Drug-resistant epilepsy (DRE) describes the condition of people with epilepsy who still experience seizures despite taking medications. DRE can lead to physical injuries, and is associated with mental illness, and increased risk of death compared to people whose epilepsy is well controlled with medications. These people may also need to attend hospital when having seizures and overall use more healthcare resources. There is limited information on the impact of DRE on healthcare resource utilisation in England.
The present study aims to better understand patient characteristics, underlying conditions, drugs, and procedures, death, healthcare resource utilisation, and associated costs among a cohort of people with DRE. People who received vagus nerve stimulation will also be compared to people with DRE who remained on anti-seizure medications as part of this study. Nationally representative data from the Clinical Practice Research Datalink linked with the Hospital Episode Statistics will be used for this study to provide up-to-date real-world information for people with epilepsy, and among those people, people who develop DRE and to better understand the impact of their condition on the risk of death and on the use of the National Health Service, in order to help improve the care of these people.
Drug-resistant epilepsy (DRE) has been estimated as affecting 30-40% of people with epilepsy, and is characterised by people experiencing recurrent epileptic seizures despite anti-seizure medications (ASMs). Based on the International League against Epilepsy (ILAE) criteria, an epileptic patient who started a third ASM (as monotherapy or combination therapy) will be defined as having DRE. People with DRE experience an increased burden in terms of healthcare resource utilisation (HCRU), including visits to emergency departments and hospitalisations. However, published real-world studies on DRE were performed in the United States, and limited evidence exists for England.
The present study will use data from the Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics (HES) in England. The primary objectives of the study are (1) to describe the characteristics and comorbidities for people with epilepsy who develop DRE; (2) to describe their treatment pathway; (3) to assess their HCRU and costs; and (4) to assess their all-cause and epilepsy-related mortality. The secondary objectives are (1) to compare the characteristics and comorbidities between people with epilepsy who underwent vagus nerve stimulation (VNS), versus people with epilepsy who develop DRE and who remain on drug-only treatment (ASMs) in a matched cohort; and (2) to compare the HCRU and associated costs between those two groups. Subgroup analyses by patients’ characteristics will be performed if numbers allow. Mortality will be reviewed as an exploratory endpoint in this comparative cohort. This study will provide up-to-date epidemiological evidence on people with DRE, their treatments, and their use of both primary and secondary care services in England. The findings may be used by clinicians, researchers, and policy makers to better characterize the unmet need in this patient population as well as improve the management and care pathways of those people within the National Health Service (NHS).
Primary objective 1: Age when first met DRE criteria in years and by decade; gender; Charlson Comorbidity Index; other comorbidities: top 10 recorded diagnoses; time from epilepsy diagnosis to meeting DRE criteria; Socioeconomic status as measured by the Index of Multiple Deprivation (IMD).
Primary objective 2: 3-years post index ASMs (e.g., counts and percentages of patients on 3, 4, 5, 6 ASMs); 3-years post-index alternative treatment: resective surgery, VNS, or deep brain stimulation (DBS) (e.g., counts and percentages of patients receiving an intervention; number of ASMs prior to the intervention); time from DRE diagnosis to treatment (ASMs, alternative treatment).
Primary objective 3: time to post-index primary care contacts (epilepsy-related general practice / other allied healthcare professional visits); counts of post-index primary care contacts per follow-up year (e.g., 1 year, 2 years, 3 years, etc.); primary care costs (including costs associated with prescriptions of ASMs); time to post-index secondary care contacts (epilepsy-related non-elective / elective inpatient admissions, all inpatient admissions, neurology department outpatient visits, accident and emergency [A&E] attendances); counts of post-index secondary care contacts per follow-up year; length of stay (LOS) and costs associated with epilepsy-related non-elective / elective inpatient admissions and all inpatient admissions; costs associated with neurology department outpatient visits and A&E attendances.
Primary objective 4: time to post-index all-cause mortality and epilepsy-related mortality; post-index all-cause mortality and epilepsy-related mortality per follow-up year
For secondary objective 1; each endpoint will be estimated and compared between the 2 strata of people with epilepsy who underwent vagus nerve stimulation (VNS); and people with epilepsy who developed DRE and remained on ASMs: Age at first recorded DRE diagnosis in years and by decade; gender; Charlson Comorbidity Index; other comorbidities: top 10 recorded diagnoses; time from epilepsy diagnosis to DRE diagnosis, IMD.
For secondary objective 2; each endpoint will be estimated and compared between the 2 strata of people with epilepsy who underwent vagus nerve stimulation (VNS); and people with epilepsy who developed DRE and remained on ASMs: time to post-index primary care contacts (epilepsy-related general practice / other allied healthcare professional visits); counts of post-index primary care contacts per follow-up year (e.g., 1 year, 2 years, 3 years, etc.); primary care costs (including costs associated with prescriptions of ASMs); time to post-index secondary care contacts (epilepsy-related non-elective / elective inpatient admissions, all inpatient admissions, neurology department outpatient visits, A&E attendances); counts of post-index secondary care contacts per follow-up year; LOS and costs associated with epilepsy-related non-elective / elective inpatient admissions and all inpatient admissions; costs associated with neurology department outpatient visits and A&E attendances.
Exploratory objective, each endpoint will be estimated and compared between the 2 strata of people with epilepsy who underwent VNS; and people with epilepsy who developed DRE and remained on ASMs: time to post-index overall mortality and epilepsy related mortality; post-index all-cause mortality and epilepsy-related mortality per follow-up year.
Craig Currie - Chief Investigator - Pharmatelligence Limited t/a Human Data Sciences
Leah Fisher - Corresponding Applicant - Pharmatelligence Limited t/a Human Data Sciences
Bronwyn Do Rego - Collaborator - LivaNova
Debra Gregory - Collaborator - Harvey Walsh Ltd
Ellen Hubbuck - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
Francesca Barion - Collaborator - LivaNova
Lara Groves - Collaborator - OPEN Health Group
Oliver Williams - Collaborator - LivaNova
Reginald Lassagne - Collaborator - LivaNova
Rohit Shankar - Collaborator - Cornwall Partnership NHS Foundation Trust
Teresa Carroll - Collaborator - OPEN Health Group
Vanessa Danielson - Collaborator - Not from an Organisation
Xiaocong Marston - Collaborator - Harvey Walsh Ltd
Debra Gregory - Collaborator - Harvey Walsh Ltd
Joanna Murphy - Collaborator - LivaNova
Maxine Dibué - Collaborator - LivaNova
Myriam Alexander - Collaborator - Harvey Walsh Ltd
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation