Use of prescription opioids with abuse-deterrent technology to address opioid abuse

Figures & data

Figure 1. Sample selection.

Table 1. Opioid utilization patterns and differences in rates of diagnosed opioid abuse following the introductions of reformulated ER oxycodone and ER oxymorphone.

A. Following the introduction of reformulated ER oxycodone
	ER oxycodone patients (N = 15,162)		ER oxycodone patients diagnosed with abuse during 15 month study period (N = 742)
Primary drug post-reformulation of ER oxycodone	N	%	Rate of Abuse	Relative Risk	p Value
Reformulated ER oxycodone	10,520	69.4	3.5%
Other ER/LA opioid without abuse-deterrent technology	3230	21.3	6.7%	1.89	<0.001
No ER/LA opioids	1412	9.3	10.9%	3.08	<0.001
IR/SA opioids	1073	7.1	11.3%	3.19	<0.001
No IR/SA or ER/LA opioids	339	2.2	9.7%	2.75	<0.001
B. Following the introduction of reformulated ER oxymorphone
	ER oxymorphone patients (N = 2285)		ER oxymorphone patients diagnosed with abuse during 15 month study period (N = 63)
Primary drug post-reformulation of ER oxymorphone	N	%	Rate of Abuse	Relative Risk	p Value
Reformulated ER oxymorphone	1149	50.3	2.1%
Reformulated ER oxycodone	157	6.9	2.5%	1.22	0.766
Other ER/LA opioid without abuse-deterrent technology	581	25.4	2.6%	1.24	0.498
No ER/LA opioids	398	17.4	5.0%	2.41	0.004
IR/SA opioids	329	14.4	4.6%	2.18	0.019
No IR/SA or ER/LA opioids	69	3.0	7.2%	3.47	0.021

Opioid abuse referred to both abuse and dependence and was identified using the following ICD-9-CM diagnosis codes: 305.5x, 304.0x, 304.7x, 965.00, 965.02, and 965.09. p Values for rates of abuse were calculated using Pearson’s chi-squared tests with reformulated ER oxycodone as the reference group (Panel A) and Fisher’s exact tests with reformulated ER oxymorphone as the reference group (Panel B).

Table 2. Sensitivity analysis: 60% threshold for defining a patient’s primary ER/LA opioid (opioid utilization patterns and differences in rates of diagnosed opioid abuse following the introductions of reformulated ER oxycodone and ER oxymorphone).

A. Following the introduction of reformulated ER oxycodone
	ER oxycodone patients (N = 15,316)		ER oxycodone patients diagnosed with abuse during 15 month study period (N = 762)
Primary drug post-reformulation of ER oxycodone	N	%	Rate of Abuse	Relative Risk	p Value
Reformulated ER oxycodone	11,228	73.3	3.6%
Other ER/LA opioid without abuse-deterrent technology	2653	17.3	7.5%	2.07	<0.001
No ER/LA opioids	1435	9.4	11.1%	3.10	<0.001
B. Following the introduction of reformulated ER oxymorphone
	ER oxymorphone patients (N = 2335)		ER oxymorphone patients diagnosed with abuse during 15 month study period (N = 64)
Primary drug post-reformulation of ER oxymorphone	N	%	Rate of Abuse	Relative Risk	p Value
Reformulated ER oxymorphone	1246	53.4	2.1%
Reformulated ER oxycodone	163	7.0	2.5%	1.18	0.771
Other ER/LA opioid without abuse-deterrent technology	526	22.5	2.7%	1.28	0.485
No ER/LA opioids	400	17.1	5.0%	2.40	0.004

Opioid abuse referred to both abuse and dependence and was identified using the following ICD-9-CM diagnosis codes: 305.5x, 304.0x, 304.7x, 965.00, 965.02, and 965.09. p Values for rates of abuse were calculated using Pearson’s chi-squared tests with reformulated ER oxycodone as the reference group (Panel A) and Fisher’s exact tests with reformulated ER oxymorphone as the reference group (Panel B).

Table 3. Sensitivity analysis: 80% threshold for defining a patient’s primary ER/LA opioid (opioid utilization patterns and differences in rates of diagnosed opioid abuse following the introductions of reformulated ER oxycodone and ER oxymorphone).

