Why are children enrolled in clinical trials?

Because clinical trials offer the most up-to-date treatment available, children who participate in a clinical trial may benefit from the newest research. Most parents derive comfort from knowing that the knowledge gained will make an important contribution to medical science, and may help other children with cancer.

What is standard treatment?

Most clinical trials divide patients into two or more groups (arms). One arm of the trial is the standard treatment, and the other arms are the experimental portions, which scientists hope will prove to be more effective or less toxic than the standard treatment. Each arm is based on preliminary, but not conclusive, information that it will be beneficial and is carefully reviewed by experts in the field before implementation.

What is randomization?

At the time the clinical trial is designed, there is no conclusive evidence to indicate which arm will prove to be superior. It is not possible to predict if your child will benefit from participating in the study. Most arms incorporate standard therapy and only a small portion of the arm contains the experimental agents. Experimental drugs have usually been used previously, but their efficacy in a given circumstance may not be known.

We had a hard time deciding whether to go with the standard treatment or to participate in the study. The "B" arm of the study seemed, on intuition, to be too harsh for her because she was so weak at the time. We finally did opt for the study, hoping we wouldn't be randomized to "B." We chose the study basically so that the computer could choose and we wouldn't ever have to think "we should have gone with the study." As it turned out, we were randomized to the standard arm, so we got what we wanted while still participating in the study.

Who designs clinical trials?

In July 1998, a Pediatric Intergroup Summit was held by the leaders of the four pediatric cancer clinical trials cooperative groups (CCG, POG, NWTSG, and IRSG). A decision was made to form a single pediatric cancer clinical trials organization. Unification of these groups will have advantages for children with cancer as well as pediatric cancer researchers. It will pool the intellectual resources of all four groups, allowing research that had not been previously possible. Large population-based studies and coordinated treatment trials will help researchers gather data that will be generalizable to the entire North American population of children with cancer. It is hoped that integration of these groups will be complete by the year 2002.

Who supervises clinical trials?

All institutions that conduct clinical trials also have an Institutional Review Board (IRB) or an ethics committee which reviews and approves all research taking place there. These boards, whose purpose is to protect patients, are made up of scientists, doctors, sometimes clergy, and often citizens from the community.

What questions should parents ask about clinical trials?

• What is the purpose of the study?

• Who is sponsoring the study? Who reviews it? How often is it reviewed? Who monitors patient safety?

• What tests and treatments will be done during the study? How do these differ from standard treatment?

• Why is it thought that the treatment being studied may be better than standard treatment?

• What are the possible benefits?

• What are all possible disadvantages?

• What are the possible side effects or risks of the study? What are the side effects of the study compared to those of standard treatment?

• How will the study affect my child's daily life?

• What are the possible long-term impacts of the study compared to those of the standard treatment?

• How long will the study last? Is this shorter or longer than standard treatment?

• Will the study require more hospitalization than standard treatment?

• Does the study include long-term follow-up care?

• What happens if my child is harmed as a result of the research?

• Compare the study to standard treatment in terms of possible outcomes, side effects, time involved, costs, and quality of life.

• Have insurers been reimbursing for care under this protocol?

What is informed consent?

During the discussions between the doctor(s) and family, all questions should be answered in language that is clearly understood by the parents, and there should be no pressure to enroll the child in the study. The objective of the informed consent process is to ensure the participants are comfortable with their choice and can comply with it.

We had many discussions with the staff prior to signing the informed consent to participate in the clinical trial. We asked innumerable questions, all of which were answered in a frank and honest manner. We felt that participating gave our child the best chance for a cure, and we felt good about increasing the knowledge that would help other children later.

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Sean missed the deadline when he was diagnosed for enrolling in a clinical trial. However, when he relapsed we did enroll him. The particular trial he was in was a randomized computer trial that decided if he was getting one or two chemotherapy agents. We felt if we enrolled him in the trial, maybe the results would help other children.

Paige (age four) took part in a clinical trial to treat her stage IV neuroblastoma. Her oncologist was the principal investigator, and he presented it to us as the best treatment plan for her. I have a stepsister who is a pediatric oncology nurse/researcher, and we discussed the treatment plan with her. Once all our questions were answered to our satisfaction, we decided to agree to the clinical trial.

No matter how comfortable you are with your child's treating oncologist, it is sometimes helpful to have another medical caregiver help sort out your options. Often, that person will be the family's pediatrician or family doctor. Second opinions can also be arranged through the Childhood Cancer Ombudsman Program, which uses volunteer specialists to provide free help to families considering the range of treatment options and informed consent process.

