Gene panel to guide antiseizure medication prescribing: Does the cost justify the benefits?

Pharmacogenomics hold the potential to identify variants associated with adverse drug reactions and treatment efficacy of anti-seizure medications. A model-based cost-utility analysis by Gordon and colleagues showed that genetically-guided therapy costs more, yielded higher quality-adjusted life years outcomes, and was considered to be cost-effective compared to usual care. The study provided preliminary evidence on the value of pharmacogenetic testing in patients with drug-resistant epilepsy. However, data input for the model was based on assumptions that need to be empirically tested. Further, there are many other factors that may affect the cost-effectiveness of pharmacogenetic testing that need to be considered, including the model of service delivery, its implementation in complex clinical service, whether clinicians will modify treatment decisions based on pharmacogenetic information, and the fidelity with which recommendation on testing is adhered to in the real-world. The cost-effectiveness analysis should be repeated when more robust data on the effectiveness of pharmacogenetics are available and conducted alongside a budget impact analysis, incorporating the direct health care resources required to implement widespread testing and potential subsequent changes in treatment.

Health Care System Costs Associated With Surgery and Medical Therapy for Children With Drug-Resistant Epilepsy in Ontario.

BACKGROUND AND OBJECTIVES: Improvement in seizure control after epilepsy surgery could lead to lower health care resource use and costs, but it is uncertain whether this could offset the high costs related to surgery. This study aimed to evaluate phase-specific and cumulative long-term health care costs of surgery compared to medical therapy in children with drug-resistant epilepsy from the health care payer perspective. METHODS: Children who were evaluated for epilepsy surgery and treated with surgery or medical therapy from 2003 to 2018 at the Hospital for Sick Children in Toronto were identified from chart review and linked to their health administrative databases in Ontario, Canada. Inverse probability of treatment weighting with stabilized weights was used to balance the baseline covariates between the 2 groups. Patients were assigned to presurgery, surgery, short-term (first 2 years), intermediate-term (2-5 years), and long-term (>5 years) postsurgery care phases on the basis of treatment trajectory. Phase-specific and cumulative long-term health care costs were evaluated. Costs were converted from Canadian to US dollars year 2018 value. RESULTS: There were 372 surgical and 258 medical patients. Costs were higher in surgical than medical patients for presurgery (3 and 39 weeks), surgery, and short-term care phase, and the attributable costs of surgery per 7 patient-days were $1,602 (95% CI $1,438-$1,785), $172 (95% CI $147-$185), $19,819 (95% CI $18,822-$20,932), and $28 (95% CI $22-$32), respectively. Costs were lower in surgical patients for intermediate- and long-term care phase, and the attributable costs were -$72 (95% CI -$124 to -$35) and -$94 (95% CI -$129 to -$63), respectively. In surgical patients, costs were highest for surgery followed by presurgery care phase, with hospitalizations accounting for the highest cost component. In medical patients, costs increased gradually from presurgery to long-term care phase. Cumulative costs were higher for surgical than medical patients in the first 7 years after surgery, but from 8 years on, costs were lower for surgical patients. DISCUSSION: This study demonstrated the long-term economic benefits of epilepsy surgery compared to medical therapy for the health care system with the use of real-world data, which would justify the high costs of surgery. The results will support future economic evaluation comparing minimally invasive treatment such as laser therapy to surgery.

A Cost Analysis of Pulse Oximetry as a Determinant in the Decision to Admit Infants With Mild to Moderate Bronchiolitis.

