Use and cost comparison of clobazam to other antiepileptic drugs for treatment of Lennox-Gastaut syndrome

Figures & data

Table 1. Antiseizure medications.

Medication/medication class	Generic name (brand)
AMPA receptor antagonist	Perampanel (Fycompa)
SVP2a binder	Levetiracetam (Keppra, Keppra XL)
Carbonic anhydrase inhibitor	Acetazolamide (Diamox)
Sodium channel inhibitor	Carbamazepine (Tegretol), Eslicarbazepine (Aptiom), Oxcarbazepine (Trileptal), Rufinamide (Banzel)
GABA analogues	Gabapentin (Neurontin), Pregabalin (Lyrica), Progabide (Gabrene), Vigabatrin (Sabril)
GABA reuptake inhibitors	Tiagabine (Gabitril)
K-channel opener	Ezogabine/Retigabine (Potiga)
NMDA receptor blockers	Felbamate (Felbatol), Sodium Channel Modulators, Lacosamide (Vimpat), Lamotrigine (Lamictal), Phenytoin (Dilantin)
T-type calcium channel	Ethosuximide (Zarontin), Methsuximide (Celontin)
Sulfamate-substituted monosaccharides	Topiramate (Topamax, Topamax ER, Qudexy XR)
Sodium channel	Zonisamide (Zonegran)
Valproic acid	Divalproex Sodium (Depakote), Valproic Acid (Depakene)
Barbiturates	Phenobarbital, Primidone (Mysoline)
Benzodiazepines	Clobazam (Onfi), Clonazepam (Klonopin, Epitril, Rivotril), Clorazepate Dipotassium (Tranxene), Diazepam (Valium, Diastat), Lorazepam (Ativan)

Notes: GABA – gamma aminobutyric acid; NMDA – N-methyl-D-aspartate; SVP2a – synaptic vesicle protein 2A.

Table 2. Baseline demographic and clinical characteristics of commercial/Medicare Supplemental patients.

	Clobazam		Non-clobazam
	N = 590		N = 1384		P-value^a
Demographic characteristics
Age in years, mean (SD)	14.8	(12.5)	31.0	(23.2)	<0.001
Age group in years, n (%)
0–5	117	19.8%	116	8.4%	<0.001
6–12	221	37.5%	266	19.2%
13–17	84	14.2%	165	11.9%
18–34	120	20.3%	314	22.7%
35–44	21	3.6%	117	8.5%
45–54	15	2.5%	129	9.3%
55–64	8	1.4%	131	9.5%
65+	4	0.7%	146	10.5%
Males, n (%)	322	54.6%	683	49.3%	0.034
Geographic region, n (%)
Northeast	138	23.4%	309	22.3%	0.41
North central	139	23.6%	280	20.2%
South	179	30.3%	461	33.3%
West	118	20.0%	290	21.0%
Unknown	16	2.7%	44	3.2%
