Increasing challenges to trial recruitment and conduct over time

Area of Science:

• Neurology
• Clinical Trials
• Pharmacology

Background:

• Recruitment and retention are critical for the success of clinical trials.
• Focal onset epilepsy requires effective treatments, necessitating well-designed clinical trials.
• Historical trends in clinical trial design may impact participant engagement and data validity.

Purpose of the Study:

• To evaluate changes in participant recruitment and retention challenges in focal onset epilepsy clinical trials over time.
• To analyze trends in participant numbers, site involvement, and completion rates in randomized clinical trials.
• To assess the evolution of placebo response rates in these trials.

Main Methods:

• Systematic analysis of randomized clinical trials for adjunct antiseizure medications in focal onset epilepsy since 1990.
• Mixed effects generalized linear models were used to analyze trends in participant numbers, site involvement, and completion rates.
• Statistical models accounted for the number of trial sites and trial-specific variability.

Main Results:

• A significant decrease in participants per site over decades, with recent trials averaging fewer than five participants.
• A decline in the progression of participants from recruitment to randomization over time.
• A concurrent increase in placebo response rates, independent of the number of trial sites.

Conclusions:

• Clinical trials for focal onset epilepsy are facing increasing difficulties in participant recruitment and retention.
• Rising placebo response rates pose a challenge to interpreting trial outcomes.
• A call to action is issued for redesigning clinical trials to address these emerging challenges.