NIH researchers offer template for simplified IC for cancer trials
Consent created for Phase I studies
It took investigators years of research to create the new consent form template for phase I oncology trials, which provides several pages of simple, clear language in an informed consent outline.
"We had done a previous study two years ago where we collected phase I oncology consent forms from around the country from comprehensive cancer centers and pharmaceutical companies," says Christine Grady, PhD, RN, acting chief of the department of bioethics and head of the section on human subjects research in the National Institutes of Health (NIH) in Bethesda, MD.
"We reviewed the content of forms to see how they defined risks, benefits, alternatives, and purposes of research," Grady explains. "We read 267 consent forms and got a real flavor for which were better and which were not as good in terms of understandability."
Some of the researchers involved were working on other studies related to informed consent as part of the process to understand what study participants understand as they go through the informed consent process, she adds.
"We've been thinking about readability and reading literature on readability and simplifying documents and using work the National Cancer Institute working group had done," Grady says.
For instance, the National Cancer Institute has developed a checklist for how to make an informed consent document easy-to-read.
One study has randomized participants to two different consent forms, including one standard form and one form that is more concise with a lower reading level.
"Our hypothesis is that understanding probably will not be much different," Grady says. "Part of the reason is because I think a lot of what people understand from a consent form is what they get from other sources, like talking to other people and checking online."
Also, while written consent forms serve many important purposes for people considering participation in clinical research, the problem is that many of these forms are too long or written in legalistic language so people read them selectively or not at all, Grady says.
"So it seems that if our goal is to help people understand the forms then we should be writing documents for them to read that are as simple as possible," she adds.
"There are people who worry about cutting information or simplifying information so that it doesn't give people everything they need to know," Grady says. "But the template in this study is deliberately written to include all of the written elements of consent as delineated in federal regulations."
The 3.5-page template resulted from investigators selecting the most important elements of the 267 consent forms they reviewed.1
It includes basic elements, such as these:
- What is the purpose of the study?
- What are the procedures of this study?
- What are the risks that I face if I enroll in this trial?
- Sample outline of possible side effects;
- What happens if I have side effects?
- How can I benefit from being in this trial?
- What are my other options if I decide not to enroll?
- Can I, or the researchers, decide to stop my participation in the study?
- Does it cost me any money to be a part of this trial?
- Who is paying for this study?
- Will my personal information remain private?
- Who can I call if I have questions?
- Will my blood or other samples be stored for future research?
The template was designed to address some of the shortcomings of standard informed consent forms.
For instance, regulations require consent forms to describe the purpose of a study, Grady says.
"For phase I oncology trials one of the things people worry about is that participants don't understand the purpose of the study and correspondingly low chances of therapeutic benefit," she explains.
The informed consent form will describe risks, benefits, and whom to contact, but within each category there are specific items relevant to a particular Phase I study, but not necessarily relevant to other phase I studies, Grady says.
Another issue is how to explain dose escalation, she notes.
"Phase I studies are done to see how safe a new agent is in human beings, so they begin at a very low dose," Grady says. "One common variation is having three people at a specific dosing level, and then if there are no side effects, you go to the next level and get three new people, and this continues to a maximum tolerated dose, meaning a dose that causes side effects."
Typically what happens in clinical research for cancer is that once a maximally-tolerated dose is quantified, then you go back one dose, and that's the dose that's used for the phase II trials, she adds.
"We want people to understand this dose escalation where they'll get a dose others will not get, and they'll get higher and higher doses, and they're more likely to have side effects," Grady says.
Researchers also worked on the language describing a study's benefits, which is a tricky concept in phase I studies.
"We thought the language that appeared in the consent form under how they could benefit had to be clear that the goal of the study was to test safety and not test the drug for treating cancer," Grady says. "The chance that someone would benefit in terms of tumor shrinkage was very low, and the main benefits they're getting in participation is in helping future patients."
The template could be adapted for other clinical trials, but its language is specific to phase I studies, she notes.
"We did things to enhance readability with very clear sections that each start with a question so the person reading it can see how it relates to them," Grady explains. "That kind of format could be used by any kind of researcher."
Another feature of the informed consent template is its use of tables and graphs.
"The important things people want to know about when entering a trial are what is the schedule, how many things do they have to do, and how long do they have to be there," Grady says. "Sometimes there's a multi-page narrative, and we thought there could be a timeline, such as on day 1 you do this and day 5 you do that."
Also, researchers thought a risks and side effects table could be useful.
"We suggested a table with two trajectories: how frequently the side effect is expected and when it might occur," Grady adds. "Those kinds of tables and graphs could be used in any kind of study."
Reference
- Koyfman SA, McCabe MS, Emanuel EJ, et al. A consent form template for phase I oncology trials. IRB Ethics & Hum Res. 2009;31(4):1-8.
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