ReviewNeurology2021
Value-Generating Exploratory Trials in Neurodegenerative Dementias.
Abstract readReview
In one paragraph
Review in Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed.
- Computerized Games versus Crosswords Training in Mild Cognitive Impairment.NEJM evidence · 2022Trial
- Review
- Clinical trials for neuropsychiatric syndromes in major and mild neurocognitive disorders: A CONSORT-based approach.International psychogeriatrics · 2025Review
- Alzheimer Combination Therapies: Overview and Scenarios.The journal of prevention of Alzheimer's disease · 2025Review
- Insights into the adoption of innovative clinical trials across therapeutic areas using clinical trials registry data and large Language models.Scientific reports · 2025Article
- Visualising the Knowledge Structure of Microglia in Alzheimer's Disease: A CiteSpace Analysis.Journal of multidisciplinary healthcare · 2025Article
- A framework for translating tauopathy therapeutics: Drug discovery to clinical trials.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol.Alzheimer's research & therapy · 2024Article
- Challenges and proposed solutions to conducting Alzheimer's disease psychosis trials.Frontiers in psychiatry · 2024Article
- Review
- Preserving the brain: forum on neurodegenerative diseases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Article
- Harnessing the potential of machine learning and artificial intelligence for dementia research.Brain informatics · 2023Review
- Multi-Site Cross-Site Inter-Rater and Test-Retest Reliability and Construct Validity of the MarkVCID White Matter Hyperintensity Growth and Regression Protocol.Journal of Alzheimer's disease : JAD · 2023Article
- Preparing for the age of therapeutic trials in frontotemporal lobar degeneration.Journal of neurology, neurosurgery, and psychiatry · 2022Article
- Challenges and progress in research, diagnostics, and therapeutics in Alzheimer's disease and related dementias.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Exploiting Focused Ultrasound to Aid Intranasal Drug Delivery for Brain Therapy.Frontiers in pharmacology · 2022Article
- On the design of early-phase Alzheimer's disease clinical trials with cerebrospinal fluid tau outcomes.Clinical trials (London, England) · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Lauren G FriedmanFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Nicholas McKeehanFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Yuko HaraFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Jeffrey L CummingsFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Dawn C MatthewsFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Jian ZhuFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Richard C MohsFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Deli WangFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Suzanne B HendrixFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Melanie QuintanaFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Lon S SchneiderFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Michael GrundmanFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Samuel P DicksonFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Howard H FeldmanFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Judith JaegerFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Elizabeth C FingerFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
J Michael RyanFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Debra NiehoffFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Susan L-J DickinsonFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Jessica T MarkowitzFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Meriel OwenFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Alessio TravagliaFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA.
Howard M FillitFrom the Alzheimer's Drug Discovery Foundation (L.G.F., N.M., Y.H., M.O., A.T., H.M.F.), New York; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas; ADM Diagnostics (D.C.M.), Inc. Northbrook, IL; Servier Pharmaceuticals (J.Z.), Boston, MA; Global Alzheimer's Platform Foundation (R.C.M.), Washington, DC; AgeneBio (R.C.M.), Inc. Baltimore, MD; AbbVie Inc. (D.W.), North Chicago, IL; Pentara Corporation (S.B.H., S.P.D.), Salt Lake City, UT; Berry Consultants (M.Q.), Austin TX; Keck School of Medicine of the University of Southern California (L.S.S.), Los Angeles; Global R&D Partners (M.G.), LLC, University of California, San Diego, La Jolla; Department of Neurosciences (H.H.F.), University of California, San Diego, La Jolla; Albert Einstein College of Medicine (J.J.), Bronx, NY; CognitionMetrics (J.J.), LLC; Department of Clinical Neurological Sciences and Robarts Research Institute (E.C.F.), Schulich School of Medicine and Dentistry, University of Western Ontario; Parkwood Institute (E.C.F.), Lawson Health Research Institute, St. Josephs Health Care, London, Ontario, Canada; Rodin Therapeutics (J.M.R.), Boston, MA; Association for Frontotemporal Degeneration (D.N., S.L.-J.D.), Radnor, PA; and Modus Outcomes LLP (J.T.M.), Cambridge, MA. hfillit@alzdiscovery.org.
Funding
USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI, ARTHUR W TOGA · 2020 to 2026
$27.8MRenewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI JESSICA KIRKLAND CALDWELL · 2015 to 2026
$22.8MNVEDARC Clinical CoreP20AG068053 · NIA · CLEVELAND CLINIC FOUNDATION · PI FOX, ROBERT J. · 2020 to 2022
$3.3MNIA NIH HHS P20 AG068053NIA NIH HHS P30 AG066530NIGMS NIH HHS P20 GM109025
Abstract
Drug development for Alzheimer disease and other neurodegenerative dementias, including frontotemporal dementia, has experienced a long history of phase 2 and phase 3 clinical trials that failed to show efficacy of investigational drugs. Despite differences in clinical and behavioral characteristics, these disorders have shared pathologies and face common challenges in designing early-phase trials that are predictive of late-stage success. Here, we discuss exploratory clinical trials in neurodegenerative dementias. These are generally phase 1b or phase 2a trials that are designed to assess pharmacologic effects and rely on biomarker outcomes, with shorter treatment durations and fewer patients than traditional phase 2 studies. Exploratory trials can establish go/no-go decision points, support proof of concept and dose selection, and terminate drugs that fail to show target engagement with suitable exposure and acceptable safety profiles. Early failure saves valuable resources including opportunity costs. This is especially important for programs in academia and small biotechnology companies but may be applied to high-risk projects in large pharmaceutical companies to achieve proof of concept more rapidly at lower costs than traditional approaches. Exploratory studies in a staged clinical development program may provide promising data to warrant the substantial resources needed to advance compounds through late-stage development. To optimize the design and application of exploratory trials, the Alzheimer's Drug Discovery Foundation and the Association for Frontotemporal Degeneration convened an advisory panel to provide recommendations on outcome measures and statistical considerations for these types of studies and study designs that can improve efficiency in clinical development.
Indexed as
Alzheimer DiseaseClinical Trials as TopicClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicDementiaDrug DevelopmentFrontotemporal DementiaHumansNeurodegenerative DiseasesOutcome Assessment, Health CareProof of Concept StudyResearch DesignTreatment FailureTreatment Outcome
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