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Alzheimer's disease drug development: old problems require new priorities
Robert E Becker1, Nigel H Greig
1Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. rebecker2008@comcast.net
CNS & Neurological Disorders Drug Targets
|January 9, 2009
Summary
Standardized protocols are crucial for reliable Alzheimer's disease (AD) clinical trials and patient care. The study emphasizes using validated biomarkers and protocol-guided practices for accurate AD diagnosis and drug development.
Area of Science:
- Neurology
- Clinical Pharmacology
- Biomarker Research
Background:
- Current Alzheimer's disease (AD) clinical trials and patient care rely on rating instruments and methods lacking standardized protocols.
- Factors like measurement error, evaluator bias, and protocol deviations can invalidate clinical trial (CT) data and patient care outcomes.
- Evidence from the Alzheimer's Disease Neuroimaging Initiative (ADNI) highlights the necessity of standardized protocols for validating biomarkers in AD.
Purpose of the Study:
- To address the limitations in precision and accuracy of rated outcomes in AD clinical trials and patient care.
- To advocate for the prioritization of validated biomarkers as outcome variables in AD drug development and patient care.
- To promote the development of protocol-guided practices, modeled after ADNI research, for effective biomarker utilization.
Main Methods:
- Review of existing methodologies in AD clinical trials and patient care.
- Analysis of evidence highlighting inaccuracies and biases in current study protocols.
- Emphasis on the Alzheimer's Disease Neuroimaging Initiative (ADNI) as a model for standardized research practices.
Main Results:
- Significant inaccuracies, imprecision, and biases have been detected in studies, potentially invalidating CT outcome data.
- Standardized protocols are essential for validating biomarkers for AD diagnosis, drug development, and patient care.
- Current AD CTs often function as efficacy tests under field conditions rather than providing clear usage guidelines.
Conclusions:
- Priority should be given to the qualification and use of biomarkers as outcome variables in AD drug development and patient care.
- Development of protocol-guided practices, similar to ADNI, is crucial for the effective use of biomarkers.
- AD CTs must define conditions for drug use, utilize biomarker surrogate endpoints, and move beyond efficacy testing under current clinical practices.
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