Urban, n (%)	529	89.7%	1224	88.4%	0.431
Plan type, n (%)
FFS	11	1.9%	97	7.0%	<0.001
EPO/PPO	379	64.2%	891	64.4%
HMO	73	12.4%	164	11.8%
POS	49	8.3%	76	5.5%
CDHP/HDHP	57	9.7%	112	8.1%
Unknown	21	3.6%	44	3.2%
Payer type, n (%)
Commercial	585	99.2%	1223	88.4%	<0.001
Medicare	5	0.8%	161	11.6%
Capitation, n (%)
Yes	36	6.1%	98	7.1%	0.429
No	554	93.9%	1286	92.9%
Index year, n (%)
2011	2	0.3%	122	8.8%	<0.001
2012	421	71.4%	737	53.3%
2013	167	28.3%	525	37.9%
Clinical characteristics
Baseline medication classes,^b n (%)
AEDs and other seizure-related medications	565	95.8%	1067	77. 1%	<0.001
Benzodiazepines	364	61.7%	289	20.9%	<0.001
NMDA receptor blockers	304	51.5%	361	26.1%	<0.001
SVP2a binder	268	45.4%	595	43.0%	0.319
Valproic acid	240	40.7%	170	12.3%	<0.0001
Sodium channel inhibitor	192	32.5%	205	14.8%	<0.001
Sulfamate-substituted monosaccharide	139	23.6%	122	8.8%	<0.001
Zonisamide	105	17.8%	100	7.2%	<0.001
GABA analogues	51	8.6%	131	9.5%	0.564
T-type calcium channel	36	6.1%	58	4.2%	0.068
Number of unique prescription classes (non-AEDs), mean (SD)	5.8	(4.9)	6.6	(6.2)	0.002
Number of pre-index AED drugs of interest, mean (SD)	1.7	(1.1)	0.5	(0.7)	<0.001
Baseline comorbidities,^c n (%)
Pain	221	37.5%	797	57.6%	<0.001
Any digestive/bowel disorder	230	39.0%	460	33.2%	0.014
Constipation	100	17.0%	143	10.3%	<0.001
Psychosis	142	24.1%	516	37.3%	<0.001
Migraine/headache	54	9.2%	377	27.2%	<0.001
Intellectual disorder	148	25.1%	156	11.3%	<0.001
Mild	13	2.2%	27	2.0%	0.716
Moderate	14	2.4%	26	1.9%	0.476
Severe/profound	58	9.8%	46	3.3%	<0.001
Other	101	17.1%	100	7.2%	<0.001
Anxiety	35	5.9%	289	20.9%	<0.001
Depression	25	4.2%	289	20.9%	<0.001
Behavioral disorder	114	19.3%	235	17.0%	0.212
Eating disorder	105	17.8%	80	5.8%	<0.0001
Sleep disorder	93	15.8%	238	17.2%	0.435
Walking/gait impairment	77	13.1%	160	11.6%	0.351
Cognitive disorder	42	7.1%	213	15.4%	<0.001
Stroke/TIA	9	1.5%	179	12.9%	<0.001
Arthritis	9	1.5%	157	11.3%	<0.001
ADHD	44	7.5%	96	6.9%	0.680
Obesity	7	1.2%	87	6.3%	<0.001
Coronary heart disease	3	0.5%	82	5.9%	<0.001

