Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study

Figures & data

Figure 1 Case definitions used to identify neuropathic pain conditions in the study sample.

Note: ^aSubjects with SCI-NeP who also have post-surgical pain were eligible to participate and considered to be in the SCI-NeP group.
Abbreviations: CLBP-NeP, chronic low back pain with neuropathic pain; HIV-NeP, human immunodeficiency virus-related peripheral neuropathic pain; pDPN, painful diabetic peripheral neuropathy; PTPS-NeP, post-trauma/post-surgical neuropathic pain; SCI-NeP, spinal cord injury with neuropathic pain; SFN, painful peripheral neuropathy with small fiber involvement.

Table 1 Sources used to assign costs to health care resources and lost productivity

Unit	Source
Health care resources related to neuropathic pain
Office visits	Fiscal year 2012 Medicare Physician Fee
Office-based procedures and tests	Schedule
Hospital outpatient visits	Fiscal year 2012 Medicare Hospital
Emergency room visits	Outpatient Prospective Payment System
Hospitalizations	Diagnosis Related Groups and Fiscal year 2012 Medicare Hospital Inpatient Prospective Payment System
Prescription medications (generic)	2012 Redbook Average Wholesale Price discounted 64.5% plus a dispensing fee
Prescription medications (brand)	2012 Redbook Average Wholesale Price discounted 16% plus a dispensing fee
Portable TENS unit	Fiscal year 2012 Medicare Durable Medical Equipment, Prosthetics, Orthotics and Supplies
Lost productivity due to neuropathic pain
Work-related lost productivity for those currently employed	Average hourly wage values obtained through the Bureau of Labor Statistics^Citation27
Unemployment Early retirement Reduced work schedule	Average hourly wage values obtained through the Bureau of Labor Statistics^Citation27
Long-term disability	Average hourly wage values obtained through the Bureau of Labor Statistics^Citation27 plus the average monthly disability payment from the Social Security Administration^Citation28

Abbreviation: TENS, transcutaneous electrical nerve stimulation.

Table 2 Neuropathic pain condition samples by pain severity level

Neuropathic pain condition	Number (%) of subjects with NeP condition
	Mild	Moderate	Severe	Missing
CLBP-NeP (n=106)	6 (5.7)	55 (51.9)	43 (40.6)	2 (1.9)
HIV-NeP (n=103)	24 (23.3)	41 (39.8)	37 (35.9)	1 (1.0)
pDPN^Citation13 (n=112)	22 (19.6)	57 (50.9)	32 (28.6)	1 (0.9)
SCI-NeP^Citation30 (n=103)	21 (20.4)	53 (51.5)	27 (26.2)	2 (1.9)
SFN^Citation32 (n=100)	23 (23.0)	43 (43.0)	33 (33.0)	1 (1.0)
PTPS-NeP^Citation31 (n=100)	14 (14.0)	48 (48.0)	35 (35.0)	3 (3.0)

Notes: A summary of the sample pain severity distribution by NeP condition appears in Schaefer et al.²⁶ Their paper “Burden of illness associated with peripheral and central neuropathic pain among adults seeking treatment in the United States: a patient-centered evaluation” was first published in Pain Medicine, Copyright ©2014. Pain Medicine is published by Wiley-Blackwell, Inc. on behalf of the American Academy of Pain Medicine.²⁶

Abbreviations: CLBP-NeP, chronic low back pain with neuropathic pain; HIV-NeP, human immunodeficiency virus-related peripheral neuropathic pain; pDPN, painful diabetic peripheral neuropathy; PTPS-NeP, post-trauma/post-surgical neuropathic pain; SCI-NeP, spinal cord injury with neuropathic pain; SFN, painful peripheral neuropathy with small fiber involvement.

