Comparative effectiveness and costs of generic and brand-name gabapentin and venlafaxine in patients with neuropathic pain or generalized anxiety disorder in Spain

Figures & data

Table 1 Details of the unit costs and lost labor productivity (2013)

Health care and non-health care resources	Unit costs (€)
Doctors’ visits
Primary care doctors visit	23.7
Emergency room visits	119.9
Hospitalization (1 day)	327.3
Specialist doctors visit	68.9
Day hospital sessions	184.8
Investigations
Laboratory tests	22.7
Conventional radiology	18.9
Diagnostic/therapeutic tests	37.9
Pharmaceutical prescription	Public selling price
Labor productivity – indirect costs
Cost per day not worked	79.5

Notes: Source of health care resources: analytical accounting of Badalona Serveis Assistencials and by Instituto Nacional de Estadística (INE).²⁹ Values are expressed in euros (€).

Figure 1 General outline of the study.

Note: An observational retrospective design involving the review of existing medical records (computerized databases with existing data dissociated) of patients under primary care and hospital follow-up who started treatment with gabapentin or venlafaxine (brand-name vs generic).

Table 2 Baseline characteristics of study series

Study groups	Gabapentin				Venlafaxine
Subgroups	Brand	Generic	Total	P	Brand	Generic	Total	P
Number of patients, %	N=400 (29.2%)	N=969 (70.8%)	N=1,369 (100%)		N=370 (44.0%)	N=471 (56.0%)	N=841 (100%)
Demographic characteristics
Average age, years	64.2 (16.4)	64.8 (15.6)	64.6 (15.9)	0.525	61.0 (17.1)	60.5 (16.9)	60.7 (17.0)	0.656
Sex (female)	56.3%	63.2%	61.1%	0.017	61.4%	66.7%	64.3%	0.110
Pension regime, SS	67.5%	66.4%	66.7%	0.683	57.3%	55.8%	56.5%	0.672
Range: 19–44 years	13.8%	11.9%	12.4%		18.1%	19.7%	19.0%
45–64 years	33.0%	36.1%	35.2%		38.9%	38.4%	38.6%
65–74 years	22.8%	19.5%	20.5%		17.3%	16.6%	16.9%
>74 years	30.5%	32.5%	31.9%	0.333	25.7%	25.3%	25.4%	0.943
General comorbidity
Average number of diagnoses	7.0 (3.8)	7.1 (3.5)	7.1 (3.6)	0.643	7.0 (3.8)	7.1 (4.0)	7.1 (3.9)	0.816
Average Charlson index	0.7 (1.1)	0.7 (1.0)	0.7 (1.0)	0.930	0.6 (0.9)	0.6 (0.8)	0.6 (0.9)	0.864
Average RUB	2.9 (0.6)	2.9 (0.6)	2.9 (0.6)	0.777	2.9 (0.6)	2.9 (0.6)	2.9 (0.6)	0.527
RUB-1	3.3%	4.4%	4.1%		3.2%	3.8%	3.6%
RUB-2	12.5%	10.2%	10.9%		13.8%	12.3%	13.0%
RUB-3	73.5%	76.4%	75.5%		73.8%	73.2%	73.5%
RUB-4	10.0%	7.4%	8.2%		8.9%	9.3%	9.2%
RUB-5	0.8%	1.5%	1.3%	0.178	0.3%	1.3%	0.8%	0.542
Associated comorbidities
Hypertension	40.3%	44.2%	43.0%	0.183	35.6%	37.6%	36.7%	0.555
Diabetes mellitus	18.8%	21.4%	20.6%	0.277	16.0%	15.1%	15.5%	0.703
Dyslipidemia	43.5%	48.2%	41.2%	0.172	44.0%	48.6%	46.6%	0.185
Obesity	17.5%	20.1%	20.5%	0.214	14.1%	17.4%	16.0%	0.198
Active smokers	22.0%	21.4%	21.5%	0.794	19.3%	21.9%	20.7%	0.361
Alcoholism	3.5%	3.2%	3.3%	0.776	5.7%	3.2%	4.3%	0.074
Ischemic heart disease	7.3%	7.8%	7.7%	0.708	5.7%	6.6%	6.2%	0.602
CVA	12.5%	12.6%	12.6%	0.963	11.4%	11.0%	11.2%	0.865
Cardiovascular event	17.5%	17.9%	17.8%	0.876	14.9%	14.9%	14.9%	0.973
Organ failure	14.0%	16.6%	15.9%	0.228	12.8%	12.7%	12.8%	0.989
Asthma	6.0%	7.2%	6.9%	0.415	6.8%	5.2%	5.8%	0.149
COPD	6.3%	5.8%	5.9%	0.737	3.5%	4.7%	4.2%	0.413
Neuropathies	2.8%	1.3%	1.8%	0.071	2.4%	1.3%	1.8%	0.204
Dementia (all types)	4.5%	2.8%	3.3%	0.106	4.3%	5.5%	5.0%	0.440
Organic psychosis	1.0%	0.7%	0.8%	0.601	4.1%	5.5%	4.9%	0.336
Malignant neoplasms	15.0%	12.2%	13.0%	0.158	7.1%	9.6%	8.5%	0.199

