Background
Methods
Literature search
Eligibility criteria
PICOS | Inclusion | Exclusion |
---|---|---|
Population | Patients with LGS, including clearly defined “probable” LGS | Other DEEs |
Intervention | Studies assessing the overall burden of illness of LGS without the impact of an intervention | Studies assessing the impact of interventionsa |
Comparator | N/A | – |
Outcomes | Prevalence/incidence Economic burden Direct and indirect costs Resource use Patient and caregiver HRQoL and broader patient-reported outcomes Mortality | – |
Study designs/publication type | Publications reporting original data, including: Healthcare insurance claims data Chart reviews Registry studies Electronic healthcare databases studies Epidemiologic surveys Observational studies Economic evaluations if they contain original data on resource utilisation and HRQoL | In vitro and in vivo studies Preclinical studies Case reports and case series Clinical studies reporting only efficacy and safety data Economic evaluations reporting on specific interventionsb Reviewsc, SLRsc, comments, letters, editorials and press releases |
Limits | Searches of conferences in Embase were limited to the previous 3 years (conferences 2018-current)d | None |
Study selection
Data extraction and synthesis
Quality assessment/risk of bias
Results
Search results
Study, year (Publication type) Country Database | Study type and source of data | Time period | Population: Number | Definition of LGS | Characteristics: Age, mean (SD; median [range]), years; Male, % | Outcomes |
---|---|---|---|---|---|---|
Burden-of-illness/costs and resource | ||||||
Piña-Garza [46] (Full) USA MEDLINE and Embase | Retrospective insurance claims analysis: Medicaid multi-state database of six states | Observation period: mean (SD): 11.1 (4.5) years (1997/98–2012/13) | Probable LGS: N=14,712 | ≥2 medical claims ≥30 days apart for specified epilepsy or unspecified epilepsy (ICD-9-CM codes) Machine-learning technique based on a number of clinical variables (including use of rufinamide during the testing & training period) | 16.3 (15.7); 52.5% male | Epidemiology Resource Direct costs |
Strzelczyk 2021 [47](Full) Germany MEDLINE, Embase and APA PsycInfo | Retrospective insurance claims analysis: Vilua Healthcare research database, entries for >4 million people i.e ~5% of the German population | 10 years (2007–2016) | Broad LGS: N=545 Narrow LGS: N=102 | Broad definition: Algorithm considering: ≥1 ICD-10 diagnosis of G40 (epilepsy)/G41 (status epilepticus) and ≥1 claim of either rufinamide or felbamate (during the year of identification), OR ≥2 different ASMs in combination with ≥1 developmental delay diagnosis and no diagnosis code for competing etiologies Narrow definition: ≥1 documented G40/G41 claim before their 6th birthday | Narrow LGS: | Epidemiology Mortality Resource Direct costs |
Chin 2021 [40] (Full) UK MEDLINE and Embase | Retrospective analysis using electronic medical records from healthcare databases: Primary care data (CPRD) linked to secondary care data (HES), and general population mortality data (ONS) | ~31 years (1987–2018) Follow-up: mean (SD; median [range]): 11.7 (8.2; 9.6 [0.2; 32.2]) years | Confirmed LGS: N=110 Probable LGS: N=146 Full cohort: N=256 | Confirmed LGS: CPRD read code for LGS Probable LGS: ICD-10 code/ CPRD read code for epilepsy Rufinamide within a year of diagnosis | Confirmed LGS: 7.0 (10.0; 3.5 [0–61]); 66% male Probable LGS: 8.9 (11.0; 4 [0–54]); 56% male Full cohort: 8.1 (10.6; 4 [0–61]); 60% male | Epidemiology Mortality Resource |
Reaven 2018 [54] (Full) (LGS vs controls) USA MEDLINE, Embase and APA PsycInfo | Retrospective insurance claims analysis: Truven Health Analytics MarketScan® Research Databases, entries for ~60 million people with commercial or Medicaid insurance coverage | 2010–2015 | Probable LGS: Commercial: N=2270 Medicaid: N= 3749 | A diagnosis code for refractory epilepsy and A diagnosis code for developmental delay/intellectual disability and A prescription for at least one selected ASM. Excluded patients with diagnosis codes for conditions suggestive of other etiologies Modified version of the algorithm developed by Piña-Garza et al [46] (above) | Commercial: 13 (9.8 [0–62]); 53.0% male Medicaid: 13 (10.5 [0–60]); 52.9% male | Resource Direct costs |
