Seizure clusters, treatment patterns, and healthcare resource utilization in patients with epilepsy: A Wisconsin-based claims analysis.

BACKGROUND: Seizure clusters are underresearched and associated with adverse outcomes in patients with epilepsy. This study was a noninterventional, retrospective claims-based analysis using the Wisconsin Health Information Organization (WHIO) All-Payer Claims Database to characterize the epilepsy population in Wisconsin, with a focus on prevalence, treatment patterns, and healthcare resource utilization (HCRU) in patients with seizure clusters prior to the introduction of nasal spray rescue medications. This timeframe allows characterization of a historical baseline for future comparisons with newer treatments. METHODS: Four cohorts were defined: (1) all-epilepsy (all patients with epilepsy); and subcohorts of: (2) patients receiving a monotherapy antiseizure medication (ASM); (3) patients receiving ASM polytherapy; and (4) patients treated for seizure clusters (ie, those taking rescue medications and ≥ 1 ASM). Primary outcomes were HCRU over a 12-month follow-up period, which were descriptively analyzed. RESULTS: Between 2017 and 2019, 16,384 patients were included in the all-epilepsy cohort; 11,688 (71.3 %) were on monotherapy, 3,849 (23.5 %) were on polytherapy, and 526 (3.2 %) were treated for seizure clusters. Twelve-month retentions to the ASM treatments were 46.7 % (7,895/16,904) in the all-epilepsy cohort, and 40.0 % (4,679/11,688) and 40.1 % (1,544/3,849) in the monotherapy and polytherapy subcohorts, respectively. Rescue medication prescriptions were obtained 1,029 times by the 526 patients in the treated seizure cluster subcohort, with infrequent refill rates (mean 1.6-1.9 times/year). A higher proportion of patients in the treated seizure cluster subcohort had epilepsy-related outpatient visits (89.7 %), other visits (71.3 %), and hospitalizations (25.3 %) than patients in the monotherapy (72.2 %, 50.2 %, 19.3 %, respectively) and polytherapy (83.3 %, 63.3 %, 22.8 %, respectively) subcohorts. Mean (standard deviation) all-cause ($114,717 [$231,667]) and epilepsy-related ($76,134 [$204,930]) costs over 12 months were higher in the treated seizure cluster subcohort than the monotherapy ($89,324 [$220,181] and $30,745 [$145,977], respectively) and polytherapy ($101,506 [$152,931] and $49,383 [$96,285], respectively) subcohorts. CONCLUSIONS: Patients treated for seizure clusters incurred higher all-cause and epilepsy-related costs and epilepsy-related HCRU than other subcohorts and had infrequent rescue medication refills. The findings of this analysis highlight the need for appropriate treatment for those patients with epilepsy experiencing seizure clusters. The effect of newer rescue medications to alter these findings will be explored in a follow-up study. Regardless, specialist providers with expertise in treating refractory epilepsy and seizure cluster patients may help to reduce the burden of seizure clusters.

Community Pharmacist-Centered training program improves confidence in delivering epilepsy care.

RATIONALE: Incorporating pharmacists into interdisciplinary healthcare teams can improve patient outcomes across disease states; however, there is little evidence describing pharmacists' contributions to epilepsy care. Previous research from our group revealed that community pharmacists are well positioned to serve as patient advocates, monitor medications, and provide education for people living with epilepsy. However, pharmacists would like to receive additional training in epilepsy management. Advanced training in neurology is not a practical approach for community pharmacists who engage daily with patients having a variety of conditions and medications. OBJECTIVE: To develop and evaluate a flexible, community pharmacist-centered training program to improve both confidence and competence in delivering epilepsy care. METHODS: The training program consisted of five 1-hour, self-paced online modules and two 90-minute synchronous virtual sessions. Topics included the classification of the epilepsies, comorbid conditions, antiseizure medicine (ASM) therapy, special populations (pregnancy, people of childbearing potential, older adults), seizure emergencies, and sudden unexpected death in epilepsy (SUDEP), as well as social determinants of health. The training program was delivered over 6 weeks to pharmacists located at two community pharmacies in Washington State. Learning was assessed using a pre- and post-training questionnaire containing questions that evaluated knowledge and confidence in the training material. RESULTS: The training program did not significantly change pharmacists' mastery of the material. However, the pharmacists' confidence in delivering the material significantly improved in 14 of the 16 areas that were evaluated. Pharmacists' mastery and confidence were strongest in areas around ASM management, SUDEP and seizure emergencies, people of child-bearing potential and older adults with epilepsy, and comorbidities, whereas social health disparities in epilepsy care remained an area that required further training. CONCLUSION: Our findings support the idea that community pharmacists are well positioned with the knowledge to play an important role in epilepsy care. However, dedicated training tailored to community pharmacists' needs may improve their confidence in providing such care.