Note: Values are expressed as percentage or mean (± standard deviation).

Abbreviations: SS, social security; RUB, resource utilization bands; CVA, cerebrovascular accident.

Figure 2 Persistence curve for initial treatment (gabapentin, venlafaxine): comparison of the brand medication with the generic.

Notes: (A) Kaplan–Meier curve for estimation of the median duration of initial treatment with gabapentin. Comparisons between subgroups (brand vs generic): Mantel–Cox log-rank test: 19.541; P<0.001. (B) Kaplan–Meier curve for estimation of the median duration of initial treatment with venlafaxine. Comparisons between subgroups (brand vs generic): Mantel–Cox log-rank test: 6.071; P=0.014.

Table 3 Characteristics of medication use: treatment adherence/compliance and persistence

Study groups	Gabapentin				Venlafaxine
Subgroups	Brand	Generic	Total	P	Brand	Generic	Total	P-value
Number of patients, %	N=400 (29.2%)	N=969 (70.8%)	N=1,369 (100%)		N=370 (44.0%)	N=471 (56.0%)	N=841 (100%)
Time since diagnosis (years)
Mean (SD)	1.5 (1.2)	1.6 (1.2)	1.6 (1.2)	0.529	2.6 (2.5)	2.7 (2.7)	2.7 (2.6)	0.712
Median (P25–P75)	1.0 (1.0–2.0)	1.0 (1.0–2.0)	1.0 (1.0–2.0)		1.0 (2.0–4.0)	1.0 (2.0–5.0)	1.0 (2.0–5.0)
Possession of treatment (months)
Mean (SD)	6.4 (3)	5.5 (3.5)	5.7 (3.4)	<0.001	7.4 (3.2)	6.9 (3.9)	7.1 (3.6)	0.047
Median (P25–P75)	6.0 (4.0–8.0)	4.0 (4.0–8.0)	5.0 (4.0–8.0)		7.0 (5.0–11.0)	7.0 (4.0–11.0)	7.0 (4.0–11.0)
Duration of treatment (months)
Mean (SD)	7.3 (3.0)	6.3 (3.1)	6.6 (3.1)	<0.001	8.8 (2.9)	8.1 (3.6)	8.4 (3.3)	0.002
Median (P25–P75)	7.0 (5.0–10.0)	5.0 (3.0–9.0)	6.0 (5.0–9.0)		9.0 (5.0–12.0)	9.0 (5.0–12.0)	9.0 (5.5–12.0)
Medication possession ratio
Mean (SD)	86.5%	81.3%	82.8%	<0.001	82.1%	78.2%	79.0%	0.045
Median (P25–P75)	85.7 (80.0–88.9)	80.0 (66.7–88.9)	83.3 (80.0–88.9)		77.7 (71.4–91.7)	83.3 (71.5–91.7)	80.0 (72.5–91.7)
Daily dose of medication
Mean (SD)	1,322.5 (524.2)	1,153.5 (451.2)	1,202.9 (479.7)	0.008	102.8 (38.4)	100.9 (35.5)	101.2 (36.8)	0.449
Median (P25–P75)	900 (900–1,800)	900 (900–1,200)	900 (900–1,800)		75 (75–150)	75 (75–150)	75 (75–150)
Range (N, %)
<900 mg/day	11 (2.8)	38 (3.9)	49 (3.6)		–	–	–
=900 mg/day	195 (48.8)	597 (61.6)	792 (57.9)		–	–	–
≤1,800 mg/day	151 (37.8)	256 (26.4)	407 (29.7)		–	–	–
>1,800 mg/day	43 (10.8)	78 (8.0)	121 (8.8)	0.003	–	–	–	0.112
<75 mg/day	–	–	–		3 (0.8)	14 (3.0)	17 (2.0)
=75 mg/day	–	–	–		226 (61.1)	262 (55.6)	488 (58.0)
≤150 mg/day	–	–	–		13 (3.5)	43 (9.1)	56 (6.7)
>150 mg/day	–	–	–		128 (34.6)	152 (32.3)	280 (33.3)
Treatment persistence (months)a
3 months	92.0%	72.3%	78.1%	<0.001	93.5%	84.7%	88.6%	<0.001
6 months	54.8%	34.5%	40.4%	<0.001	87.6%	60.5%	72.4%	<0.001
9 months	27.5%	17.8%	20.6%	<0.001	55.4%	44.4%	49.2%	0.001
12 months	18.3%	13.9%	15.8%	0.039	37.8%	31.4%	33.5%	0.052