A. Following the introduction of reformulated ER oxycodone
	ER oxycodone patients (N = 14,957)		ER oxycodone patients diagnosed with abuse during 15 month study period (N = 723)
Primary drug post-reformulation of ER oxycodone	N	%	Rate of Abuse	Relative Risk	p Value
Reformulated ER oxycodone	10,015	67.0	3.5%
Other ER/LA opioid without abuse-deterrent technology	3566	23.8	6.3%	1.83	<0.001
No ER/LA opioids	1376	9.2	10.9%	3.15	<0.001
B. Following the introduction of reformulated ER oxymorphone
	ER oxymorphone patients (N = 2227)		ER oxymorphone patients diagnosed with abuse during 15-month study period (N = 52)
Primary drug post-reformulation of ER oxymorphone	N	%	Rate of Abuse	Relative Risk	p Value
Reformulated ER oxymorphone	1093	49.1	2.0%
Reformulated ER oxycodone	145	6.5	2.8%	1.37	0.535
Other ER/LA opioid without abuse-deterrent technology	605	27.2	2.6%	1.31	0.397
No ER/LA opioids	384	17.2	4.7%	2.33	0.009

Opioid abuse referred to both abuse and dependence and was identified using the following ICD-9-CM diagnosis codes: 305.5x, 304.0x, 304.7x, 965.00, 965.02, and 965.09. p Values for rates of abuse were calculated using Pearson’s chi-squared tests with reformulated ER oxycodone as the reference group (Panel A) and Fisher’s exact tests with reformulated ER oxymorphone as the reference group (Panel B).

Table 4. Sensitivity analyses: alternative definitions of opioid abuse and alternative time periods over which abuse diagnoses could occur (differences in rates of diagnosed opioid abuse following the introductions of reformulated ER oxycodone and ER oxymorphone).

A. Following the introduction of reformulated ER oxycodone (sensitivity analysis: abuse vs. dependence diagnoses)
	ER oxycodone patients diagnosed with abuse during 15 month study period (abuse-only ICD-9-CM codes) (N = 130)			ER oxycodone patients diagnosed with dependence during 15 month study period (dependence-only ICD-9-CM codes) (N = 662)
Primary drug post-reformulation of ER oxycodone	Rate of Abuse	Relative Risk	p Value	Rate of Abuse	Relative Risk	p Value
Reformulated ER oxycodone	0.6%			3.2%
Other ER/LA opioid without abuse-deterrent technology	1.1%	1.99	<0.001	5.9%	1.86	<0.001
No ER/LA opioids	2.5%	4.42	<0.001	9.8%	3.11	<0.001
B. Following the introduction of reformulated ER oxycodone (sensitivity analysis: 6 month pre-reformulation vs. 9 month post-reformulation)
	ER oxycodone patients diagnosed with abuse during 6 month pre-reformulation (N = 372)			ER oxycodone patients diagnosed with abuse during 9 month post-reformulation (N = 372)
Primary drug post-reformulation of ER oxycodone	Rate of Abuse	Relative Risk	p Value	Rate of Abuse	Relative Risk	p Value
Reformulated ER oxycodone	1.9%			2.3%
Other ER/LA opioid without abuse-deterrent technology	3.0%	1.58	<0.001	4.9%	2.14	<0.001
No ER/LA opioids	5.3%	2.79	<0.001	7.9%	3.42	<0.001

Panel A: Opioid abuse was identified using the following ICD-9-CM diagnosis codes: 305.5x, 965.00, 965.02, and 965.09. Opioid dependence was identified using the following ICD-9-CM diagnosis codes: 304.0x and 304.7x. The patients diagnosed with abuse using the abuse-only ICD-9 CM codes and the patients diagnosed with dependence using the dependence-only ICD-9-CM codes are not mutually exclusive, as some patients may have been diagnosed with both opioid abuse and dependence, so the number of patients diagnosed with abuse and the number of patients diagnosed with abuse do not sum to the total number of patients diagnosed with abuse or dependence using both abuse and dependence ICD-9-CM codes. p Values for rates of abuse or dependence were calculated using Pearson’s chi-squared tests with reformulated ER oxycodone as the reference group.

Panel B: Opioid abuse referred to both abuse and dependence and was identified using the following ICD-9-CM diagnosis codes: 305.5x, 304.0x, 304.7x, 965.00, 965.02, and 965.09. The 9 month period post-reformulation included the 3 month transition period and the 6 month post-reformulation period. The patients diagnosed with abuse in the 6 month pre-reformulation period and the patients diagnosed with abuse in the 9 month period post-reformulation are not mutually exclusive, as some patients may have been diagnosed with abuse in both periods, so the number of abusers in each of these periods does not sum to the total number of abusers in the 15 month period. p Values for rates of abuse were calculated using Pearson’s chi-squared tests with reformulated ER oxycodone as the reference group.

Figure 2. Sensitivity analyses for ER oxycodone patients. *The core analysis uses a 70% threshold for the definition of a primary ER/LA opioid, a 15 month time period for abuse diagnosis, and both abuse and dependence ICD-9-CM diagnosis codes. p Values were <0.001 for all relative risks shown above.