ARCH SOC ESP OFTALMOL 2006; 81: 199-204

ORIGINAL ARTICLE

COST-EFFECTIVENESS OF PHOTODYNAMIC THERAPY IN AGE-RELATED MACULAR DEGENERATION
COSTE-EFECTIVIDAD DE LA TERAPIA FOTODINÁMICA EN LA DEGENERACIÓN MACULAR ASOCIADA A LA EDAD
MUSLERA E1, NATAL C2

ABSTRACT
Objective: The aim of this study was to estimate the public health service cost of visual acuity improvement or maintenance with photodynamic therapy in patients with age-related macular degeneration (ARMD). This illness is the most frequent cause of blindness in elderly patients in western countries. Methods: A cost-effectiveness analysis was carried out to compare photodynamic therapy versus no treatment. The analysis point of view was that of the health service. The improvement or maintenance of visual acuity and contrast sensitivity were considered efficacy results. Direct costs were estimated by means of cost accountancy. Quality adjusted costs per visual acuity life year gained (QACVAG) were calculated through utility values from other studies. Results: The cost per year of maintenance of visual acuity in a two-year period was 36,530 € for women and 34,804 € for men. If this cost was estimated for life expectancy in Asturias, it would be reduced to 4,298 € for women and 5,354 € for men.

RESUMEN
Objetivo: Estimar el coste para el servicio público de salud de la mejora o el mantenimiento de la agudeza visual en pacientes con degeneración macular asociada a la edad mediante la aplicación de la terapia fotodinámica con verteporfina. Método: Estudio coste efectividad desde la perspectiva de un servicio de salud teniendo en cuenta la alternativa no tratar. La medida de eficacia es la ganancia o mantenimiento de la agudeza visual y la sensibilidad al contraste. Los costes directos ligados al proceso de la intervención son estimados a partir de la contabilidad analítica. El coste ajustado por calidad, se estima con valores procedentes de otros estudios. Resultados: El coste por año ganado de mantenimiento de la agudeza visual, en un horizonte de dos años es de 36.530 € para mujeres y 34.804 € para hombres. Si el horizonte fuera la esperanza de vida en Asturias, el coste disminuye a 4.298 € y 5.354 € respectivamente. El coste por año ganado de mantenimiento de agudeza visual ajustado por calidad es,

Received: 23/6/05. Accepted: 19/4/06. Analysis and Programmes Unit. Health Service of the Principality of Asturias. Spain. 1 Graduate in Economic Sciences. 2 Graduate in Medicine. Communication partially presented at the 24th Health Economy Meeting (El Escorial 2001) and the 21st Congress of the Spanish Society of Assistance Quality (Oviedo 2003). Correspondence: Elvira Muslera Canclini Unidad de Análisis y Programas Servicio de Salud del Principado de Asturias Plaza del Carbayón, 1 y 2, 3.ª planta 33001 Oviedo Spain E-mail: elvira.muslera@sespa.princast.es

