First seizure management

In the era of evidence-based medicine the need for guidelines should be diminishing. After all, if the evidence is so clear, why would one expect clinicians to have trouble interpreting and applying it? In reality, the evidence is not so clear. Most evidence is acquired using imperfect tools from populations who have varying degrees of similarity to the specific patient sitting in front of each of us every day. Even the best clinical trials yield subtly flawed evidence, as each requires interpretation of inclusion and exclusion criteria at the time of enrollment and ascertainment of endpoints that are imperfectly reported (e.g., seizure number, adverse events, compliance). Trials are also subject to important population stratification driven by inclusion and exclusion criteria, proximity to centers conducting trials, persuasiveness of investigators in recruiting participants, and receptivity of specific patient subgroups to enrolling and completing trials. Important subgroups of patients are frequently excluded from trials, e.g., women not committed to avoiding pregnancy; patients with a history of suicidal ideation, cardiac disease, hepatic disease, renal disease, or progressive conditions that might occlude trial endpoints; and, perhaps most importantly, children and the elderly. Finally, clinical trialists build academic careers and may earn significant fractions of their income based on their success in meeting recruitment goals and completing trials, likely leading to subtle biases in the day-to-day decisions that ultimately produce evidence. While blinding and randomization reduce the effect of these issues, they may not eliminate them completely. Furthermore, most epidemiologic and natural history studies are neither blinded nor randomized, and many are not prospective.