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.

Epidemiology and Economic Outcomes Associated with Timely versus Delayed Receipt of Appropriate Antibiotic Therapy among US Patients Hospitalized for Native Septic Arthritis: A Retrospective Cohort Study.

Timely administration of appropriate antibiotic therapy is associated with better patient outcomes and lower costs of care compared to delayed appropriate therapy, yet initial treatment is often empiric since causal pathogens are typically unknown upon presentation. The challenge for clinicians is balancing selection of adequate coverage treatment regimens, adherence to antimicrobial stewardship principles to deter resistance, and financial constraints. This retrospective cohort study aimed to assess the magnitude and impact of delayed appropriate antibiotic therapy among patients hospitalized with septic arthritis (SA) in the U.S. from 2017 to 2019 using healthcare encounter data. Timely appropriate therapy was defined as the receipt of antibiotic(s) with in vitro activity against identified pathogens within two days of admission; all other patients were assumed to have received delayed appropriate therapy. Of the 517 patients admitted to hospital for SA who met all selection criteria, 26 (5.0%) received delayed appropriate therapy. In inverse-probability-treatment-weighting-adjusted analyses, the receipt of delayed appropriate therapy was associated with an additional 1.1 days of antibiotic therapy, 1.4 days in length of stay, and $3531 in hospital costs (all vs. timely appropriate therapy; all p ≤ 0.02). Timely appropriate therapy was associated with a twofold increased likelihood of antibiotic de-escalation during the SA admission.