in a two-year period. Some research in our country suggests that public health financing should be provided for interventions whose cost-effectiveness is less than 30.000 € of CVAQA. surgery and the use of angiogenic and angiostatic agents. In a number of these patients both eyes will be involved. Es recomendable una selección más rigurosa de los pacientes. Laser photocoagulation gives good results as regards the conservation of visual acuity and preservation of contrast sensitivity in patients with NVC secondary to exudative ARMD.249 € for men.52% between 75 and 84 and 5. could improve the results of this intervention (Arch Soc Esp Oftalmol 2006. maintaining this centralization for two or three years at least.931 € for women and 70. reaching 2. Prevalence increases with age. age-related macular degeneration. In addition to PT. accounting for 45 percent of cases.249 € para los hombres. 200 ARCH SOC ESP OFTALMOL 2006. photodynamic therapy would cost 66.17% for the 55-64 age group. Conclusion: This cost-effectiveness analysis allows decisions to be made about public financing. prevalence is of 0. However.88%. Conclusión: Los estudios coste-efectividad facilitan decidir sobre la pertinencia de la financiación pública. en horizonte de dos años.MUSLERA E. classic lesions potentially treatable with photodynamic therapy (PT) with verteporfin. 2.000 € por año ganado de mantenimiento de agudeza visual ajustado por calidad y en este estudio se sobrepasa holgadamente este valor.47% (4). as well as transpupillar thermal therapy. it is estimated that at present there are 1282 individuals affected by the RMT and which could be treated with PT. de 66. The purpose of this study is to estimate the cost of the improving on maintaining visual acuity in patients with predominantly classic subfoveal NVC due to ARMD by means of the application of PT with verteporfine. focusing treatment and limiting the offer to hospital centers with a broad experience in macular pathology. The study carried out by the Eye Diseases Prevalence Research Group estimated are prevalence of ARMD for all ages of 1. carrying out an annual assessment closely linked to the financing thereof (11). tanto por criterios diagnósticos como por características individuales en relación con su autonomía. The prevalence of this disease varies according to the diagnostic criteria and methods. Palabras claves: Coste-efectividad. 81: 199-204). et al. INTRODUCTION Age-related macular degeneration (ARMD) is one of the main causes of blindness in people over 50. The low-dose radiotherapy has been studied without obtaining conclusive results as yet (8. Extrapolating these data to the region of Asturias. as it does not act selectively on the pathological tissue. Thirty-six percent of these appear as subfoveal choroidal neovascularization lesions (NVC) (6). degeneración macular asociada a la edad. At present there are high expectations as regards the results of transpupillar thermal therapy which could be an option to PT (10). lo que permitiría mejorar los resultados de esta intervención.54% for the 65-74 group. terapia fotodinámica. representing between 50 percent and 17 percent according to different information sources (1-3). Algunos autores sugieren incluir sólo aquellas intervenciones que no superen los 30.9). the highest frequency is found between 75 and 84 years of age. By age group. different treatments for ARMD have been attempted such as laser photocoagulation.3% for the age group over 70 (5). The Medical Research and Technology Evaluation Agency (Agència d’Avaluació de Tecnologia i Recerca Mèdiques) established the following recommendations for PT in treating ARMD: treated only patients with a classic NVC subfoveal pattern equal or above 50 percent of the entire surface of the lesion. 0. The treatment evaluated here far exceeds this value. By age group. Key words: Cost-effectiveness. low-dose radiotherapy. The exudative form has a prevalence of 0. If costs of the QACVAG. were considered. 81: 199-204 . Patients over 84 account for 33 percent. It is recommended that the use of more restrictive patient selection. it is indicated only in extrafoveal and juxtafoveal lesions (7). photodynamic therapy. incorporating diagnostic criteria and patient autonomy indicators.931 € para mujeres y 70.76% for the over 85 age group.

81 0. they maintained stable vision in comparison to those who were given placebo. both performed in centers of Europe and the United States. quality adjusted visual acuity gain has been considered.89 0. Visual acuity was assessed utilizing the Snellen equivalent in a remote visual acuity test with a Lighthouse type following standardized refraction. the patient was referred to the area hospital where the patient of the entire autonomous community are Usefulness 0. However. b) stable vision. increase of one or more visual acuity lines.57 0. As an additional result of measurement.52 0. For calculating it.82-0. Usefulness measure according to visual acuity (15) Status Normality Intermediate 1 Intermediate 2 Legal blindness Blindness Visual acuity 20/20 – 20/25 20/30 – 20/50 20/60 – 20/100 20/200 – 20/400 Count fingers up to perception of light This study utilizes the efficiency data of the TAP clinical essay (13) because the selection of patients was similar to our group of patients (advanced age. Whereas the latter includes only patients over 50. 81: 199-204 201 . between three and five lines. defined as the proportion of patients who lost under three lines of visual acuity vis-à-vis the baseline). If positive. Sensitivity to contrast is assessed in the TAP study with the result that the patients in treatments maintained six letters after two years (p<0.3% in the TAP study) in comparison to those who did not received treatment. fulfilling the proposed criteria (11) in all cases (16).3% (p<0. For this study the first 50 patients who fulfilled a complete treatment cycle were selected. The results are shown in table I. treatment cannot be suspended until fibrosis is verified by means of angiography.47-0.40 CI 95% 0.50 ARCH SOC ESP OFTALMOL 2006.Cost effectiveness of Photodynamic Therapy SUBJECTS..001) (14).66 0. Even so. with the most restrictive being those for the TAP study (13). i. the usefulness measures estimated by Brown et al are utilized (15). The patient selection criteria are assessed regularly by means of audits. In some cases. From the essay it can be concluded that after two years of treatment. even though an improvement is detected. taking into account the no-treatment alternative. loss of under three lines. The intermediate result of measure is fibrosis. 15. The main difference between both is in the patient selection criteria. both eyes are treated. sensitivity to contrast and semi quantitative angiographic classification of retina lesions. The expected benefits is expressed as the higher proportion of patients who maintained or improved their visual acuity (15. the VIP study includes patients with better visual acuity.96 0. The classification scale is: a) improvement of vision.e. it is also possible to detect fibrosis with worsening eyesight.001) of patients lost under three lines. Measure of use of resources The itinerary followed by the patients began at the ophthalmology service of the regional reference hospital to confirm the diagnosis. younger and with choroidal neovascularization arising from different causes (13). Measure of efficiency The efficiency of PT has been measured in two clinical essays: Verteporfin in Photodynamic Therapy (VIP) and Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) (12. or no changes: c) moderate loss. PT does not at present healing results and for this reason its benefits consist in preventing a worsening of eyesight or delaying blindness.38-0.89 0. it can be stated that these two results are supplementary because.67 0. classic or predominantly classic choroidal neovascularization secondary to ARMD). and d) serious loss of six or more lines. MATERIAL AND METHODS A cost-effectiveness study is made from the perspective of a health service.73-0. Table I.29-0. which constitutes reason for dismissal. The above studies utilized three results measures: the visual acuity (the main variable of which is the response rate. with visual acuity values between 20/40 and 20/200 and classic or predominantly classic choroidal neovascularization caused by ARMD.13).

