Doctors work to boost understanding from those participating in studies related to Down syndrome, Fragile X syndrome

Doctors, researchers and drug companies are coming up with simple designs to address a complex ethical dilemma: how to make sure people with intellectual disabilities consent to join a drug trial.

With growing numbers of clinical trials getting under way involving conditions such as Down syndrome and Fragile X syndrome, researchers are trying new strategies to ensure people with the conditions, which typically involve intellectual disabilities, understand the risks and benefits of participating in trials.

To enroll in a trial, potential participants typically must first pore over often long and complex explanatory documents. Now drug companies, researchers and doctors are creating documents that use a combination of simpler text and pictures to explain everything from how a clinical trial works to potential side effects of an experimental drug. Others use flip charts, videos and audiovisual tools to explain what is happening.

A large study with funding from the National Institutes of Health is gathering data on how people with Fragile X, a genetic condition that can cause intellectual disability and other challenges, make decisions. The goal is to develop an app to help the consent process. Many times, parents or other guardians have the legal right to determine if someone with an intellectual disability can participate in a trial. But the new approach is being driven by ethical concerns of families, researchers and drug companies, and insistence by people with intellectual disabilities that they need a say in the process.

“This is an era of participatory research,” says Brian Skotko, co-director of the Down Syndrome Program at Massachusetts General Hospital, one of the sites for drug trials for people with Down syndrome. “We do not want to do research on people with Down syndrome. We want to do research with people with Down syndrome.”

Justine Dyer, 26, has Down syndrome and recently underwent screening at Massachusetts General for a trial for a Hoffmann-La Roche drug being tested to see if it improves memory, language and cognition. Her mother, Betsy Dyer, is one of Ms. Dyer’s guardians and legally must agree to her daughter’s participation but says, “I don’t want to make medical decisions for her without her fully informed consent.”

Hoffmann-La Roche’s study rules require not only that legal guardians consent, but also that participants themselves understand and agree to take part. The company created a number of tools for the trials, including pictorial consent forms, flipcharts and an animated video. The Massachusetts General team, which is also a site for a drug trial sponsored by Elan Corp. for people with Down syndrome, created its own pictorial information sheets.

In the sheets used for the Elan trial, there are photos of the three doctors and the nurse who will be seeing the patients. To illustrate that participants need to take blood tests, a cartoonlike drawing shows a woman inserting a small needle into the arm of a seated man. An X-ray photo illustrates that participants will need a lung X-ray. “This does not hurt,” the text says. Vocabulary is simplified. Instead of saying the trial will test the potential efficacy of the drug, the sheet explains that the researchers “want to test how well it works.”

“We reinforce during each visit that the person is a participant. They need to answer questions. They need to hold still for blood draws,” says Mary Ellen McDonough, senior clinical research coordinator in the hospital’s Down Syndrome Program.

The history of participation in medical research by people with intellectual disabilities is a complex and difficult one, says Brenda Finucane, associate director of the Geisinger Autism and Developmental Medicine Institute in Lewisburg, Pa., who works with individuals with intellectual disabilities on consent issues. In the past, abuses occurred, with people enrolled in studies where they were subject to potentially dangerous situations without their full understanding.

More recently, there was a reluctance within the medical and scientific community to do such studies because of the recognition of their vulnerabilities. Scientific advances are driving the new effort to develop a consent process that enables people with intellectual disabilities to participate as much as possible.

Elizabeth Berry-Kravis, professor of pediatrics, neurological science and biochemistry at Chicago’s Rush University Medical Center, runs clinical trials for people with Fragile X syndrome. She says greater understanding of brain mechanisms underlying intellectual disabilities has led to the opening of treatment trials. The hope is that the drugs might improve cognitive function, but they could also have possible side effects and require frequent doctor visits.

“I think we recognize that we would like to get as much knowledge to the patients and allow them to make as many of the decisions as possible,” Dr. Berry-Kravis says.

Most people with intellectual disabilities are classified as having a mild or moderate intellectual condition: They can perform life skills but require varying degrees of support. Still, this leaves room for a lot of variability in cognition and verbal ability.

“Given the variation, I don’t think 100% of the population will be able to participate. One size won’t fit all,” says Michael Harpold, chief scientific officer of the Down Syndrome Research and Treatment Foundation, which has focused on cognition research in Down syndrome.

Don Bailey, distinguished fellow at RTI International in Research Triangle Park, N.C., a research institute that got a grant from NIH to develop an app for informed consent for people with Fragile X syndrome, says there isn’t a lot of data analyzing how people with intellectual disabilities make decisions.

The study is enrolling 200 people with Fragile X syndrome and includes behavioral assessment and videotaping study participants doing tasks involving decision-making. Experts assess the tapes to evaluate ability to participate in the consent process. They also interview parents of children with Fragile X. The information will help in the creation of the informed consent app.

Dr. Bailey says although the app is being developed first with people who have Fragile X, he hopes the tool can ultimately be used to enhance informed consent for people with autism, Down syndrome or Alzheimer’s disease.

Justine Dyer, who hopes to start the Hoffmann-La Roche trial in April, works as a teacher’s aide at a nursery school. “I love my work,” Ms. Dyer says.

She lives in a house in Maine that she rents along with two other people with intellectual disabilities, including her fiancé. She is engaged to be married in August and brought her fiancé and mother with her when she participated in the screening for the drug trial at Massachusetts General. On the way back home, Ms. Dyer’s fiancé read the booklet again out loud and they studied the pictures together.

Her mother says that if the drug works, Justine’s memory might improve, making it easier for her to learn and retain information. Her mother would like her to have the opportunity to try additional jobs and greater independence. Justine Dyer says she wants to participate in the trial to “help other people” and because she hopes the new drug might “help me get my brain better.”