R E S E A R C H
`
`A Comparison of Daily Average Consumption (DACON) of
`Oxycodone and Oxymorphone Long-Acting Oral Tablets
`
`Mark Rubino, BS Pharm, MHA; Kent H. Summers, PhD; R. Amy Puenpatom, PhD;
`Chunmay Fu, MS; Robert L. Ohsfeldt, PhD; and Rami H. Ben-Joseph, PhD
`
`ABSTRACT
`BACKGROUND: The utilization of high-potency opioids is an important com-
`ponent of chronic pain management, and appropriate utilization of these
`medicines is a common concern of payers. Two of the most commonly
`prescribed oral long-acting opioids, oxycodone controlled-release (CR) and
`oxymorphone extended-release (ER), are FDA-approved for twice-daily
`dosing, which equates to a theoretical average consumption (DACON) of 2
`tablets per day. DACON values greater than 2 have budget and policy impli-
`cations for managed care pharmacists.
`OBJECTIVES: To assess from the perspective of the pharmacy benefit deci-
`sion maker the DACONs of oxycodone CR and oxymorphone ER.
`METHODS: The main outcome measure for the analysis was DACON.
`Pharmacy and medical claims data from a large commercially insured pop-
`ulation (i3 InVision Data Mart database) were analyzed to identify patients
`with at least 1 pharmacy claim for either oxycodone CR or oxymorphone
`ER from July 1, 2007, to September 30, 2009. After an initial 30-day titra-
`tion period, all subjects included in the study had 1 or more claims totaling
`at least a 90-day supply of either study drug during the subsequent 90
`days (DACON measurement period). Patients were excluded if there was
`evidence of a switch from one to the other study opioid during the 90-day
`measurement period. There were no limitations on the use of other opi-
`oids, either short- or long-acting, during either the DACON measurement
`period or the previous 6 months (baseline period). In addition, patients
`were excluded if the enrollee was younger than 18 years old, pregnant, did
`not have continuous insurance coverage for the 6 months before and after
`the start of the 90-day DACON measurement, or were enrolled in an HMO
`plan. Bivariate analyses were performed with between-group differences
`in DACON values assessed using t-tests and Wilcoxon rank sum tests.
`Patient characteristics including age, sex, geographic location, and base-
`line Charlson Comorbidity Index (CCI) for each drug group were evaluated
`descriptively using either the Pearson chi-square test or t-test. Multivariate
`analyses were conducted using generalized linear models (GLM) to adjust
`for the observed heterogeneity among patients in the observational data-
`base. For the GLMs, the gamma distribution and log link function were
`chosen to account for non-normal distributions of DACON. Independent
`variables included study drug, tablet strengths, age, sex, CCI, the maximum
`days gap between prescription refills during the DACON measurement
`period, and other opioid medication use. Several sensitivity analyses were
`conducted to verify all findings.
`RESULTS: The final analyses were conducted on 6,567 oxycodone CR
`patients and 796 oxymorphone ER patients. The unadjusted DACON mean
`value for the highest strength of oxycodone CR 80 milligrams (mg) was 3.9,
`compared with 2.9 for oxymorphone ER 40 mg (P < 0.001); mean DACON
`values were 3.0 versus 2.4, respectively, for lower strengths (P < 0.001)
`and 3.1 versus 2.5 for all strengths (P < 0.001). After adjusting for age, sex,
`CCI, maximum gap days, and other opioid medication use, a risk-adjusted
`mean difference in DACON remained, with oxycodone CR patients receiving
`on average 0.6 tablets more per day than those dispensed oxymorphone ER
`
`(P < 0.001). The direction, magnitude, and statistical significance of these
`differences were essentially unchanged in sensitivity analyses.
`CONCLUSIONS: On average during a 90-day time period, patients taking
`oxymorphone ER consumed 0.6 fewer tablets per day than did patients tak-
`ing oxycodone CR. Further research is necessary to see if this difference
`amounts to cost savings for health plans that provide prescription reim-
`bursement for patients with chronic pain syndromes.
`
`J Manag Care Pharm. 2011;17(5):367-76
`
`Copyright © 2011, Academy of Managed Care Pharmacy. All rights reserved.