Reaven 2019 [53] (Full) (LGS vs other DEEs; seizure events vs no events) USA MEDLINE, Embase and APA PsycInfo | Probable LGS: Commercial: N=2269 Medicaid: N= 3730 | Commercial: 13 (9.8 [0–62]); 53.0% male Medicaid: 13 (10.5 [0–60]); 52.8% male | ||||
Stockl 2019 [56] (Abstract) (Hospitalizations) USA Embase | Probable LGS: Commercial: N=2520 Medicaid: N=4613 | As above, but also patients with an acute inpatient hospitalization (≥1 day LOS) | NR | Resource | ||
Stockl 2019 [55] (Abstract) (Commercial; Costs & Resource) USA Embase | Retrospective insurance claims analysis: IBM® MarketScan® Commercial & Medicaid databases | 2015–2016 | Probable LGS: Commercial: N=1296 | ≥1 ASM claim and medical claims with ≥1 diagnosis code for LGS or refractory epilepsy or ≥1 claim for clobazam or rufinamide. The LGS cohort required a diagnosis code for LGS or all of the following: oooooo≥1 diagnosis code for refractory epilepsy oooooo≥1 diagnosis code for intellectual disability/developmental delay, ooooooNo diagnosis codes that preclude LGS | Commercial: 16.5; NR | Epidemiology Resource (ASM use only) Direct costs |
Hollenack 2019 [52] (Abstract) (Medicaid; Costs & Resource USA Embase | 2014–2015 | Probable LGS: Medicaid: N= 5186 | Medicaid: 18.3; 58.2% male | |||
Hollenack 2019 [41] (Abstract) (prevalence) USA Embase | Commercial: 2016– 2017 Medicaid: 2016 | Probable LGS: Commercial: N=2273 Medicaid: N=4786 | NR | |||
François 2017 [51] (Full) USA MEDLINE | Retrospective insurance claims analysis: Truven Health MarketScan® claims databases, entries for >40 million people with commercial or Medicaid insurance coverage | 2010–2014 | LGS pre-clobazam initiation Commercial/medicare: N=1384 Medicaid: N=1365 | ≥2 medical claims with a diagnosis of generalized convulsive or non-convulsive epilepsy ≥30 days apart, or ≥1 medical claim with a diagnosis of generalized convulsive epilepsy and ≥1 medical claim with a diagnosis of non-convulsive epilepsy (≥30 days apart (ICD-9-CM codes) ≥1 of the epilepsy diagnosis codes in the primary position ≥1 medical claim with a diagnosis for developmental disorder or cognitive impairment (ICD-9-CM codes) | Commercial/medicare: 31.0 (23.2); 49.3% male Medicaid: 24.1 (17.9); 51.8% male | Resource Direct costs |
Umeno 2019 [57] (Full) Japan Embase | Retrospective study on the use of the welfare system in children with DEEs in Japan | 2015–2016 | LGS: N=30 | Children aged 0 to 16 years diagnosed at the Department of Child Neurology, Okayama University Hospital | NR | Resource (welfare system) |
Epidemiology alone | ||||||
Trevathan 1997 [44] (Full) MADDS study USA MEDLINE and Embase | Population-based, cross-sectional study: (MADDS): a multiple-source, EEG laboratory-based, case ascertainment system across Atlanta | 1975–1977 | Children with LGS: N=23 | Epilepsy Two or more seizure types that included tonic, atonic, atypical absence, and/or myoclonic seizures with multiple falls Interictal EEG that demonstrated slow spike-wave discharges | NR; 73.9% male | Prevalence |
Autry 2010 [48] (Full) MADDS study USA | 1975–2001 | LGS: N=34 | NR; NR | Mortality | ||
Sidenvall 1996 [43] (Full) Northern Sweden MEDLINE and Embase | Observational study: Active epilepsy assessed in children aged 0–16 years in an area of northern Sweden with ~ 250,000 inhabitants (~50,000 children) | 1985–1986 | LGS: N=9 | Diagnosed using standard ILAE criteria | NR; NR | Prevalence |
Rantala 1999 [42] (Full) Finland MEDLINE and Embase | Retrospective study: Children seen at the Department of Pediatrics University of Oulu | 1976–1993 | LGS: N=25 | At least two types of the most common seizure types (tonic-axial, atonic, and absence seizures) Slow spike waves | 13.0 [6.5–17.9]; 56% male | Prevalence and incidence |
Heiskala 1997 [45] (Full) Finland MEDLINE and Embase | Retrospective study: Health records from the Helsinki metropolitan area & the province of Uusimaa | 1975–1985 | LGS: N=75 | A minimum of two types of typical though nonspecific epileptic seizures (e.g. astatic seizures, tonic seizures during sleep, and atypical absence seizures) Mental deficiency Bursts of diffuse slow spike-waves in the EEG | NR; NR | Incidence |
