Alzheimer's disease therapeutic trials: EU/US task force report on recruitment, retention, and methodology

Abstract

While we may not be able to find a cure for Alzheimer's disease (AD) in the near future, several drugs presently in trials have shown promise as possible modifiers of disease progression. However, we may not be able to demonstrate efficacy due to issues of recruitment, retention, site-to-site variability, and other methodological issues. It is thus incumbent on the scientific community to find solutions to these problems, particularly as the field moves toward preventing illness or treating the disease in its prodromal stages, where these methodological issues will become even more critical. We need to better understand why participants agree or refuse to enter drug trials, and why both primary care physicians and Alzheimer's specialists agree or refuse to involve their patients. We also need to quantify the impact of requiring imaging studies, extensive questionnaires, cognitive testing, and lumbar punctures on recruitment and retention. With these concerns in mind, an international task force meeting of experts from academia and industry in the United States, European Union, and Japan in San Diego, California on November 2, 2011 to focus on recruitment, retention and other methodological issues related to clinical trials for AD. Based on the recommendations of this Task force meeting, this Perspectives article critically reflects on the most critical and timely methodological issues related to recruitment and retention in prevention and therapeutic trials in AD, which are paralleled by a paradigm shift in the diagnostic conceptualization of this disease, as reflected by recently new proposed diagnostic criteria involving preclinical stages of the disease.

Obstacles And Opportunities In Alzheimer’s Clinical Trial Recruitment

“…The challenge of overcoming physicians’ reluctance to screen for cognitive impairment will require additional study, as will the impact of imaging studies and lumbar punctures on the willingness to refer patients for Alzheimer’s disease clinical trials. 24 Better insights are needed into what motivates patients and physicians to participate in clinical trials and strategies to overcome cultural and psychological barriers.…”

The crisis in recruitment for clinical trials in Alzheimer's and dementia: An action plan for solutions

“…The challenges associated with current models of research and development for the treatment and prevention of dementia, and the question of how to improve the productivity of these efforts, have been extensively deliberated at several meetings organized by the Alzheimer's Association's Research Roundtable, the Alzheimer's Association International Conference, Clinical Trials on Alzheimer's Disease, the Advances in Alzheimer Therapy conferences, and the EU-US Task Force [1][2][3][4][5][6][7]. These deliberations have examined contributors to the challenges, as well as potential solutions to the problems facing current therapy development efforts.…”

How to design nutritional intervention trials to slow cognitive decline in apparently healthy populations and apply for efficacy claims: A statement from the international academy on nutrition and aging task force

“…Disease modifying trials must be at least 18 months to really be able to have an effect on the disease course. (29–33). Preventive trials may require 3 to 5 years of follow-up.…”

“…Biomarkers (both CSF and imaging) may also be used as secondary outcome measures, and may be measured only in a subgroup of the total population (31–33, 35, 36). They may be especially useful when anticipating a disease modifying effect or in preventive trials.…”