What is a protocol?

The clinical trial that my child was enrolled in had three arms--A, B, and C. He was in the A portion, so we only referred to the A section of the protocol, which clearly outlined each procedure and drug to be given for the duration of the trial. It also listed the follow-up care required by that particular clinical trial.

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When Matthew was diagnosed, he was started on a protocol that was designed to answer two questions. After the induction portion of the protocol, the first question was to determine if bone marrow transplantation improved survival for children with high risk neuroblastoma. He was to receive either a transplant or several additional months of consolidation therapy. The second question was designed to answer whether or not 13 cis-retinoic acid improved the event-free survival rate. This was done through a randomization process. We hoped that Matthew would get that opportunity, and as it turned out, he was randomized to get the drug.

Many parents express anguish when discussing their child's protocol, primarily because they misunderstand that the protocol is merely a guideline. Therapy frequently needs to be modified depending on each child's response to treatment.

It took me a long time to get over my hang-up that things needed to go exactly as per protocol. Any deviations on dose or days was a major stress for me. It took talking to many parents, as well as doctors and nurses, to realize and feel comfortable with the fact that no one ever goes along perfectly and that the protocol is meant as the broad guideline. There will always be times when your child will be off drugs or on half dose because of illness or low counts or whatever. It took a long time to realize that this is not going to ruin the effectiveness, that the child gets what she can handle without causing undue harm.

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I didn't know what a protocol was when Preston was diagnosed, and I understood from the doctors that this was the "exact" regime which must be followed to cure Preston. It frightened me whenever changes were made in the protocol. After a time, I came to view the protocol as merely a guideline which is individualized for each patient according to his tolerance and reaction to the drugs.

Should parents receive the entire trial document?

Parents are sometimes not aware that this lengthy document exists. Admittedly, for some parents the full protocol could be overwhelming or boring. There are many parents, however, who throw themselves into research to better understand their child's illness. These parents may benefit from having a copy of the study document for several reasons. First, it provides a description of the clinical trials that preceded the present one and explains the reasons the investigators designed this particular study. Second, it provides detailed descriptions of drug reactions, which comforts many parents who worry that their child is the only one exhibiting extreme responses to some drugs. Third, motivated parents who have only one protocol to keep track of occasionally prevent serious errors in treatment. Physicians treat scores of children on dozens of protocols and sometimes make mistakes. And finally, for parents who are adrift in the world of cancer treatment, it can provide a bit of control over their child's life. It gives the parents a job to do: monitor their child's treatment.

Since knowledge is comfort for me, I really wanted to have the entire clinical trial document, despite its technical language. Whereas the brief protocol that I had listed day, drug, dose, the expanded version listed the potential side effects for each drug, and what actions should be taken should any occur. I learned the parameters.

What happens if parents say no?

Our son's doctor gave us the paperwork on the clinical trial to read and told us that it was our decision and that he would not pressure us. We really decided not to join the study for financial reasons. My husband was a student and we had no health insurance. One of the parts of the study required more clinic visits, and we just couldn't afford it.

Can parents remove their child?

Jesse was enrolled in a clinical trial to assess long-term consequences of radiation. The testing was free, and we were glad to participate. Unfortunately, the billing department of the hospital continually billed us in error. We tried to correct the problem, but it became such a hassle that we withdrew from the study.

Pros and cons of clinical trials

• Patients receive either state-of-the-art investigational therapy or the best standard therapy available.

• Clinical trials can provide an opportunity to benefit from a new therapy before it is generally available.

• Information gained from clinical trials will benefit children with cancer in the future.

• Children enrolled in clinical trials may be monitored more frequently throughout treatment.

• The IRB has reviewed the protocol for protection of patient's rights as well as for scientific soundness.

• Review boards of scientists oversee the operation of clinical trials.

• Participating in a clinical trial often makes parents feel that they did everything medically possible for their child.

• Some clinical trials provide all treatment and follow-up care at no cost to the family.

• The experimental arm may not provide treatment as effective as the standard, or it may generate unexpected side effects or risks.

• Not all patients in a study receive the new treatment.

• Some clinical trials require more hospitalizations, treatments, tests that may be costly or painful, or clinic visits than the standard treatment.

• Some families feel additional stress over which arm is the best treatment for their individual child.

• Participation may generate parental guilt if the child has unacceptable toxicity from the more aggressive experimental arm.

• Insurance may not cover investigational studies. Parents need to carefully explore this issue prior to signing the consent form.