Notes: ADHD – attention deficit hyperactivity disorder; AED – antiepileptic drug; CDHP – consumer-driven health plan; EPO – exclusive provider organization; FFS – fee-for-service; GABA – gamma aminobutyric acid; GI – gastrointestinal; GP – general practitioner; HDHP – high-deductible health plan; HMO – health maintenance organization; NMDA – N-methyl-D-aspartate; POS – point of service; PPO – preferred provider organization; SD – standard deviation; SVP2a – synaptic vesicle protein 2A; TIA – transient ischemic attack.

^a P < 0.05. P-values were obtained using Chi-square tests for categorical variables and t-tests for continuous variables. Fisher’s exact test was used where Chi-square test was not valid due to cells having fewer than expected counts.

^b Less than 5% of patients in both cohorts received T-type calcium channel, GABA reuptake inhibitor, barbiturate, carbonic anhydrase inhibitor, and K-channel opener.

^c Less than 5% of patients in both cohorts had a diagnosis of cortical dysplasia, tuberous sclerosis, brain lesions, heart failure, and chronic renal disease.

Bold text indicates a statistically significant difference with a p-value < 0.05.

Table 3. Baseline demographic and clinical characteristics of Medicaid patients.

	Clobazam		Non-clobazam
	N = 647		N = 1365		P-value^a
Demographic characteristics
Age in years, mean (SD)	13.7	(11.4)	24.1	(17.9)	<0.001
Age group in years, n (%)
0–5	165	25.5%	208	15.2%	<0.001
6–12	206	31.8%	267	19.6%
13–17	101	15.6%	157	11.5%
18–34	134	20.7%	342	25.1%
35–44	21	3.2%	141	10.3%
45–54	12	1.9%	144	10.5%
55–64	8	1.2%	106	7.8%
Males, n (%)	331	51.2%	707	51.8%	0.790
Race, n (%)
White	348	53.8%	691	50.6%	<0.001
Black	80	12.4%	307	22.5%
Hispanic	35	5.4%	48	3.5%
Other/unknown	184	28.4%	319	23.4%
Capitation, n (%)
Yes	183	28.3%	450	33.0%	0.035
No	464	71.7%	915	67.0%
Reason for Medicaid eligibility, n (%)
Blind/disabled individual	531	82.1%	960	70.3%	<0.001
Child (not of unemployed adult/not foster care)	73	11.3%	207	15.2%
Other^b	43	6.6%	198	14.5%
Index year, n (%)
2011	2	0.3%	133	9.7%	<0.001
2012	478	73.9%	846	62.0%
2013	167	25.8%	386	28.3%
Clinical characteristics
Developmental and cognitive disorders, n (%)	597	92.3%	1130	82.8%	<0.001
Number of unique diagnoses, mean (SD)	3.0	(2.0)	2.0	(1.7)	<0.001
Baseline medication classes,^c n (%)
AEDs and other seizure-related medications	633	97.8%	1116	81.8%	<0.001
Benzodiazepine	429	66.3%	404	29.6%	<0.001
NMDA receptor blocker	310	47.9%	384	28.1%	<0.001
SVP2a binder	306	47.3%	568	41.6%	0.016
Valproic acid	236	36.5%	209	15.3%	<0.001
Sodium channel inhibitor	217	33.5%	289	21.2%	<0.001
Sulfamate-substituted monosaccharide	176	27.2%	158	11.6%	<0.001
Zonisamide	146	22.6%	107	7.8%	<0.001
GABA analogue	49	7.6%	136	10.0%	0.083
Anxiolytics	233	36.0%	401	29.4%	0.003
Antipsychotics	93	14.4%	329	24.1%	<0.001
Hypnotics	116	17.9%	211	15.5%	0.161
Number of unique prescription classes (non-AEDs), mean (SD)	7.6	(5.9)	7.8	(6.9)	0.444
Number of pre-index AED drugs of interest, mean (SD)	1.7	(1.1)	0.5	(0.7)	<0.001
Baseline comorbidities,^d n (%)
Pain	284	43.9%	813	59.6%	<0.001
Intellectual disorder	324	50.1%	481	35.2%	<0.001
Mild	61	9.4%	144	10.6%	0.437
Moderate	90	13.9%	138	10.1%	0.012
Severe/profound	135	20.9%	162	11.9%	<0.001
Other	214	33.1%	307	22.5%	<0.001
Any digestive/bowel disorder	301	46.5%	587	43.0%	0.138
Constipation	158	24.4%	244	17.9%	0.001
Psychosis	195	30.1%	617	45.2%	<0.001
Migraine/headache	71	11.0%	411	30.1%	<0.001
Depression	40	6.2%	377	27.6%	<0.001
Behavioral disorder	164	25.4%	374	27.4%	0.332
Anxiety	48	7.4%	318	23.3%	<0.001
Eating disorder	123	19.0%	104	7.6%	<0.001
Sleep disorder	106	16.4%	252	18.5%	0.255
Cognitive disorder	58	9.0%	211	15.5%	<0.001
ADHD	60	9.3%	173	12.7%	0.026
Walking/gait impairment	74	11.4%	150	11.0%	0.765
Obesity	29	4.5%	134	9.8%	<0.001
Arthritis	12	1.9%	132	9.7%	<0.001
Stroke/TIA	18	2.8%	96	7.0%	<0.001

Notes: ADHD – attention deficit hyperactivity disorder; AED – antiepileptic drug; GI – gastrointestinal; GP – general practitioner; NMDA – N-methyl-D-aspartate; SD – standard deviation; SVP2a – synaptic vesicle protein 2A; SD – standard deviation; TIA – transient ischemic attack.

^a P < 0.05. P-values were obtained using Chi-square tests for categorical variables and t-tests for continuous variables. Fisher’s exact test was used where Chi-square test was not valid due to cells having fewer than expected counts.

^b Other includes aged individual, adult (not based on unemployed status), foster care child, and eligibility status unknown.

^c Less than 5% of patients in both cohorts received T-type calcium channel, GABA reuptake inhibitor, barbiturate, carbonic anhydrase inhibitor, and K-channel opener.

