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. 2020 Jun 1;77(6):755-763.
doi: 10.1001/jamaneurol.2020.0367.

Seven-Year Experience From the National Institute of Neurological Disorders and Stroke-Supported Network for Excellence in Neuroscience Clinical Trials

Merit Cudkowicz  1 , Marianne K Chase  1 , Christopher S Coffey  2 , Dixie J Ecklund  2 , Brenda J Thornell  1 , Codrin Lungu  3 , Katy Mahoney  1 , Laurie Gutmann  2 , Jeremy M Shefner  4 , Kevin J Staley  1 , Michael Bosch  2 , Eric Foster  2 , Jeffrey D Long  2 , Emine O Bayman  2 , James Torner  2 , Jon Yankey  2 , Richard Peters  2 , Trevis Huff  2 , Robin A Conwit  3 ; NeuroNEXT Clinical Study Sites; Shlomo Shinnar  5 , Donna Patch  5 , Basil T Darras  6 , Audrey Ellis  6 , Roger J Packer  7 , Karen S Marder  8   9 , Claudia A Chiriboga  8   9 , Claire Henchcliffe  8   9 , Joyce Ann Moran  8   9 , Blagovest Nikolov  8   9 , Stewart A Factor  10 , Carole Seeley  10 , Steven M Greenberg  1   11 , Anthony A Amato  1   11 , Sara DeGregorio  1   11 , Tanya Simuni  12 , Tina Ward  12 , John T Kissel  13 , Stephen J Kolb  13 , Amy Bartlett  13 , Joseph F Quinn  14 , Kellie Keith  14 , Steven R Levine  15 , Nadege Gilles  15 , Patricia K Coyle  16 , Jessica Lamb  16 , Gil I Wolfe  17 , Annemarie Crumlish  17 , Luis Mejico  18 , Muhammad Maaz Iqbal  18 , James D Bowen  19 , Caryl Tongco  19 , Louis B Nabors  20 , Khurram Bashir  20 , Melanie Benge  20 , Craig M McDonald  21 , Erik K Henricson  21 , Björn Oskarsson  21 , Bruce H Dobkin  22 , Catherine Canamar  22 , Tracy A Glauser  23 , Daniel Woo  23 , Angela Molloy  23 , Peggy Clark  23 , Timothy L Vollmer  24 , Alexander J Stein  24 , Richard J Barohn  25 , Mazen M Dimachkie  25 , Jean-Baptiste Le Pichon  25 , Michael G Benatar  26 , Julie Steele  26 , Lawrence Wechsler  27 , Paula R Clemens  27 , Christine Amity  27 , Robert G Holloway  28 , Christine Annis  28 , Mark P Goldberg  29 , Mariam Andersen  29 , Susan T Iannaccone  29 , A Gordon Smith  30 , J Robinson Singleton  30 , Mariana Doudova  30 , E Clarke Haley  31 , Mark S Quigg  31 , Stephanie Lowenhaupt  31 , Beth A Malow  32 , Karen Adkins  32 , David B Clifford  33 , Mengesha A Teshome  33 , Noreen Connolly  28
Affiliations

Seven-Year Experience From the National Institute of Neurological Disorders and Stroke-Supported Network for Excellence in Neuroscience Clinical Trials

Merit Cudkowicz et al. JAMA Neurol. .

Abstract

Importance: One major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders.

Observations: National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings.

