Tao, Xuguang (Grant) MD, PhD; Lavin, Robert A. MD; Yuspeh, Larry BA; Bernacki, Edward J. MD, MPH
The treatment of pain has received increasing attention over the past two decades.1–3 Opioid use for acute pain is well accepted,4–8 though opioids' role in the long-term treatment of chronic non-cancer pain is controversial for many reasons, including the high incidence of adverse drug effects, addiction risk, and the lack of evidence supporting efficacy.9–15
A previous study by the authors utilizing the same database16 looked at opioid use over a calendar period from 1999 to 2009 among Louisiana Workers' Compensation Corporation (LWCC) claims filed from 1992 to 2009. The amount and cost of opioids increased over the study period, primarily related to an increased use of long-acting (LA) opioids to treat individuals with chronic pain.16
This study attempts to examine the natural history of opioid use as the injury becomes more chronic in nature and the claim matures. Specifically, we attempted to quantify the change in the number of open claims in which opioids are prescribed and the amount of opioids used as the claim ages for lost-time claims. Also, we wanted to ascertain the impact of opioids, especially LA opioids, and amount of opioid as measured by morphine-equivalent dose (MED) on claim durations and claim closing rates.
MATERIALS AND METHODS
This study population was a subset of a population evaluated in a previous study.16 A special cohort was constructed, which included all lost-time injury claims (so-called “indemnity claims”) filed in the LWCC Claims Payment Database from 1999 to 2002 and followed for 7 years post-injury. The LWCC is a private mutual insurance company writing workers' compensation insurance for approximately 30% of the fully insured market in the State of Louisiana. Several papers have been published by these authors utilizing the same population to study various workers' compensation-related topics.17–19
Information on prescription drugs was obtained from LWCC's Pharmacy Benefit Manager (PBM). A file termed the PBM Database was constructed using the medication information. The prescription information was linked to claims of all injury years that were open between 1999 and 2009. The PBM Database included the date of the prescription, National Drug Code for each prescription, medication, medication dosage, number of pills per prescription, and the number of prescriptions during the period of 1999 to 2009. The method for MED conversion and the grouping of short-acting (SA) and LA opioid were the same as in the previous study.16
All analyses were performed by the year postaccident (incident/injury/event) to examine the relationship between claim duration and opioid use within the 7 years post-injury. The reasons this cohort was selected were (1) there was no PBM data prior to 1999, so that claims filed prior to 1999 would have incomplete drug use histories; and (2) claims filed after 2002 would have less than 7 years of claim age, so would not meet our criteria for follow-up (7 years).
The changing curves with years postaccident were simulated with linear or quadratic polynomial curves to maximize the goodness of fit. The regression models were chosen on the basis of the shape of curves. If the shape resembled a straight line, then a linear regression was used. If the shape was nonlinear, a polynomial regression was used.20 Both functions used the “least squares” method to calculate a curve that best fit the data. R2 and its P value were used to judge the goodness of fit. Values of R2 range from 0 to 1. The closer R2 was to 1, the better the goodness of fit.
Polynomials are useful for testing, for the presence of curvature and the nature of that curvature, and can be used to fit trends with complex curvature for which no particular theoretical function is known to be applicable.20
The SAS 9.1 (SAS Institute, Inc., Cary, NC) was used for analysis and significant testing. MS Excel 2007 (Microsoft, Redmond, Wash) was used for presentation of regression and curve simulations.
Analyses were performed on three mutually exclusive groups: (1) claims involving individuals who never were prescribed opioid medications, (2) claims involving individuals who ever used only SA opioids during the entire study period, and (3) claims involving individuals who ever used LA opioids (with or without SA opioids) at some point during the entire study period. Percentages of residual open claims as dependent variables, y, in these three groups were examined by the years postaccident as the independent variable, x, as previously described.