^d Less than 5% of patients in both cohorts had a diagnosis of cortical dysplasia, tuberous sclerosis, brain lesions, heart failure, chronic renal disease, and coronary heart disease.

Bold text indicates a statistically significant difference with a p-value < 0.05.

Figure 1. Non-mutually exclusive sample attrition commercial and medicare patients.

Notes: AED – antiepileptic drug. ^a Continuous enrollment could only be verified for patients with an AED prescription fill within the enrollment window, as only these patients were assigned an index date. ^b Not mutually exclusive.

Table 4. Baseline healthcare utilization of commercial/Medicare Supplemental patients and Medicaid patients.

	Commercial/Medicare Supplemental					Medicaid^b
	Clobazam		Non-clobazam			Clobazam		Non-clobazam
	N = 590		N = 1384		P-value^a	N = 647		N = 1365		P-value^a
Seizure-related health care utilization
Hospitalization, n (%)	217	36.8%	381	27.5%	<0.001	209	32.3%	296	21.7%	<0.001
Number of inpatient visits, mean (SD)	0.7	(1.3)	0.4	(0.8)	<0.001	0.5	(1.1)	0.3	(0.8)	<0.001
LOS, mean (SD)	2.6	(7.6)	1.4	(4.7)	0.001	2.2	(6.7)	1.4	(6.0)	0.010
ER visits, n (%)	177	30.0%	418	30.2%	0.929	232	35.9%	539	39.5%	0.118
Number of ER visits, mean (SD)	0.6	(1.3)	0.5	(1.0)	0.216	0.8	(2.0)	0.9	(1.8)	0.365
Physician office visits, n (%)	558	94.6%	1081	78.1%	<0.001	577	89.2%	1033	75.7%	<0.001
Number of physician office visits, mean (SD)	3.9	(3.5)	2.2	(2.3)	<0.001	3.5	(3.2)	2.1	(2.2)	<0.001
Neurologist visit, n (%)	347	58.8%	729	52.7%	0.012	60	9.3%	99	7.3%	0.117
Number of neurologist visits, mean (SD)	1.8	(2.2)	1.3	(1.7)	<0.001	0.3	(1.1)	0.2	(0.8)	0.024
PCP visit, n (%)	115	19.5%	236	17.1%	0.194	177	27.4%	390	28.6%	0.572
Number of PCP visits, mean (SD)	0.5	(1.6)	0.3	(1.0)	0.010	0.8	(1.8)	0.7	(1.5)	0.304
Laboratory visits, n (%)	254	43.1%	274	19.8%	<0.001	163	25.2%	225	16.5%	<0.001
Number of laboratory visits, mean (SD)	1.1	(2.2)	0.3	(0.9)	<0.001	0.5	(1.2)	0.3	(0.9)	<0.001
Radiology visits, n (%)	58	9.8%	110	8.0%	0.170	55	8.5%	113	8.3%	0.866
Number of radiology visits, mean (SD)	0.1	(0.4)	0.1	(0.3)	0.052	0.1	(0.4)	0.1	(0.4)	0.830
Other outpatient visits, n (%)	398	67.5%	640	46.2%	<0.001	391	60.4%	588	43.1%	<0.001
Number of other outpatient visits, mean (SD)	7.1	(23.2)	1.8	(11.5)	<0.001	10.5	(38.3)	4.7	(27.6)	0.001
All-cause healthcare utilization
Hospitalization, n (%)	303	51.4%	708	51.2%	0.935	309	47.8%	614	45.0%	0.243
Number of inpatient visits, mean (SD)	1.1	(1.7)	1.2	(1.8)	0.670	1.0	(1.8)	1.1	(2.0)	0.162
LOS, mean (SD)	5.2	(12.5)	6.5	(18.2)	0.081	5.0	(15.3)	6.7	(19.8)	0.030
ER visits, n (%)	333	56.4%	966	69.8%	<0.001	420	64.9%	998	73.1%	<0.001
Number of ER visits, mean (SD)	1.6	(2.4)	2.1	(3.2)	<0.001	2.3	(3.4)	3.4	(5.2)	<0.001
Physician office visits, n (%)	588	99.7%	1361	98.3%	0.016	636	98.3%	1310	96.0%	0.006
Number of physician office visits, mean (SD)	10.9	(7.4)	10.2	(7.6)	0.061	10.7	(7.9)	8.9	(7.2)	<0.001
Neurologist visit,^b n (%)	378	64.1%	878	63.4%	0.791	67	10.4%	135	9.9%	0.746
Number of neurologist visits, mean (SD)	2.2	(2.5)	1.9	(2.3)	0.010	0.4	(1.5)	0.3	(1.1)	0.082
PCP visit,^b n (%)	268	45.4%	852	61.6%	<0.001	321	49.6%	712	52.2%	0.286
Number of PCP visits, mean (SD)	2.1	(4.0)	3.2	(4.6)	<0.001	3.1	(5.1)	3.4	(5.2)	0.253
Laboratory visits, n (%)	406	68.8%	871	62.9%	0.012	379	58.6%	747	54.7%	0.104
Number of laboratory visits, mean (SD)	2.3	(3.0)	1.9	(3.0)	0.002	1.7	(3.9)	1.8	(3.5)	0.726
Radiology visits, n (%)	255	43.2%	768	55.5%	<0.001	254	39.3%	621	45.5%	0.008
Number of radiology visits, mean (SD)	0.9	(1.5)	1.4	(2.9)	<0.001	0.7	(1.2)	1.0	(1.7)	<0.001
Other outpatient visits, n (%)	567	96.1%	1329	96.0%	0.937	640	98.9%	1335	97.8%	0.082
Number of other outpatient visits, mean (SD)	33.0	(52.3)	18.1	(31.3)	<0.001	90.9	(91.4)	63.9	(87.7)	<0.001