Notes: Values are expressed as mean (± standard deviation) or percentage.

a Persistence was defined as time, measured in months, without discontinuing the initial treatment or without changing to another medication at least 30 days after the initial prescription.

Abbreviations: SD, standard deviation; P, percentile.

Table 4 Medication prescribed to the patients in pre-treatment (6 previous months) and treatment (12-month follow-up)

Gabapentin		Brand		Generic		Differencea	P-value
Therapeutic class	Period	N	Mean (SD) or %	N	Mean (SD) or %
Average number of drugs	Pre-treatment	400	2.3 (1.2)	969	2.6 (1.3)	0.3	<0.001
	Treatment	400	1.9 (1.1)	969	2.5 (1.4)	0.5	<0.001
	Difference		−0.34		−0.04
	P-value		<0.001		0.261
NSAIDs	Pre-treatment	244	61.0%	703	72.5%	11.5%	0.001
	Treatment	192	48.0%	674	69.6%	21.6%	<0.001
	Difference		−13.0%		−3.0%
	P-value		<0.001		0.085
Analgesics (non-narcotic)	Pre-treatment	240	60.0%	674	69.6%	9.6%	0.011
	Treatment	186	46.5%	643	66.4%	19.9%	<0.001
	Difference		−13.5%		−3.2%
	P-value		<0.001		0.076
Opiates	Pre-treatment	119	29.8%	309	31.9%	2.1%	0.689
	Treatment	110	27.5%	289	29.8%	2.3%	0.695
	Difference		−2.3%		−2.1%
	P-value		0.335		0.189
Anxiolytics	Pre-treatment	166	41.5%	455	47.0%	5.5%	0.268
	Treatment	149	37.3%	448	46.2%	9.0%	0.055
	Difference		−4.3%		−0.7%
	P-value		0.056		0.635
Antidepressants	Pre-treatment	110	27.5%	285	29.4%	1.9%	0.557
	Treatment	115	28.8%	321	33.1%	4.4%	0.429
	Difference		1.3%		3.7%
	P-value		0.559		0.005
Venlafaxine		Brand		Generic		Differencea	P-value
Therapeutic class	Period	N	Mean (SD) or %	N	Mean (SD) or %
Average number of drugs	Pre-treatment	371	2.3 (1.5)	471	2.6 (1.6)	0.3	0.002
	Treatment	371	2.0 (1.4)	471	2.5 (1.5)	0.4	<0.001
	Difference		−0.25		−0.10
	P-value		0.001		0.117
NSAIDs	Pre-treatment	168	45.4%	257	54.6%	9.2%	0.044
	Treatment	143	38.6%	259	55.0%	16.4%	0.002
	Difference		−6.8%		0.4%
	P-value		0.017		0.870
Analgesics (non-narcotic)	Pre-treatment	161	43.5%	216	45.9%	2.3%	0.699
	Treatment	160	43.2%	221	46.9%	3.7%	0.607
	Difference		−0.3%		1.1%
	P-value		0.924		0.676
Opiates	Pre-treatment	56	15.1%	74	15.7%	0.6%	0.887
	Treatment	65	17.6%	73	15.5%	−2.1%	0.748
	Difference		2.4%		−0.2%
	P-value		0.217		0.901
Anxiolytics	Pre-treatment	238	64.3%	353	74.9%	10.6%	0.009
	Treatment	191	51.6%	318	67.5%	15.9%	0.006
	Difference		−12.7%		−7.4%
	P-value		<0.001		<0.001
Antidepressants	Pre-treatment	56	15.1%	75	15.9%	0.8%	0.787
	Treatment	49	13.2%	70	14.9%	1.7%	0.667
	Difference		−1.9%		−1.0%
	P-value		0.734		0.876
Antipsychotic agents	Pre-treatment	54	14.6%	89	18.9%	4.3%	0.427
	Treatment	48	13.0%	88	18.7%	5.7%	0.358
	Difference		−1.6%		−0.2%
	P-value		0.343		0.889

