Increased seizure frequency graphs in medication trials: FDA labels vs. peer-review.

OBJECTIVE

Anti-seizure medications (ASMs) typically reduce seizure frequency (SF) in some patients. However, even when the ASM is effective, some patients experience increased SF after initiation largely due to natural fluctuations. Graphical communication of those that experience an increase can vary between trial publications. We assessed the difference in graphical representation of the percentage of patients showing increased SF in ASMs trials between the U.S. Food and Drug Administration (FDA) approved prescribing labels and those in the peer-reviewed literature.

METHODS

We searched peer-reviewed literature for the initial publication of randomized clinical efficacy trials referenced in the prescribing labels of FDA-approved ASMs for adjunctive treatment of epilepsy from (2000-2024). We then assessed whether a systematic difference existed in the choice to graphically display the percentage of patients with an increase in SF.

RESULTS

There were 16 ASMs approved for adjunctive treatment between 2000-2024. There were 43 studies referenced for clinical efficacy in the 16 labels. Peer-reviewed journals included graphs SF increases in 23 % (95 % CI: 12 % to 39 %) compared to FDA-approved labels in 63 % (95 % CI: 35 % to 85 %). The absolute difference in the presence of the graphs was 39 % (95 % CI: 8 % to 65 %) (Chi-squared = 6.359, p-value = 0.012). When text and tables were included peer-review journals presented SF increases in 51 % of the trials (22 out of 43).

CONCLUSION

Compared to FDA-approved labels, the peer-reviewed publications of the last 16 FDA-approved ASMs under-informed clinicians about the percentage of patients with increased SF, which may impact informed shared decision-making.