Conclusions and relevance: NeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Chase reported grants from National Institutes of Health (NIH) during the conduct of the study. Dr Coffey reported grants from NIH/National Institute of Neurological Disorders and Stroke (NINDS) during the conduct of the study. Dr Ecklund reported grants from NIH during the conduct of the study. Dr Lungu reported honoraria from Elsevier for editorial work. Dr Shefner reported grants from NINDS during the conduct of the study and outside the submitted work. Dr Foster reported grants from NIH/NINDS during the conduct of the study and personal fees from Ferring Pharmaceuticals outside the submitted work. Dr Long reported personal fees from Vaccinex, TripleT, Wave Life Sciences, Roche, Azevan Pharmaceuticals, uniQure, and Genentech outside the submitted work. Dr Torner reported grants from NIH during the conduct of the study. Dr Shinnar reported grants from NINDS during the conduct of the study. Dr Darras reported grants from NINDS during the conduct of the study; personal fees from Genentech, Biogen, Cytokinetics, Vertex, Roche, and Sarepta Therapeutics; grants from SMA Foundation, Cure SMA, Biogen, AveXis, FibroGen, PTC, Roche, Santhera, Sarepta, and Summit; and other support from Elsevier UpToDate outside the submitted work. Dr Marder reported grants from Columbia during the conduct of the study; grants from NIH, Huntington’s Disease Society of America, CHDI, Parkinson Foundation, The Michael J. Fox Foundation for Parkinson’s Research, Teva, Auspex, Genentech, and Azevan; and personal fees from Voyager, Novartis, CHDI Foundation, and Parkinson Foundation outside the submitted work. Dr Chiriboga reported grants and personal fees from AveXis, Biogen, and Roche and personal fees from Genentech and Cytokinetics outside the submitted work. Dr Henchcliffe reported grants from NINDS during the conduct of the study and grants from NIH/ National Center for Advancing Translational Sciences outside the submitted work. Dr Moran reported grants from NINDS during the conduct of the study. Dr Factor reported grants from NIH (U10 NS077366) during the conduct of the study; personal fees from Lundbeck, Teva, Sunovion, Biogen, Acadia, Neuroderm, Acorda, CereSpir, Bracket Global, and CNS Ratings; grants from Ipsen, Medtronic, Boston Scientific, Teva, US WorldMeds, Sunovion, Vaccinex, Voyager, Jazz Pharmaceuticals, Eli Lilly and Company, CHDI Foundation, and The Michael J. Fox Foundation for Parkinson’s Research outside the submitted work; and royalties for textbooks from: Blackwell Futura, Demos Medical Publishing, and Springer. Dr Greenberg reported grants from the NIH during the conduct of the study. Dr Amato reported grants from NIH during the conduct of the study and outside the submitted work. Dr Simuni reported personal fees from Acadia, AbbVie, Adamas Pharmaceuticals, Anavex Life Sciences, Allergan, Acorda Therapeutics, BlueRock Therapeutics, Denali Therapeutics, NeuroDerm, Neurocrine Biosciences, Revance, Sanofi, Sunovion, Teva, Takeda, Voyager, and US WorldMeds; grants from Biogen, Roche, NeuroDerm, Sanofi, Sun Pharma, NINDS, Michael J. Fox Foundation for Parkinson’s Research, Parkinson’s Foundation; and personal fees from Michael J. Fox Foundation for Parkinson’s Research and Parkinson’s Foundation during the conduct of the study. Dr Kissel reported grants from NIH during the conduct of the study. Dr Quinn reported grants from NIH during the conduct of the study. Dr Keith reported grants from NINDS during the conduct of the study. Dr Coyle reported grants from SUNY Stony Brook during the conduct of the study; other support from Accordant, Alexion, Bayer, Biogen, Celgene, Genentech/Roche, Genzyme/ Sanofi, GlaxoSmithKline, Mylan, Novartis, Serono, TG Therapeutics, Teva, and Oxford PharmaGenesis; and grants from Genentech/Roche, Novartis, Actelion, Alkermes, Corrona, MedDay, NINDS, and Patient-Centered Outcomes Research Institute outside the submitted work. Dr Iqbal reported grants from NINDS NeuroNEXT Infrastructure Grant during the conduct of the study. Dr Bowen reported grants from NINDS during the conduct of the study. Dr Nabors reported personal fees from Karyopharm Therapeutics, BTG Pharma, Blue Earth Diagnostics, and KIYATEC outside the submitted work. Dr Bashir reported grants from National Institutes of Health during the conduct of the study and other support from National Multiple