Table 3 Demographic and clinical characteristics overall and by degree of severitya

Characteristic	Overall (n=624)	Mild (n=110)	Moderate (n=297)	Severe (n=207)	P-valueb
Age, years					0.0293
Mean (SD)	55.5 (13.7)	58.3 (15.1)	55.7 (13.2)	53.6 (13.3)
Sex, n (%)					0.0222
Male	346 (55.4)	71 (64.5)	169 (56.9)	101 (48.8)
Female	278 (44.6)	39 (35.5)	128 (43.1)	106 (51.2)
Race, n (%)					0.0015
Missing	11 (1.8)	1 (0.9)	6 (2.0)	4 (1.9)
American Indian or Alaska Native	9 (1.4)	1 (0.9)	3 (1.0)	5 (2.4)
Asian	5 (0.8)	1 (0.9)	2 (0.7)	2 (1.0)
Black or African American	100 (16.0)	13 (11.8)	37 (12.5)	47 (22.7)
White	448 (71.8)	89 (80.9)	230 (77.4)	122 (58.9)
Multiracial	11 (1.8)	2 (1.8)	4 (1.3)	5 (2.4)
Other	40 (6.4)	3 (2.7)	15 (5.1)	22 (10.6)
Ethnicity, n (%)					0.0151
Missing	28 (4.5)	5 (4.5)	10 (3.4)	12 (5.8)
Hispanic	53 (8.5)	5 (4.5)	21 (7.1)	27 (13.0)
Non-Hispanic	543 (87.0)	100 (90.9)	266 (89.6)	168 (81.2)
Education level, n (%)					<0.0001
Missing	15 (2.4)	2 (1.8)	6 (2.0)	7 (3.4)
Up to high school/GED	238 (38.1)	20 (18.2)	106 (35.7)	106 (51.2)
Beyond high school	371 (59.5)	88 (80.0)	185 (62.3)	94 (45.4)
Employment status, n (%)					<0.0001
Missing	12 (1.9)	4 (3.6)	3 (1.0)	5 (2.4)
Employed for pay	118 (18.9)	30 (27.3)	64 (21.5)	24 (11.6)
Disabled	294 (47.1)	27 (24.5)	131 (44.1)	129 (62.3)
Retired	147 (23.6)	40 (36.4)	74 (24.9)	30 (14.5)
Unemployed	36 (5.8)	6 (5.5)	16 (5.4)	14 (6.8)
Other	17 (2.7)	3 (2.7)	9 (3.0)	5 (2.4)
BPI-SF Pain Severity Index					N/A
n	614	110	297	207
Mean (SD)	5.5 (2.2)	2.0 (1.1)	5.2 (0.8)	7.7 (1.1)
Time since first NeP symptoms, years					0.0330
n	619	109	296	204
Mean (SD)	9.5 (8.2)	7.8 (6.5)	9.6 (8.5)	10.1 (8.5)
Time since NeP diagnosis, years					0.0059
n	623	110	296	207
Mean (SD)	7.8 (6.8)	6.3 (5.9)	7.9 (6.8)	8.5 (7.2)
Able to walk, n (%)					0.2720
Missing	2 (0.3)	1 (0.9)	0 (0.0)	1 (0.5)
No	74 (11.9)	8 (7.3)	38 (12.8)	27 (13.0)
Health insurance, n (%)					N/A
Missing	1 (0.2)	1 (0.9)	0 (0.0)	0 (0.0)
Yes	582 (93.2)	101 (91.8)	277 (93.3)	194 (93.7)
NeP prescription coverage, n (%)					0.1116
Missing	5 (0.8)	3 (2.7)	2 (0.7)	0 (0.0)
Yes	545 (87.3)	95 (86.4)	266 (89.6)	174 (84.1)
Number of comorbid conditionsc					<0.0001
Mean (SD)	3.2 (2.1)	2.5 (1.7)	3.0 (2.1)	3.8 (2.2)

Notes:

a Scores on the Brief Pain Inventory Pain Severity scale were used to classify average pain severity; ten subjects did not respond to all items needed to calculate a BPI Pain Severity Index score and thus were not included in the pain severity analysis

b P-values across pain severity levels are from the Kruskal–Wallis test for continuous variables; chi-squared test for number of comorbid conditions, and Fisher’s Exact test for the remaining categorical variables and are based on nonmissing data

c among subjects with at least one comorbid condition (overall, n=515; mild, n=87; moderate, n=241; severe, n=180). A summary of demographic and clinical characteristics also appears in Schaefer et al.²⁶ Their paper “Burden of illness associated with peripheral and central neuropathic pain among adults seeking treatment in the United States: a patient-centered evaluation” was first published in Pain Medicine, Copyright ©2014. Pain Medicine is published by Wiley-Blackwell, Inc. on behalf of the American Academy of Pain Medicine.²⁶