Notes:

a Percentage difference (treatment and pre-treatment; generic vs brand). During the study period, the patients were taking various medications at the same time.

Abbreviations: SD, standard deviation; NSAIDs, nonsteroidal anti-inflammatory drugs.

Table 5 Use of health care resources and working days lost due to sickness

Study groups	Gabapentin							Venlafaxine
Subgroups	Brand		Generic		Total		P-value	Brand		Generic		Total		P-value
Number of patients, %	N=400 (29.2%)		N=969 (70.8%)		N=1,369 (100%)			N=370 (44.0%)		N=471 (56.0%)		N=841 (100%)
Type of resource	Use (%)	Mean (SD)	Use (%)	Mean (SD)	Use (%)	Mean (SD)		Use (%)	Mean (SD)	Use (%)	Mean (SD)	Use (%)	Mean (SD)
Primary care visits	100.0	12.5 (9.8)	100.0	15.5 (10.6)	100.0	14.6 (10.5)	<0.001	100.0	11.1 (9.8)	100.0	13.9 (10.6)	100.0	12.7 (10.3)	<0.001
Laboratory tests	50.0	0.8 (1.1)	65.7	1.1 (1.2)	61.1	1.0 (1.2)	<0.001	43.0	0.7 (1.0)	56.3	1.0 (1.1)	50.4	0.9 (1.1)	0.002
Conventional radiology	40.7	0.7 (1)	54.4	0.9 (1.0)	50.4	0.8 (1.0)	<0.001	28.6	0.5 (1.0)	35.0	0.5 (0.9)	32.2	0.5 (0.9)	0.458
Diagnostic tests	13.7	0.1 (0.4)	19.4	0.2 (0.5)	17.8	0.2 (0.5)	0.006	10.5	0.1 (0.8)	8.9	0.1 (0.4)	9.6	0.1 (0.6)	0.259
Days of hospitalization	8.7	0.3 (1.1)	7.0	0.3 (1.8)	7.5	0.3 (1.6)	0.359	4.6	0.2 (1.2)	4.9	0.3 (3.3)	4.8	0.3 (2.6)	0.543
Medical specialist visits	59.2	2.4 (3.6)	71.5	2.6 (3.6)	67.9	2.5 (3.6)	0.414	43.8	1.9 (3.8)	57.1	1.7 (2.5)	51.2	1.8 (3.1)	0.430
Day hospital sessions	3.0	0.2 (1.4)	4.2	0.3 (1.9)	3.9	0.3 (1.8)	0.492	3.0	0.1 (0.6)	1.9	0.1 (0.6)	2.4	0.1 (0.6)	0.536
Emergency room visits	25.7	0.4 (0.8)	50.6	0.7 (0.8)	43.3	0.6 (0.8)	<0.001	25.9	0.4 (0.9)	42.3	0.6 (0.8)	35.1	0.5 (0.9)	0.006
Working days lost	10.5	4.8 (20.0)	10.9	4.9 (21.2)	10.8	4.9 (20.9)	0.897	9.5	4.5 (21.5)	10.8	5.1 (22.4)	10.2	4.8 (22.0)	0.722