Sclerosis Society outside the submitted work. Dr McDonald reported grants from the NIH during the conduct of the study; grants and other support from Sarepta Therapeutics, PTC Therapeutics, Santhera Pharmaceuticals, Capricor Therapeutics, Italfarmaco, Astellas Pharma, Cardero Therapeutics, and grants and other from Catabasis; and grants from Roche and Pfizer outside the submitted work. Dr Oskarsson reported grants from NINDS during the conduct of the study. Dr Canamar reported grants from University of California, Los Angeles during the conduct of the study. Dr Glauser reported grants NINDS during the conduct of the study. Dr Woo reported grants from NIH during the conduct of the study. Dr Clark reported grants from NIH during the conduct of the study. Dr Vollmer reported grants from National Institute of Neurological and Communicative Disorders and Stroke during the conduct of the study; grants and personal fees from Biogen, Genentech/Roche, Rocky Mountain MS Center, andF. Hoffmann-La Roche; personal fees from Siranax, Celgene, EMD Serono, and Novartis; and grants from Actelion and TG Therapeutics outside the submitted work. Dr Dimachkie reported serving asa consultant or on the speaker’s bureau for Alnylam, Audentes Therapeutics, CSL Behring, Sanofi Genzyme, Momenta, Nufactor, RMS Medical, Shire/Takeda, and Terumo. Dr Dimachkie received grants from Alexion, Alnylam Pharmaceuticals, Amicus, BioMarin, Bristol-Myers Squibb, Catalyst, CSL Behring, Food and Drug Administration/ Orphan Products Development, GlaxoSmithKline, Genentech, Grifols, Muscular Dystrophy Association, NIH, Novartis, Genzyme, Octapharma Plasma, Orphazyme, UCB Biopharma, ViroMed Laboratories, and TMA. Dr Benatar reported grants from NIH during the conduct of the study and personal fees from Viela Bio outside the submitted work. Dr Steele reported grants from NINDS during the conduct of the study. Dr Wechsler reported other support from Biogen, Athersys, AAN Telestroke Webinar, Silk Road, and Forest Devices during the conduct of the study. Dr Clemens reported grants from NIH during the conduct of the study. Dr Amity reported grants from NINDS during the conduct of the study. Dr Holloway reported grants from University of Rochester during the conduct of the study. Dr Annis reported grants from University of Rochester during the conduct of the study. Dr Goldberg reported grants from NIH during the conduct of the study. Dr Iannaccone reported grants from NIH during the conduct of the study; grants from NIH, grants from Muscular Dystrophy Association, and grants from Cure SMA; and other support from AveXis, Biogen, Catabasis, Eli Lilly and Company, FibroGen, Regeneron Pharmaceuticals, Sarepta Therapeutics, Scholar Rock, Mallinckrodt, and PTC Therapeutics outside the submitted work. Dr Singleton reported grants from NINDS during the conduct of the study. Dr Haley reported grants from University of Virginia during the conduct of the study and other support from NINDS outside the submitted work. Dr Malow reported personal fees from Neurim Pharmaceuticals, Vanda Pharmaceuticals, and Janssen Pharmaceuticals and grants from Neurim Pharmaceuticals and Autism Speaks outside the submitted work. Dr Clifford reported personal fees from Biogen, Takeda, Sanofi, Pfizer, Amgen, Genentech, GlaxoSmithKline, Merck/Serono, Inhibikase Therapeutics, Dr. Reddy’s Laboratories, Shire, F. Hoffmann-La Roche, Atara Biotherapeutics, Wave Life Sciences, and MitsubishiTanabe Pharma outside the submitted work. Dr Teshome reported grants from NIH/NINDS during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.
Network Organization IRB indicates institutional review board; NINDS, National Institute of Neurologic Diseases and Stroke; PI, principal investigator.
Figure 2.
Figure 2.
Preaward Process ESC indicates extramural science committee; NEC, National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) executive committee; NINDS, National Institute of Neurologic Diseases and Stroke. a First study funded prior to NeuroNEXT formation.
Figure 3.
Figure 3.
Funded Studies: Preaward and Postaward Timeline FPFV indicates first patient, first visit; NoGA, notice of grant award.
Figure 4.
Figure 4.
Network Metrics and Recruitment Curves for NN101 to NN104 cIRB indicates central institutional review board; LPLV, last patient, last visit.
See this image and copyright information in PMC

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