Average MED per day as well as 5th and 95th percentile MED distributions were analyzed by the years postaccident for claims involving individuals prescribed only SA opioids. Similar analyses by the years postaccident were performed for claims ever associated with LA opioids during the lifetime of the claim; however, these LA opioid claims were divided into two subgroups: group A claims involving individuals who were ever prescribed LA opioids but were prescribed LA opioids with or without SA opioids during the particular year postaccident and group B claims involving individuals who were ever prescribed LA opioids but were prescribed only SA opioids during the particular year postaccident. The reason for this division was to better characterize these groups and to understand nuances of opioid-prescribing patterns. For this analysis, claims of individuals who were ever prescribed only SA opioids during the particular year postaccident (and never prescribed LA opioid medications during the study period) were classified as group C. These three groups were mutually exclusive, and the sum of the three groups was equal to the total number of individuals who were treated with an opioid in a given year. The changing curves were simulated with polynomial curves using the method described earlier, with MED per day as the dependent variable and the year postaccident as the independent variable.
The Kaplan–Meier (KM) method21 was used to generate unresolved claim curves and calculate the mean and median claim duration by opioid prescription status, as well as the significance for claimants who never were prescribed opioids, claimants who were prescribed only SA opioids, and claimants who were ever prescribed any LA opioid.
Table 1 presents the general information of the study cohort by year of accident and the year postaccident. A total of 11,394 lost-time claims were followed and 93.5% of them closed at some point during the 7 years of follow-up. Table 1 also shows that the percentage of claims of individuals who were ever prescribed opioids increased from 43.3% to 80.8% among the proportion of residual open claims during the 7 years of follow-up. Claims of individuals who ever received only SA opioids increased from 38.1% to 51.2%, whereas claims of individuals who ever received LA opioids experienced a nearly sixfold increase from 5.2% to 29.6% during the same study period, indicating that claims associated with opioids—especially LA prescriptions—closed at a slower rate.
As shown in Fig. 1, the shape of the curve of percentage of claims associated with SA opioid medications only is different from the more linear representation of claims associated with any LA opioid medications. The only-SA opioid medication group increases with claim duration until the third year postaccident, then it starts to decrease, fitting a polynomial trend line (y = −0.0108x2+ 0.1499x + 0.294, R2 = 0.9954, P < 0.001), whereas the LA opioid medication group increases by 3.7% annually in a linear manner (y = 0.0371x + 0.0141, R2 = 0.9913, P < 0.001). Both trend curves are statistically significant.
Table 2 indicates that the means of MED increases with claim duration. In this analysis, the claims of individuals who were ever prescribed LA opioid medications during the 7-year study period were split into two groups (groups A and B), because they might not use LA opioid medications every claim year. Group A represents claims of individuals who were prescribed LA opioids with or without SA opioids during a particular year postaccident. Group B represents claims of individuals who were prescribed LA opioids at some point during the 7-year study period but were only prescribed SA opioids in the particular year postaccident (and were not prescribed any LA opioids during that particular study year). Group C represents claims of individuals who were ever prescribed only SA opioids, but never prescribed LA opioid medications during the study period. For group A (LA opioid with or without SA opioid), the MED increased from 10.0 mg/day to 143.2 mg/day over the 7-year study period. The top 5% of claimants were prescribed 250 to 500 mg/day after the second year postaccident. For group B (claims of individuals who were ever prescribed an LA opioid but were prescribed only an SA opioid in that particular year), the mean use of SA opioid MED increased from 3.1 mg/day to 57.7 mg/day. For group C (claims of individuals who were ever prescribed only SA opioid medications), the mean use of SA opioid MED increased from 1.3 mg/day to 18.9 mg/day.
Figure 2 indicates the shapes of curves and regression results of the three exclusive claim groups in Table 2. For all three claim groups, the average MED (y) increases with the years postaccident (x), fitting polynomial models. For claims of individuals who had LA opioids prescribed in the year (group A), MED (y) = −4.1615x2 + 55.444x − 38.052 (R2 = 0.9871, P < 0.001). The MED per day increases with the years postaccident but the rate of increase slows and flattens after the fourth year postaccident. Among claims of individuals who ever had LA opioids prescribed but received only SA opioid prescriptions in that particular year (group B), the SA MED (y) = 0.4904x2 + 2.5365x + 3.2015 (R2 = 0.97, P < 0.001). Because β1 and β2 are both positive, that means that not only the daily MED increases with the years postaccident but also the speed of increase accelerates. Among claims of individuals who were never prescribed LA opioids and prescribed only SA opioid medications (group C), the daily SA MED (y) = −0.4183x2 + 6.272x − 4.3498 (R2 = 0.9956, P < 0.001). In this last group, the curve increases but flattens just below 20 mg/day after the fifth year postaccident.
