Meeting News Coverage

Conference aims at consensus strategy for developing disease-modifying therapies for children with type 1 diabetes

ALEXANDRIA, Va. — Developing disease-modifying therapies for children with type 1 diabetes may require different clinical trial and approval pathways than currently assumed, agreed researchers, ethicists and regulators attending a consensus conference on the topic.  

“The promise of disease modifying therapies — that we could prevent or delay the onset of the clinical disease, or we could improve the clinical experience for people with diabetes — has not yet been achieved, but we all want to get there,” said conference co-chair Carla Greenbaum, MD, director of the diabetes program at Benaroya Research Institute in Seattle, which cosponsored the meeting with the American Diabetes Association, Juvenile Diabetes Research Foundation and Type 1 Diabetes Exchange.

The “provocative conclusion” of the meeting, said Greenbaum in the day’s final discussion, is that “we may be able to move to doing clinical trials in children without proving efficacy first in adults.”

Although type 1 diabetes may develop at any age, emerging data reveal different pathophysiology and clinical course of the disease in children and adults, according to presenters Peter Gottlieb, MD, of the University of Colorado, and Stephen Gitelman, MD, of the University of San Francisco.

“I think these findings do point to children having a fundamentally different disease process than adults,” Gitelman said.

Desmond Schatz, MD, reviewed data from clinical trials conducted over the past decade that showed different results in participants by age. For example, he noted that in the rituximab and abatacept trials, positive efficacy was driven by patients younger than 18 years.

“Had we just used the adult population, we would not have seen that effect,” Schatz said.

In other studies, no difference in efficacy was found between age cohorts. “We cannot extrapolate from adults to children,” Schatz said.

“Past disasters” have resulted in legislation to ensure that products that will be used in children have been studied in them, said Dianne Murphy, MD, director of the office of pediatric therapeutics at the FDA in Silver Spring, Maryland. She outlined underlying considerations and procedures for studying and gaining approval for pediatric drug indications.

Wrapping up the presentations, ethicist David Wendler, PhD, head of the Unit on Vulnerable Populations at the NIH Clinical Center in Bethesda, Maryland, said, “The reason to do trials in adults before children is the assumption that you’re going to get data in the adults that is relevant to what you want to do in children. If that’s not true, then doing the trials in adults is just not helping you with your dilemma about doing the trials in children.”

Wendler said that clinical trials conducted in children can be appropriate if the benefits outweigh the risks. Younger children cannot consent to participation so, if possible, studies should start with older children first.

Organizers intend to publish a consensus conference report in Diabetes Care.

For more information:

Presented at: Defining Pathways for the Development of Disease Modifying Therapies in Children with Type 1 Diabetes Consensus Conference; January 14, 2015; Alexandria, Va.

Disclosures: The consensus conference is presented in collaboration with Type 1 Diabetes TrialNet, Immune Tolerance Network and ISPAD.

ALEXANDRIA, Va. — Developing disease-modifying therapies for children with type 1 diabetes may require different clinical trial and approval pathways than currently assumed, agreed researchers, ethicists and regulators attending a consensus conference on the topic.  

“The promise of disease modifying therapies — that we could prevent or delay the onset of the clinical disease, or we could improve the clinical experience for people with diabetes — has not yet been achieved, but we all want to get there,” said conference co-chair Carla Greenbaum, MD, director of the diabetes program at Benaroya Research Institute in Seattle, which cosponsored the meeting with the American Diabetes Association, Juvenile Diabetes Research Foundation and Type 1 Diabetes Exchange.

The “provocative conclusion” of the meeting, said Greenbaum in the day’s final discussion, is that “we may be able to move to doing clinical trials in children without proving efficacy first in adults.”

Although type 1 diabetes may develop at any age, emerging data reveal different pathophysiology and clinical course of the disease in children and adults, according to presenters Peter Gottlieb, MD, of the University of Colorado, and Stephen Gitelman, MD, of the University of San Francisco.

“I think these findings do point to children having a fundamentally different disease process than adults,” Gitelman said.

Desmond Schatz, MD, reviewed data from clinical trials conducted over the past decade that showed different results in participants by age. For example, he noted that in the rituximab and abatacept trials, positive efficacy was driven by patients younger than 18 years.

“Had we just used the adult population, we would not have seen that effect,” Schatz said.

In other studies, no difference in efficacy was found between age cohorts. “We cannot extrapolate from adults to children,” Schatz said.

“Past disasters” have resulted in legislation to ensure that products that will be used in children have been studied in them, said Dianne Murphy, MD, director of the office of pediatric therapeutics at the FDA in Silver Spring, Maryland. She outlined underlying considerations and procedures for studying and gaining approval for pediatric drug indications.

Wrapping up the presentations, ethicist David Wendler, PhD, head of the Unit on Vulnerable Populations at the NIH Clinical Center in Bethesda, Maryland, said, “The reason to do trials in adults before children is the assumption that you’re going to get data in the adults that is relevant to what you want to do in children. If that’s not true, then doing the trials in adults is just not helping you with your dilemma about doing the trials in children.”

Wendler said that clinical trials conducted in children can be appropriate if the benefits outweigh the risks. Younger children cannot consent to participation so, if possible, studies should start with older children first.

Organizers intend to publish a consensus conference report in Diabetes Care.

For more information:

Presented at: Defining Pathways for the Development of Disease Modifying Therapies in Children with Type 1 Diabetes Consensus Conference; January 14, 2015; Alexandria, Va.

Disclosures: The consensus conference is presented in collaboration with Type 1 Diabetes TrialNet, Immune Tolerance Network and ISPAD.