Notes: Values are expressed as percentage (%) of patients or mean (± standard deviation) per patient; Use = percentage of patients using the specified resource.

Abbreviation: SD, standard deviation.

Table 6 Health care and non-health care costs (lost labor productivity) by study group

Study groups	Gabapentin				Venlafaxine
Subgroups	Brand	Generic	Total	P-value	Brand	Generic	Total	P-value
Number of patients, %	N=400 (29.2%)	N=969 (70.8%)	N=1,369 (100%)		N=370 (44.0%)	N=471 (56.0%)	N=841 (100%)
Health care costs	1,083.3 (844.5)	1,274.8 (1,051.4)	1,218.8 (998.9)	0.001	948.7 (805.9)	1,106.7 (1,302.5)	1,037.2 (1,113.9)	0.041
Primary care costs	751.7 (479.9)	850.6 (445.7)	821.7 (458)	<0.001	686.4 (517.9)	805.7 (545)	753.2 (536.2)	0.001
Doctors’ visits	296.5 (231.5)	367.0 (251.3)	346.4 (247.7)	<0.001	263.2 (231.2)	328.7 (251.7)	299.9 (244.9)	<0.001
Laboratory tests	18.7 (25.9)	25.5 (27.4)	23.5 (27.1)	<0.001	16.6 (23.6)	21.9 (25.7)	19.6 (25.0)	0.002
Conventional radiology	12.4 (18.3)	17.0 (19.7)	15.6 (19.4)	<0.001	9.1 (18.3)	10.0 (16.4)	9.6 (17.2)	0.458
Investigations	5.7 (14.8)	8.7 (19.5)	7.8 (18.3)	0.006	5.6 (28.6)	3.9 (13.5)	4.7 (21.5)	0.259
Main study medication	255.5 (109.8)	207.5 (67)	221.5 (84.7)	<0.001	205 (153.1)	166.6 (207.7)	183.5 (186.5)	0.003
Concomitant medicationa	163.0 (315.0)	224.9 (291.6)	206.8 (299.8)	<0.001	186.8 (332.7)	274.6 (351.3)	236.0 (345.8)	0.002
Hospital care costs	331.6 (614.6)	424.2 (858.1)	397.1 (795.6)	0.050	262.3 (534.5)	301.0 (1,139.4)	284.0 (923.2)	0.546
Days of hospitalization	81.8 (357.9)	110.5 (579.7)	102.1 (524.7)	0.359	67.2 (378.1)	102.8 (1,074.3)	87.2 (841.9)	0.543
Hospital visits	166.6 (251.4)	178.5 (244.8)	175 (246.7)	0.414	130.0 (259.1)	118.2 (172.5)	123.4 (214.9)	0.430
Day hospital sessions	39.7 (250.9)	53.0 (351.1)	49.1 (325)	0.492	15.5 (103.8)	11.0 (105.2)	13.0 (104.6)	0.536
Hospital emergencies	43.5 (93.5)	82.2 (97.3)	70.9 (97.7)	<0.001	49.6 (104)	69.0 (99.7)	60.4 (102.0)	0.006
Non-health care costs (productivity)	378 (1,592.8)	390.9 (1,688.9)	387.1 (1,660.9)	0.897	360.1 (1,708.7)	403.4 (1,779.3)	384.4 (1,747.7)	0.722
Total costs, unadjusted	1,461.4 (1,835.8)	1,665.6 (2,053.7)	1,605.9 (1,994)	0.048	1,308.8 (1,920.8)	1,510.1 (2,197.1)	1,421.6 (2,081.3)	0.040
Adjusted costsb			Difference				Difference
Health care costs	1,057	1,277	−220	<0.001	928	1,110	−182	0.020
95% CI	959–1,155	1,213–1,341			814–1,042	1,006–1,215
Primary care costs	722	855	−133	<0.001	670	796	−126	0.001
95% CI	678–766	826–884			616–724	747–845
Specialist care costs	335	422	−87	0.075	257	314	−57	0.388
95% CI	255–415	370–474			161–353	226–402
Non-health care costs (productivity)	340	442	−102	0.307	362	438	−76	0.546
95% CI	178–504	336–549			181–544	272–604
Total adjusted costs	1,398	1,720	−322	0.008	1,290	1,549	−259	0.035
95% CI	1,200–1,596	1,590–1,849			1,072–1,509	1,350–1,749

