Developing Integrated Frameworks for Go/No Go Decision Making

Developing a new drug for AD is a complex and costly process. At each stage, research teams make decisions about whether to move forward with the drug's development ("Go") or stop it ("No-Go").

Making these decisions wisely is essential to avoid wasting time and resources on ineffective drugs.

A publication by Wessels, A.M. et al. (2021) in Drug Discovery Today discusses how researchers in drug development for AD can use a combination of methods and tools to develop algorithms to make informed decisions about whether to continue or halt the development of a potential drug.

One of the considerations shared in the paper is the value of considering integrated frameworks and using various tools to support the development of go/no-go algorithms that are appropriate for your trial.

? Tools to Consider in Integrated Frameworks for Go/No-Go Criteria:

1. Target Engagement: One key component is to determine if the drug is engaging with its intended target in the brain. This typically happens in early-phase studies (Phase I) involving a small number of participants. If the drug doesn't hit the target effectively, it might not be worth continuing.
2. Physiological Measures: It's also important to assess how the drug affects physiological measures downstream from target engagement. Techniques employed include quantitative electroencephalography (qEEG) and event-related potentials (ERPs) to measure brain activity. These measurements provide indirect evidence of whether the drug is affecting brain function in the desired way.
3. Digital Biomarkers: Digital tools (like digital cognitive tests) have become important "digital biomarkers." These tests can help evaluate the drug's impact on cognitive function, which is a key consideration in AD drug development.
4. Composite Scales: Composite scales are derived from existing scales that measure various aspects of cognitive function and clinical outcomes. These scales provide a more comprehensive view of how the drug is affecting patients.
5. Traditional Cognitive Scales: Traditional cognitive tests are used to evaluate the drug's impact on specific cognitive functions, such as memory, attention, and executive function.

It's important to note that there's no one-size-fits-all approach. The specific tools and methods used to develop your go/no-go algorithm depend on the drug being developed and the knowledge available about its mechanism of action. Various combinations will emerge to suit the needs of your trial.

We encourage you to read the FULL publication here.

Citation: Wessels, A.M. et al. Cognitive Go/No-Go decision-making criteria in Alzheimer’s disease drug development, Drug Discov Today (2021), https://doi.org/10.1016/j.drudis.2021.01.012?