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A Linezolid Prior Authorization Program: Clinical and Economic Outcomes | Page 2

Published Online: April 16, 2014
Catherine I. Starner, PharmD, BCPS; R. Scott McClelland, PharmD; Yang Qiu, MS; Richard A. Zabinski, PharmD; Nancy Cotter, PharmD; and Patrick P. Gleason, PharmD, BCPS, FCCP
Unadjusted comparisons between groups were performed with the χ² test for categorical variables, Fisher’s exact test for those with counts less than 5, Wilcoxon rank-sum test for counts, and the likelihood ratio test for expenditures. A logistic regression model was used to test hospitalization and ED visit differences between the intervention and comparison groups, with adjustment for: age group, male gender, Charlson Comorbidity Index score categories (0 as the reference, 1-2, and greater than or equal to 3), zip code–derived education dichotomized to those with a bachelor’s degree or above and all others, zip code–derived income dichotomized to $0 to $49,999 and greater than or equal to $50,000, existence of baseline hospitalization or ED visit, and hierarchical presence of specific ICD-9–coded infectious organisms (Table 1) with Group 2 as the reference. The logistic regression fit was assessed using the C-statistic and Hosmer-Lemeshow goodness-of-fit statistic. Cost analyses were performed using the generalized linear model with Gamma distribution and adjusted for the same covariates listed above. The overall fit of the generalized linear model was assessed using the scaled deviance and Pearson χ² goodness- of-fi t statistic. All statistical testing was performed using SAS version 9.2 (Cary, North Carolina). All P values were 2-sided with an a priori alpha of .05. A sensitivity analysis was performed repeating all analyses using a 60- day follow-up period, post index date.

RESULTS

The Figure shows the analysis fl ow for the intervention and comparison health plan members. Of the 1,167,888 eligible members exposed to the PA in the intervention group, 217 (2 per 10,000) had a rejected linezolid index claim between January 1, 2011, and June 30, 2011. The prevalence of members who were continuously enrolled 6 months prior to their index claim was 185 (85.3%) of the 217 members with a linezolid rejected claim. The comparison group had 77 (1 per 10,000) members with a paid linezolid claim, and 69 (89.6%) met analysis criteria. A χ² test was performed to test the difference in rate of linezolid prescribing between the 2 groups, and the intervention group had a significantly higher linezolid prescribing rate compared with the comparison group. (P <.001). This difference refl ects national antibiotic prescribing trends, which show higher rates in the South.11

Table 1 shows that all baseline characteristics were similar, except that the intervention group had a significantly lower percentage of members with a zip code–derived median income of >$50,000 (P = .032). In addition, directional differences existed between the categories of infectious organisms (category 1: infections with drug resistant organisms specific to vancomycin, MRSA pneumonia, septicemia, or carrier status was found in 27.0% vs 39.1% of members; and category 2: infections due to undefined organisms found in 61.1% vs 50.7% of members, among intervention and comparison groups, respectively).

The unadjusted number of offi ce visits, hospitalizations, and ED visits are shown in Table 2. During the 30-day follow-up, the intervention group had an average of 3.0 office visits (standard deviation [SD] 2.1) and the comparison group 2.0 (SD 1.4), P = .332. There were no statistical differences in unadjusted hospitalizations (14.6% vs 17.4%) or ED visits (18.4% vs 14.5%) between the intervention and comparison groups, respectively.

During the 30-day follow-up, a paid claim for linezolid was found in 99 (53.5%) of 185 members initially denied linezolid coverage as a result of the PA (Table 3). The mean time to linezolid claim was 2 days from the index date. The presence of any antibiotic claim, including linezolid, was found in 157 (84.9%) intervention group members, with an average time to first claim of 2 days. There were 28 (15.1%) intervention group members with no antibiotic claims during the 30-day follow-up. This subset of 28 members had baseline characteristics similar to those of the full intervention group (data not shown). There were 4 denials after a member had initiated the PA process. Denials were based on the approval criteria listed in the Methods section. The 4 members had culture information indicating that their respective organisms would be susceptible to other antibiotics, and in all cases, linezolid had not been started when the request came in. Also, a subanalysis comparing unadjusted counts of offi ce visits (2), hospitalizations (4 [14.3%]) and ED visits (5 [17.9%]) showed no statistical differences versus the comparison group during the 30-day follow-up.

