Monday, March 30, 2009

The protocol

A protocol is a written plan for treating a disease. Just like a recipe for baking a cake,
it has a list of ingredients, the amounts to use, and the order to use them so the recipe
has the best chance for success. The protocol document lists the drugs, dosages, and
tests for each segment of treatment and follow-up. It usually also contains a diagram
(called a roadmap) that shows when each drug and test is given. If your child is
enrolled in a clinical trial, the protocol will outline the treatment for each arm.
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.
If the family chooses not to enroll in a clinical trial, they will be given a protocol for
standard treatment (often the standard arm of the clinical trial).
The portion of the protocol devoted to the schedule may be five to twenty-five pages
long. The family may also be given an abbreviated version (one to two pages) to pro-
vide quick and easy reference on a daily basis. This part of the protocol is frequently
called the “roadmap.” Parents and teenage patients should review these documents
carefully with the oncologist so that all portions are understood. It will be the parent’s
responsibility to make the appropriate appointments and give oral medications at the
correct times.
Many parents express anguish when their child’s protocol changes during treatment.
An important point to remember is that the protocol is a guideline that is frequently
modified, depending on each child’s response to treatment.
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 several years, I came to view the protocol as
merely a guideline that is individualized for each patient according to his
tolerance and reaction to the drugs. We ended up deleting whole sections
of Preston’s protocol due to extreme side effects. He has been off therapy
for five years now with no relapse.
• • • • •
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.
• • • • •
I sobbed every night for an entire week when Christine was first
taken off chemotherapy for low counts. I was convinced that the
immunosuppression was due to a relapse. That was two years ago, and
we have changed her dosages almost every two weeks due to erratic
counts. I wish I had known how normal it is to go off protocol.

Questions to ask about clinical trials

To fully understand the clinical trial that has been proposed, here are some impor-
tant questions to ask the oncologist:
• 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
• 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 the standard
• 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?
When discussing the clinical trial with the oncologist, you’ll need the information to
review later. Many parents bring a tape recorder or a friend to take notes. Some
parents write down all of the doctor’s answers for later reference.
Informed consent
True informed consent is a process—not merely an explanation and signing of docu-
ments. Informed consent requires that:
1. All the treatments available to the child have been laid on the table and discussed—
not just the treatment available at your hospital or through your doctor, but all the
treatments that could be beneficial, wherever they are given.
2. The parents and, to the extent possible, the child, have discussed these options
and decided that they want to consider one of them.
3. The option selected is thoroughly discussed, with all its benefits and risks clear
4. Those aspects of the study that are considered experimental and those that a
standard are clearly described.
A fully informed medical decision weighs the relative merits of a therapy after fu
disclosure of benefits, risks, and alternatives.
During the discussions between the doctor(s) and family, all questions should b
answered in language that is clearly understood by the parents and child, and the
should be no pressure to enroll the child in the study. The objective of the informe
consent process is that the participants are comfortable with their choice and ca
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.
The form that parents sign will have language similar to the following: “The stud
described above has been explained to me, and I voluntarily agree to have my chil
participate in this study. I have had all of my questions answered, and understan
that all future questions that I have about this research will be answered by the inve
tigators listed above.”
The study that our institution was participating in at the time of my
daughter’s diagnosis was attempting to lessen the treatment to reduce
neurotoxicity yet still cure the disease. My family began a massive
research effort on the issue, and we had several family friends who were
physicians discuss the case with the heads of pediatric oncology at their
institutions. The consensus was that since my daughter was at the high
end of the high-risk description, it was advisable to choose the standard
care, which was more aggressive.
Although we believe strongly in clinical trials, we decided to opt for
the standard treatment because she had a poor prognosis, and we felt
that she would need the cranial radiation, despite the possibility of late
side effects.
By the time a study is published in the literature, doctors on the cutting edge of treat-
ment are two to four years into improving that treatment or learning of its shortcom-
ings. For this reason, it is best to make decisions in partnership with knowledgeable
medical caregivers, rather than in isolation.
No matter how comfortable you are with your child’s treating oncologist, it may be
helpful to have another medical caregiver help sort out your options. Often, that per-
son will be the family’s pediatrician or family doctor. Second opinions can be obtained
from physicians at other institutions in your community or region, or any of the larger
pediatric cancer centers. They will arrange to review the information and outline rec-
ommendations. It is most useful to get a second opinion from a center that treats sig-
nificant numbers of patients with your child’s diagnosis. Most pediatric oncologists
are happy to facilitate this process for you.
When my son was diagnosed, we were told we had two options:
a clinical trial or standard treatment. We decided to get a second
opinion before making our decision. Our pediatrician, my husband,
and I met in the doctor’s office for a telephone conference with a
pediatric oncologist from a major treatment center. We each presented
our concerns. Our pediatrician thought of some issues neither my
husband nor I had considered. I think we all came away better informed
of our options.
Second opinions can also be arranged through the Childhood Cancer Ombudsman
Program, which uses volunteer specialists to provide free help to families consider-
ing the range of treatment options and engaged in the informed consent process. (See
Appendix C, Resource Organizations, for contact information.)