TABLE 6.

Identified gaps in the literature related to drug‐resistant epilepsy

Type of outcome	Gaps in the literature
General gaps	RCTs evaluated ASM compared to placebo; did not evaluate specific ASM combinations
	Non‐RCTs evaluated ASM combinations; however, they were retrospective, did not have a control group, and/or had small sample sizes
	Limited research conducted among African countries/ethnic groups and women who are pregnant
	Inconsistent reporting of concomitant non‐pharmacologic interventions (i.e., medical marijuana use or ketogenic diet). It is unclear what is the optimal interplay of non‐pharmacologic and pharmacologic treatments
Clinical outcomes	Evaluation of specific ASM combinations were not included as a primary end point for RCTs, or ASMs were grouped based on similar mechanisms
	Unclear how individual and/or specific ASM combinations worsen seizure control since this was specifically reported in a few studies (five of 26 studies)
Humanistic outcomes	Limited number of studies (two or less) evaluating each humanistic outcome
	Limited number of studies (n = 1) evaluating SUDEP, and results appear to be inconsistent with other reports
Economic outcomes	Limited number of studies (n = 1) reporting economic outcomes, including healthcare costs, QALY, cost‐utility analyses, and ICER
	Evaluation of cost may have limited generalizability given health care and payment systems vary widely between countries
DRE term and definition(s)	Inconsistent use of terms, such as refractory or DRE
	Inconsistent use of DRE definition for inclusion criteria
	In general, it is difficult to align inclusion criteria with ILAE definition of DRE to ensure appropriate trials of ASMs prior to inclusion

Abbreviations: ASM, antiseizure medication; DRE, drug‐resistant epilepsy; ICER, incremental cost‐effectiveness ratio; ILAE, International League Against Epilepsy; QALY, quality‐adjusted life years; RCT, randomized controlled trial; SUDEP, sudden unexpected death in epilepsy.