`
`What is already known about this subject
`• Daily average consumption (DACON), the term often used to
`describe the average number of dosage units dispensed per day,
`has been studied for several chronic diseases using retrospective
`analyses of administrative claims data. Two DACON analyses
`have been performed for long-acting opioids using prescription
`claims databases, one for patients with lower back pain and
`another in a California Medicaid population.
`• In an observational study of commercially insured patients with
`lower back pain, Berner et al. (2011) reported that DACON for the
`maximum strength tablet of oxycodone controlled-release (CR)
`80 mg was 3.9 tablets per day, which was significantly higher
`than the DACON of 2.9 for equipotent oxymorphone extended-
`release (ER) maximum strength tablet of 40 mg (P < 0.001).
`• In the study of the California Medicaid pharmacy claims by
`Malkin et al. (2002), the mean number of oxycodone CR tablets
`per day across all strengths was 3.4.
`
`What this study adds
`• This study assessed utilization patterns in a large, managed care,
`commercially insured sample and calculated DACON for subjects
`taking oxycodone CR (n = 6,567) versus those taking oxymor-
`phone ER (n = 796).
`• The unadjusted DACON mean value for the highest strength of
`oxycodone CR 80 mg was 3.9, compared with 2.9 for oxymor-
`phone ER 40 mg (P < 0.001); mean DACON values were 3.0 versus
`2.4, respectively, for lower strengths (P < 0.001) and 3.1 versus 2.5
`for all strengths (P < 0.001).
`• After adjusting for potential confounders, a risk-adjusted mean
`difference in DACON remained, with oxycodone CR patients
`receiving on average 0.6 tablets more per day than those dis-
`pensed oxymorphone ER (P < 0.001).
`
`www.amcp.org Vol. 17, No. 5
`
`June 2011
`
`JMCP Journal of Managed Care Pharmacy 367
`
`ENDO - Ex. 2059
`Amneal v. Endo
`IPR2014-00360
`
`

`

`A Comparison of Daily Average Consumption (DACON) of Oxycodone and Oxymorphone Long-Acting Oral Tablets
`
`Opioid analgesics are indicated for moderate to severe
`
`pain and are an important component of chronic pain
`management. In the United States in 2009, 62% of out-
`patient prescriptions for long-acting opioid (LAO) analgesics
`were used for musculoskeletal conditions and injuries, 14%
`for headaches and nerve pain, and 11% for pain associated
`with neoplastic disease.1 LAOs represented approximately 9%
`of all U.S. outpatient opioid prescriptions in 2009.1 The global
`market for all opioids was $9.6 billion in 2008 and is expected
`to grow to almost $12 billion by 2018.1-4 Commercial and gov-
`ernment payers have identified this class of medicines as an
`opportunity for cost and quality management to curb inappro-
`priate utilization with step-therapy, quantity limits, and prior
`authorization programs. These programs have focused on the
`management of chronic pain with LAOs.5-7
`Two commonly used, oral, branded LAOs are OxyContin
`(oxycodone controlled-release [CR]) and Opana ER (oxy-
`morphone extended-release). Unpublished data suggest that
`these 2 products had prescription shares of 86.4% and 11.4%,
`respectively, in the branded LAO market as of October 2010.8
`In assessments of the utilization of these 2 products, it may
`be helpful to consider daily average consumption (DACON),
`the term often used to describe the average number of dosage
`units dispensed per day based on claims data. The term has
`been used in association with the treatment of chronic dis-
`eases, such as diabetes,9 hypertension,10 and arthritis.11 Both
`oxycodone CR and oxymorphone ER are U.S. Food and Drug
`Administration (FDA)-approved for twice-daily dosing,12,13
`which equates to a theoretical DACON of 2 tablets per day.
`DACON values greater than 2 have budget and policy implica-
`tions for managed care pharmacists.
`A study by Malkin et al. (2002) compared pharmacy claims
`for oxycodone CR and fentanyl transdermal patches with dose
`administration guidelines in each manufacturer’s prescribing
`information.14 For all dosage strengths of oxycodone CR, the
`average number of tablets supplied per day was 3.4, ranging
`from 2.9 for the 10 milligram (mg) tablets to 5.2 for the 80
`mg tablets. This analysis measured all pharmacy claims for
`these medications regardless of the number of claims for each
`patient. As such, the selection criteria did not include a require-
`ment for chronic use.