OBJECTIVES: A previous randomized controlled trial showed that artificially elevating the pulse oximetry display resulted in fewer hospitalizations with no worse outcomes. This suggests that management decisions based mainly on pulse oximetry may unnecessarily increase health care costs. This study assessed the incremental cost of altered relative to true oximetry in infants with mild to moderate bronchiolitis. METHODS: A cost analysis was undertaken from the health care system and societal perspectives using patient-level data from the randomized controlled trial, with a 5-day time horizon after emergency department visit. Infants aged 4 weeks to 12 months with mild to moderate bronchiolitis were randomized to pulse oximetry measurements with true or altered saturation values displayed by artificially increasing saturation 3% points above true values. Direct and indirect health care costs were measured. Sensitivity analyses were performed to assess parameter uncertainty. RESULTS: From the health care system perspective, the average cost per patient was Can $1155 for altered oximetry and $1967 for true oximetry, with a net savings of $812. From a societal perspective, the average cost per patient was $1559 for altered oximetry and $2473 for true oximetry, with a net savings of $914. Probabilistic analyses demonstrated that altered oximetry remained the less costly study group, with an average savings of $810 (95% confidence interval, $748-$872) from the health care system perspective and $910 (95% confidence interval, $848-$973) from the societal system perspective. CONCLUSIONS: Reliance on oximetry as a major determinant in the decision to hospitalize infants with mild to moderate bronchiolitis is associated with significantly greater costs.

Economic burden of epilepsy in children: A population-based matched cohort study in Canada.

OBJECTIVE: The economic burden of childhood epilepsy to the health care system remains poorly understood. This study aimed to determine phase-specific and cumulative long-term health care costs in children with epilepsy (CWE) from the health care payer perspective. METHODS: This cohort study utilized linked health administrative databases in Ontario, Canada. Incident childhood epilepsy cases were identified from January 1, 2003 to June 30, 2017. CWE were matched to children without epilepsy (CWOE) on age, sex, rurality, socioeconomic status, and comorbidities, and assigned prediagnosis, initial, ongoing, and final care phase based on clinical trajectory. Phase-specific, 1-year and 5-year cumulative health care costs, attributable costs of epilepsy, and distribution of costs across different ages were evaluated. RESULTS: A total of 24 411 CWE were matched to CWOE. The costs were higher for prediagnosis and initial care than ongoing care in CWE. Hospitalization was the main cost component. The costs of prediagnosis, initial, and ongoing care were higher in CWE than CWOE, with the attributable costs at $490 (95% confidence interval [CI] = $352-$616), $1322 (95% CI = $1247-$1402), and $305 (95% CI = $276-$333) per 30 patient-days, respectively. Final care costs were lower in CWE than CWOE, with attributable costs at -$2515 (95% CI = -$6288 to $961) per 30 patient-days. One-year and 5-year cumulative costs were higher in CWE ($14 776 [95% CI = $13 994-$15 546] and $39 261 [95% CI = $37 132-$41 293], respectively) than CWOE ($6152 [95% CI = $5587-$6768] and $15 598 [95% CI = $14 291-$17 006], respectively). The total health care costs were highest in the first year of life in CWE for prediagnosis, initial, and ongoing care. SIGNIFICANCE: Health care costs varied along the continuum of epilepsy care, and were mainly driven by hospitalization costs. The findings identified avenues for remediation, such as enhancing care around the time of epilepsy diagnosis and better care coordination for epilepsy and comorbidities, to reduce hospitalization costs and the economic burden of epilepsy care.

Early economic evaluation of MRI-guided laser interstitial thermal therapy (MRgLITT) and epilepsy surgery for mesial temporal lobe epilepsy.

