Vaishali D. Patel, PharmD, MS

 To develop a cost-offset model from a US payer perspective comparing glaucomatous progression and costs among primary open-angle glaucoma (POAG) patients using bimatoprost, latanoprost, or travoprost.

 A Markov cohort model was used to estimate glaucomatous progression for POAG patients over 7 years. The model assumed bimatoprost-treated patients had lower resulting intraocular pressure (IOP) (by 1 mm Hg) for all presenting IOP categories than latanoprost- or travoprost-treated patients. Patients with lower IOP were assumed to have lower probability of progression. Those that progressed were assumed to do so at a rate of —0.6 dB per year. Direct costs associated with mean deviation score categories were applied to each treatment cohort to calculate the expected 7-year costs of treating patients with each prostaglandin analogue (PGA). Literature was used to support assumptions. A budget impact analysis was conducted where all travoprost patients switched to generic latanoprost and where all bimatoprost patients switched to generic latanoprost. The base case market share was 22% bimatoprost, 23% travoprost, and 55% latanoprost.

 Model results demonstrate that for a managed care plan with 9500 PGA-treated glaucoma patients, exclusive bimatoprost use would prevent progression in 136 additional individuals compared with exclusive travoprost or latanoprost treatment. Model results demonstrate that greater IOP reduction from bimatoprost is associated with increased cost savings compared with latanoprost or travoprost treatments.

 Model results demonstrate that greater IOP reduction from bimatoprost could reduce managed care spending.

	Greater intraocular pressure (IOP) reduction with bimatoprost is associated with cost savings compared with treatment with latanoprost or travoprost.

		In a health plan with 9500 prostaglandin analogue—treated glaucoma patients, exclusive bimatoprost use would prevent progression in an estimated 136 incremental patients over 7 years compared with exclusive travoprost or latanoprost treatment.

		Exclusive treatment with bimatoprost would generate cost savings from reduced resource utilization estimated at $4009 per avoided progression of early glaucoma and $4543 per avoided progression of advanced glaucoma over 7 years.

		Cost benefits of lower IOP provide incentive for health system—level policies to promote bimatoprost use.

	More than 2 million people in the United States 40 years and older have glaucoma.

 Primary open-angle glaucoma (POAG) is the most common form of the disease. While there are numerous risk factors associated with glaucoma progression,

 intraocular pressure (IOP) is one of the only known modifiable risk factors that can be controlled to prevent progressive optic neuropathy.

	The incidence of glaucoma is expected to rise with the continued growth of the elderly population and is a leading cause of preventable blindness in the United States.

 Glaucoma costs the healthcare system an estimated $2.9 billion annually in direct medical expenditures.

 An analysis using a Markov model to replicate health events over the remaining lifetime of someone newly diagnosed with glaucoma estimated that the cost of care for people with POAG was higher than that of people without the disease by $1688 over their expected lifetime, or approximately $137 per year.

 Lee et al estimated the average direct cost of treatment for glaucoma to range from $523 per patient per year to $2125 per patient per year depending upon the stage of disease (early vs severe).

 Given the burden of glaucoma on the healthcare system, there is a financial incentive to delay or prevent glaucomatous progression and associated visual field loss.

	Multiple medical therapies that are intended to lower IOP are available, the most common of which are prostaglandin analogues (PGAs).

 and are not associated with the significant systemic side effects associated with topical beta blockers, such as bronchospasm, shortness of breath, depression, fatigue, impotence, hair loss, heart failure, and bradycardia.

	Latanoprost, travoprost, and bimatoprost are once-daily PGAs that lower IOP effectively and continuously, allowing for flat diurnal curves with few systemic side effects.

 Numerous randomized clinical trials have demonstrated that patients achieve greater IOP lowering with bimatoprost than either latanoprost or travoprost.

 Furthermore, a recent meta-analysis of multiple studies concluded that bimatoprost has greater efficacy than latanoprost or travoprost.

 reported on the latanoprost to bimatoprost switching patterns of an HMO. The study found that the HMO achieved a high switch rate, with few patients switching back. Moreover, there was a statistically significant reduction in mean IOP for patients who switched from latanoprost to bimatoprost. Similar studies that examined high switch rates from latanoprost to travoprost did not demonstrate a statistically significant reduction in mean IOP.

