Costeffectiveness of latanoprost, travoprost and bimatoprost for the treatment of glaucoma in Norway, Sweden and Denmark, using a decisionanalytic health economic model
【摘要】 To evaluate the costeffectiveness of latanoprost, travoprost and bimatoprost monotherapy in open angle glaucoma in Norway, Sweden and Denmark(Scandinavia).METHODS: A Markov decisionanalytic health economic model was developed to estimate the comparative costeffectiveness of prostaglandin analogs. Health states were stable and progressed glaucoma. Transition probabilities for both primary open angle and exfoliation glaucoma were populated with data from published medical literature. Clinical practice patterns were derived from surveys obtained from 45 ophthalmologists dispersed throughout each country. Specific unit costs for each country were used for medications, clinic visits, diagnostics and therapies. Qualityoflife weights were assigned for visual acuity from 0.500.84. The time horizon was five years. All analyses were from a payer perspective and cost results were discounted at 3% per annum.RESULTS: Latanoprost was less expensive and more effective than bimatoprost and travoprost in both Norway and Sweden. Latanoprost was up to 4% less expensive in Sweden and Norway and the costs of all three medicines were within 1.5% of each other in Denmark. In Denmark bimatoprost dominated travoprost and was slightly less expensive than latanoprost while latanoprost was more effective than bimatoprost or travoprost. Effectiveness was within a narrow range for all products in each country.CONCLUSION: Latanoprost provides a costeffective alternative to other available prostaglandin analogs in Scandinavia.
【关键词】 cost latanoprost travoprost bimatoprost
INTRODUCTION
Prostaglandin analogs are frequently prescribed as monotherapy for the treatment of glaucoma over timolol maleate because of their greater ocular hypotensive efficacy[1]. Latanoprost (XalatanTM, Pfizer, Inc., New York, NY) was the first prostaglandin analog made available in 1996. Recently, two other prostaglandins, travoprost (TravatanTM, Alcon, Fort Worth, TX) and bimatoprost (LumiganTM, Allergan, Irvine, CA), have become available. Some investigators have noted a slight efficacy advantage, in shortterm prospective trials, of these newer products over latanoprost[2].
In contrast, other authors have observed few clinically important differences among these prostaglandins[3]. However, shortterm prospective trials do not analyze the longterm visual outcomes of a medication. Other factors might influence a medicines effectiveness in preventing longterm visual loss such as the patients persistency with the medicine, side effects and compliance.
In addition, longterm treatment involves a cost to make the medication available. In some markets the patient may pay all or a portion of this cost. In other markets, most commonly in Europe, society pays the cost of the medicine for the patient through government mandated collected revenues.
Apart from the unit price of the medicine, however, additional influences may exist on the longterm treatment cost associated with the medicine including: number and type of side effects, quality of intraocular pressure control, as well as persistency (not requiring a change in medication) and blindness rates. Unfortunately, little clinical data are available that compare latanoprost, travoprost and bimatoprost regarding longterm effectiveness and cost of therapy. The purpose of this study was to evaluate the longterm costeffectiveness of latanoprost, travoprost and bimatoprost monotherapy in open angle glaucoma in Scandinavia by use of a Markov decisionanalytic health model.
MATERIALS AND METHODS
Procedures A Markov model was created to assess the costeffectiveness in association with the quality of life gained [qualityadjusted life years (QALY)]. A QALY is an outcome measure (the unit of benefit) in this cost utility analyses. This type of model has the advantage in analyzing medical situations when the treatment outcomes and costs may be dissimilar. Consequently, the model allows determination of cost per unit of benefit of treatment. The unit of benefit chosen for glaucoma was the prevention of disease progression as defined by further thinning of the optic nerve head or worsening of the visual field[4]. The time horizon for our model was five years. A Markov model was chosen specifically for this evaluation in glaucoma patients because both the cost and effectiveness were variables that needed to be analyzed longterm.
