An expert panel convened by the Alzheimer’s Drug Discovery Foundation (ADDF) and the Association for Frontotemporal Degeneration (AFTD) has provided new guidance on best practices for the design of early drug trials for Alzheimer’s disease, frontotemporal degeneration (FTD), and other neurodegenerative dementias.
Development of an Alzheimer’s drug costs an estimated eight times more than for a cancer drug, and takes nearly twice as long. The panelists believe that greater efficiencies in clinical trials can help to achieve proof of concept more rapidly and at lower costs. They focused on early Phase I and II exploratory trials, which assess a drug’s safety and pharmacologic effects on patients. Exploratory studies with optimized study designs can terminate programs not likely to succeed and efficiently move promising programs through the clinical trial process. Later Phase II and III trials measure clinical outcomes such as memory and ability to perform daily functions.
“The majority of clinical development costs come from later stage Phase IIb and Phase III studies, which require long treatment periods and a large number of patients to detect meaningful changes in cognitive, behavioral, and functional endpoints,” said Howard Fillit, MD, ADDF founding executive director and chief science officer. “Results from exploratory Phase IIa trials are the critical inflection point when researchers decide which drugs to move into these larger and more expensive trials, so clearly these Phase IIa trials need to be as rigorous and well-designed as possible.”
By adopting best practices in designing exploratory trials, researchers and companies can be more confident in using their results to make the all-important go/no-go decisions about advancing drugs to larger late-stage trials. The four key panel recommendations are to:
- Employ rigorous statistical analyses and procedures, engaging statisticians in trial design as early as possible.
- Incorporate the appropriate biomarker and clinical endpoints that reflect the drug’s mechanism of action and the specific study population.
- Leverage historical data to determine appropriate outcome measures that are well-aligned with the disease and mechanism of action for the treatment.
- Consider novel clinical development plans to increase efficiency in moving a drug candidate into larger clinical trials or determining that it is ineffective as quickly as possible; avoid “cookie cutter” trial designs that are not optimized or tailored.
“These four recommendations can lead to more efficient trials, with substantial financial savings, as well as more strategic and effective engagement of patients,” said AFTD CEO Susan L-J Dickinson. “The latter is a key concern for a rare disease like FTD where the low number of patients pushes the need for strategic study design, with patients enrolled only in studies that will provide a clear and accurate readout of therapeutic efficacy.”
The guidance was published in the May 18 issue of Neurology®, the medical journal of the American Academy of Neurology.
Edited by Gary Cramer