Kaufmann Reports on Major Clinical Trial Weakness


GGC researcher calls for better outcome measures for neurodevelopmental disorders

Dr. Walter Kaufman

Newer and better ways to measure outcomes in clinical trials for neurodevelopmental disorders are necessary if such trials are to be successful, reports
a new study published in the Journal of Neurodevelopmental Disorders.

Dr. Walter Kaufmann, Ravenel Boykin Curry Chair in Genetic Therapeutics and Director of the Center for Translational Research (CTR) in the Greenwood Genetic
Center’s Greenville office, was the senior author of the study which he says has important implications for all clinical trials.

In a review of 22 clinical trials for Fragile X syndrome, the most common inherited form of intellectual disability and the most common single gene cause
of autism, the authors found that many of the trials failed in part because of the deficiencies of the outcome measures.

The genetic cause for Fragile X syndrome was identified in 1991 and rapid progress has been made in the ensuing 26 years, including understanding of the
pathophysiology of the condition, creation of animal models, and the identification of drugs that rescue these features in mouse models.

This relatively rapid progress caused great excitement among the Fragile X community, and numerous clinical trials have been implemented in the past decade
– nearly all have failed.

“Part of the problem with these trials is that the tools that are being used to measure the drugs’ effectiveness are of limited or moderate quality,” said
Kaufmann. “Many of the current outcome measures being used to assess cognitive improvement and behavioral changes in response to the drugs have not
been proven to have reliability, validity or sensitivity to treatment.”

“These drugs may have had a benefit to the patient, but if we’re not able to measure that, it is considered a failure,” he said. “And without concrete
evidence to show efficacy, the trials are halted or never progress to the next level.”

Another shortcoming of the measures is that many are of better utility for long-term assessment, rather than the relatively short duration of most clinical

If scientists can’t objectively and consistently show that a drug is having a meaningful impact on function and quality of life, the NIH and FDA will not
move these trials forward toward an effective treatment, Kaufmann said.

Since joining GGC in 2015, Kaufmann and his team have been committed to advancing clinical trials for neurodevelopmental disorders, including Fragile X
syndrome, Rett syndrome and autism. A key goal of the CTR has been to develop effective outcome measures for these disorders including scales, questionnaires,
and biomarkers.

“Measures for Fragile X syndrome were evaluated for this study because of the numerous clinical trials already done for this disorder,” said Kaufmann,
“but the same issues exist for other neurodevelopmental disorders, including autism. We must be able to quantitatively demonstrate therapeutic efficacy
for these complex disorders. That is the key to success.”

Coauthors on this study include researchers from Johns Hopkins University School of Medicine, Rush University, Cincinnati Children’s Hospital, Stanford
University, University of California Davis, and Novartis Pharmaceuticals

The full article can be accessed at https://jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-017-9193-x

For more information, contact Lori Bassett

Adult man smiling with his mother

Meet Reuben

Reuben has been part of the GGC family for nearly all of his life! He was diagnosed with propionic acidemia as an infant and receives life-saving care from GGC's metabolic treatment team Dr. Schroer, Mitzi, and Dr. Burns. Reuben lights up our office every time he visits!...

In The News