Joseph C. Cappelleri, PhD, MPH, MS

: Humana implemented a step therapy (ST) policy on pregabalin for Medicare and commercial plans effective January 2009, and lifted the policy for Medicare plans in April 2013. This study examined the impact of ST on pregabalin utilization and therapeutic alternatives, as well as medical and total healthcare costs for FDA-approved pain indications for pregabalin.

: A retrospective, interrupted time series analysis was conducted using Humana Research Database’s Medicare and commercial claims from January 2007 to April 2014.

: Segmented regression analyses with 2 change points, January 2009 and April 2013, accounted for policy implementation and lift. Utilization was reported as the mean number of claims per 100,000 members per month for time trend and level change following ST changes. Medical and total healthcare costs were reported in dollars per 1000 members per month.

: The ST implementation resulted in a statistically significant decrease in pregabalin use by Medicare members (P <.001), while its lift resulted in a nonsignificant increase in pregabalin use by Medicare members (P = .072). There was no change in trend after the ST implementation or lift. Utilization of gabapentin in Medicare saw a consistent increase following the implementation of the pregabalin ST. Medical and total healthcare costs for diabetic peripheral neuropathy, fibromyalgia, and post herpetic neuralgia among the Medicare and commercial populations increased throughout the study period, but did not appear to be impacted by the pregabalin ST.

: Although Humana’s ST edit policy shifted members away from pregabalin, no significant cost savings were achieved by restricting medication access to patients.

This study examined the impact of a pregabalin step therapy policy on utilization and medical costs in Humana’s Medicare and commercial plans.

The pregabalin step edit resulted in a significant decrease in pregabalin use in both the Medicare and commercial plans, with an expected increase in utilization in the anticonvulsant category, which contained the prerequisite step therapy gabapentin.

The step therapy edit shifted Humana members away from pregabalin without a statistically significant impact on disease-related medical costs or total healthcare costs, which increased throughout the study period for both commercial and Medicare plans.

Health plan payers utilize formulary management strategies like prior authorizations, step therapy (ST) policies, cost sharing, mandatory generic substitution, and therapeutic interchange in an effort to control pharmacy expenditures on higher-cost branded medications. Pregabalin is a branded medication indicated for pain conditions including diabetic peripheral neuropathy (DPN), fibromyalgia (FM), and post herpetic neuralgia (PHN).

Humana Inc implemented a ST policy for pregabalin for its Medicare and commercial plans effective January 2009. Beneficiaries, new to pregabalin therapy, were required to have previous treatment, intolerance, or contraindication to gabapentin before pregabalin therapy would be covered. Gabapentin, an anticonvulsant with the same mechanism of action as pregabalin, is a therapeutic alternative used by health plans to treat neuropathic pain.

In addition to gabapentin and pregabalin, there are several other guideline-recommended therapies for the treatment of neuropathic pain and fibromyalgia, including opioids, serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs).

 The ST policy for pregabalin was lifted in April 2013 for all Medicare plans, but remained in effect for commercial plans, which enabled comparison between Medicare and commercial members.

Studies have examined healthcare resource use and costs related to pregabalin use for the treatment of pain associated with DPN, FM, and PHN.

 A previous study examining the impact of a pregabalin ST restriction on pregabalin utilization and costs among Medicare members in a large United States health plan found that after controlling for differences in age and comorbidity burden between restricted and unrestricted groups, implementation of a pregabalin ST restriction was associated with increased medical costs.

 However, increased medical costs were offset by lower prescription drug costs of initiating therapy with generic gabapentin, and no net difference was observed in total healthcare costs.

Another study compared members in a state Medicaid program that implemented a pregabalin prior authorization with members in state Medicaid programs with no restriction, and found decreased pregabalin use in the restricted population, with increased opioid utilization compared with the unrestricted population.

 Other restriction studies comparing commercial and Medicare plan data similarly observed decreases in pregabalin utilization with increases in gabapentin utilization and no statistically significant impact on DPN- or PHN-related medical costs.

This study is unique in that it allowed for the assessment and impact of implementing and lifting a restriction on pregabalin use in the same health plan, rather than comparison across different plans as has been previously described. We employed an interrupted time series design: Separate time series models were estimated for pregabalin utilization, the utilization of therapeutic alternatives, medical costs, and total healthcare costs related to DPN, FM and PHN, conditions for which pregabalin has FDA-approved indications.

This study utilized data from Humana Research Database (Humana, Louisville, Kentucky), containing enrollment, medical, and pharmacy claims data from January 2007 to April 2014. Data sources were merged using de-identified patient data. The finalized protocol was approved by an independent institutional review board.

An interrupted time series design was used to evaluate the longitudinal effects of the ST restriction for pregabalin use.

 The use of interrupted time series design is very common in drug utilization research and its use has increased in recent years. When randomized controlled studies are not feasible, an interrupted time series analysis is the strongest quasi-experimental design available to researchers assessing the impact of an intervention.

Separate time series models were estimated for pregabalin utilization, the utilization of therapeutic alternatives, and medical and total (pharmacy + medical) healthcare costs related to DPN, FM, and PHN, conditions for which pregabalin has an FDA-labeled indication. Although approved for treatment with pregabalin, spinal cord injury-related neuropathic pain (SCI-NeP) patients were not included in this study due to lack of consensus on identifying NeP in SCI in the data and the extremely low prevalence of the condition.

