Real-World Evaluation of Clinical Response and Long-Term Healthcare Resource Utilization Patterns Following Treatment with a Digital Therapeutic for Chronic Insomnia.

Background and Objectives: This analysis evaluated insomnia severity and long-term impact on healthcare resource utilization (HCRU) and costs after treatment with Somryst® (previously called SHUTi), a digital therapeutic delivering cognitive behavioral therapy for insomnia (CBT-I). Methods: Change from baseline in insomnia severity index (ISI) score was assessed using last observed ISI score. A pre/post analysis of claims data was conducted, comparing HCRU in patients with self-identified sleep problems who successfully initiated the therapeutic (index date) between June 1, 2016 and December 31, 2018. Results: A total of 248 patients were analyzed (median age 56.5 years, 57.3% female, mean ISI score 19.13, 52.4% treated with sleep aid medications pre-index). After 9 weeks, mean ISI score declined by 37.2% from baseline (19.1 vs 12.0), 58.8% of patients achieved ISI responder status (ISI score improved by =>7; NNT: 1.7), and 26.6% of patients achieved insomnia remission (ISI score <8; NNT for remission: 3.8). After two-year follow-up, post-index events were reduced (compared to 2 years pre-index) for emergency department visits (-53%; IRR: 0.47; 95% CI 0.27, 0.82; P=0.008), hospiatizations (-21%; IRR: 0.79; 95% CI 0.46, 1.35; P=0.389) and hospital outpatient visits (-13%; IRR: 0.87; 95% CI 0.66, 1.14; P=0.315). Slightly increased rates were observed for ambulatory surgical center visits (2%; IRR: 1.02; 95% CI 0.73, 1.44; P=0.903) and office visits (2%; IRR: 1.02; 95% CI 0.92, 1.14; P=0.672). The number of patients treated with sleep aid medications dropped 18.5% (52.4% pre-index vs 42.7% post-index). Average number of prescriptions decreased from 3.98 pre-index to 3.73 post-index (P= 0.552). Total two-year cost reduction post-index vs pre-index was $510,678, or -$2059 per patient. Conclusion: In a real-world cohort of patients with chronic insomnia, treatment with a digital therapeutic delivering CBT-I was associated with reductions in insomnia severity, emergency department visits, and net costs.

Real-World Reductions in Healthcare Resource Utilization over 6 Months in Patients with Substance Use Disorders Treated with a Prescription Digital Therapeutic.

BACKGROUND AND AIMS: Substance use disorders (SUDs) affect approximately 40.3 million people in the USA, yet only approximately 19% receive evidence-based treatment each year. reSET® is a prescription digital therapeutic (PDT) and the only FDA-authorized treatment for patients with cocaine, cannabis, and stimulant use disorders. This study evaluated real-world healthcare resource utilization (HCRU) and associated costs 6 months after initiation of reSET in patients with SUD. METHODS: A retrospective analysis of HealthVerity PrivateSource20 data compared the 6-month incidence of all-cause hospital facility encounters and clinician services in patients treated with reSET (re-SET cohort) before (pre-index period) and after (post-index period) reSET initiation (index). Incidence was compared using incidence rate ratios (IRR). HCRU-related costs were also assessed. RESULTS: The sample included 101 patients (median age 37 years, 50.5% female, 54.5% Medicaid-insured). A statistically significant decrease of 50% was observed in overall hospital encounters from pre-index to post-index (IRR 0.50; 95% CI 0.37-0.67; P < 0.001), which included inpatient stays (56% decrease; IRR 0.44; 95% CI 0.26-0.76; P = 0.003), partial hospitalizations (57% decrease; IRR 0.43; 95% CI 0.21-0.88; P = 0.021), and emergency department visits (45% decrease; IRR 0.55; 95% CI 0.38-0.80; P < 0.004). Additionally, some clinician services declined significantly including pathology and laboratory services: other (54% decrease; IRR 0.46; 95% CI 0.28-0.76; P = 0.003); pathology and laboratory services: drug assays prior to opioid medication prescription (37% decrease; IRR 0.63; 95% CI 0.41-0.96; P = 0.031); and alcohol and drug abuse: medication services (46% decrease; IRR 0.54; 95% CI 0.41-0.70; P < 0.001). Reductions in facility-encounters drove 6-month reSET per-patient cost reductions of $3591 post-index compared to pre-index. CONCLUSIONS: Use of reSET by patients with SUD is associated with durable reductions in HCRU and lower healthcare costs over 6 months compared to the 6 months before PDT treatment, after adjusting for covariates, providing an economic benefit to the healthcare system.