Notes: ER – emergency room; LOS – length of stay; PCP – primary care physician; SD – standard deviation; USD – United States dollars.

^a P < 0.05. P-values were obtained using Chi-square tests for categorical variables and t-tests for continuous variables.

^b The majority of claims do not have information on physician specialty.

Bold text indicates a statistically significant difference with a p-value < 0.05.

Table 5. Baseline healthcare costs of commercial/Medicare Supplemental patients and Medicaid patients.

	Commercial/Medicare Supplemental					Medicaid^b
	Clobazam		Non-clobazam			Clobazam		Non-clobazam
	N = 590		N = 1384		P-value^a	N = 647		N = 1365		P-value^a
Annual seizure-related costs in 2014 USD, mean (SD)
Total	$33,478	(58,431)	$12,709	(36,420)	<0.001	$23,219	(84,306)	$7687	(25,092)	<0.001
Medical	$24,066	(56,142)	$10,563	(35,194)	<0.001	$15,544	(82,673)	$5951	(24,374)	<0.001
Hospitalization	$15,013	(48,020)	$7366	(30,951)	<0.001	$10,016	(80,795)	$4108	(22,651)	<0.001
ER	$961	(3549)	$793	(2314)	0.933	$297	(941)	$353	(979)	0.164
Physician office	$1581	(3770)	$562	(1438)	<0.001	$654	(1675)	$246	(699)	<0.001
Neurologist	$384	(577)	$214	(363)	<0.001	$33	(149)	$15	(80)	0.085
PCP	$115	(382)	$51	(190)	0.077	$66	(183)	$53	(247)	0.355
Laboratory	$350	(1434)	$82	(621)	<0.001	$28	(172)	$16	(98)	<0.001
Radiology	$146	(805)	$126	(632)	0.138	$57	(375)	$43	(212)	0.593
Other outpatient	$6015	(22,108)	$1634	(11,555)	<0.001	$4491	(16,426)	$1186	(8086)	<0.001
Prescription	$9411	(12,416)	$2146	(5596)	<0.001	$7676	(12,866)	$1736	(4262)	<0.001
Annual all-cause costs in 2014 USD, mean (SD)
Total	$73,486	(110,918)	$49,632	(89,843)	<0.001	$62,989	(120,325)	$38,370	(70,243)	<0.001
Medical	$58,116	(100,102)	$43,866	(86,376)	<0.001	$49,667	(105,654)	$34,292	(68,737)	<0.001
Hospitalization	$30,441	(81,555)	$24,727	(70,535)	0.168	$17,858	(96,153)	$14,498	(58,921)	0.076
ER	$3450	(8543)	$4671	(9646)	<0.001	$1404	(3194)	$2036	(4009)	<0.001
Physician office	$4502	(7071)	$2841	(5036)	<0.001	$2516	(3508)	$1579	(2738)	<0.001
Neurologist	$483	(681)	$344	(524)	<0.001	$52	(262)	$27	(151)	0.576
PCP	$419	(1124)	$476	(1275)	<0.001	$254	(791)	$239	(538)	0.874
Laboratory	$679	(1978)	$369	(1163)	<0.001	$103	(278)	$101	(253)	0.038
Radiology	$542	(1799)	$930	(3911)	<0.001	$196	(639)	$224	(586)	0.010
Other outpatient	$18,500	(40,352)	$10,329	(27,363)	<0.001	$27,590	(39,437)	$15,854	(28,874)	<0.001
Prescription	$15,370	(36,617)	$5766	(18,940)	<0.001	$13,321	(45,428)	$4078	(7315)	<0.001

