Use of Healthcare Claims Data to Generate Real-World Evidence on Patients With Drug-Resistant Epilepsy: Practical Considerations for Research.

Objectives: Regulatory bodies, health technology assessment agencies, payers, physicians, and other decision-makers increasingly recognize the importance of real-world evidence (RWE) to provide important and relevant insights on treatment patterns, burden/cost of illness, product safety, and long-term and comparative effectiveness. However, RWE generation requires a careful approach to ensure rigorous analysis and interpretation. There are limited examples of comprehensive methodology for the generation of RWE on patients who have undergone neuromodulation for drug-resistant epilepsy (DRE). This is likely due, at least in part, to the many challenges inherent in using real-world data to define DRE, neuromodulation (including type implanted), and related outcomes of interest. We sought to provide recommendations to enable generation of robust RWE that can increase knowledge of "real-world" patients with DRE and help inform the difficult decisions regarding treatment choices and reimbursement for this particularly vulnerable population. Methods: We drew upon our collective decades of experience in RWE generation and relevant disciplines (epidemiology, health economics, and biostatistics) to describe challenges inherent to this therapeutic area and to provide potential solutions thereto within healthcare claims databases. Several examples were provided from our experiences in DRE to further illustrate our recommendations for generation of robust RWE in this therapeutic area. Results: Our recommendations focus on considerations for the selection of an appropriate data source, development of a study timeline, exposure allotment (specifically, neuromodulation implantation for patients with DRE), and ascertainment of relevant outcomes. Conclusions: The need for RWE to inform healthcare decisions has never been greater and continues to grow in importance to regulators, payers, physicians, and other key stakeholders. However, as real-world data sources used to generate RWE are typically generated for reasons other than research, rigorous methodology is required to minimize bias and fully unlock their value.

Patterns of utilization and cost of healthcare services and pharmacotherapy among patients with drug-resistant epilepsy during the two-year period before neurostimulation: A descriptive analysis of the journey to implantation based on analyses of a large United States healthcare claims database.

OBJECTIVE: To conduct a descriptive assessment of patterns of utilization and cost of healthcare services and pharmacotherapies among patients with drug-resistant epilepsy (DRE) before neurostimulator implantation. METHODS: Using a large United States healthcare claims database, we identified all patients with DRE who were implanted with neurostimulators between January 1, 2012, and December 31, 2019. Patients without an epilepsy diagnosis on their implantation date were excluded, as were those without (1) anti-seizure medication (ASM) dispenses within 12 months of implantation date, and (2) continuous enrollment for the 24-month period before this date. Demographic and clinical characteristics were assessed over the two-year period before implantation, as were patterns of utilization and cost of healthcare services and pharmacotherapy. Care was assessed as all-cause or epilepsy-related, with the latter defined as all medical (inpatient and outpatient) care resulting in diagnoses of epilepsy and all ASM dispenses. RESULTS: Eight hundred sixty patients met all selection criteria. Among these patients, comorbidities were common, including depression (27%), anxiety (30%), and learning disabilities (25%). Fifty-nine percent of patients had ≥1 all-cause hospitalizations; 57% had ≥1 epilepsy-related admissions. Patients averaged 8.6 epilepsy-related visits to physicians' offices, including 5.1 neurologist visits. Mean all-cause and epilepsy-related healthcare costs during the pre-implantation period were $123,500 and $91,995, respectively; corresponding median values were $74,567 and $53,029. Median monthly all-cause healthcare costs increased by 138% during the 24-month period (from $1,042 to $2,481 in the month prior to implantation); median epilepsy-related costs, by 290% (from $383 to $1,492). CONCLUSIONS: The two-year period before neurostimulator implantation is a long and costly journey. Estimates likely minimize the burden experienced during this period, given that seizure frequency and severity-and corresponding impacts on quality of life-were unavailable in these data. Further research is needed to understand the clinical, economic, and psychological impact of the time between DRE onset and implantation among qualifying patients.

Impact of Vagus Nerve Stimulation for the Treatment of Drug-resistant Epilepsy on Patterns of Use and Cost of Health Care Services and Pharmacotherapy: Comparisons of the 24-Month Periods Before and After Implantation.