BACKGROUND: MRI-guided laser interstitial thermal therapy (MRgLITT) is a new minimally invasive treatment for temporal lobe epilepsy (TLE), with limited effectiveness data. It is unknown if the cost savings associated with shorter hospitalization could offset the high equipment cost of MRgLITT. We examined the cost-utility of MRgLITT versus surgery for TLE from healthcare payer perspective, and the value of additional research to inform policy decision on MRgLITT. METHODS: We developed a microsimulation model to evaluate quality adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) of MRgLITT versus surgery in TLE, assuming life-time horizon and 1.5% discount rate. Model inputs were derived from the literature. We conducted threshold and sensitivity analyses to examine parameter uncertainties, and expected value of partial perfect information analyses to evaluate the expected monetary benefit of eliminating uncertainty on probabilities associated with MRgLITT. RESULTS: MRgLITT yielded 0.08 more QALYs and cost $7,821 higher than surgery, with ICER of $94,350/QALY. Influential parameters that could change model outcomes include probabilities of becoming seizure-free from disabling seizures state and returning to disabling seizures from seizure-free state 5 years after surgery and MRgLITT, cost of MRgLITT disposable equipment, and utilities of disabling seizures and seizure-free states of surgery and MRgLITT. The cost-effectiveness acceptability curve showed surgery was preferred in more than 50% of iterations. The expected monetary benefit of eliminating uncertainty for probabilities associated with MRgLITT was higher than for utilities associated with MRgLITT. CONCLUSIONS: MRgLITT resulted in more QALYs gained and higher costs compared to surgery in the base-case. The model was sensitive to variations in the cost of MRgLITT disposable equipment. There is value in conducting more research to reduce uncertainty on the probabilities and utilities of MRgLITT, but priority should be given to research focusing on improving the precision of estimates on effectiveness of MRgLITT.

Influence of patient, caregiver, and family factors on unmet healthcare needs in children with drug-resistant epilepsy undergoing epilepsy surgery evaluation.

OBJECTIVE: The aim of this study was to assess whether patient, caregiver, and family factors correlate with unmet healthcare needs in children with drug-resistant epilepsy (DRE) who were evaluated for epilepsy surgery. METHODS: Caregivers of children with DRE completed questions on unmet healthcare needs, including physical and mental needs. Patient (demographic, seizure severity, and comorbidities), caregiver (sociodemographics, depression, and anxiety), and family (family functioning, resources, and demands) factors were evaluated. A series of bivariable regression was conducted to assess the associations with unmet needs (overall, physical, and mental needs), followed by multivariable regression. RESULTS: Of the 86 children with DRE, 32 (37.2%) reported having overall unmet healthcare needs, 21 (24.4%) have unmet physical, and 13 (15.1%) have unmet mental healthcare needs. Multivariable regression showed that the odds of overall unmet needs in children were higher in patients with higher depressive symptoms (odds ratio [OR] = 1.7, p = 0.03), and caregivers who were unemployed (OR = 3.8, p = 0.008). The odds of unmet physical needs in children were higher among patients with higher depressive symptoms (OR = 2.0, p = 0.02), caregivers who were older (OR = 1.1, p = 0.02), and caregivers who were unemployed (OR = 6.5, p = 0.008). There were no significant correlates between patient, caregiver, and family factors with unmet mental needs (all p > 0.05). INTERPRETATION: Children with DRE were at risk for not receiving needed healthcare. Patient factors such as patient depressive symptoms, and caregiver factors such as caregivers' age and employment status were associated with unmet needs. Identifying the predictors of unmet healthcare needs is a necessary step in addressing unmet needs in this population with DRE.

Predictors of intellectual functioning after epilepsy surgery in childhood: The role of socioeconomic status.

OBJECTIVE: The objective of this study was to evaluate the association between socioeconomic status and intellectual functioning in children with medically refractory epilepsy, before and after resective epilepsy surgery. Family environment is a strong contributor to cognitive development in children and has been recently shown to play a significant role in intellectual outcome after surgery in children with epilepsy. METHODS: One hundred children who had undergone resective epilepsy surgery and completed preoperative and postoperative assessments of IQ as part of clinical care were included in the study. We evaluated the impact of epilepsy-related variables, income quintile, and residence location on IQ. RESULTS: Greater improvements in IQ after surgery were associated with an older age at surgery (ß=.235, p=.018). Higher IQ scores at follow-up were associated with an older age of seizure onset (ß=.371, p<.001), older age at surgery (ß=.356, p<.001), unilobar epileptogenic focus (ß=.394, p<.001), and mesial temporal sclerosis (ß=.338, p=.001) or tumor (ß=.457, p<.001) in comparison with malformation of cortical development; age at seizure onset did not remain as a significant predictor in multivariable regression analysis. Income quintile, residence location, seizure control, and antiepileptic medication use were not significant predictors. CONCLUSIONS: Epilepsy-related variables were the strongest predictors of IQ and postoperative change in IQ. We were unable to identify a significant association between IQ and socioeconomic status. Future research should evaluate the impact of multiple aspects of family environment.

