Do neurologists agree in diagnosing drug resistance in adults with focal epilepsy?

Abstract

Objective: To evaluate interrater agreement in categorizing treatment outcomes and drug responsiveness status according to the International League Against Epilepsy (ILAE) definition of drug-resistant epilepsy. Methods: A total of 1053 adults with focal epilepsy considered by the investigators to meet ILAE criteria for drug resistance were enrolled consecutively at 43 centers and followed up prospectively for 18-34 months. Treatment outcomes for all antiepileptic drugs (AEDs) used up to enrollment (retrospective assessment), and on an AED newly introduced at enrollment, were categorized by individual investigators and by 2 rotating members of a 16-member expert panel (EP) that reviewed the patient records independently. Interrater agreement was tested by Cohen's kappa (k) statistics and rated according to Landis and Koch's criteria. Results: Agreement between EP members in categorizing outcomes on the newly introduced AED was almost perfect (90.1%, k = 0.84, 95% confidence interval [CI] 0.80-0.87), whereas agreement between the EP and individual investigators was moderate (70.4%, k = 0.57, 95% CI 0.53-0.61). Similarly, categorization of outcomes on previously used AEDs was almost perfect between EP members (91.7%, k = 0.83, 95% CI 0.81-0.84) and moderate between the EP and investigators (68.2%, k = 0.50, 95% CI 0.48-0.52). Disagreement was related predominantly to outcomes considered to be treatment failures by the investigators but categorized as undetermined by the EP. Overall, 19% of patients classified as having drug-resistant epilepsy by the investigators were considered by the EP to have "undefined responsiveness."Significance: Interrater agreement in categorizing treatment outcomes according to ILAE criteria ranges from moderate to almost perfect. Nearly 1 in 5 patients considered by enrolling neurologists to be "drug-resistant" were classified by the EP as having "undefined responsiveness."

Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options

“…In due course, we may come to discover that there are many mechanisms or contributors to drug resistance. For now, it is reassuring that categorization according to the definition has proven to be dependable in practice (Mula et al, 2019;Zaccara et al, 2019).…”

Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug‐resistant focal epilepsy

“…13 As shown in Table 1, three of four patients in the ITT population had already discontinued at least two AEDs in the past, with the three most frequent reasons being lack of efficacy in 71.8% of cases, lack of efficacy and tolerability in 10.6%, and adverse effects in 9.8%. A detailed analysis, including reasons for disagreement, is reported in a separate publication.…”

“…A detailed analysis, including reasons for disagreement, is reported in a separate publication. 13 As shown in Table 1, three of four patients in the ITT population had already discontinued at least two AEDs in the past, with the three most frequent reasons being lack of efficacy in 71.8% of cases, lack of efficacy and tolerability in 10.6%, and adverse effects in 9.8%. Three-quarters of patients (74.5%) were taking two or more AEDs at enrollment.…”

Clinical Management of Drug Resistant Epilepsy: A Review on Current Strategies

“…In a study evaluating the interrater agreement of the ILAE DRE definition between members of an epilepsy expert panel and individual investigators, 19% of patients were classified as having DRE by the investigators while considered to have “undefined responsiveness” by the expert panel. 11 These divergences were mostly related to ASD dosage and/or the choice of the previously failed ASD. ASD prematurely withdrawn before having been titrated up to efficacious dose because of adverse events are not be considered as a failure for DRE criteria.…”