`A recent retrospective analysis of administrative claims
`data for commercially insured patients, conducted by Berner
`et al. (2011), compared the DACON of oxycodone CR and
`oxymorphone ER in patients with lower-back pain.15 DACON
`was 3.2 tablets per day for all strengths of oxycodone CR,
`compared with 2.7 tablets per day for all strengths of oxy-
`morphone ER (P < 0.01). DACON for the maximum strength
`tablet of oxycodone CR 80 mg was 3.9 tablets per day, which
`was significantly higher than the DACON of 2.9 for equipotent
`oxymorphone ER maximum strength tablet of 40 mg (P < 0.01).
`Berner et al. estimated that if a health plan were to substitute
`
`oxymorphone ER 40 mg tablets for oxycodone CR 80 mg
`tablets in the 688 patients in their analysis, the monthly cost
`difference would be $217,985 based on the DACON differ-
`ence, assuming per tablet wholesale acquisition costs (WAC) of
`$10.96 and $10.83, respectively.
`Since these drugs are indicated for moderate to severe pain
`regardless of etiology14,15 and most managed care pharmacists
`do not have access to or include diagnostic codes in their drug
`utilization evaluations, a broader analysis using information
`readily available to managed care professionals might be more
`relevant to payers than a disease-specific analysis.
`
`■■  Methods
`Study Scope
`We conducted a retrospective analysis of a database from
`United Healthcare, a large U.S. managed health care plan.
`The study data were gathered from a commercially insured
`population using the i3 InVision Data Mart database (Ingenix,
`Eden Prairie, MN). The database consists of aggregated medi-
`cal and pharmacy claims for more than 20 million members
`during the study period. This database was chosen because
`both oxycodone CR and oxymorphone ER were subject to
`the same formulary tier status and quantity limits, (i.e., tier 3
`coverage without prior authorization and equal quantity lim-
`its of 124 tablets per month). The study period encompassed
`dates of service from January 1, 2007, to March 31, 2010, in
`order to collect data for a sufficient number of patients with
`claims for the 2 study LAOs and provide a 6-month roll-in and
`a 6-month roll-out period to demonstrate continuous health
`plan coverage. The database consists of de-identified integrated
`records from outpatient, inpatient, pharmacy claims, lab result
`records, and enrollment data sets. Because all records were de-
`identified, Institutional Review Board approval for the study
`was not sought.
`
`Sample Selection and Characteristics
`The objective of the study was to measure DACON for each
`study drug (oxycodone CR or oxymorphone ER) for the treat-
`ment of chronic pain in usual practice. In the prescription drug
`claims data, there is no specific identification as to whether
`a prescription for a study drug was filled for treatment of an
`acute episode of pain or chronic pain. Accordingly, the days
`supplied for each prescription were used to infer whether treat-
`ment was for acute pain (generally less than 15 days supplied)
`or chronic pain (30 or more days supplied).
`Given that the focus of the study was on the use of opi-
`oids for chronic pain, the beginning of a treatment episode
`for chronic pain was defined as the first instance of a 30-day
`supply of the patient’s initial opioid therapy, identified using
`pharmacy claims with dates of service from July 1, 2007, to
`September 30, 2009 (Figure 1). The 30-day supply requirement
`could be satisfied by either an initial pharmacy claim with 30
`
`368 Journal of Managed Care Pharmacy
`
`JMCP
`
`June 2011 Vol. 17, No. 5 www.amcp.org
`
`

`

`A Comparison of Daily Average Consumption (DACON) of Oxycodone and Oxymorphone Long-Acting Oral Tablets
`
`FIGURE 1
`
`Study Sample Selection
`
`January 1, 2007
`
`July 1, 2007
`12 months continuous eligibility
`
`March 31, 2010
`
`Baseline covariate measurement period
`(180 days)
`
`Adjustment
`period
`(30 days)
`Initial 30-day claim
`
`DACON measurement period
`(90 days)
`
`DACON = daily average consumption.