Reduced Healthcare Resource Utilization in Patients with Opioid Use Disorder in the 12 Months After Initiation of a Prescription Digital Therapeutic.

BACKGROUND AND AIMS: reSET-O, an FDA-authorized prescription digital therapeutic (PDT) delivering cognitive behavioral therapy and contingency management to patients with opioid u®se disorder (OUD), may help improve clinical outcomes. One-year differences in healthcare resource utilization (HCRU) and costs post-PDT initiation were evaluated. METHODS: Retrospective analysis of healthcare claims data compared all-cause HCRU (across hospital facility encounters [sum of inpatient stays, treat-and-release emergency department [ED] visits, partial hospitalizations, and hospital outpatient department visits] and clinician services [procedure categories]) after PDT initiation (index) between reSET-O patients and controls. Overall and Medicaid-specific differences in HCRU, costs, and buprenorphine adherence were evaluated. FINDINGS: Cohorts included 901 reSET-O patients (median age 36 years, 62.4% female, 73.9% Medicaid) and 978 controls (median age 38 years, 51.1% female, 65.4% Medicaid). Compared to the control group, the reSET-O group experienced 12% fewer total unique hospital encounters (non-significant), driven by 28% fewer inpatient stays (IRR 0.72; 95% CI 0.55-0.96; P = 0.02), 56% fewer hospital readmissions [IRR 0.44; 95% CI 0.20-0.93; P = 0.033]), and 7% fewer ED visits (IRR 0.93; 95% CI 0.79-1.09; P = 0.386). Total clinician services increased by 1391 events versus controls. Differences were greater among the Medicaid patients. Adjustment for concomitant baseline substance use and mental health disorders resulted in similar HCRU incidence rate ratios. Changes in all-cause HCRU drove per-patient per-year cost differences of - $2791 versus controls (- $3832 versus Medicaid controls). Adjusted mean medication possession ratio was 0.848 (SE 0.0118) at 12 months for reSET-O patients, which was significantly higher than controls (0.761 [SE 0.0108]; P < 0.001). CONCLUSIONS: Use of reSET-O is associated with significant and durable real-world reductions in ED and inpatient (including readmissions) utilization, reduced net costs, and increased clinician services and buprenorphine adherence. Differences in costs versus controls were greatest among Medicaid patients. INFOGRAPHIC.

Five-year budget impact of a prescription digital therapeutic for patients with opioid use disorder.

BACKGROUND: Opioid use disorder (OUD) is associated with high healthcare resource utilization (HCRU) and costs. reSET-O is an FDA-cleared prescription digital therapeutic that delivers neurobehavioral therapy as an adjunct to treatment-as-usual (TAU; buprenorphine, face-to-face counseling, and contingency management). METHODS: A budget impact model was developed to evaluate reSET-O as an adjunct to TAU in OUD for a 1 million-member US mixed health plan over a 5-year time horizon. Model inputs included treatment costs and medical costs of hospitalizations, partial hospitalizations, intensive care unit stays, and emergency department visits. RESULTS: The base-case results and the alternative scenario analysis showed the addition of reSET-O was projected to result in consistently lower total yearly costs vs TAU and no treatment. The estimated total and per member per month (PMPM) budget impact over 5 years was -$763,026 and -$0.0116, respectively. When the upper range of cost estimates was used, the total and PMPM budget impacts over 5 years were -$2,481,563 and -$0.0378, respectively. Sensitivity analysis showed results were most sensitive to the proportion of patients untreated. CONCLUSION: The introduction of reSET-O in addition to TAU for OUD has the potential to reduce healthcare resource utilization and costs from 12 weeks up to 5 years.

Comparison of Healthcare Resource Utilization Between Patients Who Engaged or Did Not Engage With a Prescription Digital Therapeutic for Opioid Use Disorder.