Health resource utilization varies by comorbidities in children with epilepsy.

OBJECTIVES: Comorbidities in adults with epilepsy have been shown to significantly increase health resource utilization (HRU). The current study aimed to determine whether a similar association exists among children with epilepsy in a universal health insurance system. METHODS: Health administrative databases in Ontario, Canada were used to evaluate the frequency of neurologist visits, emergency department (ED) visits, and hospitalizations. We evaluated the association between HRU and comorbidities, including depression, anxiety, learning disability, attention deficit hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD), adjusting for age, sex, residence, and socio-economic status. RESULTS: The frequency of neurology visits was increased by comorbid depression, ASD, and learning disability (adjusted relative risk [aRR]=1.29-2.07; p<.01). The frequency of ED visits was increased by all comorbidities (aRR=1.26-2.83; p<.0001). The frequency of hospitalizations was increased by comorbid depression, anxiety, ASD, and learning disability (aRR=1.77-7.20; p<.0001). Learning disability had the largest impact on HRU. For each additional comorbidity, the frequency of neurology visits, ED visits, and hospitalizations increased by 1.64 to 3.16 times (p<.0001). CONCLUSIONS: Among children with epilepsy, mental health and developmental comorbidities were associated with increased HRU, and different comorbidities influenced different types of HRU. In addition, we highlight the importance of identifying and managing these comorbidities, as they increased the risks of costly HRU such as ED visits and hospitalizations.

The influence of socioeconomic status on health resource utilization in pediatric epilepsy in a universal health insurance system.

OBJECTIVES: It is unknown if there is a disparity in health resource utilization (HRU) among children with epilepsy in a universal health insurance system. The aims of this study were to evaluate whether socioeconomic status (SES) influenced the pattern of HRU among children with epilepsy, and to determine if neurology visits were associated with emergency department (ED) visits and hospitalizations. METHODS: Health administrative databases were used to identify HRU among children with epilepsy in Ontario, Canada. The frequency of neurology visits, ED visits, and hospitalizations were assessed for 1 year. SES was measured using dissemination area income and deprivation index. The association between SES and HRU was evaluated, adjusting for age, sex, residence, and comorbidities. Subsequently, we assessed whether neurology visits influenced ED visits and hospitalizations, adjusting for age, sex, residence, comorbidities, and SES. RESULTS: Deprivation index was a more sensitive measure of disparity in HRU than dissemination area income. Status epilepticus-related ED visits and hospitalizations were most expensive but accounted for a small proportion of total costs. Higher deprivation was associated with fewer neurology visits (relative risk [RR] 0.85-0.89), more frequent ED visits (RR 1.08-1.36), and hospitalizations (RR 1.27). Increased neurology visits were associated with more frequent ED visits (RR 1.10) and hospitalizations (RR 1.15). The associations between neurology visits and ED visits as well as hospitalizations varied by deprivation index, in that neurology visits were associated with increased ED visits and hospitalizations and the increase was higher in the most deprived relative to the least deprived (all p < 0.0001). SIGNIFICANCE: We found disparity in HRU by SES despite the universal health insurance system. More frequent neurology visits were associated with more frequent ED visits and hospitalizations after adjusting for SES, probably related to epilepsy severity. Our study identified an at-risk population for high resource use that may require additional support to reduce ED visits and hospitalizations.

Socioeconomic status influences time to surgery and surgical outcome in pediatric epilepsy surgery.

