Biomarker and Clinical Trial Design Support for Disease-Modifying Therapies: Report of a Survey of the EU/US: Alzheimer’s Disease Task Force

  • Jeffrey CummingsEmail author
  • N. Fox
  • B. Vellas
  • P. Aisen
  • G. Shan
  • EU/US Alzheimer’ Disease Task Force
Brief Report



Disease-modifying therapies are urgently needed for the treatment of Alzheimer’s disease (AD). The European Union/United States (EU/US) Task Force represents a broad range of stakeholders including biopharma industry personnel, academicians, and regulatory authorities.


The EU/US Task Force represents a community of knowledgeable individuals who can inform views of evidence supporting disease modification and the development of disease-modifying therapies (DMTs). We queried their attitudes toward clinical trial design and biomarkers in support of DMTs.


A survey of members of the EU/US Alzheimer’s Disease Task Force was conducted. Ninety-three members (87%) responded. The details were analyzed to understand what clinical trial design and biomarker data support disease modification.


Task Force members favored the parallel group design compared to delayed start or staggered withdrawal clinical trial designs to support disease modification. Amyloid biomarkers were regarded as providing mild support for disease modification while tau biomarkers were regarded as providing moderate support. Combinations of biomarkers, particularly combinations of tau and neurodegeneration, were regarded as providing moderate to marked support for disease modification and combinations of all three classes of biomarkers were regarded by a majority as providing marked support for disease modification. Task Force members considered that evidence derived from clinical trials and biomarkers supports clinical meaningfulness of an intervention, and when combined with a single clinical trial outcome, nearly all regarded the clinical trial design or biomarker evidence as supportive of disease modification. A minority considered biomarker evidence by itself as indicative of disease modification in prevention trials. Levels of evidence (A,B,C) were constructed based on these observations.


The survey indicates the view of knowledgeable stakeholders regarding evidence derived from clinical trial design and biomarkers in support of disease modification. Results of this survey can assist in designing clinical trials of DMTs.

Key words

Alzheimer’s disease clinical trials biomarkers EU/US Task Force 


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Copyright information

© Serdi and Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Jeffrey Cummings
    • 1
    Email author
  • N. Fox
    • 2
  • B. Vellas
    • 3
  • P. Aisen
    • 4
  • G. Shan
    • 5
  • EU/US Alzheimer’ Disease Task Force
  1. 1.Cleveland Clinic Lou Ruvo Center for Brain HealthLas VegasUSA
  2. 2.Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of NeurologyUniversity College LondonLondonUK
  3. 3.Department of Geriatric MedicineUniversity Toulouse IIIToulouseFrance
  4. 4.Alzheimer’s Therapeutic Research InstituteUniversity of Southern CaliforniaSan DiegoUSA
  5. 5.Department of Environmental and Occupational Health, Epidemiology and Biostatistics Program, School of Community Health SciencesUniversity of Nevada Las VegasLas VegasUSA

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