15% (36 eyes) were released due to remission of the lesion (fibrosis).MUSLERA E. Equipment cost Ophthalmic laser Infusion pump 5. The mean number of sessions was 5.4 505.5%. Taking into account the efficacy date of the TAP clinical essay. Applying this effectiveness measure to our data we obtained the cost values presented in table II.729 € and the cost per «successful» patient —those who improved or maintained their visual acuity due to the application of PT. Storeroom management cost 4. The cost per year gained of visual acuity in a 2-year timeframe — the period for which we have information — is of 34. Fibrosis occurred in 70% of patients who followed a complete cycle.2 years and men 71.298 € 202 ARCH SOC ESP OFTALMOL 2006. with 26%. It is possible to enhance the study perspective by including the assumption that visual acuity is maintained during the life expectancy and adding information about the quality of life of affected patients. only 12% exhibited slight improvement. The considered discount rate is of 2. These sessions are repeated not more than eight times. Only in one case we had release due to treatment failure in the 6th session.2 49. and 16 patients were lost in two years. The cost per patient was of 10. which accounts for 65% of each session cost (table II). et al. Cost per patient and visual acuity gained year in Asturias Costs Cost per patient Cost per patient who maintains or improves eyesight Cost per year of maintained visual acuity (2 years): • Men • Women Cost per year of maintained visual acuity (assuming stability during life expectancy period) • Men (13 years) • Women (17 years) Amount (€) 10. This situation is foreseeable because the number of aggregated favorable cases increases in a smaller proportion (only one more) between the 7th and 8th session. 70% maintained visual acuity and 18% exhibited a reduction thereof. This was calculated by applying the usefulness indices of the Sharma study to the visual acuity years gained in our population (17) because our study is retrospective and it is not possible to apply any quality of life index.530 € 5. cleaning. 81: 199-204 . For the first assumption we utilized the life expectancy estimation for Asturias for the age bracket 70-74 for men (during which they commence treatment).4 1301.4 39. difference between option of not treating and the treatment— amounted to 71. Table III.2 30. The marginal cost (cost of each additional session) reaches in the fourth session the minimum value of 6. electricity.050 €. and 17 years for women in the same age bracket. an estimation of the cost was made. The estimation considered the direct costs linked to the process of the intervention from when the patient is diagnosed to the time of release due to fibrosis or after two years from treatment initiation. security. a checkup appointment is set for three months. water. documents Total session cost Euros 39. The abandonments accumulated in the last sessions.8.530 € for women. 63. The mean age of women was 71. Materials Verteporfin injection Material for angiography 3. Finally.993 € and in the fifth session it increases to 28. For calculating costs. followed by ROI of the equipment (photo-coagulating ophthalmic laser).525 € (table III).6 1252. only 15% more of individuals who underwent PT achieved stable vision (loss of under 3 lines) vis-à-vis the patients who were given placebo.7 253.7 % 2 68 2 26 2 100% RESULTS Of all the treatments applied. Personnel 2.611 €. the visual acuity test was carried out on the same day as the angiography and treatment with verteporfine.525 € 34. Table II. we utilized the analytical accountancy of the area hospital.729 € 71.3 30. which is of 13 years. In the group of the study.2 1915. The total cost (cost of all sessions given to patient during the period) reached 549.0 251. In addition. Here. Cost per session at the study hospital Costs per item 1.354 € 4. adjusted for quality of maintenance of visual acuity.08 per patient. General costs Maintenance.804 € 36. the highest value.804 € for men and 36. The most important cost is the medication (verteporfin). attended to.

