Can IC be improved in Phase I cancer trials?
Pediatric oncology research issues reviewed
An interesting thing happened when researchers asked parents of children involved in Phase I oncology studies about their experiences with informed consent: Parents had a lot to say.
“Parents wanted to talk about communication with professionals about research,” says Liza-Marie Johnson, MD, MPH, MSB, chair and bioethics consultant of the hospital ethics committee, clinical researcher, and a lead hospitalist at St. Jude Children’s Research Hospital in Memphis, TN. Johnson was the lead author of a study about informed consent, communication, and parents of children enrolled in Phase I oncology trials.
Their suggestions and comments resulted in researchers designing a Phase I communication model, focusing on educating families about Phase I trials at specific time points during a child’s illness. They also worked on a Phase I fact sheet to distribute to families.1
The one-page fact sheet, titled, “Phase I Clinical Oncology Trial: A Brief Overview,” uses color borders to separate its various sections, which include the following:
• Purpose of Phase I Trials
• Some definitions, including:
- Maximum tolerated dose (MTD): “The highest dose of a drug that can be given safely without severe side effects.”
- Dose limiting toxicity (DLT): “Serious side effects caused by a dose of the Phase I drug.”
- Cohort
- Dose escalation
- Dose finding
- Palliative care
• Available Support Services and Contact
• Additional Contact Information.1
The fact sheet quickly became popular, and researchers received emails from doctors requesting it, Johnson notes. “One doctor wrote, ‘When can I start using this sheet? I have these families crying in my clinic because they didn’t realize the trial they’re trying is not expected to cure their child.’”
The problem was that informed consent forms were 30-plus pages long and had too much required language, some physicians told researchers. Others suggested that because each family is so different there should be different levels of information, including downloadable information that people could use on their iPads. Still others asked for visual as well as written materials and better verbal communication with families.1
Parents talked about how much information they had read, what they were learning to deal with their children’s illness, and about their experience with being involved in a Phase I trial: “We know darn well the trial is to figure out the doses and what the best way to… we all know that, but that’s not in our heart what we’re on it for,” one parent said.1
“I think that hope is very powerful,” Johnson says. “We want to accurately portray the risks and benefits, but we don’t want to crush everyone’s hope.”
In an earlier study, researchers asked parents to identify the likelihood that their child would benefit from a Phase I study, and a lot of parents refused to answer the question, Johnson recalls. “We think they understood the likelihood of benefit was low, and they didn’t want to put a number on it.”
The study includes a chart of the trajectory for children with cancer. It begins with diagnosis. The next step is standard treatment or a diagnosis of incurable disease or poor prognosis. If standard treatment results in a relapsed or refractory disease and with the diagnosis of incurable disease, the next steps are one of these three: salvage chemotherapy, no cancer therapy, or Phase I trial.1
“Families have to choose between a Phase I trial where the purpose is not cure, although, certainly, some drugs go from Phase I to Phase III, so there can be drugs that have a really profound benefit,” Johnson explains. “But for the most part the purpose is safety and efficacy: They may have reduced disease burden, a reduction in symptoms, and it may extend the length of their lives.”
Parents choose to have their child participate in a Phase I trial to show they’re not giving up on their child and out of a desire to help other families, Johnson says.
The option of no more cancer-directed therapy means the family likely will go home or the child will receive some oral chemotherapies with few side effects that can slow down the disease progression, but there will be no cure of the disease, she adds.
“Salvage chemotherapy, which is the second-line agents, might have some effect, but based on previous studies, it’s unlikely to work,” Johnson says.
Informed consent in a Phase I trial needs to begin with basic scientific concepts and the purpose of a Phase I trial, Johnson suggests.
“The definition the parents came up with was that Phase I trials were to identify and develop new drugs to treat childhood cancer,” she says.
The definition also notes, “In a Phase I trial, researchers are trying to evaluate safety. This includes determining a safe dose range (MTD) and identifying side effects. It is unlikely that the treatment in a Phase I study will cure your child. Possible benefits could include symptom reduction and the opportunity to help others in the future. The Phase I trial is voluntary and you can decide not to participate. You can talk to your doctors to stop being in the study at any time.”1
After starting to work on the basic definitions that would be used for the fact sheet, the research team discussed it and wrote a rough draft with some input from the organization’s art department, Johnson says.
The fact sheet was pilot tested, presented to the IRB, and the feedback has been universally positive, she adds.
Since it was published in the journal Cancer, it is available for other institutions to use, as well, she says.
“This is something an oncologist can use when talking with a family about a Phase I study: ‘We have this study your child may be eligible for. I’m going to give you this sheet that tells you what a Phase I study is. Read it over, and when you come to clinic, we can talk about whether or not you want her to be in a Phase 1 study,’” Johnson says.
“About 65% of children diagnosed with cancer in the U.S. will enroll in a clinical trial,” she adds. “Not all families will need a Phase I study, but if there’s a family whose child is eligible for Phase I, then the oncologist can give the fact sheet to them before talking about the specifics of the trial.”
REFERENCE
- Johnson LM, Leek AC, Drotar D, et al. Practical communication guidance to improve Phase I informed consent conversations and decision-making in pediatric oncology. Cancer. 2015 Jul 15;121(14):2439-48.
An interesting thing happened when researchers asked parents of children involved in Phase I oncology studies about their experiences with informed consent: Parents had a lot to say.
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