BACKGROUND: A prescription digital therapeutic (PDT) (reSET-O®) may expand access to behavioral treatment for patients with opioid use disorder (OUD) treated with buprenorphine, but long-term data on effectiveness are lacking. OBJECTIVE: To compare real-world healthcare resource utilization (HCRU) among patients who engaged with reSET-O and buprenorphine compared to similar patients in recovery treated with buprenorphine who did not fill their reSET-O script or engage with the PDT beyond week one. METHODS: A retrospective analysis of facility and clinical service claims data was conducted in adults with PDT initiation and between 12 weeks and 9 months of continuous enrollment in a health plan after initiation. Patients who filled their prescription and engaged with the therapeutic were compared to patients who filled the prescription but did not engage beyond week one (NE), and patients who did not fill the prescription (NR) (the latter two groups combined into one group hereafter referred to as "non-engagers"). Comparisons were analyzed using a repeated-measures negative binomial model of encounters/procedures, adjusted for number of days in each period. Associated cost trends assessed using current Medicare reimbursement rates. RESULTS: A total of 444 patients redeemed a prescription and engaged with the PDT (mean age 37.5 years, 63.1% female, 84% Medicaid), and 64 patients did not engage with the PDT (mean age 39.5 years, 32.8% female, 73.4% Medicaid). Total cost of hospital facility encounters was $2693 for engaged patients vs $6130 for non-engaged patients. Engaged patients had somewhat higher rates of certain clinician services. Total facility and clinician services costs for engaged vs non-engaged patients were $8733 vs $11,441, for a net cost savings over 9 months of $2708 per patient who engaged with reSET-O. CONCLUSION: Patients who engaged with an OUD-specific PDT had a net cost reduction for inpatient and outpatient services of $2708 per patient over 9 months compared to patients who did not engage with the PDT, despite similar levels of buprenorphine adherence.

Cost-Effectiveness Analysis of a Prescription Digital Therapeutic for the Treatment of Opioid Use Disorder.

The lack of adequate treatment for many patients with opioid use disorder (OUD) has led to high medical costs ($90B in 2020). An analysis of the cost-effectiveness (cost-utility) of reSET-O, the first and only FDA-approved prescription digital therapeutic (PDT) for the treatment of OUD, is needed to inform value assessments and healthcare decision making. To evaluate the cost-utility of reSET-O in conjunction with treatment-as usual (TAU) compared to TAU alone. A third-party payer-perspective decision analytic model evaluated the cost-effectiveness of reSET-O + TAU relative to TAU (i.e., oral buprenorphine, face-to-face counseling, and contingency management [immediate rewards for negative drug tests logged]) alone over 12 weeks. Clinical effectiveness data (retention in therapy and health state utilities) were obtained from the peer-reviewed literature, while resource utilization and cost data were obtained from a published claims data analyses. Over 12 weeks, the addition of reSET-O to TAU resulted in a gain of 0.003 quality-adjusted life years (QALYs), and $1,014 lower costs, resulting in economic dominance vs. TAU. reSET-O + TAU's was economically dominant (less costly, more effective) vs. TAU alone over 12 weeks, a result that was driven by a reduction in medical costs after initiation of reSET-O observed in a recent real-world claims analysis.

Real-world use and clinical outcomes after 24 weeks of treatment with a prescription digital therapeutic for opioid use disorder.

