - including myself - who treat cancer aren't satisfied with the treatment they have to offer patients. We as a community of physicians who treat cancer have a strong interest in improving current therapies that we recognize are far from perfect and, in some cases, are ineffective. So most practicing oncologists are very open to referrals of patients for trials. Those of us involved with the Clinical Trials Office are committed to a collegial relationship with referring physicians and to caring for these patients together. We make it a point to communicate with the referring physician about the progress of the patient and about the nature of the trial. Usually the patient goes back to the referring physician after the trial. We'd like to consider the referring physicians as partners with us.
Q: Is that where the Community Affiliates Program fits in?
SIKIC: Absolutely. One of director Charlotte Jacobs' initiatives for the Clinical Cancer Center has been to build a community affiliates program between Stanford and Northern California medical centers and large private groups. The major goals of the affiliates program are to facilitate the partnership between referring physicians and Stanford in clinical research, to make innovative therapies available for patients from those practices and medical centers and to encourage them to work with us in therapies that may at times be administered in their own practices. It really is a two-way street. They may send us some patients whose treatments, including specialized tests, may only be done at Stanford. Sometimes the FDA or a company will mandate that a phase I trial may only be done at one center because of unique risks and the need for uniform observation and follow-up. On the other hand there are other trials that can be done in the community that may be initiated at Stanford or centered at Stanford, but where we share protocols with our affiliates.
GREKOWICZ: The pattern that we've seen is that patients will come here for their trial and then return home to see their oncologists and family physicians. Patients tend to want to be treated locally. And we're willing to train their personnel as well to make sure that they are ready to do the trial at their site.
LUM: The affiliates program involves the networking of knowledge and the ability to facilitate patient care - including transfer to Stanford for appropriate referral services.
YUEN: I think the trials office is a useful focal point for our affiliates, as well as a central place for us as researchers to come to.
Q: That brings up an interesting point. Is centralization an advantage or just more bureaucracy?
YUEN: It's always a double-edged sword. With a central office you give up your control over hiring, but it simplifies the process. I think what Stanford is doing here now with the trials office and other enhancement provides much help with little or no downside. Some institutions have almost all of their trials processing centralized. The University of Michigan is one example.
Q: At what point do researchers usually come to you?
GREKOWICZ: When they have a protocol that they're interested in. We can get the logistics off and running from that point.
Q: What do you do for researchers?
LUM: Depending on the investigators we really try to "handle" all aspects of clinical research. We go beyond trials administration. For example, Brandy and I do a lot of "shopping" for trials at all levels, especially for phase I and II trials targeting a specific tumor type and innovative therapies.
SIKIC: Bert has special expertise in cancer pharmacology in the area of drug disposition and how drugs are handled by the body as well pharmacokinetics and pharmacodynamics, and so he is expert in those areas in cancer. He also has a strong biostatistical background. One of the resources we offer to investigators is advice on design of studies and analysis of data, in large part based on Bert's expertise and my own.
GREKOWICZ: We've started building databases for each individual trial so researchers don't have to shop around for someone to put that together for them.
Q: Can you give some examples of agents you have brought here for testing?
SIKIC: We've started the first pivotal trial, phase III, on an antisense DNA drug, [Antisense altinucleotide DNA drug, Isis 3521, from Isis Pharmaceuticals Inc. in San Diego] that Bert, Alan, oncologist George Fisher, staff physician Ranjana Advani and our research nurse, Joanne Halsey, have been working with since the earliest stages. This is particularly patient-friendly because all patients will receive standard chemotherapy. In phase I and II, we showed that the antisense drug plus the standard treatment of carboplatin and paclitaxel produced results in lung cancers that were markedly better than historical experience with the chemotherapy alone.
Q: Alan, how has the CTO helped you as a junior faculty member?
YUEN: On the planning level, the CTO team was helpful in terms of picking up on things I might not have anticipated. For example, they were helpful in identifying where treatment could be administered, what skill level was required and how to incorporate that into the budget. The trials office staff arrived at a budget they thought was fair and in several cases negotiated with the sponsor, which helped me stay out of that loop. It's helped me reduce legwork enormously. In the past, I needed to develop a budget, calculate the personnel and estimate all costs. Some of the details are fairly rote and routine, but they are time-consuming, so it's better when they are done by someone who is familiar with the process.
Q: Can you cite an example?
YUEN: Pricing requires someone who has contacts with laboratory or radiology suppliers familiar with research pricing and also what elements need to be included. I'd often have to make multiple contacts before I found and received the lower research rate. The details change constantly. Knowing that there is a research rate is far different from finding out what that rate is.
Q: Don't you as a faculty member have support staff?
YUEN: Certainly I do have some access to support staff - particularly on an ongoing project. What's difficult is having support designated during the start-up phase. Also multiple trials can quickly overburden departmental support. For example, I went to the CTO with three trials in quick succession, so I was grateful for their resources during the "surge" period. Along those lines, I think the trials office will be especially helpful in the future in providing a pool of research personnel so researchers can gain the support of partial personnel. As an individual, it's hard to plan time for a data manager or research nurse. At any given time you may not need a full-time person - you may need a half-time person, a quarter-time person, a 10 percent person. That's particularly true with people just starting out. Sometimes we can piggyback onto some downtime of another researcher.
LUM: Once the protocol has been established, Amy becomes actively involved in taking over the regulatory affairs management of the trial. Amy will prepare a trial, send it off for IRB approval and work on the budget to send over to the contracting office. Then she'll work with the Research Management Group at Stanford to make sure all the necessary elements are in place. Even after approval, Amy has been very involved in programming clinical databases to collect data for trials. For the ISIS protocol she developed databases for Joanne Halsey, the research nurse, to enter data and do reports so that we can monitor response, toxicity and other factors.