Beilmann 1999 [39] (Full) Estonia MEDLINE | Observational study: Patients with epilepsy seen at the Tartu University Hospital, sourced through multiple methods | 1995 –1997 | NR | Diagnosed using standard ILAE criteria | NR; NR | Prevalence |
HRQoL | ||||||
Auvin 2021 [61] (Full) UK and France | Observational study: On-line surveys | 2018–2019 | Patients and/or caregivers of individuals with DEEs estimated a patient’s health state from vignettes of hypothetical patients | NA | NA; NA | Patient HRQoL: quantitative (VAS) |
Radu 2019 [62] (Abstract) NR Embase | Observational study: On-line surveys | 2018 | NA | NA; NA | Patient HRQoL: quantitative (VAS) | |
Gallop 2010 [58] (Full) US, UK & Italy MEDLINE, Embase and APA PsycInfo | Observational study: Open-ended interviews and HRQoL instruments | NR | Parents of patients with LGS recruited through support groups and websites (UK and US) and through clinicians (Italy): N=40 | NR | Caregiver HRQoL: Quantative (SF-36v2, HADS) and qualitative Patient HRQoL: Qualitative | |
Murray 1993 [60] (Full) Australia MEDLINE, Embase and APA PsycInfo | Observational study: Questionnaires & in-depth interviews | NR | Parents of patients with LGS who attended a self-help group: N=41 | NR | Caregiver HRQoL: Qualitative | |
Gibson 2014 [59] (Full) USA MEDLINE, Embase and APA PsycInfo | Observational study: General experience and parent survey | NR | Parents of patients with LGS who had contacted a support hotline: N=96 surveys returned | NR | [3.5–36 years]; NR | Caregiver HRQoL: Qualitative |
Study | Country | Study type | Year | Population (n) | Incidence/prevalence | Mortality | |
---|---|---|---|---|---|---|---|
Parameter | Value | ||||||
Piña-Garza 2017 [46] (Full) | USA | Retrospective claims analysis | 2012/13 | Probable LGS patients N=14,712 | Proportion of epilepsy patients with probable LGS (10-year age groups) | 8.4% at age 10 decreasing to 2% in the 60-year-old cohort | NR |
Strzelczyk 2021 [47] (Full) | Germany | Retrospective claims analysis | 2016 | Broad LGS N=545 Narrow LGS N=102 | Prevalence (standardized to German GKV population) | Broad LGS: 39.2 per 100,000 people Narrow LGS: 6.5 per 100,000 people | Broad LGS: 10.01% [157 events] Narrow LGS: 2.88% [six events] (p < 0.001 vs control) Control: 0.01% [one event] |
Chin 2021 [40] (Full) | UK | Retrospective analysis of electronic medical records | 2017 | Confirmed LGS: N=74 for prevalence Probable LGS: N=106 for prevalence Full cohort: N=180 for prevalence; N=122 for mortality | Prevalence (standardized to UK CPRD population) | Confirmed LGS: 2.89 per 100,000 people* Probable LGS: 4.20 per 100,000 people* Full cohort: 5.78 per 100,000 people* | Crude mortality rate per 1000 person-years: Confirmed LGS: 6.12 [11 events] Probable LGS: 4.17 [7 events] Full cohort: 18 events |
Hollenack 2019 [41] (Abstract) | USA | Retrospective claims analysis | 2016/ 2017 | Probable LGS: Commercial: N=2273 Medicaid: N=4786 | Prevalence | Commercial: 13.0 per 100,000 people* Medicaid: 60.8 per 100,000 people* | NR |
Trevathan 1997 [44] MADDS study (Full) | USA | Population-based, cross-sectional study | 1975–1977 | LGS: N=23 | Prevalence of LGS at age 10 years Proportion of epilepsy patients with LGS | 26 per 100,000 people* 4% of epilepsy patients | NR |
Autry 2010 [48] MADDS study (Full) | Original cohort: 1975–1977 Follow-up: 1975 to 2001 | LGS: N=34 | NR | NR | Mortality ratio (95% CI): 13.92 (7.19-24.31) for LGS vs 3.11 (2.39-3.98) for all epilepsy | ||
Sidenvall 1996 [43] (Full) | Northern Sweden | Observational | 1985 | LGS: N=9 | Prevalence N (%) of epilepsy patients with LGS | 20 per 100,000 people* n=9 (5.8%) of all epilepsy cases | NR |
Rantala 1999 [42] (Full) | Finland | Retrospective | 1976–1993 | LGS: N=25 | Prevalence | 28 per 100,000 people (95% CI: 18–41)* | NR |
Annual incidence | 1.93 per 100,000 children <15 years (95% CI: 1.25-2.85/100,000) | ||||||
Heiskala 1997 [45] (Full) | Finland | Retrospective | 1975–1985 | LGS (broad definition): N=75 LGS children 0–14 years: N=NR | Annual incidence | Broad definition: 2.1 per 100,000 people Children 0–14 years: 1.9 per 100,000 | NR |
Beilmann 1999 [39] (Full) | Estonia | Observational | 1997 | LGS: N=NR | Prevalence | 10 per 100,000 people* | NR |