`
`days supplied, or by multiple pharmacy claims for the initial
`opioid therapy with less than 30 days supplied, each closely
`proximate in time, such that the sum of the days supplied was
`at least 25 over the first 30 days after the date of the initial
`study drug fill. Patients were included if gap(s) between phar-
`macy claims were 5 days or less during the 30-day adjustment
`period. From the database, 26,921 oxycodone CR users and
`2,842 oxymorphone ER users satisfied the criteria for chronic
`opioid use.
`An additional sample restriction was that individuals with
`an initial pharmacy claim for oxycodone CR could not have
`a subsequent claim for oxymorphone ER (or vice versa) dur-
`ing the 120 days following the date of the initial study drug
`claim. A total of 29,308 patients satisfied these requirements:
`26,721 oxycodone CR users and 2,587 oxymorphone ER users
`(Figure 2). No sample exclusions relating to the use of opioids,
`other than the 2 study drugs, were applied. However, the use
`of short- or long-acting opioids during the 30 days prior to the
`DACON measurement period was measured and examined in
`all multivariate analysis.
`As shown in Figure 1, DACON was measured during the
`90-day period beginning 30 days after the initiation of the
`study opioid therapy. The rationale for skipping the first 30
`days of therapy when measuring DACON was an assumption
`that potential dosage modifications would be most likely to
`occur during the initial phase of a new treatment episode for
`chronic pain therapy. In terms of the measurement of DACON,
`the most relevant potential modification is a change in the
`number of units prescribed per day. Because the intent of the
`study was to measure DACON for “stable” chronic therapy, the
`first 30 days were excluded from the measurement of DACON.
`Focusing DACON measurement over a 90-day period is
`consistent with the current standard of care for chronic pain
`management according to treatment guidelines.16,17 All study
`patients were required to have a cumulative total of at least 90
`days supply for the initial study drug on 1 or more claims dur-
`ing the DACON measurement period.
`Patients younger than 18 years of age were also excluded, as
`
`were patients who might have been pregnant, identified using
`International Classification of Diseases, Ninth Revision, Clinical
`Modification (ICD-9-CM) codes 633, 640-646, 761, V23.2,
`V22, V61.5-V61.7, V72.40, or V72.42 in any diagnosis field on
`the claim. Individuals without continuous insurance coverage
`for the 6 months before and after the start of the 90-day mea-
`surement period were excluded, as were patients enrolled in a
`health maintenance organization (HMO) because some claims
`were missing due to capitated arrangements with certain phy-
`sicians. After all sample inclusion and exclusion criteria were
`applied, the final study cohort consisted of 6,567 oxycodone
`CR patients and 796 oxymorphone ER patients (Figure 2). As
`a sensitivity analysis, we also evaluated a subsample (n = 6,501
`oxycodone CR, n = 788 oxymorphone ER) after excluding
`patients representing the highest 1% of the DACON sample
`distribution.
