The research also involved a Parent Advisory Group to help in the study design and analysis, with parents representing all the study sites, including: Rainbow; Children's Hospital Medical Center, Cincinnati, OH; Children's Hospital Los Angeles, CA; Children's Hospital of Philadelphia, PA; Children's National Medical Center in Washington, DC; and the MD Anderson Cancer Center in Houston, TX. The study was supported by the National Institutes of Health and the Children's Oncology Group, a network of pediatric medical centers.
As part of the study, researchers observed and audiotaped the informed consent conferences involving 137 families at the six medical centers from July 1, 1999 to December 31, 2001. The patients were children, all newly diagnosed with acute leukemia. Childhood cancer treatment commonly involves the option of participation in clinical trials, which have revolutionized pediatric cancer treatment and significantly improved outcomes. In fact, the authors note that: "Thousands of children with cancer have been enrolled in randomized clinical trials over the past 40 years. The cure of childhood leukemia, one of the great success stories of modern medicine, has been a direct result of these trials."
In every case conference taped and studied, the medical team explained to parents various options in treatment and presented the concept of randomization, which means that as part of the clinical trial, the child would be randomly assigned to one of multiple treatment options. After the conference, researchers interviewed parents, asking them questions to determine whether or not they understood what randomization meant for their child:
- In this clinical research study, how will it be decided which treatment your child will receive?
- If your child enrolled in this clinical research study, will you be able to choose the treatment option you want?
The researchers concluded that half of the parents did not understand randomization, and, in fact, those who did not understand the concept were more likely to consent to their child's participation in the clinical trial. Their most important findings:
- There were no significant differences observed in how randomization was explained to parents of racial minority, and yet only 27% of minority parents understood the concept compared to 69% of non-minority parents.
- Parents with less education and lower socioeconomic status were much less likely to understand randomization.
- The presence of a nurse at the conference was associated with improved understanding.
- The longer the conference, the better the understanding (the mean conference duration in cases demonstrating parental understanding was 83 minutes, compared with 74 minutes in cases without parental understanding).
- Parents who read the informed consent document thoroughly were more likely to understand randomization.
With these important revelations, the researchers are now conducting a new study to explore the impact of various interventions: Does understanding improve if a nurse meets with parents before the informed consent conference to begin preliminary explanations? Does understanding improve if physicians are specifically trained in communicating these concepts before the conference with parents? What kind of special training for physicians and nurses is most effective?
"When faced with a cancer diagnosis for their child, parents are always going to feel anger and frustration," says Holly Rupnow, who serves on the Parent Advisory Group for the study. Mrs. Rupnow's daughter Skye, 7 years old, is in remission from acute leukemia, diagnosed in 1999 and treated at Rainbow Babies & Children's Hospital in a clinical trial. "Everything is happening so fast. The mind just shuts down when doctors are presenting you with so much information. If there is anything we can do to minimize the shock and enhance parental understanding, we should do it. That's why a study like this is so important, and why I am involved."
Dr. Kodish and his colleagues caution that the study results should not be interpreted as being critical of clinical trials. "The fact that optimal informed consent was not obtained does not make these studies unethical," they write. "Certainly, the medical professionals who participated in this study did their best to explain what parents needed to know," adds Dr. Kodish. "But the communications were inconsistent, with inconsistent results. This study helps us to design better communication tools to improve the overall process and quality of informed consent."
"This important work adds to the growing body of evidence that questions the effectiveness of the informed consent process," said Ralph I. Horwitz, MD, Dean and Vice President of Medical Affairs, Case Western Reserve University School of Medicine. "The findings are especially notable since they apply to children and their parents who are often omitted from such research. The ongoing studies by Dr. Kodish and his colleagues are urgently needed to provide children and their parents the understanding and protections they need."
In an accompanying JAMA editorial, Jeremy Sugarman, MD, MPH, MA, writes that the study provides "an important foundation for needed discussion and deliberation regarding the efficacy of the current system to protect children as research participants and are useful for measuring the thickness of the ice on which the ethical justification for this research rests." Dr. Sugarman is currently at the Phoebe R. Berman Bioethics Institute at Johns Hopkins University.