PURPOSE: To evaluate real-world prescription digital therapeutic (PDT) use and associated clinical outcomes among patients with opioid use disorder (OUD). PATIENTS AND METHODS: A real-world observational evaluation of patients who filled either a 12- or 24-week (refill) prescription for the reSET-O® PDT. The PDT content consists of 67 interactive lessons unlocked in sequence during use as well as the chance to earn rewards for progress and/or negative urine screens. Engagement/retention data (ongoing engagement in weeks 9-12, or 21-24) were collected via the PDT and analyzed with descriptive statistics. Substance use was evaluated as a composite of patient self-reports and urine drug screens (UDS). Missing UDS data were assumed to be positive. A regression analyses of hospital encounters for 12- vs. 24-week prescriptions controlling for covariates was conducted. RESULTS: In a cohort of 3,817 individuals with OUD who completed a 12-week PDT prescription, a cohort of 643 was prescribed a second 12-week 'refill' prescription, for a total treatment time of 24 weeks. Mean age of the 24-week cohort was 39 years, 56.7% female. At 24 weeks of total treatment: abstinence in the last 4 weeks of treatment was 86% in an analysis in which patients with no data are assumed to be positive for illicit opioids. Over 91% of patients were retained in treatment. An analysis of matched insurance claims showed that those treated for 24 weeks had a 27% decrease in unique hospital encounters compared to those who got the first 12-week prescription only. CONCLUSIONS: These data present real-world evidence that a second prescription (24 weeks) of a PDT for OUD is associated with improved outcomes, high levels of retention, and fewer hospital encounters compared to a single prescription for a PDT.PLAIN LANGUAGE SUMMARYPrescription digital therapeutics (PDTs) are software-based treatments that are FDA-authorized to improve clinical outcomes for serious diseases and conditions. The reSET-O PDT consists of 67 interactive lessons unlocked in sequence during use as well as the chance to earn rewards for progress and/or negative urine screens. Multiple studies show that a single 12-week PDT prescription for opioid use disorder (OUD) helps patients engage in treatment, reduces substance use, and helps patients remain in treatment, but to date there has been no evaluation of how patients who receive a 'refill' second prescription engage with the therapeutic and whether the positive effects on substance use and retention are durable across a second 12 weeks (total of 24 weeks) of treatment.This real-world analysis evaluated 643 patients from 12 U.S. states who were prescribed a second PDT prescription. 93% of this cohort completed 8 or more core lesson modules in the second prescription period, 85% completed at least half of core modules, and 64% completed all 32 core modules. Patients used the PDT outside of clinic hours about 40% of the time. 94.4% of patients had 80% or greater negative reports of opioid use across the second 12 weeks of treatment. A 27% decrease in unique hospital encounters was observed in patients who completed a second prescription vs. patients who completed only one prescription.These data show that a second prescription of a PDT for OUD is associated with postive patient outcomes. Patients showed durable and high levels of engagement with the PDT, reduced substance use, and improved treatment retention through 24 weeks of treatment.

Real-world changes in US health system hospital-based services following treatment with a prescription digital therapeutic for opioid use disorder.

Outcomes associated with buprenorphine therapy for the treatment of opioid use disorder (OUD) are suboptimal. reSET-O is an FDA-authorized prescription digital therapeutic (PDT) delivering neurobehavioral therapy via mobile devices to patients with OUD treated with buprenorphine. This analysis evaluated the net impact of reSET-O on medical costs among actively-engaged reSET-O patients using real-world observations. This real-world retrospective analysis of health care claims between October 2018 and October 2019 evaluated health care resource utilization up to 6 months before and 6 months after the initiation of a reSET-O prescription after accounting for the subset of patients not continuing on therapy after week 1 (non-engaged patients). Repeated-measures negative binomial models compared incidences of hospital-based encounters/procedures adjusted for days in each period as well as associated costs. The number needed to treat (NNT) to avoid an inpatient visit was calculated. Of the 351 patients who were prescribed reSET-O, 321 met the criteria of active engagement. Treatment with reSET-O was associated with a substantial reduction in medical costs of -$765,450 (-$2,385/patient, $235/patient greater than a previous analysis in which non-engaged patients were included) in the 6-month period after initiation. The gross reSET-O prescription cost of $584,415 ($1,665/patient) was substantially offset by $49,950 ($142.31/patient) in refunds to payers. The medical cost reduction in engaged patients offset the cost of the therapeutic resulting in an overall cost reduction of -$230,985 in this cohort (net savings of -$720 per patient). The number needed to treat to avoid an inpatient visit was 4.8. Engagement and continued treatment with reSET-O in patients with OUD treated with buprenorphine is associated with substantial real-world reductions in medical costs in the 6-month period following the initiation of the reSET-O prescription.

Evaluation of the cost-utility of a prescription digital therapeutic for the treatment of opioid use disorder.