`
`Calculation of DACON
`The DACON for each patient was calculated by dividing the
`total number of tablets dispensed during the 90-day DACON
`measurement period by 90 days. Measurement of total number
`of tablets dispensed was based on the sum of units supplied
`on all insurance claims submitted by all pharmacies during
`the 90-day DACON measurement period. For patients with a
`pharmacy claim for a study drug during the 90-day DACON
`measurement period with days supplied extending beyond the
`end of the DACON measurement period, the total number of
`tablets for the last pharmacy claim was converted to an aver-
`age number of tablets per day, with that daily average applied
`to the number of days between the final pharmacy claim and
`the end of the 90-day DACON measurement period. For days
`representing gaps between days supplied within the 90-day
`DACON period, a daily value of zero (0) units supplied was
`applied. For example, if a patient filled a 30-day prescription
`on day 1 of the DACON measurement period, and then filled
`another 30-day prescription on day 35 of the DACON period,
`there was a gap of 4 days (days 31 through 34), during which
`no units were supplied. No sample restriction relating to the
`
`www.amcp.org Vol. 17, No. 5
`
`June 2011
`
`JMCP Journal of Managed Care Pharmacy 369
`
`

`

`A Comparison of Daily Average Consumption (DACON) of Oxycodone and Oxymorphone Long-Acting Oral Tablets
`
`FIGURE 2
`
`Sample Selection Flowchart
`
`Patients with at least 1 pharmacy claim for oxycodone CR or
`oxymorphone ER from January 1, 2007, through March 31, 2010
`n = 87,956
`
`Patients with at least 1 pharmacy claim for oxycodone CR or
`oxymorphone ER from July 1, 2007, through September 30, 2009
`n = 68,618
`
`Patients with chronic oxycodone CR use
`(30-day supply of the patient’s initial oxycodone CR)
`n = 26,971
`
`Patients with chronic oxymorphone ER use
`(30-day supply of the patient’s initial oxymorphone ER)
`n = 2,842
`
`Oxycodone CR cohort — no oxymorphone ER claims for 120 days
`n = 26,721
`
`Oxymorphone ER cohort — no oxycodone CR claims for 120 days
`n = 2,587
`
`Oxycodone CR cohort — patients aged 18 years
`or older with continuous enrollmenta
`n = 11,436
`
`Oxymorphone ER cohort — patients aged 18
`years or older with continuous enrollmenta
`n = 1,190
`
`Oxycodone CR cohort — patients not pregnantb
`n = 11,345
`
`Oxymorphone ER cohort — patients not pregnantb
`n = 1,187
`
`Oxycodone CR cohort — patients not HMO-enrolled
`n = 9,905
`
`Oxymorphone ER cohort — patients not HMO-enrolled
`n = 1,101
`
`Oxycodone CR cohort — patients with at least 90 days
`supply during the DACON measurement periodc
`n = 6,567
`
`Oxymorphone ER cohort — patients with at least 90 days
`supply during the DACON measurement periodc
`n = 796
`
`aContinuous enrollment was measured 6 months prior to and after the start of the DACON measurement period.
`bPossible pregnancy was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes 633, 640-646, 761, V23.2, V22,
`V61.5-V61.7, V72.40, or V72.42 in any diagnosis field on the claim 6 months prior to and after the start of the DACON measurement period.
`cIndicates that patient had 1 or more claims with a cumulative days supply totaling at least 90 days during the 90-day DACON measurement period following the 30-day
`adjustment period.
`CR = controlled-release; DACON = daily average consumption; ER = extended-release; HMO = health maintenance organization.
`
`maximum number of gap days allowed was applied, as long as
`the cumulative days supplied for all pharmacy claims during
`the DACON period was at least 90 days. However, as part of the
`sensitivity analysis, DACON results for patients with different
`frequencies of maximum gap days are reported.
`Patients were assigned to dosage strength groups based on
`the dosage strength on the first day of the DACON measure-
`ment period. An equivalent potency assumption for the 2
`
`products was employed to provide potentially more relevant
`comparisons of DACON within similar dosage strengths. The
`equivalent potency assumption used a 2:1 (oxycodone CR:
`oxymorphone ER) dosage conversion ratio, which was derived
`from a study examining the efficacy and safety of oxymor-
`phone ER compared with placebo, with oxycodone CR as the
`active control, among patients with low back pain.18 Both drugs
`demonstrated similar analgesia that was superior to placebo,
`
`370 Journal of Managed Care Pharmacy
`
`JMCP
`
`June 2011 Vol. 17, No. 5 www.amcp.org
`
`

`

`A Comparison of Daily Average Consumption (DACON) of Oxycodone and Oxymorphone Long-Acting Oral Tablets
`
`where the relative dose of oxymorphone ER (79.4 mg per day)
`was approximately one-half that of oxycodone CR (155 mg per
`day). Thus, we calculated DACON separately for the highest
`dosage strengths of the 2 drugs (oxycodone CR 80 mg and
`oxymorphone ER 40 mg) and for all lower dosage strengths
`(oxycodone CR 60, 40, 30, 20, 15, and 10 mg; oxymorphone
`ER 30, 20, 15, 10, 7.5, and 5 mg).
