Clinical Research

All prominent stem-cell transplant programs are involved with clinical research. The goal of that research is to make stem-cell transplantation more effective and safer, to find new indications for the procedure, and to learn more precisely how bone marrow cells (stem cells) work. You probably will be asked to participate in some of the studies currently ongoing within IBMT. In this page we will try to explain what the different types of study are, and what you should know to make an informed decision.

Randomized Clinical Trials

When a new therapy (drug or procedure) has shown real promise, it is important to determine whether this new therapy is more effective than the existing ("standard") therapy. This is studied through a randomized clinical trial, also called a "phase III study".

Since participating physicians might be biased towards one of the therapies, it is important that patients be assigned by chance to the two treatment arms ("randomized"). In case of a drug, often the physician who treats the patient is not aware whether the patient receives the new or the old drug, again to avoid bias in reporting the effects. This is called the physician is "blinded". For emergency matters, a research pharmacist is always aware which drug the patient is receiving. Such phase III studies are generally considered the definitive test whether a new therapy is superior. For drugs, blinded randomized clinical trials are the standard to obtain approval as a new drug from the Food and Drug Administration (FDA). Before official FDA approval has been obtained, new ("experimental") drugs are only available as part of studies.

To make a decision about participation in a phase III study, it is good to realize that this is not a test between a good and a bad therapy. To make it to a phase III study, an experimental drug (or procedure) must have shown real promise in earlier studies (phase I and II). The decision is whether to participate in a comparison between a standard therapy and a therapy which is hopefully better, but might prove to be slightly worse than the standard therapy. Your physicians will provide you with the information they have, but obviously they do not know the future outcome of the study.

At times, randomized clinical trials do not involve a new drug or procedure, but compare two therapies which both are considered standard-of-care. In such situations, nobody can claim that their therapy is better, although many physicians will have a preference for one or the other therapy. That preference has to do with personal experience, style of practice etc., but has no true scientific basis; it is a bias!

Randomized clinical studies can be initiated either by individual researchers or centers, by a group of collaborating centers (eg, Southwestern Oncology Group), or by drug companies. To fulfill the requirements of such studies, extensive records will have to be kept on each patient, and additional laboratory tests are often necessary. Before agreeing to participate, you should ask questions about what additional tests will be necessary and whatever other questions you may have. All data collected about your participation in these studies will be confidential, and submission of data will never mention your name.

Phase II Studies

When a new drug has been developed, it is important to test it for activity under a number of different conditions. For example, a new anti- cancer drug should be tested against different types of cancer to see where the drug is most effective. Once this has been determined, phase II studies try to answer the question exactly how active the new drug is in this particular setting. In the example of the new anti-cancer drug, how active exactly is this drug against breast cancer, which appeared to be the most promising tumor in the earlier studies? To find the answer, many patients with breast cancer are treated with the experimental drug, to determine the percentage of responders and the extent of the response. In situations such as breast cancer, where active drugs are already available, patients are only eligible for phase-II studies after they have failed standard therapy. In situation where no acceptable standard therapy is available, phase-II studies sometimes are first-line therapy.

Patients considering participation in phase-II studies should be aware that they will receive treatment with a promising drug, but that complete data on the chance for benefit and on the risks are not available yet.

Phase I Studies

Very early clinical testing of a new drug will involve treatment of patients to determine the side effects of the drug, the maximum dose tolerated, and a first impression about the beneficial effects of the drug. With anti-cancer drugs, this means treating patients with a wide array of tumors, to determine whether any tumors have a better chance of responding. Since no beneficial effect can be predicted, only patients whose cancers are not responding to standard therapies are invited to participate. Both possible benefit and possible risks are quite uncertain. Before deciding to participate in phase I studies, you should obtain information about the known risks of this drug, and about other experimental treatments. Not trying additional treatment is an option you should also consider!

Some patients are nervous about participation in clinical studies. They may well feel like "guinea pigs" and are afraid that their best interests will not be taken into account. These emotions are understandable, but ill-founded. All progress made in the field on cancer came from the testing of new drugs that proved more effective than older ones. Further progress will depend on patients willing to be active participants in the evaluation of the new generation of drugs. Similarly, randomized studies are the only way to select the optimal therapy from among several good therapies. In many instances, randomized clinical trials are the standard of care. All research studies of IBMT are under the supervision of an Institutional Review Board, which consists of a group of physicians and laypersons who review each study to guarantee that the interests of the patients are protected.

Nevertheless, patients should never feel coerced to participate in a clinical study. You have a right to be included in clinical studies, not an obligation! If you decide not to participate in studies proposed to you, you will receive the same high standard of care from IBMT physicians and nurses as patients who elect to participate. Patients can receive excellent care without ever being part of a research study.

Even if you choose not to participate is any studies, IBMT will still collect data on your therapy, your response and the outcome of the treatment. IBMT is under the obligation to submit outcome data to several agencies. IBMT is accredited by the Foundation for Accreditation of Hematopoietic Cell Therapy (FAHCT). In fact, IBMT was among the first four programs in the country to obtain accreditation from this prestigious body. Submission of outcome data to transplant registries is required by FAHCT (http://www.unmc.edu/Community/fahct/). Similarly, for unrelated donor transplants, outcome data have to be submitted to the National Marrow Donor Program (NMDP). Finally, many large insurance companies require submission of data on all transplants performed in order for a center to obtain "center of excellence" status. For all these submissions, patients will be identified with a "unique patient number" only, and never by name!

If you have remaining questions or concerns, please discuss them with the IBMT physician, clinic nurses, or the transplant coordinator. The patient advocate is the person with the specific role to protect your interests.