Notes: ER – emergency room; LOS – length of stay; PCP – primary care physician; SD – standard deviation; USD – United States dollars.

^a P < 0.05. P-values for differences in cost were obtained using the Wilcoxon-Mann-Whitney test.

^b The majority of claims do not have information on physician specialty.

Bold text indicates a statistically significant difference with a p-value < 0.05.

Table 6. Treatment patterns of commercial/Medicare Supplemental patients and Medicaid patients.

	Commercial/Medicare Supplemental				Medicaid
	Clobazam		Non-clobazam		Clobazam		Non-clobazam
Treatment Patterns	N = 590		N = 1384		N = 647		N = 1365
Number of index AED prescription claims, mean (SD)	5.5	(2.6)	4.6	(2.8)	5.7	(2.6)	4.6	(2.7)
Total days on index AED, mean (SD)	140.1	(50.8)	119.5	(62.6)	138.7	(51.5)	114.1	(64.3)
Changes to index treatment, n (%)
Augmentation	67	11.4%	127	9.2%	65	10.1%	111	8.1%
Switching	29	4.9%	91	6.6%	30	4.6%	86	6.3%
Discontinuation	162	27.5%	531	38.4%	162	25.0%	545	39.9%
Continued index therapy	332	56.3%	635	45.9%	390	60.3%	623	45.6%
Time to change in index treatment in days, mean (SD)
Time to augmentation	60.8	(50.2)	49.6	(55.6)	70.6	(58.0)	59.3	(63.1)
Time to switch	76.2	(50.9)	69.0	(51.0)	99.4	(47.0)	59.0	(46.1)
Time to discontinuation	60.4	(36.8)	47.9	(35.4)	55.0	(33.6)	45.1	(36.9)
Total days on any AED,^a mean (SD)	166.0	(29.6)	138.4	(54.0)	164.4	(33.3)	134.5	(56.8)
All AED^a discontinuation rate, n (%)	68	11.5%	458	33.1%	72	11.1%	462	33.8%
Time to discontinuation from all AEDs^a in days, mean (SD)	71.4	(37.9)	52.3	(36.6)	62.4	(35.0)	49.5	(38.3)

Notes: AED – antiepileptic drug; SD – standard deviation.

^a Eight AEDs were considered in the study.

Table 7. Pre-index and post-index healthcare costs among clobazam patients in the commercial/Medicare Supplemental and Medicaid populations.