The Markov model was developed using TreeAge Pro 2005 Healthcare software (release 1.5, TreeAge Software, Inc., Williamstown, MA) based on available data up to the end of the 2005 year. The model analyzed the cost effectiveness of beginning monotherapy treatment with the available prostaglandin analogs, latanoprost, travoprost or bimatoprost. The potential of developing progressive glaucomatous visual field loss over five years based on previous studies evaluating progression at different mean intraocular pressure levels in primary open angle and exfoliation glaucoma was demonstrated by the model[ 5]. Glaucomatous progression was assumed to be slow and staged over time. Patients beginning the model in year one were assumed to have early glaucomatous damage consistent with being begun on monotherapy.
We based our utility weights on different levels of glaucoma published by Kobelt using 0.84 for mild visual loss, 0.72 for advanced (the second progressed state)[6]. Since our model required an intermediate state (the first progressed state), which is not described in the literature, we used a utility derived between the two described states from Kobelt by the following formula: 8472/2=78. Also, we used the 0.50 utility weight for legal blindness. For the medical outcomes for each country, specific literature was used when possible. If country specific information was not available then generalized medical literature was used. Differences in progression rates between primary open angle and exfoliation glaucoma were calculated by the known incidence of glaucoma in each index country[7]. To determine frequency of visits and procedures, as well as indications for laser and conventional therapy, we collected surveys from practicing ophthalmologists dispersed throughout the countries: 12 in Norway, 14 in Sweden and 19 in Denmark. Participants were randomly chosen from physician lists specific to each country. The doctors were reimbursed for their answers. One physician was randomly chosen from respondents for a personal interview to assure accuracy of the survey data and results.
To create the model (presented as supplemental online material due to size) we assumed that a glaucoma patient would begin one of the following prostaglandin analog monotherapies: latanoprost, travoprost or bimatoprost. The model supposed that on the initial treatment patients (50% male or female of an average age for a primary open angle glaucoma patient of 66 years) would enter into one of four health states based on percentages in the literature: controlled (i.e. pressure ≤18mmHg) without a side effect, uncontrolled (i.e. pressure ≥18mmHg) without a side effect, discontinue the medication due to a side effect and be controlled on the new medicine, or discontinue the medication due to a side effect and be uncontrolled on the new medicine[1,2,8]. Patients were presumed prescribed each of the three prostaglandins in a 1∶1∶1 ratio. The cycle length was assumed to be one year. Previously published persistency rates were used to determine discontinuation rates during the first year of therapy[911]. We assumed that patients who discontinued a prostaglandin analog would be switched to timolol maleate, and additional visits and procedures associated with the change were calculated.
The cohort of patients initially controlled (i.e., pressure ≤18mmHg) without a side effect were assumed to be stable or progressed based on known rates in the literature[12] . We presupposed that those who were stable (no additional glaucomatous optic disc or visual field progression) maintained therapy, and remained stable, for the remaining life of the model. Those who were unstable, i.e., suffered progression, received a second medication. Control rates for the new lower pressure (assumed 15mmHg) using two medicines were presumed to be equal among all Markov branches since prior literature does not differentiate glaucoma medicines at such low levels of pressure. This adjunctive therapy cohort progressed or remained stable according to previously published rates for 15mmHg[5] . Stable patients again were assumed to maintain their therapy, and to remain stable, for the remaining life of the model. Unstable patients, at such a low pressure, were progressed to trabeculectomy at rates determined from previously published success/failure rates[13]. We believed that laser trabeculoplasty would have only a minimal further hypotensive effect in a patient with a pressure of 15mmHg, so this therapy was excluded.
The cohort of patients initially uncontrolled had a second medication (timolol maleate) added and transition probabilities for control were based on known response rates. Those who were controlled with adjunctive therapy were assumed to maintain their therapy, and to be stable, for the remaining life of the model. Those who were uncontrolled on two medicines entered either the stable or unstable Markov branch and were assumed to undergo argon laser trabeculoplasty (ALT). The controlled cohort of these patients were considered not to progress for the remaining life of the model. Those uncontrolled after ALT, based on rates from previous literature, were progressed to trabeculectomy at previously published success/failure rates.
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