`
`Statistical Analysis
`Bivariate analyses were performed to illustrate the type of anal-
`ysis that most managed care pharmacists could replicate using
`pharmacy claims data alone. Differences in mean (standard
`deviation [SD]) values of DACON between oxycodone CR and
`oxymorphone ER were analyzed using t-tests for continuous
`variables. Since median values are less sensitive than means to
`outliers, we also calculated medians and Wilcoxon Rank Sum
`nonparametric tests.19 Patient variables for age, sex, geographic
`location, Charlson Comorbidity Index (CCI, a proxy measure
`for comorbidity that assigns weights for 19 chronic conditions
`calculated from all diagnosis code fields in patient medical
`claims in the 6-month baseline period prior to the start of
`the DACON measurement period20,21) other opioid use, and
`maximum gap days were evaluated descriptively using Pearson
`chi-square tests for categorical variables and t-tests for continu-
`ous variables.
`In addition, multivariate analyses were conducted using
`generalized linear models (GLM) to adjust for the observed het-
`erogeneity among patients in the observational database. The
`normality assumption was tested by using the Kolmogorov-
`Smirnov Test. For the GLM model, the gamma distribution and
`log link function were chosen to account for the non-normal
`distribution of the dependent variable (DACON). Independent
`variables included study drug (oxycodone CR vs. oxymor-
`phone ER), the highest strength versus the lower strengths
`of each drug, age, sex, the number of maximum gap days
`during the DACON measurement period, and the CCI. Since
`other opioid analgesic use prior to the DACON measurement
`period may affect DACON, both short-acting opioid (SAO) and
`LAO use during the 30 days before the DACON measurement
`period were also included in the GLM model as independent
`variables. The variables were (a) the use of 1 or more SAOs; (b)
`the use of 1 or more LAOs in addition to the study LAO; and
`(c) the use of both SAOs and LAOs.
`The mean values from the GLM models were the estimated
`marginal means (sometimes called least square means) of the
`dependent variable (DACON), calculated as predicted values
`of DACON for each of the 2 study drug groups holding all
`independent variables at mean values. The estimated marginal
`SD values were also calculated from the predicted dependent
`variable using the same method as the marginal means calcu-
`lation.
`The following sensitivity analyses were conducted. First, a
`
`subsample excluding the top 1% DACON outliers from each
`study drug group was analyzed because the means of DACON
`from the claims databases can be sensitive to extreme outli-
`ers.22 Second, we analyzed a subsample excluding patients with
`a diagnosis of cancer, measured during the 6-month periods
`before and after the start of the 90-day DACON measurement
`period and defined as ICD-9-CM codes 140-208 but including
`those with nonmelanoma skin cancer (ICD-9-CM code 173)
`because this type of neoplasm would not be considered as
`cancer in our definition.23,24 This analysis was done to reflect
`utilization by patients managing chronic noncancer pain, a
`common subset used in pain studies. Third, we calculated
`DACON results for patients with different frequencies of maxi-
`mum gap days to determine if differences in the continuity of
`chronic pain therapy affected DACON measurement. Fourth,
`we evaluated these populations without cancer in both scenar-
`ios: including DACON outliers and excluding outliers. Fifth,
`we analyzed the cohorts including cancer patients in both
`scenarios but omitting opioid medication variables including
`(a) the use of 1 or more SAOs; (b) the use of 1 or more LAOs
`in addition to the study LAOs; and (c) the use of both SAOs
`and LAOs. All analyses were performed using SAS version 9.2
`(SAS Institute Inc., Cary, North Carolina) and an a priori alpha
`level of 0.05.
