Economic Implications of Potential Drug–Drug Interactions in Chronic Pain Patients

Robert Taylor Jr; Joseph V Pergolizzi Jr; R Amy Puenpatom; Kent H Summers

Expert Rev Pharmacoeconomics Outcomes Res. 2013;13(6):725-734.

Review Limitations

Several limitations should be considered in interpreting the data presented in this review. First, the review presents data from five studies, with only three studies providing an estimate of the prevalence of DDIs. Results of these studies may not represent the entire pain patient population. Second, the studies utilized only two Market Scan databases that were the Commercial database and the Medicare Supplemental database. Although the databases are large (i.e., covering more than 100 million members), it may not represent subpopulation such as those from medium and small firms, the Medicaid population and retirees without Medicare supplemental insurance provided by employers. In addition, the costs of DDEs from the older population could be slightly higher compared with the DDE costs of the >65 years old US population because the Medicare supplemental database includes payments information from self-insured companies. Since this study presents the cost results in a relative value and not absolute numbers, the upward bias could be nearly diminished.

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Next Section

Abstract and Introduction
Review Methodology
Prevalence of DDEs
Association of DDEs & Age
Association Between DDEs & Health Service Use
Relationship Between DDEs & Cost
Polypharmacy
Interventions
Expert Commentary
Review Limitations
Five-year View
References
Sidebar

Table 1. Background information on five retrospective claims database studies in patients with chronic pain.
Study (year)	Patients (n)	Patient population	Demographics	DDE definition	Total DDEs (n)	Ref.
Pergolizzi et al. (2011)	100,159	Chronic lower back pain	Female: 60% From South US region: 43% >45 years old: 77.8%	DDE is defined as exposure to a specific opioid metabolized through the CYP450 system and concomitant therapy with another CYP450- metabolized medication with at least a one-day overlap in supplies	27,289	[27]
Pergolizzi et al. (2011)	102,016	Osteoarthritis	Female: 66.8% From South US region: 37.2% >45 years old: 93.1%	A DDE is defined exposure to a specific opioid metabolized by the CYP450 system and concomitant therapy with another CYP450- metabolized medication at least a one-day overlap in days supplied within the 30-day window of time immediately following the index date	26,457	[28]
Pergolizzi et al. (2011)	43,686	Osteoarthritis	Females (after propensity score matching) <65 years old: 63.8% >65 years old: 70.5% Region <65 years old 46% >65 years old 28% Mean age <65 year cohort: 53.6 years Mean age >65 year cohort: 76.8 years	A DDE is defined exposure to a specific opioid metabolized by the CYP450 system and concomitant therapy with another CYP450- metabolized medication at least a one-day overlap in days supplied within the 30-day window of time immediately following the index date	4489	[30]
Pergolizzi et al. (2011)	42,742^†	Chronic low back pain	Females (after propensity score matching) <65 years old: 58.5% >65 years old: 67.9% Region (South) <65 years old: 47.3% >65 years old: 31.6% Mean age <65 year cohort: 48.45 years Mean age >65 year cohort: 76.2 years	A DDE is defined exposure to a specific opioid metabolized by the CYP450 system and concomitant therapy with another CYP450- metabolized medication at least a one-day overlap in days supplied within the 30-day window of time immediately following the index date	5313^†	[29]
Summers et al.(2011)	322,343^† 170,086^‡	Chronic pain excluding pregnancy-related claims, health maintenance organization enrollment or cancer claims (exception nonmelanoma skin cancer)	DDE vs no-DDE Age^†: 49.9 versus 47.8 years Female^†: 68.6 vs 49.3% Region (South)^†: 50.2 vs 47.8 Age^‡ : 50.0 vs 49.1 years Female^‡ : 62.5 vs 62.5% Region (South)^‡ : 49.5 vs 49.5%	A DDE is defined exposure to a specific opioid metabolized by the CYP450 system and concomitant therapy with another CYP450- metabolized medication at least a one-day overlap in days supplied within the 30-day window of time immediately following the index date	114,185^† 85,043^‡	[31]

^†Before propensity score matching;
^‡After propensity score matching.
DDE: Drug–drug exposure.

Table 2. Total 6-month payments (medical and prescription drugs) in noncancer patients, chronic low back painand osteoarthritis patients in both drug–drug exposures and non-drug–drug exposures groups grouped by older and younger patients.
	DDE		No DDE		Mean difference	p-value
	Mean (SD)	Median	Mean (SD)	Median	Mean difference	p-value
General population (18–64 year old)
Older and younger	$8165 ($11,357)	$4498	$7498 ($11,688)	$3751	$667	<0.0001
cLBP
Older	$7806 ($7859)	$5584	$7043 ($8001)	$5038	$763	0.013
Younger	$7086 ($8370)	$4810	$6353 ($8352)	$4089	$733	<0.001
OA
Older	$9829 ($11,721)	$5589	$8622 ($10,131)	$5056	$1207	0.001
Younger	$9469 ($12,192)	$4992	$8382 ($14,078)	$4219	$1087	0.004

Patients with DDE had significantly higher payments in all groups regardless of age.
*p-values were calculated based on bias-adjusted bootstrap t-test for all continuous data because of skewed distribution of the cost data [57]. To analyze categorical variables, the chi square test was used.
cLBP: Chronic low back pain; DDE: Drug–drug exposure; OA: Osteoarthritis; SD: Standard deviation.

Table 3. Total medical and prescription 6-month payments for noncancer pain patients, chronic low back pain, and osteoarthritis patients in both drug–drug exposures and non-drug–drug exposures groups grouped by older and younger patients.
	DDE		No DDE		Mean difference	p-value
	Mean (SD)	Median	Mean (SD)	Median	Mean difference	p-value
General population (18–64 year old)
Medical	$5520 ($10,505)	$1880	$5222 ($10,689)	$1700	$298	<0.0001
Rx	$2646 ($3262)	$1736	$2276 ($3907)	$1159	$369	<0.0001
cLBP
65 years and older (medical payments)	$5324 ($7084)	$3043	$4757 ($7248)	$2753	$567	0.045
65 years and older (Rx payments)	$2482 ($2481)	$1963	$2286 ($2521)	$1682	$196	0.044
Younger (18–64 years; medical)	$5045 ($7188)	$2872	$4788 ($7576)	$2634	$257	0.101
Younger (18–64 years; Rx)	$2041 ($2706)	$1187	$1565 ($2349)	$821	$476	<0.0001
OA
Older (medical)	$7312 ($11,192)	$3106	$6242 ($9489)	$2574	$1070	0.002
Older (Rx)	$2517 ($2484)	$1952	$2381 ($2608)	$1797	$137	0.106
Younger (medical)	$7175 ($11,396)	$2814	$6574 ($13,508)	$2546	$601	0.097
Younger (Rx)	$2294 ($2862)	$1452	$1808 ($2299)	$1090	$486	<0.001

Patients with DDE had higher payments for both cLBP and OA groups and regardless of age group.
*p-values were calculated based on bias-adjusted bootstrap t-test for all continuous data because of skewed distribution of the cost data [57]. To analyze categorical variables, the chi square test was used.
cLBP: Chronic lower back pain; DDE: Drug–drug exposure; OA: Osteoarthritis.
Data taken from [29–31].