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Framework for Clinical Trials in Cerebral Small Vessel Disease (FINESSE): A Review

Markus, Hugh S.; Van Der Flier, Wiesje M.; Smith, Eric E.; Bath, Philip; Biessels, Geert Jan; Briceno, Emily; Brodtman, Amy; Chabriat, Hugues; Chen, Christopher; De Leeuw, Frank Erik; Egle, Marco; Ganesh, Aravind; Georgakis, Marios K.; Gottesman, Rebecca F.; Kwon, Sun; Launer, Lenore; Mok, Vincent; O'Brien, John; Ottenhoff, Lois; Pendlebury, Sarah; Richard, Edo; Sachdev, Perminder; Schmidt, Reinhold; Springer, Melanie; Tiedt, Stefan; Wardlaw, Joanna M.; Verdelho, Ana; Webb, Alastair; Werring, David; Duering, Marco; Levine, Deborah; Dichgans, Martin


Hugh S. Markus

Wiesje M. Van Der Flier

Eric E. Smith

Stroke Association Professor of Stroke Medicine

Geert Jan Biessels

Emily Briceno

Amy Brodtman

Hugues Chabriat

Christopher Chen

Frank Erik De Leeuw

Marco Egle

Aravind Ganesh

Marios K. Georgakis

Rebecca F. Gottesman

Sun Kwon

Lenore Launer

Vincent Mok

John O'Brien

Lois Ottenhoff

Sarah Pendlebury

Edo Richard

Perminder Sachdev

Reinhold Schmidt

Melanie Springer

Stefan Tiedt

Joanna M. Wardlaw

Ana Verdelho

Alastair Webb

David Werring

Marco Duering

Deborah Levine

Martin Dichgans


Importance: Cerebral small vessel disease (SVD) causes a quarter of strokes and is the most common pathology underlying vascular cognitive impairment and dementia. An important step to developing new treatments is better trial methodology. Disease mechanisms in SVD differ from other stroke etiologies; therefore, treatments need to be evaluated in cohorts in which SVD has been well characterized. Furthermore, SVD itself can be caused by a number of different pathologies, the most common of which are arteriosclerosis and cerebral amyloid angiopathy. To date, there have been few sufficiently powered high-quality randomized clinical trials in SVD, and inconsistent trial methodology has made interpretation of some findings difficult. Observations: To address these issues and develop guidelines for optimizing design of clinical trials in SVD, the Framework for Clinical Trials in Cerebral Small Vessel Disease (FINESSE) was created under the auspices of the International Society of Vascular Behavioral and Cognitive Disorders. Experts in relevant aspects of SVD trial methodology were convened, and a structured Delphi consensus process was used to develop recommendations. Areas in which recommendations were developed included optimal choice of study populations, choice of clinical end points, use of brain imaging as a surrogate outcome measure, use of circulating biomarkers for participant selection and as surrogate markers, novel trial designs, and prioritization of therapeutic agents using genetic data via Mendelian randomization. Conclusions and Relevance: The FINESSE provides recommendations for trial design in SVD for which there are currently few effective treatments. However, new insights into understanding disease pathogenesis, particularly from recent genetic studies, provide novel pathways that could be therapeutically targeted. In addition, whether other currently available cardiovascular interventions are specifically effective in SVD, as opposed to other subtypes of stroke, remains uncertain. FINESSE provides a framework for design of trials examining such therapeutic approaches..


Markus, H. S., Van Der Flier, W. M., Smith, E. E., Bath, P., Biessels, G. J., Briceno, E., …Dichgans, M. (2022). Framework for Clinical Trials in Cerebral Small Vessel Disease (FINESSE): A Review. JAMA Neurology,

Journal Article Type Article
Acceptance Date Jun 17, 2022
Online Publication Date Aug 15, 2022
Publication Date Aug 15, 2022
Deposit Date Aug 17, 2022
Journal JAMA Neurology
Print ISSN 2168-6149
Electronic ISSN 2168-6157
Publisher American Medical Association (AMA)
Peer Reviewed Peer Reviewed
Keywords Neurology (clinical)
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