 The impact of this superior efficacy of bimatoprost on direct medical costs has not been evaluated to date.

	The primary objective of this study was to develop a cost-offset model from a payer perspective to compare glaucomatous progression and costs among POAG patients treated with bimatoprost, latanoprost, or travoprost in the United States. The analysis aimed to support the hypothesis that a reduction in IOP leads to a decreased risk of glaucoma progression, which in turn leads to cost savings from less healthcare resource utilization; specifically, due to bimatoprost’s greater efficacy in IOP reduction compared with travoprost and latanoprost, its use should lead to cost savings for payers. Fewer advanced glaucoma patients would result in lower expenses as increased resources needed for advanced disease stages are avoided.

) was constructed (1) to evaluate the difference in glaucomatous progression rates with bimatoprost, travoprost, or latanoprost; and (2) to provide a cost-offset analysis for these PGAs. This analysis was driven by the link between the treatments’ clinical efficacy, as represented by IOP after treatment (called the resultant IOP) and resource utilization. The model accounted for various healthcare resources (detailed below), the use of which increased with the resultant IOP. As the model assumed that IOP increase is associated with increased glaucomatous progression risk (detailed below), this analysis demonstrated the cost savings that arise from decreasing resource utilization due to the prevention of disease progression. While a cost-offset analysis provides useful insight into whether an intervention is worth financing from a budgetary standpoint, it is based on efficacy and resource utilization assumptions that may differ from real world rates and practices.

	The model calculated results over a 7-year period in a hypothetical health plan of 1,000,000 members. Given the slow-progressing nature of glaucoma, a 7-year time horizon was utilized, as in previous studies.

 Progression was defined as the loss of visual field as it is measured by the mean deviation (MD) score. POAG prevalence was assumed to be 1.9% (ie, 19,000 plan members had glaucoma).

 the PGA treatment rate was estimated at 50% (N = 9500).

	A subsequent budget impact analysis assumed bimatoprost as a first-line treatment with PGA market share as follows: 22% bimatoprost, 23% travoprost, and 55% latanoprost.

 This budget impact analysis compared the total cost to the payer, including the cost of the PGAs, medical costs (such as physician visits), and other glaucoma medication costs between different market share scenarios. In general, these budget impact analyses are useful for estimating systemwide (eg, medical and pharmacy) budget impact; they are often used by managed care organizations

 to justify therapy reimbursement. While these analyses are limited in that they do not account for the full impact of clinical and patient outcomes and therefore do not establish the overall value of the product, they are not intended to do so; budget impact analyses are intended to present a financial perspective when considering a particular therapeutic decision.

	Two scenarios were explored: In scenario A, all bimatoprost patients were switched to generic latanoprost, resulting in a market share of 0% bimatoprost, 23% travoprost, and 77% latanoprost. In scenario B, all travoprost patients were switched to generic latanoprost; market shares were 22% bimatoprost, 0% travoprost, and 78% latanoprost.

	This model accounted for 3 different payer situations: all Medicare Part D patients, all commercial patients, and a mix of Medicare Part D and commercial patients. Medicare Part D patients included the assumed number of individuals covered by the plan who were 65 years or older. Commercial patients included the assumed number of individuals on the plan who were younger than 65 years.

	Intraocular pressure ranges 19-21, 22, 23, 24, 25, and 26 (all mm Hg) and the percentage of patients allocated to them were based on a population-based study (the Beaver Dam Eye Study).

 The resultant IOP with bimatoprost treatment was calculated by reducing the presenting IOP by 27%.

 As the model assumes a 1 mm Hg reduction advantage for bimatoprost over latanoprost or travoprost,

 the resultant IOPs for the latter PGAs were calculated by adding 1 mm Hg to the resultant IOP scores calculated for bimatoprost. This resultant IOP value was the basis of the patients’ probability of progression (discussed in the Progression Rate section).

	As supported by literature, a baseline mean deviation (MD) score of —4 decibels

 (dB) for early glaucoma patients or —10 dB

 for advanced glaucoma patients was assigned to the “worse seeing eye” of each patient cohort.

