GREENVILLE, SC - Jul 14, 2017 - 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 in the Journal of Neurodevelopmental Disorders.

Dr. Walter Kaufmann, Ravenel Boykin Curry Chair in Genetic Therapeutics and Director of the Greenwood Genetic Center's Center for Translational Research (CTR), 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 form Fragile X syndrome was identified in 1991 and rapid progress has been made in the ensuing 26 years, including understanding the pathophysiology of the condition, creation of animal models, and the identification of drugs that rescue the phenotype in mouse models.

This relatively rapid progress cause 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 or behavioral changes in response to the drugs have not been proven to have reliability, validity, or sensitivity to treatment.

"Some of these drugs may have been beneficial 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 assessments, rather than the relatively short duration of most clinical trials.

"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 also 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

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