The influence of social determinants of health on epilepsy treatment delays in an Arizona Medicaid population.

OBJECTIVE: The purpose of this study was to better understand the role of social determinants of health (SDoH) in both treatment delays and treatment gaps for individuals with epilepsy (IWE) enrolled in Arizona's Medicaid program using predictive models at the population and individual levels. METHODS: In this retrospective cohort study, two statistical regression models were developed using Arizona Medicaid medical and pharmacy claims records from 2015-2019 and selected census tract-level SDoH data. Three treatment outcomes were defined: timely treatment (treated within thirty days); delayed treatment (treated after thirty days); and untreated. For the first model, least squares regression was used to regress the epilepsy treatment delays on selected SDoH factors at the population-level. For the second model, multinomial logistic regression was used to estimate associations between epilepsy treatment delays and individual-level sociodemographic factors. RESULTS: Of the 5965 IWE identified with a new epilepsy diagnosis during the study period, 43.1% were treated with a mean delay of 180 days. Among the treated population, 42% received timely treatment. A treatment gap of at least 40.6% and potentially up to 56.9% was calculated. Individuals with epilepsy diagnosed in an inpatient setting or in emergency departments were more likely to be treated and receive timely treatment than those diagnosed in an office or clinic setting. Individuals with epilepsy diagnosed in "other" settings were more likely to go untreated or receive delayed treatment than a patient diagnosed in an office or clinic. Compared to IWE aged 31-50 years, IWE aged 0-30 years were more likely to receive timely treatment, IWE aged 51-64 years were more likely to receive delayed treatment, and IWE aged 65 years or older were more likely to go untreated. Widowed IWE were more likely to go untreated relative to single patients. Individuals with epilepsy experiencing homelessness were also more likely to go untreated. Unemployed IWE were more likely to go untreated or receive delayed treatment. Native American IWE were more likely to go untreated compared to White patients. CONCLUSIONS: Treatment gaps and treatment delays are experienced by IWE in the Arizona Medicaid population. The SDoH factors predicted to impact treatment delays include care setting, age, race, marital status, homelessness, and employment.

Association Between Adverse Events and Discontinuation of Antiepileptic Drugs Among Drug-Naïve Adults with Epilepsy.

BACKGROUND: Adherence to antiepileptic drugs (AEDs) remains the primary management tool to prevent recurrent seizures in patients with epilepsy. Adverse events associated with AEDs could have an impact on adherence and result in treatment failures. OBJECTIVE: The goal of this study was to assess the association between adverse events and discontinuation of AEDs for AED-naïve patients with epilepsy. Our second objective was to estimate the economic burden of AED discontinuation. METHODS: We retrospectively analyzed IBM MarketScan administrative data from 2014 to 2017. The cohort consisted of new users of AEDs with an epilepsy diagnosis and with two or more subsequent AED claims. Outpatient and inpatient cohorts were analyzed separately. Adverse events were identified by injury codes (E-CODES) or by International Classification of Diseases, Ninth/Tenth Edition (ICD-9/10) codes for disease manifestations reported in the literature or product inserts (LADE). Discontinuation of AEDs was defined as a gap of ≥ 60 days without a refill. All cost comparisons were based on 1:1 propensity-score matching. Associations between adverse events and discontinuation were estimated using logistic regression, adjusting for predefined covariates such as age, sex, Charlson Comorbidity Index, insurance type, and AED type. RESULTS: The overall discontinuation rate was 9% (E-CODES rate was 0.1% and LADE rate was 27%). The discontinued group was older (56.1 vs. 52.8 years; p < 0.0001). Adults aged ≥ 65 years had the highest discontinuation rate (11%). Patients who discontinued had fewer AED claims (6.8 vs. 9.2; p < 0.0001), more outpatient claims (19.3 vs. 17.8; p < 0.0001), and longer hospital stays (6.6 vs. 5.3 days; p < 0.0001). Differences in daily outpatient costs between patients with and without adverse events were statistically significant (E-CODES $US213 vs. 105; p = 0.001; LADE $US188 vs. 161; p < 0.0001). Additionally, total cost of AEDs in the outpatient cohort was higher for patients with adverse events (E-CODES and LADE). There was no association between E-CODES and AED discontinuation; however, there was a positive association between LADE and discontinuation in the outpatient cohort but a negative association in the inpatient cohort. CONCLUSION: We found that total costs of prescriptions claimed and total costs of outpatient visits among the outpatient cohort were higher for those with adverse drug events than for those without. An association between adverse events and discontinuation was inconclusive because it depended on the target population and how the adverse events were identified.