PURPOSE: This study examines the impact of vagus nerve stimulation (VNS) as treatment for drug-resistant epilepsy (DRE) on the use and cost of health care services and pharmacotherapy. METHODS: Using a large US health care claims database, we identified all patients with DRE who underwent VNS between January 1, 2012 and December 31, 2019. VNS implantation date was designated as the index date, and patients had to be continuously enrolled for the 24-month period before this date (preindex period). Outcomes included all-cause and epilepsy-related hospitalization, emergency department (ED) visits, and health care costs; health care claims resulting in an epilepsy diagnosis and all claims for antiseizure medications were deemed epilepsy related. Preindex data, except care related to preoperative medical clearance for VNS, were used to estimate multivariate regression models predicting outcomes during the 24-month postindex period (follow-up period). Predicted outcomes during follow-up were then compared with observed values. As a sensitivity analysis, we also replicated all analyses among subgroups defined by comorbid depression. FINDINGS: A total of 659 patients underwent VNS for DRE and met the selection criteria. For the composite outcome of all-cause hospitalizations and ED visits, observed values were 42% lower than expected during the 24-month follow-up period; for the composite outcome of epilepsy-related hospitalizations and ED visits, observed values were 49% lower (P < 0.001 for both). Observed mean total all-cause costs, inclusive of costs of the procedure, were not significantly different than expected costs by month 19 of follow-up; mean total epilepsy-related costs were comparable by month 18. Findings were similar in subgroups with and without depression, although nominally greater differences (observed - expected) were seen in those with comorbid depression. IMPLICATIONS: Our findings suggest that VNS is associated with decreased risk of hospitalization or ED visits (all cause and epilepsy related) during the 2-year period subsequent to implantation and may become cost-neutral within 2 years of implantation (vs continued medical management of DRE without VNS). Although expected outcomes were estimated based on the 24-month period before implantation, the degree to which they approximated what would have happened in the absence of VNS is unknowable. Further research is needed to better understand the extend and duration of the impact of VNS on seizure frequency and severity and health-related quality of life, including its performance among those with and without comorbid depression.

Comparison of utilization and cost of healthcare services and pharmacotherapy following implantation of vagus nerve stimulation vs. responsive neurostimulation or deep brain stimulation for the treatment of drug-resistant epilepsy: analyses of a large United States healthcare claims database.

AIM: Vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) all are options for drug-resistant epilepsy (DRE). However, little is known about how the choice of neurostimulation impacts subsequent healthcare costs. MATERIALS AND METHODS: We used a large US healthcare claims database to identify all patients with epilepsy who underwent neurostimulation between 2012 and 2019. Eligible patients were identified and stratified based on procedure received (VNS vs. RNS/DBS). VNS patients were matched by propensity scoring to RNS/DBS patients. Use and cost of healthcare resources and pharmacotherapy were ascertained over the 24-month period following neurostimulation, incorporating all-cause and epilepsy-related measures. Disease-related care was defined based on diagnoses of claims for medical care and relevant pharmacotherapies. RESULTS: Seven hundred and ninety-two patients met all selection criteria. VNS patients were younger, were prescribed a higher pre-index mean number of anti-seizure medications (ASMs), and had higher pre-index levels of use and cost of epilepsy-related healthcare services. We propensity matched 148 VNS patients to an equal number of RNS/DBS patients. One year following index date (inclusive), mean total all-cause healthcare costs were 50% lower among VNS patients than RNS/DBS patients, and mean epilepsy-related costs were 55% lower; corresponding decreases at the two-year mark were 41% and 48%, respectively. LIMITATIONS: Some clinical variables, such as seizure frequency and severity, quality of life, and functional status were unavailable in the database, precluding our ability to comprehensively assess differences between devices. Administrative claims data are subject to billing code errors, inaccuracies, and missing data, resulting in possible misclassification and/or unmeasured confounding. CONCLUSIONS: After matching, VNS was associated with significantly lower all-cause and epilepsy-related costs for the two-year period following implantation. All-cause and epilepsy-related costs remained statistically significantly lower for VNS even after costs of implantation were excluded.

For some people with epilepsy, medications do not work very well. For these people, other treatment options exist. One such treatment is neurostimulation. There are three types of neurostimulators­vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS). All three devices are known to reduce seizures in patients who have tried several medications. However, it is not known how these devices impact the costs of care. We compared the use and costs of medical care over 2 years between patients who got VNS and those who got RNS/DBS. Before comparing the groups, we made sure that they were balanced. Patients who got VNS were less likely than patients who got RNS/DBS to go to the hospital during the follow-up period. Patients who got VNS also had lower healthcare costs than patients who got RNS/DBS during follow-up. These differences were seen for all medical care costs. These differences also were seen in the costs of care for epilepsy. Our results suggest that the use of VNS is associated with fewer hospitalizations than RNS/DBS, and also that use of VNS is associated with lower healthcare costs than RNS/DBS.