Objective: Progress in basic neuroscience has led to identification of molecular targets for treatment in fragile X syndrome (FXS) and other neurodevelopmental disorders; however, there is a gap in translation to targeted therapies in humans. One major obstacle to the demonstration of efficacy in human trials has been the lack of generally accepted endpoints to assess improvement in function in individuals with FXS. To address this problem, the National Institutes of Health convened a meeting of leading scientists and clinicians with the goal of identifying and standardizing outcome measures for use as potential endpoints in clinical trials in FXS.
Methods: Participants in the meeting included FXS experts, experts in the design and implementation of clinical trials and measure development, and representatives from advocacy groups, industry, and federal agencies.
Results: The group generated recommendations for optimal outcome measures in cognitive, behavioral, and biomarker/medical domains, including additional testing and validation of existing measures and development of new measures in areas of need. Although no one endpoint or set of endpoints could be identified that met all criteria as an optimal measure, recommendations are presented in this report.
Conclusion: The report is expected to guide the selection of measures in clinical trials and lead to the use of a more consistent battery of measures across trials. Furthermore, this will help to direct research toward gaps in the development of validated FXS-specific outcome measures and to assist with interpretation of clinical trial data by creating templates for measurement of treatment efficacy.
*Departments of Pediatrics, Neurological Sciences, and Biochemistry, Rush University Medical Center, Chicago, IL;
†Department of Psychiatry and Behavioral Sciences, University of California, Davis School of Medicine, Sacramento, CA;
‡MIND Institute, University of California, Davis Medical Center, Sacramento, CA;
§Center for Interdisciplinary Brain Sciences Research and Departments of Psychiatry and Behavioral Sciences, Radiology and Pediatrics, Stanford University School of Medicine, Stanford, CA;
¶National Institute of Mental Health, National Institutes of Health, Bethesda, MD;
‖Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
Address for reprints: Elizabeth Berry-Kravis, MD, PhD, Rush University Medical Center, 1725 West Harrison, Suite 718, Chicago, IL 60612; e-mail: firstname.lastname@example.org.
E. B.-K. has received funding to consult and conduct clinical trials in fragile X syndrome (FXS) from Novartis, Seaside Therapeutics, and Roche and has received grant funding from the National Institutes of Health (NIH), Centers for Disease Control, FRAXA Research Foundation, and the National Fragile X Foundation (NFXF). D. H. has received funding to consult and conduct clinical trials in FXS from Novartis, Seaside Therapeutics, and Roche, and has received grant funding from the NIH, Department of Defense, FRAXA Research Foundation, the John Merck Foundation, and the NFXF. L. A. has received grant funding from the NIH and NFXF and funding to provide services to Roche TCRC, Inc., and to consult with Hoffmann-La Roche, Inc. A. L. R. has received consulting fees from Novartis and grant funding from the NIH. A. B. -M. and T. K. U. have nothing to disclose. The views expressed in this article are those of the authors and do not necessarily represent the views of the National Institutes of Health or the United States Government.
Disclosure: The authors declare no conflict of interest.
Participants in the Outcome Measures Working Groups have been listed in the Acknowledgments.
Received October , 2012
Accepted May , 2013