`
`■■  Results
`Demographics
`Oxycodone CR users were older than those using oxymor-
`phone ER (mean ages of 49 vs. 47 years, respectively, P < 0.001;
`Table 1). There was no significant difference in sex distribu-
`tion between the 2 groups; females were 48.3% and 51.8% of
`the oxycodone CR and oxymorphone ER groups, respectively
`(P = 0.065). There were differences in the regions in which
`the prescriptions were dispensed. The proportion of patients
`who had a CCI of 3 or more was higher for oxycodone CR
`(32.2%) than oxymorphone ER (25.6%, P < 0.001). In terms of
`other opioid use 30 days prior to the DACON measurement
`period, there were no statistically significant between-group
`differences in the proportion using SAOs (70.6% vs. 73.0% for
`oxycodone CR and oxymorphone ER, respectively, P = 0.163)
`or LAOs (13.6% vs. 12.2%, P = 0.275). There was no statisti-
`cally significant between-group difference in the proportion
`of patients with both at least 1 SAO claim and at least 1 LAO
`in addition to the study drug (9.5% vs. 7.4%, respectively,
`P = 0.058). In addition, there was no statistically significant
`between-group difference in the average maximum gap days
`during the DACON measurement period for oxycodone CR
`users and oxymorphone ER users (3.1 days vs. 2.9 days,
`respectively, P = 0.343).
`
`Bivariate Analyses of DACON
`In the entire sample, (including the top 1% DACON outliers),
`
`www.amcp.org Vol. 17, No. 5
`
`June 2011
`
`JMCP Journal of Managed Care Pharmacy 371
`
`

`

`A Comparison of Daily Average Consumption (DACON) of Oxycodone and Oxymorphone Long-Acting Oral Tablets
`
`TABLE 1
`
`Demographic Characteristics of the Study Sample, All Patients Including Top 1% DACON Outliers
`
`Age (years) mean [SD]
`Maximum gap days mean [SD]
`
`Demographic Variable
`
`Oxycodone CR
`(n = 6,567)
`49.3
`[11.9]
`3.1
`[5.7]
`n
`%
`
`Oxymorphone ER
`(n = 796)
`47.1
`[10.9]
`2.9
`[5.6]
`n
`%
`
`P Value a
`< 0.001
`0.343
`
`Sex
`Female
`Male
`Regionb
`Northeast
`Midwest
`South
`West
`Charlson Comorbidity Index, 6-month baseline period
`0
`1
`2
`3 or more
`At least 1 SAO in the 30 days prior to the DACON measurement period
`At least 1 LAO in addition to study drug in the 30 days prior to the DACON measurement period
`Both at least 1 SAO and at least 1 LAO in addition to study drug in the 30 days prior to the DACON
`measurement period
`aPearson chi-square tests for categorical variables (sex, region, CCI category, and use of LAOs and SAOs) and t tests for continuous variables (age, maximum gap days).
`bRegion data were missing for 1 study subject.
`CCI = Charlson Comorbidity Index; CR = controlled-release; DACON = daily average consumption; ER = extended-release; LAO = long-acting opioid; SAO =short-acting opi-
`oid, SD = standard deviation.
`
`51.8%
`48.2%
`
`7.0%
`23.2%
`53.5%
`16.2%
`
`31.9%
`10.4%
`32.0%
`25.6%
`73.0%
`12.2%
`7.4%
`
`0.065
`
`
`< 0.001
`
`
`
`
`< 0.001
`
`
`
`
`0.163
`0.275
`0.058
`
`3,172
`3,395
`
`625
`1,423
`3,091
`1,427
`
`2,040
`561
`1,852
`2,114
`4,637
`892
`622
`
`48.3%
`51.7%
`
`9.5%
`21.7%
`47.1%
`21.7%
`
`31.1%
`8.5%
`28.2%
`32.2%
`70.6%
`13.6%
`9.5%
`
`412
`384
`
`56
`185
`426
`129
`
`254
`83
`255
`204
`581
`97
`59
`
`the unadjusted DACON mean value for the highest strength of
`oxycodone CR was 3.9 tablets compared with 2.9 tablets for
`oxymorphone ER (P < 0.001), 3.0 versus 2.4 for lower strengths
`(P < 0.001), and 3.1 versus 2.5 for all strengths (P < 0.001;
`Table 2a). For all dosage strengths, the difference in median
`DACONs was 0.7 tablet (P < 0.001), which was consistent with
`the difference in means of 0.6 tablet (P < 0.001). When exclud-
`ing the top 1% DACON outliers (DACON range of 9.7 to 33.0
`for oxycodone CR and 6.5 to 10.4 for oxymorphone ER), there
`was again a statistically significant difference in DACON means
`overall and at the higher and lower strengths (0.6, 0.9, and 0.5
`tablet, respectively, all P < 0.001; Table 2b). Over all dosage
`strengths after excluding outliers, the differences in median
`and mean DACONs were again 0.7 and 0.6 tablet, respectively
`(P < 0.001).