The logistic regression model found no difference in hospitalization (P = .566), ED visits (P = .332), or combined hospitalizations/ED visits (P = .661) between the intervention and comparison groups (Table 4). The generalized linear model showed the intervention group had 37% lower pharmacy costs (relative cost [RC] 0.63, P = .016) and 38% lower total cost of care (RC 0.62, P = .012) than the comparison group. Mean per member overall total costs of care after adjusting for covariates were $5868 lower in the intervention group, P = .012 (Table 5). There was no difference in adjusted medical costs (P = .155) between groups (Table 5). The zip code–derived income difference between the 2 groups was significantly different and is consistent with the income differences between the Midwest and Southern United States that are found in the US Census data. Higher income may influence willingness to forgo insurance coverage and pay out of pocket for linezolid. Therefore, zip code–derived income was included in the multivariate model. Through inclusion of income in the multivariate model, the independent impact of the difference in income between the 2 groups on the study outcomes has been accounted for statistically.19

In the 60-day sensitivity analysis, average member linezolid plus all other antibiotic costs remained signifi cantly lower, by $714 for the intervention group ($2083 vs $2847 for the comparison). The number of members with no evidence of any antibiotic claims in the 60-day follow-up dropped to 23 (12.4%), down from 15.1%. Overall, total adjusted costs remained lower in the intervention group; however, not statistically significantly lower. The logistic regression model continued to demonstrate no difference in hospitalizations (P = .466), ED visits (P = .891) or combined hospitalizations/ED visits (P = .851) between the intervention and comparison groups.

The differences in cost for the intervention group resulted in overall savings from the linezolid PA program. The average total cost per member for linezolid was $1303 higher in the comparison group, P = .004 (Table 3). During the 30-day follow-up, mean member linezolid plus all other antibiotic costs were $1680 in the intervention group and $2595 in the comparison group, for a per patient $915 difference (P <.001). Net antibiotic savings from the linezolid PA was $169,275 (185 patients  $915) or $0.024 per member per month (PMPM) ($169,275 divided by [1,167,888 members  6 months]).

Per year, it takes approximately 15 hours to develop criteria for, 10 hours to implement, and 9 hours to maintain a PA program. Clinical review fees average $20 to $25 per case. Implementation costs for the intervention group were $2250 (15 + 10 hours  $90 per hour). Ongoing operational costs are $0.0005 PMPM [(9 hours  $90 per hour) + (332 cases per year  $20 per case)] / (1,167,888 covered lives / 12 months per year). Given that implementation occurred prior to our analysis, and that the ongoing costs are so low, the net savings would not be affected by administrative costs.

DISCUSSION

In April 2013, the geographic pattern of US outpatient antibiotic prescribing was highlighted, and researchers noted that up to 50% of antibiotic prescriptions may be unnecessary and contribute to resistance.11 We identified a diagnosis of drug-resistant microorganisms or MRSA in approximately one-third of members attempting to utilize linezolid; continued off-label use could further potentiate resistance. A health plan or PBM can influence appropriate use through implementation of a PA program. In this study, the linezolid PA resulted in no statistically significant differences in hospitalizations or ED visits. The intervention group appreciated a $0.024 PMPM antibiotic savings over a 30-day follow-up period with both clinical and economic findings maintained at 60 days. These results demonstrate that such a program aimed at the antibiotic linezolid could be applied without a concern for an increase in negative clinical consequences.

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Issue: March/April 2014
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