The aims of this study were to evaluate the influence of socioeconomic status (SES) on time-to-surgery (TTS) and surgical outcome in children with treatment-resistant epilepsy in a universal health care system. The cohort consisted of children who had undergone resective epilepsy surgery between 2001 and 2013 in Canada. The patients' postal codes were linked to Statistics Canada National Household Survey data to obtain dissemination area income, which was used to infer SES. Time-to-surgery was defined as the interval from date of epilepsy onset to date of surgery. Seizure outcome was classified using ILAE classification. The associations between SES and TTS, as well as SES and surgical outcome, were assessed. Two hundred eighty-four children who had epilepsy surgery were included. Patients in the lowest income quintile had a significantly higher TTS relative to the highest income quintile (ß=0.121, p=0.044). There were no significant associations between income quintiles and seizure-free surgical outcome (odds ratio (OR)=0.746-1.494, all p>0.05). However, patients in the lowest income quintile had a significantly lower odds of an improvement in seizure frequency relative to the highest income quintile (OR=0.262, p=0.046). The TTS was not uniform across SES in spite of the existence of a universal health care system. This finding highlights the need to address social and economic barriers for epilepsy surgery to improve access to this potentially curative treatment. Those with lower SES had lower likelihood of improvement in seizure control following epilepsy surgery and may require additional support including social and financial support to mitigate the discrepancies in seizure control following surgery between SES levels.

Patient and hospital characteristics are associated with cost of hospitalizations in children with epilepsy.

We assessed patient and hospital characteristics and cost of hospitalizations in children with epilepsy, using the United States (U.S.) Kids' Inpatient Database (KID2009). There were 114,256 pediatric admissions for epilepsy in 2009. Admission rate was highest in those with the lowest household income. Private, urban teaching, and nonchildren's hospitals and hospitals in the Southern U.S. admitted the most patients. The average length of hospitalization was 5.4days, and adjusted cost was $6656/day of admission. The cost of hospitalizations was higher in those with the highest household income versus in those with lower income, private versus Medicare/Medicaid insurance, admissions to private versus public hospitals, urban teaching versus nonteaching or rural hospitals, and children's versus nonchildren's hospitals. Epilepsy comorbidities did not increase the cost of hospitalization. We found that the number and cost of hospitalizations in children with epilepsy vary by patient and hospital characteristics. Such findings are essential for informing future health plans and policy decisions on resource allocation.

Cost-effectiveness of pediatric epilepsy surgery compared to medical treatment in children with intractable epilepsy.

PURPOSE: Due to differences in epilepsy types and surgery, economic evaluations of epilepsy treatment in adults cannot be extrapolated to children. We evaluated the cost-effectiveness of epilepsy surgery compared to medical treatment in children with intractable epilepsy. METHOD: Decision tree analysis was used to evaluate the cost-effectiveness of surgery relative to medical management. Fifteen patients had surgery and 15 had medical treatment. Cost data included inpatient and outpatient costs for the period April 2007 to September 2009, physician fee, and medication costs. Outcome measure was percentage seizure reduction at one-year follow-up. Incremental cost-effectiveness ratio (ICER) was assessed. Sensitivity analysis was performed for different probabilities of surgical and medical treatment outcomes and costs, and surgical mortality or morbidity. RESULTS: More patients managed surgically experienced Engel class I and II outcomes compared to medical treatment at one-year follow-up. Base-case analysis yielded an ICER of $369 per patient for each percentage reduction in seizures for the surgery group relative to medical group. Sensitivity analysis showed robustness for the different probabilities tested. CONCLUSION: Surgical treatment resulted in greater reduction in seizure frequency compared to medical therapy and was a cost-effective treatment option in children with intractable epilepsy who were evaluated for epilepsy surgery and subsequently underwent surgery compared to continuing medical therapy. However, larger sample size and long-term follow-up are needed to validate these findings.