Figure 3 indicates that claims involving opioids stay open significantly longer than claims not involving opioids, and claims ever involving LA opioids remain open significantly longer than claims ever involving only SA opioids. By the end of the third year postaccident, only 12.5% of claims in which opioids were not prescribed were still open. However, at the same point in time, 39.2% of claims in which SA opioids were prescribed were open, and 86.3% of claims in which any LA opioid was ever prescribed were still open. Log-rank and Wilcoxon signed rank tests (SAS 9.1) show that the difference among the 3 curves are significant (p < 0.001).
Table 3 indicates that opioid prescriptions, especially LA opioid prescriptions, were associated with increased claim durations. The average durations for claims in which opioids were not prescribed, only SA opioids were prescribed, and an LA opioid was prescribed were 414.6, 929.8, and 2,025 days, respectively. The difference between the median and mean durations in Table 3 is illustrated by the duration curves (Figure 3), which are skewed to the right, representing a smaller number of individuals with longer duration claims in each group. The LA opioid group is an exception because 36.8% of the claims remained open at the conclusion of the study; consequently, the right end of the skewed curve for this group was truncated at the end of this 7-year study.
Though opioids may be efficacious for short-term pain relief and are commonly prescribed for chronic back pain, the efficacy of opioids for the treatment of chronic pain has not been definitively established. Chronic use of opioids is associated with a significant number of complications, including physical dependence, tolerance, endocrine and immune abnormalities, hyperalgesia, respiratory depression, and overdose.9–15,22 Substance use disorders have been observed in patients taking opioids for back pain, and aberrant medication-taking behaviors occur in up to 24% of cases.7 In a small group of workers (6%) with compensable back injuries who received opioids long term, opioid doses increased substantially, and only a minority showed clinically important improvement in pain and function.4
A Washington health maintenance organization study revealed an odds (hazard) ratio of 8.9 for death with high daily doses of opioids of greater than or equal to 100 mg MED per day.23 Another study showed that the total prevalence of opioid-related deaths varied from 0.46 to 1.78 per 1000 deaths from 2003 to 2006 with a total of 12 deaths over a period of 4 years. There were five deaths definitely related to opioid prescriptions with an increasing rate of 0 to 1.43 per 1000 deaths over a period of 4 years. An increased relative risk was also observed for morbidity related to overdose in the study.24
This study followed 11,394 lost-time claims and found that the percentage of claims that ever used an opioid increased from 43.3% to 80.8% among the remaining open claims at the conclusion of the 7-year study period. Claims of individuals who were ever prescribed an LA opioid increased nearly sixfold from 5.2% to 29.6% and continued to linearly increase, whereas claims of individuals who were ever prescribed an SA opioid only increased from 38.1% to 56% by the third year and decreased to 51% at the end of the seventh year postaccident. Long-duration claims tended to be associated with LA opioid prescriptions as well as higher annual opioid dosages (MED).
With regard to opioid dosage, group A (LA with or without an SA opioid), MED increased from 10.0 mg/day to 143.2 mg/day for claims of individuals who were prescribed LA opioids in each year postaccident (Table 2). Although a plateau was observed around 140 mg/day in mean MED starting with the fourth year postaccident, the top 5% of claims had a high MED (between 250 mg/day and 500 mg/day) after the second year postaccident. Furthermore, MED of the top 5% of claims in group A continues to increase, whereas MED of the top 5% of claims of Groups B and C are steady. It would be expected that individuals receiving chronic opioid therapy would stabilize at a daily opioid dose or only experience small incremental dose increases over time. The mean use of SA opioid MED for group B (claims of individuals who were ever prescribed LA opioids but were only prescribed SA opioids in a particular study year) increased from 3.1 mg/day to 57.7 mg/day, and this increase continued over the duration of the study. A possible explanation for the increase in MED in this group might be that individuals dissatisfied with high-dose LA opioids have reverted back to increasing doses of SA opioids. Furthermore, the mean MED for group B was almost three times greater than the SA opioid mean MED for individuals who were never prescribed LA opioids (group C) by year 7, and it was continuing to increase at the end of the study, whereas the mean MED for Groups A and C had achieved a plateau by the fourth or fifth year postaccident. The continued escalating doses of opioids in group B and in the top 5% of group A suggest that individuals in these groups may warrant more careful medication monitoring. The increase that we observed in our study is similar to the increases in peak MED observed by Franklin et al19 (132 mg/day MED), who studied the relationship between daily dose of opioids and opioid-related deaths underscoring the need for monitoring at these levels.