 Baseline MD score for the “better seeing eye” was estimated based upon a correlation with the worse seeing eye using the following equation:

	BetterEYEMD = (WorseEYEMD —1.83) / 1.307.

	The annual probability of progression was estimated using the resultant IOP following PGA treatment. It was estimated from literature that a 1 mm Hg decrease in IOP would reduce the probability of glaucoma progression by 10%

 was the benchmark. Based on the Early Manifest Glaucoma Trial data, the probability that a patient with an IOP of 21 mm Hg would progress was 10.2%.

 Therefore, the calculation for progression probability for IOP values other than 21 mm Hg was estimated using the following equation:

	After PGA treatment, the probability of progression remained constant throughout the model. Based on data from the Early Manifest Glaucoma Trial,

 patients who progressed did so at a mean rate of —0.6 dB/year (Table 1).

	The model also considered the impact of IOP fluctuation on probability of progression. The percentage of patients with IOP fluctuation greater than 3 mm Hg was 7.8% for latanoprost and 2.5% for bimatoprost.

 The percentage of patients on travoprost with high fluctuation was assumed to be similar to or greater than the percentage of those on latanoprost

; therefore, the percentage of travoprost patients with IOP fluctuation greater than 3 mm Hg defaulted to 7.8%. Inclusion of IOP fluctuation in the model was supported by a literature review that demonstrated that individuals who had an IOP fluctuation greater than 2 standard deviations would be 3 times more likely to experience glaucomatous progression.

 The risk ratio (progression due to IOP fluctuation) was calculated as follows: 30% (probability of progression among patients with IOP fluctuation of >2 mm Hg)

 / 9.7% (probability of progression among patients with IOP fluctuation of 

	The annual per-patient PGA cost was calculated based on drug cost (average wholesale price [AWP] or Medicare), dispensing fees ($2 for each brand name drug and $3 for generic drugs), copays,

 rebates, and pharmacy discounts (which were 15% of the monthly cost of branded products and 17% of the monthly cost of generic products; Table 1). Rebates and copays were subtracted from the price to get the net cost to the managed care payer. As there were no data for the generic price of latanoprost, it was assumed that the cost of generic latanoprost would be 80% of the branded price. A lower copay for the generic ($10 instead of $25)

 was also assumed. The number of office visits and visual field tests were predicted from the MD score and IOP value.

 The annual number of concomitant glaucoma medications (non-PGA) was predicted from the MD score (Y[number of glaucoma medications] = 0.70 — 0.0455 [MD score]), as derived from literature on the number of medications by stage.

 Surgery was applied as a per-eye cost and the number of surgeries per year was estimated using literature on the annual rate of surgery by stage.

 For nonprogressors, the annual rate of surgery was assumed to be the literature-based rate for the stage of disease corresponding to the MD score in the model. For progressors, this annual rate was assumed to be higher based on literature showing that those who had disease stage progression were more likely to receive surgery (rate ratio of 1.92).

 The model conservatively assumed that patients who underwent surgery discontinued their medication and were therefore dropped out of the cohort. Direct medical and non-PGA pharmacy costs, which were based on resource utilization estimates, were applied to each treatment cohort to calculate the expected 7-year costs (

). Unit costs for office visits, visual field tests, additional non-PGA glaucoma medications, and surgeries were based on resource utilization and 2008 Current Procedural Terminology codes (Table 2).

 A discount rate of 3% for future costs was applied.

 Results were presented as total annual costs and annual per member per month (PMPM) costs.

	Two 1-way sensitivity analyses were conducted for the estimated reduction in risk of progression per 1 mm Hg change in IOP. The base case assumed that there is a 10% reduction in the risk of progression per 1 mm Hg decrease in IOP. The sensitivity analyses assumed that this reduction in risk is 19%. This parameter change was tested for both less severe and more severe glaucoma patients.

	Four 1-way sensitivity analyses were conducted for the price of generic latanoprost. Since the analysis was originally conducted, generic latanoprost has entered the market. Therefore, the sensitivity analyses assessed how the results would change should the price of generic latanoprost be as low as $16.44

 These results were calculated for patients with less severe and more severe disease.

	This study is a health-related outcomes analysis based on available peer-reviewed literature and therefore was not subject to approval by an institutional review board.

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