Alternative Payment Models in Medical Oncology: Assessing Quality-of-Care Outcomes Under Partial Capitation.

BACKGROUND: Alternative payment models (APMs) in healthcare are emerging that reward quality of care over quantity of services. Most bundled payment programs that are described in published studies are related to episodes for a surgical inpatient hospital stay. With outpatient services, monthly capitated payments are an alternative to bundled payments for specialty services. OBJECTIVE: To assess the association of a capitated contractual arrangement between a primary care physician group and an oncology clinic group with the quality of care received. METHODS: We evaluated the effect of an oncology group's transition from a fee-for-service (FFS) arrangement to a partial-capitated-payment model with a primary care group. We compared outcomes for patients who received treatment after implementation of the new arrangement (ie, postcontract capitated group) with outcomes of patients receiving treatment before the change (ie, precontract capitated group). In addition, we conducted a parallel analysis of patients from a population that was not affected by the contract to assess temporal effects (ie, postcontract FFS group vs precontract FFS group). All patients were enrolled in Medicare Advantage plans of a single health plan (ie, Humana), and outcomes were measured using claims data provided by that company. Patients in the 2 precontract groups received treatment between July 1, 2010, and June 30, 2011; patients in the 2 postcontract groups received treatment between January 1, 2013, and December 31, 2013. Age- and sex-adjusted all-cause hospitalization, complications from cancer treatment, and ambulance transfers during 6 months of follow-up were evaluated. RESULTS: In the population subject to the partial-capitated-payment model, the postcontract group (N = 305) was younger than the precontract group (N = 165). In a subset of patients in the 2 capitated groups who had Deyo-Charlson Comorbidity Index (CCI) RxRisk scores, the postcontract capitated group had significantly higher CCI scores. Adjusted odds ratios for the postcontract capitated group versus the precontract capitated group showed no difference in the likelihood that any of the outcomes would occur. However, the mean number of chemotherapy-related complications and ambulance transports were greater postcontract. In the parallel analysis of the population not affected by the new payment arrangement, no differences were found between the pre- and postcontract groups. This suggests that temporal changes potentially affecting patients in the capitated and FFS populations would not have influenced postcontract outcomes. CONCLUSIONS: After the implementation of partial-capitated payments for medical oncology services in the oncology practice, the likelihood of a patient experiencing at least 1 event of a specific adverse outcome did not change; however, the average number of some adverse events did increase, which may in part be explained by a higher level of underlying morbidity in the postcontract group. The overall findings of this study suggest that quality of care was not compromised in this APM.

Missed Opportunities for Human Papillomavirus Vaccine Initiation in an Insured Adolescent Female Population.

BACKGROUND: This study assessed the initiation of HPV vaccination in insured adolescent females in relation to physician visits and receipt of other vaccines routinely given at the same age. METHODS: January 1, 2010, and September 31, 2015. Vaccination administration was determined by using Current Procedural Terminology codes. A missed opportunity was defined as the absence of an HPV vaccine at the following encounter types: visits with a 4-valent meningococcal conjugate vaccine (MenACWY) or tetanus, diphtheria, and acellular pertussis (Tdap) vaccine claim; well adolescent visits; or any encounter with a primary care provider (PCP). Missed opportunities were stratified by type of provider (pediatrician or nonpediatrician). RESULTS: Among 14588 adolescent girls, only 6098 (41.8%) initiated the HPV vaccine series. HPV vaccine was given at 37.1% of visits when a Tdap or MenACWY vaccine was administered, 26.0% of well adolescent visits and 41.8% of PCP visits. Pediatricians had fewer missed opportunities than nonpediatricians to administer HPV (50.7% vs 60.8%), as well as Tdap, although the difference was larger for Tdap (7.0% vs 29.6%). CONCLUSIONS: These data indicate that pediatricians and nonpediatricians alike are missing opportunities to administer the HPV vaccine when other adolescent vaccines are given. Efforts should be focused on converting these missed vaccination opportunities into cancer-prevention visits.

