A panel of experts convened by the Alzheimer’s Drug Discovery Foundation (ADDF) and the Association for Frontotemporal Degeneration (AFTD) has provided new guidelines on best practices for the design of early drug trials for Alzheimer’s, frontotemporal degeneration (FTD), and other neurodegenerative dementias.
It is estimated that developing an Alzheimer’s drug costs eight times more than an anti-cancer drug and takes almost twice as long. Panellists believe that greater efficiency in clinical trials can help achieve the proof of concept faster and at a lower cost. They focused on early phase I and II exploratory studies that assessed the safety of a drug and its pharmacological effects on patients. Exploratory studies with optimized study designs can end programs that are unlikely to be successful and efficiently move promising programs through the clinical trial process. Later phase II and III studies measure clinical outcomes such as memory and the ability to perform daily functions.
“Most of the clinical development costs come from later Phase IIb and Phase III studies that require long treatment times and large numbers of patients to detect significant changes in cognitive, behavioral, and functional endpoints,” said Howard Fillit, MD, ADDF founding director and chief science officer. “The results of exploratory phase IIa studies are the critical turning point in researchers deciding which drugs to include in these larger, more expensive studies. Therefore, these phase IIa studies must be as rigorous and well-designed as possible.”
By adopting best practices in designing exploratory studies, researchers and companies can be more confident of using their findings to make critical go / no-go decisions about advancing drugs into larger, late-stage studies. The four main recommendations of the panel are:
- Use rigorous statistical analysis and procedures to involve statisticians as early as possible in the study design.
- Include the appropriate biomarker and clinical endpoints that reflect the drug’s mechanism of action and the specific study population.
- Use historical data to identify appropriate measures of outcome that are well matched to the disease and how the treatment works.
- Consider novel clinical development plans to increase the efficiency of including a drug candidate in larger clinical trials or to determine if it is ineffective as soon as possible. Avoid test designs that are not optimized or bespoke.
“These four recommendations can result in more efficient studies with significant financial savings and more strategic and effective patient engagement,” said Susan LJ Dickinson, CEO of AFTD. “The latter is a key concern for a rare disease like FTD that requires a strategic study design because of the small number of patients. Patients are only included in studies that provide a clear and accurate indication of therapeutic efficacy.”
The guidelines were published in the May 18 issue of neurology®, the American Academy of Neurology’s medical journal.
Edited by Gary Cramer