`In analyses stratified by continuity of therapy during the
`DACON measurement period, among the 48.3% (n = 3,181) of
`oxycodone CR patients and 47.9% (n = 381) of oxymorphone ER
`patients with no gap in days supplied during the DACON mea-
`surement period, mean DACON was 3.4 tablets for oxycodone
`CR and 2.7 tablets for oxymorphone ER, for a difference of 0.7
`tablets per day (P < 0.001; Table 2c). The median DACON was
`3.1 tablets for oxycodone CR and 2.2 tablets for oxymorphone
`ER, for a difference of 0.9 tablets per day (P < 0.001). Among
`
`the 33.9% (n = 2,226) of oxycodone CR patients and 37.2%
`(n = 296) of oxymorphone ER patients with 1-5 day maximum
`gaps in days supplied during the DACON period, the differ-
`ences in mean and median DACONs were 0.6 and 0.7 units,
`respectively. Finally, among the remaining 17.7% (n = 1,160) of
`oxycodone CR patients and 14.9% (n = 119) of oxymorphone
`ER patients with a maximum gap of more than 5 days sup-
`plied during the DACON period, the differences in mean and
`median DACONs were 0.6 and 0.3 units, respectively. Thus,
`DACON differences were larger among patients with no gap in
`daily supply compared with patients with gaps. DACON dif-
`ferences for every maximum gap day category were statistically
`significant (P < 0.001).
`
`Multivariate Analyses
`After adjusting in GLMs for age, sex, comorbidities, highest
`strength versus lower strengths, maximum gap days, and con-
`current SAO and LAO use during the 30 days prior to the mea-
`surement period, a statistically significant risk-adjusted mean
`difference in DACON remained, with oxycodone CR patients
`receiving on average 0.6 tablets more per day than those dis-
`pensed oxymorphone ER (P < 0.001; Table 3). The same results
`were obtained when DACON outliers were excluded from the
`analysis and when variables relating to the extent of maximum
`
`372 Journal of Managed Care Pharmacy
`
`JMCP
`
`June 2011 Vol. 17, No. 5 www.amcp.org
`
`

`

`A Comparison of Daily Average Consumption (DACON) of Oxycodone and Oxymorphone Long-Acting Oral Tablets
`
`TABLE 2
`
`Bivariate Analyses of DACON by Study Drug
`
`Oxycodone CR
`
`Oxymorphone ER
`
`Mean Median
`
`SD
`
`n
`
`Mean Median
`
`SD
`
`Difference
`in Means
`
`T Test
`P Value
`
`Difference
`in Medians
`
`Wilcoxon Rank
`Sum Test
`P Value
`
`n
`2a. Strength, all patients
`Highesta
`3.2
`3.9
`930
`Lowera
`2.7
`3.0
`5,637
`2.8
`3.1
`Overall
`6,567
`2b. Strength, excluding 1% DACON outliersb
`Highesta
`902
`3.6
`3.2
`Lowera
`5,599
`2.9
`2.7
`Overall
`6,501
`3.0
`2.8
`2c. Maximum gap days, all patients
`< 0.001
`0.9
`< 0.001
`0.7
`1.2
`2.2
`2.7
`381
`1.9
`3.1
`No gap
`3,181
`3.4
`< 0.001
`0.7
`< 0.001
`0.6
`0.9
`2.0
`2.4
`296
`1.5
`2.7
`1-5 days
`2,226
`3.0
`< 0.001
`0.3
`< 0.001
`0.6
`1.0
`2.0
`2.2
`119
`1.7
`2.3
`More than 5 days
`1,160
`2.8
`aHighest dosage strength = oxycodone CR 80 mg; oxymorphone ER 40 mg. Lower dosage strengths = oxycodone CR 60, 40, 30, 20, 15, and 10 mg; oxymorphone ER 30, 20,
`15, 10, 7.5, and 5 mg.
`bThe range of DACON values in the