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Designing Trials of Disease Modifying Agents for Early and Preclinical Alzheimer’s Disease Intervention: What Evidence is Meaningful to Patients, Providers, and Payers?

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The Journal of Prevention of Alzheimer's Disease Aims and scope Submit manuscript

Abstract

Background

Drug development for disease modifying agents in Alzheimer’s disease (AD) is focused increasingly on targeting underlying pathology in very early stages of AD or in cognitively normal patients at elevated risk of developing dementia due to Alzheimer’s. Very early interventional studies of this type have many uncertainties, including whether they can provide the clinical results that payers, providers, and patients will wish to see for decisions. This paper describes an initiative to create greater transparency for researchers to anticipate these decision needs.

Objective

to create multi-stakeholder–vetted recommendations for the design of studies in later phases of drug development to evaluate the ability of disease modifying agents to delay or prevent the onset of dementia due to Alzheimer’s disease (AD).

Design

A multi-stakeholder expert workgroup and overseeing steering group were convened to discuss current advances in early interventional clinical trial design and the evidence needs of patients, providers, and payers. Eight teleconferences and one in-person all-day meeting were held. Meetings were recorded and summary notes prepared between sessions. Final conclusions were consolidated by the project team with the workgroup Chair based on these discussions and were reviewed by group members.

Setting

The in-person meeting was held in Baltimore, MD

Participants

In total, 36 stakeholders representing life sciences industry, payers or health technology assessors, patient advocates and research advocacy organizations, regulators, clinical experts and academic or NIH researchers.

Intervention

N/A.

Measurements

N/A.

Results

Certain aspects of clinical trial design were deemed important to address stakeholder decision needs for future Alzheimer’s prevention drugs even as the field rapidly progresses. These include the need for more robust behavioral and psychological outcome data in early symptomatic disease and the need to update activities of daily living measures to include “digital independence.”

Conclusions

Amyloid, tau, and biomarkers of neurodegeneration should be included in trials and studied in relation to other early measures of change meaningful to individuals with AD, their families, and health plans. These measures include early sensitive changes in behavioral and psychological measures and ability to navigate the contemporary digital landscape. Additional work is needed to generate more robust behavioral and psychological outcome data in early symptomatic disease, and to generate multistakeholder consensus on early measures of change and magnitudes of change that will be meaningful to patients, providers, and payers.

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Author information

Authors and Affiliations

  1. Center for Medical Technology Policy, 401 E. Pratt Street, Suite 631, Baltimore, MD, 21202, USA

    Donna A. Messner & J. Al Naber

  2. Johns Hopkins University (retired), Baltimore, MD, USA

    P. Rabins

  3. Eli Lilly, Indianapolis, USA

    A. C. Downing & M. Irizarry

  4. University of Utah, Salt Lake City, USA

    N. L. Foster & S. Gabler

  5. AveXis, Inc., Bannockburn, USA

    O. Dabbous

  6. Alzheimer’s Drug Discovery Foundation, New York, USA

    H. Fillit

  7. Aetna (Retired), Hartford, USA

    R. Krakauer

  8. New Hampshire Department of Health and Human Services, Concord, USA

    D. Lotz

  9. Patient Advocate / University of Utah Health Care, Salt Lake City, USA

    E. Payzant

  10. Keck School of Medicine, Los Angeles, USA

    L. Schneider

  11. Patient advocate / Beating Alzheimer’s by Embracing Science (BABES), Ramona, USA

    J. Tyrone

  12. Humana, Louisville, USA

    D. Van Amerongen

  13. GNS Healthcare, Cambridge, USA

    D. Wuest

Authors
  1. Donna A. Messner
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  2. P. Rabins
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  3. A. C. Downing
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  16. D. Wuest
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Corresponding author

Correspondence to Donna A. Messner.

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Messner, D.A., Rabins, P., Downing, A.C. et al. Designing Trials of Disease Modifying Agents for Early and Preclinical Alzheimer’s Disease Intervention: What Evidence is Meaningful to Patients, Providers, and Payers?. J Prev Alzheimers Dis 6, 20–26 (2019). https://doi.org/10.14283/jpad.2018.42

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  • DOI: https://doi.org/10.14283/jpad.2018.42

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