The availability of data counted on evenly spaced intervals allows for the measurement of changes in both level and trend. Monthly time series data were examined for any changes in level and trend (slope) across the following 3 time periods: (a) pre-January 2009, before the ST policy went into effect for Medicare and commercial members; (b) January 2009 to April 2013, while the ST policy was in effect for Medicare and commercial members; and (c) May 2013 to April 2014, after the ST policy was lifted for Medicare members (Figure 1).

Humana members were included if they filled pharmaceutical claims under the Medicare Advantage and Pharmacy Benefits (MAPD) plan or Pharmacy Drug Plan for the Medicare population (hereafter, Medicare), and under the fully-insured or drug-plan-only plan for the commercial population. The unit of measure for this interrupted time series was claims per 100,000 members per month (P100KMPM). Utilization was measured for pregabalin, as well as for therapeutic alternatives used in the treatment of DPN, FM, and PHN, which included anticonvulsants, opioids, SNRIs, and SSRIs. Pharmacy claims for any particular month were excluded from the study if the member filling the claim did not have continuous enrollment for all days in that particular month.

For medical costs, all medical claims of Medicare and commercial members having at least 2 claims with recorded diagnoses for any condition of interest (DPN, FM or PHN), in any position, at least 30 days apart, were examined. Medical costs include total condition-related medical costs (Humana-allowed amounts and member out-of-pocket expenditures) for hospital inpatient stays, emergency department visits, outpatient and physician office visits, procedures and lab tests.

Members were included in the monthly assessments for the entire study period as long as they were enrolled for the full month. Medical costs were reported in dollars per 1000 members per month. Total healthcare costs summed the dollars associated with DPN-, FM- or PHN-related pharmacy and medical claims.

Segmented regression analysis was used to measure the degree to which the step edit impacted the utilization of pregabalin, the utilization of alternative therapeutic classes, and medical costs related to DPN, FM, and PHN. Segmented regression models were estimated for pregabalin as well as for therapeutic alternatives used to treat these pain conditions. Utilization for the therapeutic alternatives was examined at the drug class level. The segmented regression analysis accounted for 2 change points: January 2009 (step-edit implementation for Medicare and commercial plans) and April 2013 (step edit lift for Medicare plan only).

5* time since lifting of ST policy restrictiont + et

Yt is the mean number of claims per 100,000 members for month t;

0 estimates the baseline level at time zero, mean number of prescriptions per 100,000 members per month;

1 estimates the baseline trend, the change in the mean number of prescriptions per 100,000 members that occurs in each month before the step edit;

2 estimates the level change in the mean monthly number of prescriptions per 100,000 members immediately after the ST policy restriction was implemented;

3 estimates the change in trend in the mean monthly number of prescriptions per 100,000 members after the ST policy restriction, compared with the monthly trend before the step edit;

4 estimates the level change in the mean monthly number of prescriptions per 100,000 members immediately after the ST policy restriction was lifted;

5 estimates the change in trend in the mean monthly number of prescriptions per 100,000 members after the ST policy restriction was lifted; and

Autocorrelation was evaluated by visually inspecting the residual plot after fitting a simple linear regression model and by computing a Durbin-Watson statistic and P value.

 If autocorrelation was detected, an autoregressive model was estimated via the ARIMA procedure in STATA (StataCorp LP, College Station, Texas). Parameter estimates including coefficients, standard errors, 95% CIs, and P values from the segmented regression model were reported. All data analyses were conducted using SAS version 9.3 (SAS Institute Inc, Cary, North Carolina), as well as STATA version 12.

Visual inspection of the utilization trends in tandem with interpretation of the segmented regression model is necessary to fully appreciate the results of studies using interrupted time series. Table 1 reports the segmented regression results for the number of prescriptions P100KMPM for the drug classes of interest using segment labels that correspond with the labels found in the study design figure (Figure 1). Results for commercial members are also reported alongside the Medicare results for comparison.

The number of prescription claims per 100,000 eligible Medicare and commercial members is reported in Figure 2 for all months beginning in January 2007 and ending in April 2014. Two vertical, dotted lines mark the start and end dates of the pregabalin ST restriction policy (January 2009 and April 2013, respectively).

A closer examination of pregabalin utilization may be seen in eAppendix Table 1 and in eAppendix Figure 1 (eAppendices available at www.ajpb.com). Estimates of level and trend in each segment for the segmented regression models can be seen in eAppendix Table 2. In addition, the therapeutic categories of anesthetics, muscle relaxants, nonsteroidal anti-inflammatory drugs, and TCAs were included in the analysis and may be seen in eAppendix Figure 2 and eAppendix Table 3.

Visual inspection of the 2 panels in Figure 2 indicated a decline in the number of pregabalin prescription fills for both Medicare (Figure 2a) and commercial members (Figure 2b), coinciding with the start of the ST restriction policy. For Medicare members, the decline was followed by a gradual rise before the ST edit was lifted, and continued after the ST edit was lifted (Figure 2a). For the commercial population, the initial decline was followed by a continued tapered decline. There was no visible upsurge throughout the remainder of the study period for commercial members (Figure 2b).

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This study examined the impact of a pregabalin step therapy policy on utilization and medical costs in Humana’s Medicare and commercial plans.
 