Advertisement

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

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

Abstract

Background

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.

Objectives

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.

Design/Setting/Particiants

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.

Measurements/Results/Conclusions

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.

Conclusion

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 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cummings J, Lee G, Mortsdorf T, Ritter A, Zhong K. Alzheimer’s disease drug development pipeline: 2017. Alzheimer’s & Dementia: Translational Research & Clinical Interventions 2017;3:367–384.Google Scholar
  2. 2.
    Alzheimer’s Association. Changing the trajectory of Alzheimer’s disease: how a treatment by 2025 saves lives and dollars. Chicago, IL: 2015.Google Scholar
  3. 3.
    Cummings JL, Fox N. Defining disease modification for Alzheimer’s disease clinical trials. J Prev Alz Dis 2017;4:109–115.Google Scholar
  4. 4.
    Cummings JL. Disease modification and neuroprotection in neurodegenerative disorders. Transl Neurodegener 2017;In press.Google Scholar
  5. 5.
    Soto M, Abushakra S, Cummings J, et al. Progress in Treatment Development for Neuropsychiatric Symptoms in Alzheimer’s Disease: Focus on Agitation and Aggression. A Report from the EU/US/CTAD Task Force. J Prev Alzheimers Dis 2015;2:184–188.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Vellas B, Aisen PS, Sampaio C, et al. Prevention trials in Alzheimer’s disease: an EU-US task force report. Prog Neurobiol 2011;95:594–600.CrossRefPubMedGoogle Scholar
  7. 7.
    Vellas B, Hampel H, Rouge-Bugat ME, et al. Alzheimer’s disease therapeutic trials: EU/US Task Force report on recruitment, retention, and methodology. J Nutr Health Aging 2012;16:339–345.CrossRefPubMedGoogle Scholar
  8. 8.
    Vellas B, Carrillo MC, Sampaio C, et al. Designing drug trials for Alzheimer’s disease: what we have learned from the release of the phase III antibody trials: a report from the EU/US/CTAD Task Force. Alzheimers Dement 2013;9:438–444.CrossRefPubMedGoogle Scholar
  9. 9.
    Vellas B, Bateman R, Blennow K, et al. Endpoints for Pre-Dementia AD Trials: A Report from the EU/US/CTAD Task Force. J Prev Alzheimers Dis 2015;2:128–135.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Queensland Treasury. Presenting survey results, report writing. Queensland Government Statistician’s Office, Australia: 2015.Google Scholar
  11. 11.
    Leber P. Observations and suggestions on antidementia drug development. Alzheimer Dis Assoc Disord 1996;10 Suppl 1:31–35.CrossRefPubMedGoogle Scholar
  12. 12.
    Bodick N, Forette F, Hadler D, et al. Protocols to demonstrate slowing of Alzheimer disease progression. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines. The Disease Progression Sub-Group. Alzheimer Dis Assoc Disord 1997;11 Suppl 3:50–53.PubMedGoogle Scholar
  13. 13.
    Cummings JL. Defining and labeling disease-modifying treatments for Alzheimer’s disease. Alzheimers Dement 2009;5:406–418.CrossRefPubMedGoogle Scholar
  14. 14.
    Jack CR, Jr., Bennett DA, Blennow K, et al. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 2016;87:539–547.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Serdi and Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Jeffrey Cummings
    • 1
  • 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

Personalised recommendations