Important clinical trials are routinely left empty. Why?
The Lymphoma Research Foundation (LRF) interviewed Dr.’s Vose and Fisher, members of LRF’s Scientific Advisory Board.
Clinical trials have defined the way the majority of patients are treated in America today. Through this mechanism, trial drugs get tested, evaluated and either are rejected or incorporated into treatment. Clinical trials, however, are woefully under-supported. What barriers exist to getting patients into these trials?
Julie M. Vose, M.D.,
Neumann M. and Mildred E. Harris Professor,
Chief, Hematology/Oncology, Professor of Medicine,
Nebraska Medical Center
Richard 1. Fisher, M.D.,
Samuel E. Durand Professor of Medicine,
University of Rochester,
Chief, Hematology-Oncology Unit and
Director of Cancer Services, Strong Health and
Director of James P. Wilmot Cancer Center, Rochester, NY
Q: What is your interest in this subject?
Dr. Vose: My clinical focus is to improve the treatment of patients with lymphoma. The only way I can do that is through research and then applying that research in clinical trials. It's the core of my work. For example, the efficacy of such important new drugs as Rituxan® and Bexxar™, used in the treatment of relapsed lymphomas, were discovered through clinical trials.
Dr. Fisher: I've been a clinical investigator, especially with lymphoma, since 1975. I conduct not only local trials, but trials for the National Cancer Institute. One of the largest trials I've run was the National Higher Priority Lymphoma Study published in the New England Journal of Medicine in 1993. The study compared four different chemotherapy regimens to determine which was the most effective and least toxic. That study changed the practice of medicine in this country by essentially eliminating the use of toxic, more costly, but not more effective treatments being widely used at that time.
Q: How are patients recruited for clinical trials?
Dr. Vose: Patients are usually referred by a private oncologist, who in some cases tracks the trial in his or her own office. The trial must be explained to the patient, consent forms need to be filled out, the patient monitored while on therapy, and results observed and recorded. This can entail lots of data and paperwork. In some instances, clinical trials are held at specialized medical centers in larger cities, and patients may have to travel.
Dr. Fisher: I would say about 80% of clinical trials are conducted in a doctor's office where the patient already goes for treatment. Also, there are now increasing numbers of patients who seek out trials. This new advocacy group, which includes members of LRF, researches the Internet and is more vocal about ways they want to be treated.
Q: Do doctors routinely inform patients of clinical trials?
Dr. Vose: Not always. Many clinical trials are not being filled, or they're filled at a very slow rate. Only about 2% of adult cancer patients participate in clinical trials. For example, we were unable to complete a recent monoclonal antibody trial here due to lack of referrals. We needed 15 people. We had three. It takes a lot of time for oncologists to explain the procedures, to fill out the paperwork. Most have very busy practices. And they're not reimbursed for the extra time they spend, or for the staff hours needed to track results.
Dr. Fisher: Some clinical trials require the doctor to fill out a 150-page notebook, per patient. As they say, time is money. It's far easier and economically profitable for doctors to just treat their patients rather than introduce a clinical protocol.
Q: What are other reasons doctors may not inform patients about clinical trials?
Dr. Vose: In some cases, doctors may be afraid a patient may not be referred back to them after the trial. They will lose the patient. This is more of a concern if the trial is conducted at a medical center. This occurs in a minority of cases.
Dr. Fisher: Doctors feel they should give the patient the best answers when it comes to treatment options. They may feel that it's not exactly an indication of their expertise if they're sending a patient off to randomized trials to find this out. That's a minority of doctors, but they do exist.
Q: Does the insurance industry, especially the proliferation of HM0s, act as a barrier to filling trials?
Dr. Vose: Yes, that is a barrier. With many of the HM0s, patients can only be treated at certain centers. It's almost impossible to get a referral to a major medical center. In my opinion, those patients are not being offered the best care. All possible treatments are not being made available to the patient.
Dr. Fisher: This all goes back to the question of money. Insurance companies want to save money. Even if the trial delivers standard therapy, insurance companies often refuse the cost because it's labeled as "research." This problem is not unique to just HMOs, but occurs with other insurance companies as well. Some states have now passed laws mandating coverage of cost of care on clinical trials by insurance companies.
Q: Are patients sometimes reluctant to participate in a trial?
Dr. Vose: Sometimes a patient may think he or she will be treated as a sort of guinea pig. The thought implies that we would test any old mix of drug on them. Patients need to realize that before any drug is introduced into a clinical trial, it has been through exhaustive testing already, in the lab and on animals. They're receiving a drug that is based on our best information of what would be beneficial to them.
Dr. Fisher: Patients will sometimes be concerned that a double-blind study is being conducted, one in which there's a chance they would receive a placebo, representing no treatment at all. But in oncology, you rarely get a placebo. You're always getting what the standard of care is. Also, some patients just don't want to be randomized. They want to have their choice of treatment. The problem is, unless we do a clinical trial we don't know what the best choice is.
Dr. Vose: Patients should realize that in a clinical trial, they will receive at least the standard of care, and usually above the standard. Also, they will have access to the newest drugs for the treatment of lymphoma, the ones that have been determined to hold the most promise. There have been some studies conducted that show that patients almost always have a better outcome in trials, compared to patients who do not participate.
Q: What are some solutions to increasing participation in trials?
Dr. Vose: We need better education for the patient. They need to know what is available to them. When a patient is first diagnosed, it's often a very traumatic time. They need to be encouraged to get second opinions, research what treatments are available, and get the very best therapy for their condition. Also, insurance companies need to pay for patients on clinical trials, a battle which is best fought through the legislature.
Dr. Fisher: When training physicians, we need to continue to instill this fact: part of their purpose is to further progress in the treatment of disease. The primary way they can accomplish that is by putting their patients into clinical trials. It's largely in the hands of a physician seeing the patient to make the recommendation. Some do that very well, some never dothat and some occasionally do that. We have to increase the group that occasionally does that. We can make it easier for them. Simplify data forms. Reimburse their costs for the extensive time it takes to fill out forms. Doctors do not make money on clinical research. It helps to appeal to their altruism, but we need to reduce the burden and sacrifice it places on their practice.
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