Does Hepatitis C Treatment Adherence Affect Risk of Liver Transplantation? A Historical Cohort Study.

BACKGROUND: Chronic hepatitis C virus (HCV) is the primary cause of liver failure leading to transplantation, and medication adherence is essential to the therapeutic efficacy of HCV treatments. While there is evidence linking poor adherence with increased utilization and cost, published literature lacks examination of the association between medication adherence and risk of liver transplant. In addition, the impact of HCV treatment on total costs of liver transplantation is not well documented. OBJECTIVES: To compare (a) the relative risk of liver transplant by adherence in patients treated for HCV and (b) the total health care costs in treated and untreated patients who require liver transplant. METHODS: This observational, historical cohort study was conducted using administrative data from the Humana Research Database. To be included, patients were required to have a documented HCV diagnosis or treatment between January 1, 2008, and June 30, 2013. Patients were excluded if they had a hepatitis B diagnosis, were not fully insured by a commercial or Medicare Advantage Prescription Drug plan, or were outside the age range of 19-89 years. No minimum pre- or post-index enrollment period was required, and patients were followed for their entire post-index enrollment through December 31, 2013. The study population was divided into treated and untreated groups and then subdivided by presence or absence of a liver transplant. Date of liver transplant was defined as the index date for untreated liver transplant patients; otherwise, the index date was defined as either the date of first observed HCV treatment or diagnosis date (if no treatment or liver transplant). Cox proportional hazards models were used to estimate the relative risk of liver transplant by level of treatment adherence (> 80%, 50%-79%, and < 50%) based on proportion of days covered. General linearized models with log link and gamma distribution were used to compare median total health care costs from index date until end of study period (or death/disenrollment, whichever came first) between treated and untreated liver transplant patients. All costs were converted to 2013 U.S. dollars and reported as total costs per patient and per patient per month (PPPM) to account for varying follow-up periods. RESULTS: Of the 53,423 patients identified with HCV, 10,377 met exclusion criteria, leaving 43,046 patients (primarily Caucasian, males, mean age of 58 years) in the initial cohort. Only 6.29% (n = 2,708) of the total HCV cohort received HCV treatment, and less than 1% (n = 366, 0.8%) received a liver transplant. Although there were no significant differences in the risk of liver transplant by adherence level, there was an upwards trend in the rate of liver transplant as adherence worsened (> 80%: 1.25%; 50%-79%: 1.30%; and < 50%: 1.99%), and the average days to liver transplant was longer with higher adherence (> 80%: 683; 50%-79%: 623; < 50%: 454). Only 48 (13.11%) patients who received a liver transplant were treated for HCV. Adjusted median total and PPPM health care costs measured from index date until end of the study period were significantly higher for patients who received HCV treatment compared with those who did not (total=$231,139 vs. $86,167, adjusted P < 0.001; PPPM=$20,583 vs. $5,778, adjusted P = 0.008), driven by HCV-related medical costs and total pharmacy costs. CONCLUSIONS: Adherence with HCV regimens did not affect risk of liver transplant, underscoring the need for further evidence linking treatment adherence to future liver transplant risk. HCV-treated patients who required liver transplant incurred significantly higher health care costs than those without HCV treatment before liver transplant. Introduction of newer all-oral direct-acting antiviral regimens, with higher acquisition costs, will require further research to more accurately assess medication adherence and its relationship with transplantation, as well as with total health care costs. DISCLOSURES: No outside funding supported this research. Ems, Worley, Racsa, Gregory, Anderson, and Holt are employees of Humana. Brill has participated in a physician advisory board at Humana. The authors have no other financial disclosures to report. Study concept and design were contributed by Ems, Racsa, Worley, and Anderson, along with Gregory, Brill, and Holt. Racsa took the lead in data collection, along with Ems and Worley. All authors participated in data interpretation. Anderson, along with the other authors, wrote the manuscript, which was revised by Brill and Holt, with assistance from the other authors.