Importance of Clinical Trials

	Dr. Nancy A. Kernan Assistant Chief, Bone Marrow Transplant Service and Chair of the Board of Directors of the National Marrow Donor Program

Nancy A. Kernan, Assistant Chief of the Pediatric Bone Marrow Service, is a member of the Memorial Sloan-Kettering Research Council, which sets the research agenda for the Center. Dr. Kernan reflects on the enormous value and impact of clinical trials to patients.

"This work is truly exciting to be a part of. What has been done in leukemia, for example, is an achievement that is unique to pediatric oncology. In the past, all of the children with leukemia died from their disease. Today, the overall survival rate is 72 percent. These children grow up to become adults living normal lives. It is truly gratifying to watch former patients go off to college and later get married. Our next challenge is to take the 72 percent and raise it to 100 percent.

"An example of a clinical trial that had a tremendously positive effect on our patients was using unrelated donor marrow transplants to successfully treat blood diseases such as leukemia. We did our first unrelated donor transplant at Memorial Sloan-Kettering in 1988. Before that time this treatment didn't exist. Today it is considered a true curative treatment option for a patient." Possible matched donors are located through a centralized data network known as the National Marrow Donor Registry. The National Marrow Donor Program now facilitates 100 to 125 transplants a week nationwide.

Approximately 75 percent of children with cancer in the United States will be treated on a clinical trial, also known as a protocol. This number is in sharp contrast to the 1 to 5 percent of adults with cancer who are enrolled in clinical trials.

How are clinical trials initiated at Memorial Sloan-Kettering? "It's a complex process, involving an enormous cooperative effort among physicians, scientists, and other health-care professionals. Our protocols are written at a very high standard and subjected to intense scrutiny, both internally and externally," says Dr. Kernan.

"Typically, a clinical trial is initiated by a physician who believes a new drug could be effective based on laboratory studies. The first step is that a protocol is written and circulated within the Department of Pediatrics as well as outside the institution, if the study is to be performed at more than one center. If a drug is new and not commercially available, the protocol must be also be acceptable to the company that will manufacture it as well as to the Food and Drug Administration's Investigational Drug Committee, which issues new drug licenses. All parties -- from the investigators to the pharmaceutical company -- must agree that the drug will be used as proposed in the treatment plan.

Once the protocol exists, then the consent form, which details the possible risks and benefits of the study to the patient, is written by the physician who is leading the trial.

"If other specialties are to be involved, the protocol is reviewed by members in the participating departments," explains Dr. Kernan. "For example, if a new drug is going to be tested for its effect on a tumor, it's necessary to have a radiologist who will agree to measure all the tumors for the protocol. Once all the involved departments have read and signed off on the protocol, it is reviewed by Memorial Sloan-Kettering's Research Council. Upon the Research Council's approval, the protocol is presented to the Center's Institutional Review Board (IRB).

Any hospital that carries out research with people has an IRB. This board reviews all new studies to make sure that the patient's rights and welfare are protected. The board evaluates whether the potential benefits for the patient outweigh the foreseeable risks and whether the consent form adequately informs the patient of the risks.

Once a clinical trial is approved, eligible patients are enrolled in the study. The results (toxicity and responses) are monitored regularly by individuals trained in the conduct of clinical trials. Once a year the IRB reviews the progress of the trial to determine if it is safe to continue the trial. Every clinical trial must be approved annually, for as long as the trial is open.