In a recent paper published in Neurology, dementia experts provided guidance on the best practices for designing early drug trials for FTD, Alzheimer’s, and other neurodegenerative dementias.

The paper, “Value-Generating Exploratory Trials in Neurodegenerative Dementias,” focuses on early phase 1 and 2 exploratory drug trials, which asses a drug’s safety and pharmacologic effects. AFTD CEO Susan L-J Dickinson, MSGC, and Scientific Director Debra Neihoff, PhD, assisted in authoring the research that investigates how early-stage drug trials should be designed for optimal success in later drug trial stages.

Exploratory studies with optimized study designs, as outlined in the paper, can eliminate programs that won’t be likely to succeed throughout the clinical trial process. The panel of experts, which was convened by AFTD and the Alzheimer’s Drug Discovery Foundation (ADDF), suggested four key recommendations for exploratory trial study designs, including employing rigorous statistical analyses and procedures that engage statisticians in the trial design as early as possible. Other recommendations also pointed to incorporating the appropriate biomarker and clinical endpoints that reflect the drug’s mechanism of action and the specific study population.

“[The] four recommendations can lead to more efficient trials, with substantial financial savings as well as more strategic and effective engagement of patients,” Dickinson said in a press release. “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.”

Dr. Howard Fillit, founding Executive Director and Chief Science Officer of ADDF, said in the press release that “results from exploratory phase 2a trials are the critical inflection point when researchers decide which drugs to move into these larger and more expensive trials, so clearly these phase 2a trials need to be as rigorous and well-designed as possible.”

The majority of clinical development costs come from late-stage phase 2b and phase 3 studies, Fillit noted, adding that these studies “require long treatment periods and a large number of patients to detect meaningful changes in cognitive, behavioral, and functional endpoints.

“We clearly need exploratory trials to be rigorous and efficient,” Fillit continued. “But this is about working toward the ultimate success — effective treatment strategies, which will likely be a combination drug approach that hits several of the biological pathways involved in the neurodegenerative process of dementia. That means being able to take multiple shots on goal — testing a wide variety of plausible drug candidates to identify the most promising ones.”

Read the full Neurology paper here.