Notes: Values are expressed as mean (± standard deviation).

a Concomitant medication (antipsychotic agents, antidepressants, anxiolytics, opiates, analgesics, and non-steroidal anti-inflammatory drugs);

b adjusted for covariates (age, sex, medication possession ratio, treatment persistence, time since diagnosis, resource utilization bands, and Charlson index). All cost values are expressed in €.

Abbreviation: CI, confidence interval.

Table 7 Variation of pain intensity and anxiety symptoms between baseline and treatment discontinuation by study group

Variable	Brand	Generic	Difference/OR (95% CI)a	P-value
Pain intensity (VAS)
Start of treatment	7.1 (1.5)	7.2 (1.4)	−0.1 (−0.1; 0.3)	0.340
Treatment discontinuation	3.6 (2.4)	4.1 (2.0)	−0.5 (−0.7; −0.2)	<0.001
Change start-discontinuation (pts)	−3.5 (2.0)	−3.1 (1.8)	−0.5 (−0.7; −0.2)	<0.001
Relative variation (%)	−51.0 (27.5)	−43.2 (22.5)	−7.8 (−10.7; −4.9)	<0.001
Responders (↓ ≥50%), %	64.3	38.8	3.1 (2.4; 4.1)b	<0.001
Remission (<4 pts), %	58.3	37.6	2.7 (2.0; 3.5)b	<0.001
Anxiety symptoms (HAM-A)
Start of treatment	24.8 (6.9)	25.6 (6.7)	−0.9 (−1.9; 0.2)	0.108
Treatment discontinuation	9.5 (2.6)	13.0 (5.1)	−3.4 (−4.0; −2.9)	<0.001
Change start-discontinuation (pts)	−15.7 (5.7)	−12.3 (5.5)	−3.4 (−4.0; −2.9)	<0.001
Relative variation (%)	−61.5 (10.1)	−48.2 (13.6)	−13.2 (−15.1; −11.4)	<0.001
Responders (↓ ≥50%), %	67.0	39.1	5.5 (3.8; 8.1)b	<0.001
Remission (<7 pts), %	15.9	1.9	10.7 (5.1; 22.8)b	<0.001

Notes: Values are expressed as mean (± standard deviation) unless otherwise specified. VAS, range 0–10; HAM-A, range 0–56;

a values adjusted for age, sex, and score at start of treatment;

b OR.

Abbreviations: OR, odds ratio; CI, confidence interval; VAS, visual analog scale; pts, points; HAM-A, Hamilton Anxiety Rating Scale.

Instituto Nacional de Estadística 20132013 Labour Costs Survey Available from: http://www.ine.es/dyngs/INEbase/es/operacion.htm?c=Estadistica_C&cid=1254736060920&menu=ultiDatos&idp=1254735976596Accessed March 1, 2014

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