Q: Is the trials office primarily set up for industry contracts or government-sponsored research?
YUEN: The trials office seems particularly useful in industry contracts where there appears to be more room for negotiation on details of the protocol and reimbursement.
GREKOWICZ: We're perfectly comfortable working with NIH or other government grants, but right now the vast majority of our protocols are with industry. By the way, Alan already had research staff onboard for his latest trial, but we could have helped him with that as well.
Q: Can patients contact Stanford directly to find out if they're eligible for an available trial?
GREKOWICZ:
Patients do this all the time. They access our Web site [http://cancercenter.stanford.edu].
Sometimes
patients find a trial through the NIH clinical trials Web site or other
informational sources, such as Stanford's Health Library
[http://www-med. stanford.edu/healthlibrary/], or 650-725-8400.
Q: What is your relationship with ACCESS?
LUM: We work very closely with them. In the cancer clinical trials office we've really stayed out of the systems and process part of the issue and we've gotten more into the hands-on aspects of, "let's take it to IRB, let's take it to contracts, let's hire people for you to do your research." So we're really in the trenches, day in and day out. We're an operations center; we're a launch pad.
Q: How do you relate to the Research Management Group?
LUM: We work closely in terms of budget processing. They help us ensure that all the necessary budgetary elements are in place for a successful clinical trial at Stanford. Is your budget designed so there is enough money to have research personnel? Are all the laboratory tests or necessary exams, such as chest X-rays, that are research-oriented budgeted for? They've helped us to determine how to best design our budgets.
GREKOWICZ: I've worked proactively with the research process managers, so when we send a protocol over they aren't going to send it back to me and say, "This is insufficient." We are not going to waste time bouncing it back and forth. I will try to cover everything, give them what they want to see.
Q: Do you think cancer has some unique requirements that make conducting clinical trials systematically different from other disciplines?
LUM: I think you might find a variety of opinions but the longer I spend in the trenches, the more similarities I see than differences in terms of the research process. There's a very generic pile of stuff that doesn't matter whether you're putting a pacemaker in somebody or a shunt, or trying a new anti-cancer agent. Cancer drugs are somewhat different in that many have toxic properties to a greater degree than other drugs, but the more directed biologic and molecular targeted therapies are changing that somewhat. But the process of getting those drugs on the market for all patients is still the same.
Q: So do you envision a single trials office at Stanford someday?
LUM: Consolidation might be possible if there were an institutional consensus. I think we are developing some expertise which could translate to other disciplines. But our goal is to run the best cancer trials office that we can, working closely with other offices throughout the medical center - and the research and clinical communities.
Q: What else do you support besides trials?
SIKIC: We build and support a research network; we hold brown-bag lunches for research nurses, data managers and research assistants who do clinical trials. These are held every two to three months.
LUM: We also have the clinical trials forums. In those monthly morning sessions we usually have two presentations of a clinical trial. One is a developing trial at Stanford, something that is just being put together, often by a junior faculty member or a fellow. The other presentation is a more mature clinical trial with at least preliminary data. The majority of presentations have involved medical oncology but they vary across disciplines and have included radiation therapy, pediatric oncology, immunology and vaccine trials.
SIKIC: We also have had scientists from industry come and tell us about some of the exciting new drugs being developed. We stress translational aspects of the clinical research. Most of our presentations are really of interest to anyone who is interested in cancer therapy, whether it be a student in cancer biology or medicine or a trainee, or somebody who is actively working in the area.
LUM: The forums help build a Stanford community of knowledge so that the faculty, fellows and research personnel know what's going on here. So if a patient calls and says. "I have lung cancer, I'm looking for a trial, would doctor so-and-so's trial work for me?" then the research nurse might be able to say, "No you're not eligible for my trial, but Dr. Yuen has this trial that you may qualify for." The third component is general clinical trials methodology. So even if the immunologist comes to the clinical trials forum on pediatric oncology, the basic concepts of clinical trials design and implementation and the generic thought process of clinical research is a part of that meeting. It's really a no-lose situation.
Q: Are there any benefits to patients for participating in phase I trials?
LUM: Patients may find palliative care benefits, particularly if they have exhausted all current FDA-approved treatments. We may see quality-of-life improvements from the therapy itself or from better management of nausea or pain medications. This also applies to patients in phase II and III trials as well.
SIKIC: It's true that historically the chances of obtaining remission in the first stages of a phase I trial have been low, but that may be changing. There are particular kinds of phase I trials where the chances of a remission may be very high. For some trials, we are continuing standard drugs in combination with the investigational agent, so what the patient gets is value-added. And remember, all of our best cancer drugs were first used in phase I cancer trials. For example, remissions in breast and ovarian cancers were observed in phase I trials of liposomal doxorudicin or pacliltaxel. That includes ovarian cancers that hadn't responded to other treatments.
Q: Overall, what would you hope to achieve in the next decade in terms of drug development?
SIKIC: Bringing new drugs to patients that are more specific for cancers, that are likely to be less toxic and that are targeted at rational biological targets. I think it will be more likely than in the past to produce remissions, or at least offer disease stabilization. One of the goals of these new generations of treatments is to convert many cancers that are currently deadly into chronic diseases. If we could make a cancer, such as breast or lung cancer, into something like mild hypertension or diabetes, that would be a great victory. I think that is achievable.
