The Case for Master Protocols for Rare Neurological Diseases

Area of Science:

• Neuroscience
• Clinical Trials
• Rare Diseases

Background:

• Master protocol trials enable simultaneous multiple hypothesis testing within a unified framework.
• These designs hold potential applicability for rare diseases, including rare neurological disorders.
• A multistakeholder conference in May 2025 focused on master protocols for rare neurological conditions.

Purpose of the Study:

• To explore the application of master protocol trial designs in rare neurological disorders.
• To examine the potential benefits of master protocols for rare disease research.
• To use neuronal ceroid lipofuscinoses as a specific example for applying master protocols.

Main Methods:

• Review of master protocol trial designs.
• Application of master protocol concepts to rare neurological disorders.
• Case study using neuronal ceroid lipofuscinoses.

Main Results:

• Master protocols can facilitate simultaneous multiple hypothesis testing.
• Shared protocol elements and infrastructure can reduce costs and improve efficiency.
• This approach may accelerate therapeutic delivery for rare diseases.

Conclusions:

• Master protocol trials offer a promising framework for rare neurological disorders.
• Implementing master protocols can enhance efficiency and reduce costs in rare disease drug development.
• Accelerated therapeutic delivery is a key potential outcome for patients with rare neurological conditions.