The estimated average claim durations for claims of individuals who were never prescribed opioids, claims of individuals who were ever prescribed only SA opioids, and claims of individuals who ever were prescribed any LA opioid were 414.6, 929.8, and 2025 days, respectively. The results showed that utilization of opioid medications, especially LA opioid preparations, was associated with slower closing rates and increased claim duration. Though LA opioids are generally prescribed in higher daily MED than SA opioids, reduced claim closure is probably related to total opioid dose, rather than specific to LA opioids, as evidenced by the continued increase in group B (Figure 2), which was exposed to LA opioids but continues to utilize increasing doses of SA opioids. Furthermore, the ratios of open claims in year 1 postaccident (when LA opioid claims peak) to year 7 postaccident in Table 2 for Groups A, B, and C are 34.1%, 20.0%, and 7.5%, which correlate with the relative MEDs for each group. Finally, review of Louisiana claim duration reveals that longer claim duration is associated with not returning to work, which suggests that the prescription of opioids, especially in higher doses, is not associated with an improvement in function adequate to return individuals to work.
A Canadian workers' compensation study analyzed opioid prescriptions in lost-time claims to determine trends in use and the association between early prescription and future recovery. For 137,175 subjects between the years 2000 and 2005, all opioid prescriptions within the first year were analyzed. Claimants receiving early opioid prescriptions experienced delayed suspension of benefits or delayed recovery controlling for injury severity. However, this analysis only examined first year data.25
Both SA and LA opioids have been considered in the overall pharmacotherapeutic treatment of patients with chronic non-cancer pain.26 Workers may prefer the SA opioids because they experience more immediate analgesia that they need when performing job-related physical activities and they may not require the same level of analgesia when they leave work. Conversely, providers may prefer to prescribe SA opioids because there is less regulatory scrutiny and they are easier to order/reorder. Little is known about patient and physician characteristics that may influence physicians' decisions concerning prescription of opioids for acute and chronic pain.27 Not surprisingly, workers with more severe injuries are more likely to receive prescription opioids, but reasons for prescription disparities among patients and providers warrant further study.
A recent study by the Workers Compensation Research Institute has examined interstate variations in use of narcotics across 17 larger states.28 Louisiana was one of the four states that stood out as a location where injured workers received significantly more narcotics per claim than in the other 13 study states. The authors acknowledged the limitations of their study in that it looks at nonsurgical claims with only 24 months of average life. Our study resolves many of these limitations due to the longer duration of claims that are analyzed and the year post methodology.
Delayed claim closure rates correlate with use of opioids, especially LA/high-dose opioids, as evidenced by the increasing percentage of open claims associated with opioid use at the end of 7 years. In Louisiana, delayed lost-time claims settlements are strongly associated with not returning to work, which is consistent with previous observations that opioids are associated with delayed return to work.25 Opioid use in the LA opioid population rapidly increased above the 100 MED associated with increased risk for accidental death attributed to opioids.22 At the conclusion of the study, two groups continued to receive increasing doses of opioid medications: (1) the top 5% of the highest opioid using group (ever used LA opioids) and (2) individuals who resumed SA opioids after a trial of LA opioids. Consistent with previously published reviews,29–33 these individuals, who were receiving very high opioid doses or who never achieved a chronic stable opioid dose, would benefit from closer monitoring and more focused evaluations because their escalating opioid use may be related to substance abuse, misuse, or diversion.22 Additional research should focus on whether these groups, which are continuing to receive increasing doses of opioids (without achieving a chronic stable dose), are primarily responsible for the delayed closure rates. Future studies should also examine whether there is a difference in patterns of opioid use between lost-time claimants and medical leave–only claimants.
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