Abbreviations: BPI-SF, Brief Pain Inventory Short Form; GED, General Educational Diploma; NeP, neuropathic pain; SD, standard deviation; N/A, not available.

Figure 2 Proportion of subjects prescribed medications to manage neuropathic pain by pain severity level.^a

Notes: Scores on the Brief Pain Inventory were used to classify average pain severity; ten subjects did not respond to all items needed to calculate a pain severity score and thus were not included in the pain severity analysis. ^aThe figure includes all reported classes, excluding miscellaneous agents, with ≤2% of subjects prescribed one or medications in the class. ^bOpioids (all) include strong short-acting opioids, long-acting opioids, and weak short-acting opioids; subjects may be taking more than one opioid.
Abbreviations: AED, antiepileptic drug; NSAIDs, nonsteroidal anti-inflammatory drugs; SNRIs, serotonin-norepinephrine reuptake inhibitors; TCAs, tricyclic antidepressants.

Table 4 Health care resource utilization for neuropathic pain stratified by pain severitya

NeP-related HRU	Overall (n=624)	Mild (n=110)	Moderate (n=297)	Severe (n=207)	P-valueb
Number of NeP medications prescribed in past 6 months					<0.0001
Mean (SD)	2.0 (1.4)	1.3 (1.1)	2.1 (1.4)	2.3 (1.5)
Median (range)	2 (0–9)	1 (0–5)	2 (0–7)	2 (0–9)
Number of nonprescription medications used in past 4 weeks					0.0022
Mean (SD)	0.9 (1.2)	0.6 (1.1)	1.0 (1.3)	1.0 (1.2)
Median (range)	0 (0–5)	0 (0–5)	1 (0–5)	1 (0–5)
Physician office visits in past 6 months					0.0001
Mean (SD)	3.3 (2.6)	2.4 (2.2)	3.4 (2.6)	3.6 (2.7)
Median (range)	2 (0–10)	2 (0–10)	3 (0–10)	3 (0–10)
Nonphysician office visits in past 6 months					0.5805
Mean (SD)	0.2 (1.3)	0.2 (0.6)	0.2 (0.7)	0.3 (2.1)
Median (range)	0 (0–27)	0 (0–3)	0 (0–6)	0 (0–27)
Tests and procedures in past 6 months					0.8842
Mean (SD)	0.8 (1.7)	0.7 (1.4)	0.8 (1.8)	0.8 (1.7)
Median (range)	0 (0–13)	0 (0–7)	0 (0–13)	0 (0–10)
Hospitalizations in past 6 months					0.0844
Mean (SD)	0.0 (0.1)	0.0 (0.0)	0.0 (0.1)	0.0 (0.2)
Median (range)	0 (0–2)	0 (0)	0 (0–1)	0 (0–2)
Emergency room visits in past 6 months					0.1056
Mean (SD)	0.0 (0.2)	0.0 (0.0)	0.0 (0.2)	0.0 (0.2)
Median (range)	0 (0–2)	0 (0)	0 (0–2)	0 (0–1)
Hospital outpatient visits in past 6 months					0.0071
Mean (SD)	0.0 (0.1)	0.0 (0.0)	0.0 (0.0)	0.0 (0.2)
Median (range)	0 (0–2)	0 (0)	0 (0)	0 (0–2)

Notes: Resource use data in this table are based on information recorded on the case report form by the physician and/or site.

a Scores on the Brief Pain Inventory were used to classify average pain severity; ten subjects did not respond to all items needed to calculate a pain severity score and thus were not included in the pain severity analysis

b Kruskal–Wallis test for continuous variables across pain severity categories.