Background: The opioid epidemic continues to generate a significant mental and physical health burden on patients, and claims the life of almost 150 Americans daily. Making matters worse, an increase in relapses and/or opioid-related deaths has been reported in more than 40 U.S. states since the start of the COVID-19 pandemic. Opioid use disorder (OUD) is one of the single most expensive disorders in the United States, generating average medical costs of $60B from just 2 million Americans diagnosed with the disorder. In commercial use since 2019, reSET-O is a non-drug, prescription digital therapeutic (PDT) that delivers evidence-based neurobehavioral treatment for OUD and helps overcome the barriers associated with access to care, stigma, and social distancing. Although shown to be cost effective and efficacious in clinical trials and real-world evidence studies, respectively, information on its value for money from a health utilities and cost per quality-adjusted life-year is needed to inform policy discussions.Objectives: To evaluate the impact of reSET-O on health utilities and assess its overall cost per quality-adjusted life year (QALY) gained vs. treatment-as-usual (TAU).Methods: Decision analytic model comparing reSET-O plus TAU to TAU alone (i.e. buprenorphine, face-to-face counseling, and contingency management) over 12 weeks. Clinical effectiveness data (abstinence and health utility) were obtained from a clinical trial, and resource utilization and cost data were adapted from a recent claims data analysis to reflect less frequent face-to-face counseling with the therapeutic.Results: The addition of reSET-O to TAU decreases total health care costs by -$131 and resulted in post-treatment utility values within population norms, with a corresponding gain of 0.003 QALYs. reSET-O when used adjunctively to TAU was economically dominant (less costly, more effective) vs. TAU alone.Conclusion: reSET-O is an economically-dominant adjunctive treatment for OUD and is associated with an overall reduction in total incremental cost vs TAU.

Real-world reduction in healthcare resource utilization following treatment of opioid use disorder with reSET-O, a novel prescription digital therapeutic.

INTRODUCTION: Buprenorphine medication assisted treatment (B-MAT) adherence for opioid use disorder (OUD) is suboptimal. reSET-O, an FDA-cleared prescription digital therapeutic, delivers neurobehavioral therapy (community-reinforcement approach+fluency training+contingency management) to B-MAT-treated OUD patients. METHODS: This retrospective claims study (10/01/2018-10/31/2019) evaluated healthcare resource utilization up to 6 months before/after reSET-O initiation. Repeated-measures negative binomial models compared incidences of encounters/procedures. Net change in costs was assessed. RESULTS: Among 351 patients (mean age 37; 59.5% female; 82.6% Medicaid), 334 had pharmacy claims and 240 (71.9%) received buprenorphine pre-/post-index (medication possession ratio 0.73 and 0.82, respectively; P = 0.004). Facility encounters decreased, with 45 fewer inpatient (P = 0.024) and 27 fewer emergency department (ED) visits (P = 0.247). Clinical encounters with largest changes were drug testing (638 fewer; P < 0.001), psychiatry (349 fewer; P = 0.036), case management (176 additional; P = 0.588), other pathology/laboratory (166 fewer; P = 0.039), office/other outpatient (154 fewer; P = 0.302), behavioral rehabilitation (111 additional; P = 0.124), alcohol/substance rehabilitation (96 fewer; P = 0.348), other rehabilitation (66 fewer; P = 0.387), mental health rehabilitation (61 additional; P = 0.097), and surgery (60 fewer; P = 0.070). Changes in facility/clinical encounters saved $2,150/patient. CONCLUSION: reSET-O initiation was associated with fewer inpatient, ED, and other clinical encounters, increased case management/rehabilitative services, and lower net costs over six months. EXPERT OPINION: Real-world evidence is helpful in evaluating the effectiveness of interventions in usual-care conditions, outside of controlled research environments. Large observational studies based on health care claims are important to understand the actual pharmacoeconomic and outcomes impact of interventions at the health care system and population level.

Exhalation delivery system with fluticasone improves quality of life and health status: pooled analysis of phase 3 trials NAVIGATE I and II.

BACKGROUND: Chronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP) seriously impairs health-related quality of life (HRQoL). This analysis describes the impact of the exhalation delivery system with fluticasone (EDS-FLU) on HRQoL, assessed by the 36-item Short-Form Health Survey version 2 (SF-36v2), and on utilities, assessed via the Short-Form 6-Dimension (SF-6D), in patients with CRSwNP. METHODS: Post hoc analysis of pooled randomized clinical trial data (NAVIGATE I and II; N = 643) to examine change from baseline in SF-36v2 and SF-6D at end-of-double-blind (EODB: 16 weeks) and end-of-open-label (EOOL: 24 weeks; following 8 weeks of open-label treatment) for EDS-FLU vs placebo (EDS-PBO). Baseline characteristics predictive of change in SF-36 and SF-6D scores were assessed. RESULTS: Mean baseline SF-36v2 scores were below population norms. At EODB, mean improvement was greater for all SF-36v2 domain and component scores with EDS-FLU (range: 2.9 [physical functioning] to 5.11 [bodily pain {BP}]) vs EDS-PBO (range: 0.81 [mental health] to 2.87 [BP]) (each comparison p < 0.01); physical and mental component score improvements within the EDS-FLU group exceeded the minimal clinically important difference (MCID). Clinically meaningful and statistically significant improvements in SF-6D utility scores were seen in EDS-FLU-treated patients compared to EDS-PBO-treated patients (0.058 vs 0.023, respectively, p < 0.001). At EOOL, SF-36v2 and SF-6D mean scores were at or above population norms, with clinically meaningful and statistically significant improvements from baseline. CONCLUSION: In this pooled analysis of 2 large pivotal EDS-FLU trials, health domain and health utilities improvements were significantly greater with EDS-FLU than EDS-PBO and were comparable to population norms.

