Outcome measures for clinical trials in fragile X syndrome
Elizabeth Berry-Kravis, David Hessl, Leonard Abbeduto, Allan L Reiss, Andrea Beckel-Mitchener, Tiina K Urv, Outcome Measures Working Groups, Michael Aman, Katie Clapp, Scott Hall, David Hessl, Becky Kronk, Ave Lachiewicz, Robert Noll, Lawrence Scahill, Leonard Abbeduto, Elizabeth Berry-Kravis, Heather Cody Hazlett, Stephen Hooper, Bryan King, Amy Lightbody, Richard Paylor, David Posey, Paul Wang, Becky Zorovic, Craig Erickson, Randi Hagerman, Walter Kaufmann, Eric Klann, Joseph Piven, Allan Reiss, Linmarie Sikich, Nicole Tartaglia, Michael Tranfaglia, Elizabeth Berry-Kravis, David Hessl, Leonard Abbeduto, Allan L Reiss, Andrea Beckel-Mitchener, Tiina K Urv, Outcome Measures Working Groups, Michael Aman, Katie Clapp, Scott Hall, David Hessl, Becky Kronk, Ave Lachiewicz, Robert Noll, Lawrence Scahill, Leonard Abbeduto, Elizabeth Berry-Kravis, Heather Cody Hazlett, Stephen Hooper, Bryan King, Amy Lightbody, Richard Paylor, David Posey, Paul Wang, Becky Zorovic, Craig Erickson, Randi Hagerman, Walter Kaufmann, Eric Klann, Joseph Piven, Allan Reiss, Linmarie Sikich, Nicole Tartaglia, Michael Tranfaglia
Abstract
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.
Conflict of interest statement
Conflicts of Interest and Source of Funding: EBK 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, CDC, FRAXA Research Foundation, and the NFXF. DH 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, DOD, FRAXA Research Foundation, the John Merck Foundation and the NFXF. LA has received grant funding from the NIH and the NFXF. ALR has received consulting fees from Novartis and grant funding from the NIH. AB-M and TKU have nothing to disclose. The views expressed in this article are those of the authors and do not necessarily represent the views of the NIH or the United States Government.
Figures
Source: PubMed