Time-to-event clinical trial designs: Existing evidence and remaining concerns

Area of Science:

• Neurology
• Clinical Trial Design
• Epilepsy Research

Background:

• Traditional epilepsy clinical trial designs have remained static for decades, posing challenges for patient recruitment and safety.
• Current placebo-controlled trials require prolonged participant exposure to placebo, increasing risks like sudden unexpected death in epilepsy (SUDEP).
• Increasing therapeutic options for epilepsy complicate recruitment in trials with lengthy placebo maintenance periods.

Purpose of the Study:

• To evaluate the efficacy and patient-friendliness of time-to-event trial designs in epilepsy.
• To address concerns regarding recruitment challenges and safety risks associated with traditional epilepsy trial methodologies.
• To explore innovative trial designs that minimize placebo exposure and enhance participant safety.

Main Methods:

• Review of evidence from re-analyzed prior epilepsy trials.
• Analysis of a published time-to-second seizure trial.
• Incorporation of experience from an ongoing blinded epilepsy trial.
• Discussion of remaining concerns and limitations of time-to-event designs.

Main Results:

• Time-to-event trials demonstrate potential for improved patient recruitment and reduced placebo exposure.
• Evidence suggests these designs can mitigate the risks associated with prolonged placebo use in epilepsy trials.
• Analysis of prior and ongoing trials supports the feasibility and benefits of time-to-event methodologies.

Conclusions:

• Time-to-event trials represent a promising advancement in epilepsy research methodology.
• These innovative designs offer a more patient-friendly approach, enhancing safety and potentially increasing trial participation.
• Addressing limitations and concerns is crucial for the widespread adoption of time-to-event trials in epilepsy drug development.