Impact of seizure frequency reduction on health-related quality of life among clinical trial subjects with refractory partial-onset seizures: A pooled analysis of phase III clinical trials of eslicarbazepine acetate.

BACKGROUND: Subjects who received eslicarbazepine acetate (ESL) as adjunctive therapy experienced significantly greater seizure frequency reduction (SFR) than placebo in three phase III, randomized, double-blind trials. This analysis compared changes in health-related quality of life (HRQOL) between treatment responders and non-responders across the pooled, per-protocol population (N=842) using the validated Quality of Life in Epilepsy Inventory-31 (QOLIE-31). METHODS: QOLIE-31 scores were calculated for Total Score (TS) and seven subscales; higher scores indicate better HRQOL. Mean changes from baseline were calculated. Analysis of covariance examined least square mean (LSM) differences in final scores between responders (≥50% and ≥75% SFR) and non-responders. Clinical significance was based on established minimal clinically important differences (MCIDs). RESULTS: Mean changes were greater among responders for TS (5.2 versus 1.4 for ≥50% SFR; 7.5 versus 1.9 for ≥75% SFR) and all subscales. Additionally, the percentage of subjects with changes meeting or exceeding MCIDs was higher among responders for TS (48.4% versus 33.9% for ≥50% SFR; 56.9% versus 35.8% for ≥75% SFR) and all subscales. Responders had significantly higher final scores for TS (LSM difference=4.0 for ≥50% SFR; LSM difference=5.7 for ≥75% SFR) and all subscales except emotional well-being at ≥50% SFR. LSM differences exceeded MCIDs at ≥75% SFR for TS and five of seven subscales, and two subscales at ≥50% SFR. In a subgroup analysis with placebo removed, LSM differences were larger overall. SIGNIFICANCE: In clinical trials of adjunctive ESL, higher levels of SFR were associated with greater improvements in HRQOL.

Severity and burden of partial-onset seizures in a phase III trial of eslicarbazepine acetate.

OBJECTIVE: The objective of this study was to compare posttreatment seizure severity in a phase III clinical trial of eslicarbazepine acetate (ESL) as adjunctive treatment of refractory partial-onset seizures. METHODS: The Seizure Severity Questionnaire (SSQ) was administered at baseline and posttreatment. The SSQ total score (TS) and component scores (frequency and helpfulness of warning signs before seizures [BS]; severity and bothersomeness of ictal movement and altered consciousness during seizures [DS]; cognitive, emotional, and physical aspects of postictal recovery after seizures [AS]; and overall severity and bothersomeness [SB]) were calculated for the per-protocol population. Analysis of covariance, adjusted for baseline scores, estimated differences in posttreatment least square means between treatment arms. RESULTS: Out of 547 per-protocol patients, 441 had valid SSQ TS both at baseline and posttreatment. Mean posttreatment TS for ESL 1200 mg/day was significantly lower than that for placebo (2.68 vs 3.20, p<0.001), exceeding the minimal clinically important difference (MCID: 0.48). Mean DS, AS, and SB were also significantly lower with ESL 1200 mg/day; differences in AS and SB exceeded the MCIDs. The TS, DS, AS, and SB were lower for ESL 800 mg/day than for placebo; only SB was significant (p=0.013). For both ESL arms combined versus placebo, mean scores differed significantly for TS (p=0.006), DS (p=0.031), and SB (p=0.001). CONCLUSIONS: Therapeutic ESL doses led to clinically meaningful, dose-dependent reductions in seizure severity, as measured by SSQ scores. CLASSIFICATION OF EVIDENCE: This study presents Class I evidence that adjunctive ESL (800 and 1200 mg/day) led to clinically meaningful, dose-dependent seizure severity reductions, measured by the SSQ.