Abbreviations: HRU, health resource utilization; NeP, neuropathic pain; SD, standard deviation.

Figure 3 Impact of neuropathic pain on employment status by pain severity level.

Notes: Scores on the Brief Pain Inventory were used to classify average pain severity; ten subjects did not respond to all items needed to calculate a pain severity score and thus were not included in the pain severity analysis.

Figure 4 Impact of neuropathic pain on productivity and daily activity evaluated using the WPAI questionnaire, by pain severity level.

Notes: Scores on the Brief Pain Inventory were used to classify average pain severity; ten subjects did not respond to all items needed to calculate a pain severity score and thus were not included in the pain severity analysis. Overall WPAI was measured on 0%–100% scale. ^aBased on subjects employed for pay who completed the WPAI (n=108, overall; n=29, mild; n=60, moderate; n=19, severe); ^bbased on all subjects who responded to this question (n=612, overall; n=108, mild; n=294, moderate; n=203, severe).
Abbreviation: WPAI, Work Productivity and Activity Impairment.

Figure 5 Adjusted least squares mean estimates for annualized costs per subject from multiple linear regression adjusted for confounding demographic and clinical variables.

Notes: Scores on the Brief Pain Inventory were used to classify average pain severity; ten subjects did not respond to all items needed to calculate a pain severity score and thus were not included in the pain severity analysis. *Covariates remaining in the model were: age, pain severity, time since diagnosis, insurance coverage, and comorbidities (headache/migraine, fibromyalgia, restless leg syndrome, irritable bowel syndrome, cognitive dysfunction, and other) for direct costs to payer; pain severity, race, employment status, and comorbidities (chronic fatigue syndrome, anxiety, and other) for direct costs to subjects; age, pain severity, Hispanic ethnicity, walking ability, time since diagnosis, employment status, worker’s compensation, and comorbidities (fibromyalgia, restless leg syndrome, and anxiety) for indirect costs; and age, pain severity, race, time since diagnosis, employment status, prescription coverage, worker’s compensation, and comorbidities (fibromyalgia, restless leg syndrome, anxiety, and other) for total costs. ^aP<0.0001 for the model; ^bP<0.05 versus mild; ^cP<0.05 versus moderate.

Figure 6 Mean annualized adjusted cost per subject varied by neuropathic pain condition.^a

Notes: ^aSignificant differences were observed across NeP type for total direct costs to payers (P<0.0001), total direct costs to subjects (P<0.0001), total indirect costs (P<0.0001), and grand total costs (P<0.0001). Adjusted least squares mean estimates from multiple linear regression adjusted for confounding demographic and clinical variables. Specifically, covariates remaining in the overall model for direct costs to payers: age, pain severity, time since diagnosis, insurance coverage, and comorbidities (headache/migraine, fibromyalgia, restless leg syndrome, irritable bowel syndrome, cognitive dysfunction, and other); for direct costs to subjects: race, pain severity, employment status, and comorbidities (chronic fatigue syndrome, anxiety, and other); for total indirect direct costs: age, Hispanic ethnicity, walking ability, pain severity, time since diagnosis, employment status, worker’s compensation, and comorbidities (fibromyalgia, restless leg syndrome, and anxiety); and for grand total costs: age, race, pain severity, time since diagnosis, prescription coverage, employment status, worker’s compensation, and comorbidities (fibromyalgia, restless leg syndrome, anxiety, and other). Data by NeP type have been published previously (see pDPN,¹³ SCI-NeP,³⁰ PTPS-NeP,³¹ and SFN³²); in these publications models were used to examine costs within each sub-group, and as such adjusted costs differ somewhat from those presented herein.
Abbreviations: CLBP-NeP, chronic low back pain with neuropathic pain; HIV-NeP, human immunodeficiency virus-related peripheral neuropathic pain; pDPN, painful diabetic peripheral neuropathy; PTPS-NeP, post-trauma/post-surgical neuropathic pain; SCI-NeP, spinal cord injury with neuropathic pain; SFN, painful peripheral neuropathy with small fiber involvement.

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