	Commercial/Medicare Supplemental (N = 314)					Medicaid (N = 358)
	Pre-clobazam		Post-clobazam		P-value^a	Pre-clobazam		Post-clobazam		P-value^a
Healthcare costs
Annual seizure-related costs in 2014 USD, mean (SD)
Total	$33,289	(54,938)	$35,083	(46,149)	0.029	$27,541	(109,816)	$28,493	(44,016)	<0.001
Medical	$23,740	(52,288)	$19,958	(43,090)	0.004	$18,965	(108,221)	$14,442	(39,754)	0.036
Hospitalization	$13,711	(41,266)	$11,639	(32,128)	0.094	$12,608	(106,674)	$7805	(35,724)	0.006
ER	$908	(2612)	$662	(3441)	0.002	$304	(892)	$196	(502)	0.003
Physician office	$1873	(4673)	$1278	(1981)	0.005	$728	(1422)	$657	(1485)	0.001
Neurologist	$448	(672)	$355	(508)	0.022	$30	(142)	$17	(77)	0.100
PCP	$116	(391)	$81	(298)	0.072	$76	(212)	$65	(194)	0.303
Laboratory	$397	(1385)	$270	(1026)	0.177	$34	(226)	$46	(324)	0.378
Radiology	$124	(689)	$92	(476)	0.366	$58	(436)	$29	(181)	0.336
Other outpatient	$6727	(25,573)	$6018	(20,393)	0.733	$5234	(17,472)	$5708	(17,619)	0.263
Prescription	$9549	(12,578)	$15,125	(13,735)	<0.001	$8576	(14,445)	$14,051	(16,375)	<0.001
Annual all-cause costs in 2014 USD, mean (SD)
Total	$73,319	(117,534)	$81,389	(110,776)	<0.001	$68,565	(150,749)	$73,153	(102,307)	<0.001
Medical	$57,090	(107,206)	$59,292	(93,302)	0.411	$52,667	(131,965)	$52,937	(89,727)	0.880
Hospitalization	$28,079	(84,526)	$29,097	(57,815)	0.308	$20,860	(124,848)	$18,809	(70,923)	0.506
ER	$3228	(7792)	$3128	(9189)	0.102	$1382	(2714)	$1194	(2122)	0.421
Physician office	$4984	(8060)	$4243	(5961)	0.076	$2596	(3365)	$2431	(3329)	0.024
Neurologist	$546	(763)	$457	(686)	0.013	$50	(290)	$23	(113)	0.055
PCP	$456	(1317)	$311	(777)	0.060	$235	(447)	$236	(423)	0.509
Laboratory	$725	(1965)	$580	(1525)	0.294	$111	(333)	$130	(516)	0.309
Radiology	$471	(1467)	$341	(978)	0.214	$203	(715)	$131	(404)	0.028
Other outpatient	$19,603	(47,316)	$21,903	(48,312)	0.073	$27,516	(37,829)	$30,242	(40,282)	0.092
Prescription	$16,229	(35,832)	$22,098	(44,556)	<0.001	$15,898	(58,577)	$20,215	(36,680)	<0.001

Notes: ER – emergency room; PCP – primary care physician; SD – standard deviation; USD – United States dollars.

^a P-values in bold <0.05. P-values for unadjusted differences in categorical variables were obtained using McNemar’s test to account for pre-post design. Similarly, P-values for count variables were obtained using paired t-tests. P-values for difference in mean costs were obtained using Wilcoxon signed-rank test (non-parametric version of a paired t-test) and P-values for difference in median costs were obtained using Wilcoxon signed rank test.

Bold text indicates a statistically significant difference with a p-value < 0.05.

Figure 2. Proportion of patients utilizing seizure-related healthcare resources pre- vs post-clobazam.

Notes: ER – emergency room; PCP – primary care physician. P-values in bold < 0.05. P-values for unadjusted differences in categorical variables were obtained using McNemar’s test to account for pre-post design.

Figure 3. Mean number of seizure-related healthcare services utilized pre- vs post-clobazam.

Notes: AED – antiepileptic drug; ER – emergency room; PCP – primary care physician. P-values in bold < 0.05. P-values for count variables were obtained using paired t-tests to account for pre-post design. *Includes clobazam.

Figure 4. Proportion of patients utilizing all-cause healthcare resources pre- vs post-clobazam.

Notes: ER – emergency room; PCP – primary care physician. P-values in bold < 0.05. P-values for unadjusted differences in categorical variables were obtained using McNemar’s test to account for pre-post design.

Figure 5. Mean number of all-cause healthcare services utilized pre- vs post-clobazam.

Notes: ER – emergency room; PCP – primary care physician. P-values in bold < 0.05. P-values for count variables were obtained using paired t-tests to account for pre-post design.