said limitations do not invalidate the shown results. who consider a life expectancy of 11 years without gender differentiation (17).249 66. For this reason it is extremely important that treated patients must exhibit good visual acuity. If it is assumed that the results will be maintained during the life expectancy period. With a similar analysis.Cost effectiveness of Photodynamic Therapy In a two-year scenario. To justify the priority which can be given to PT within the public services portfolio we have the criterion established by the study of Sacristán et al who considered as cost-effective (in Spain) the interventions with a value per year of quality-adjusted gained visual acuity not exceeding 30. The same conclusion was reached by Hopley et al (20) three years later. The benefits of PT consist in maintaining or slightly improving visual acuity. In this study the yearly cost for the health services for maintaining visual acuity in ARMD patients by applying PT is in the area of 36. the cost estimate for each year of quality-adjusted gained visual acuity is of 66. This estimate is detailed in table IV.354 € for men and 4. ARCH SOC ESP OFTALMOL 2006.931 9. subject to the results of the essays still in process (18). DISCUSSION Although some questions remain. Cost per year of quality-adjusted gained visual acuity Item Cost per year of maintaining visual acuity (2 years) • Men • Women Cost per year of maintaining visual acuity (in life expectancy period) • Men (13 years) • Women (17 years) Amount (€) adjusted maintained visual acuity— this reference must be taken into account in decision-making because the cost for that results increases to 68. in the light of the results. to establish whether allocating public funds to PT is justified. 70. The life expectancy timeframe for PT analysis has been utilized by other authors (18) but it has important limitations because we still don’t have documented evidence indicating that benefits are sustained at such a long term.000 €. From the viewpoint of health services it is necessary to determine the cost-effectiveness ratio of PT and. Even though the measure of health results is somewhat different in this study —year of qualityTable IV.298 € for women. costs go down substantially: 5. The recommendations which arise of the study are the need of improving early detection —eyes with many druses or hyperpigmentation are at greater risk (21)— and the definition of treatment protocols allowing for increased effectiveness.298 € for women (table III). which must be considered as a decision-making support tool for public health services resource managers. In this way. The limitations of the study are firstly in its retrospective nature. The option is to do nothing because other therapeutic options are in experimental stages or have proved to have negligible efficiency rates. Patricio Adúriz Alonso revealing to us some of the mysteries of ophthalmology. which prevents the utilization of quality-of-life questionnaires and a greater control of the application of PT in both eyes.000 € (19). Additional limitations relate to the size of the studied sample due to the low prevalence of the disease in the general population with a long-term intervention which has been introduced in clinical practice only recently. However. The number of patients who complete the treatment is limited and does not allow for further analyses. it would be possible to construct cost scenarios for different benefits. If we estimate that the benefits are maintained up to the patients’ life expectancy age. 81: 199-204 203 .794 ACKNOWLEDGEMENTS The authors would like to express their gratitude to the Hospital del Oriente de Asturias for their help in data collection and Dr.000 €. such as functional indices because maintaining eyesight in independent elderly people is more valuable than for dependent people. This scenario is also shown by Sharma et al.743 7. at this time PT is the choice for exudative ARMD.354 € for men 4. It would be more adequate for future benefits to be related to more global evaluations of patients. Sharma et al (17) consider that this intervention is moderately cost-effective for patients with an initial VA of 20/40 and costineffective for patients with a VA of 20/200 (this is the VA for most of our patients.249 € for men. the results go down to 5. far from the current situation (which borders legal blindness).931 € for women and 70. with only 28% having higher values).

Evaluación de un modelo de alta resolución para el tratamiento de la neovascularización subretiniana (NVSR) con verteporfín en el Principado de Asturias. 81: 199-204 . 17. 22: 536-544. The prevalence of age-related maculopathy in Iceland: Reykjavik eye study. Friedman DS. Risk of age-related macular degeneration in eyes with macular drusen or hyperpigmentation: The Blue Mountains Eye Study cohort. Smith D. 7. Pinto JL. Arch Ophthalmol 2001. Marcus DM. Del Llano J. Arch Ophthalmol 2004. Terapia fotodinámica en el tratamiento de la degeneración macular asociada a la edad. Johnson MH. Natal-Ramos C. Meads C. but how big is its effect? Results of a sytematic review. Munoz B. Bird AC. Treatment of Age-Related Macular Degeneration with Photodynamic therapy (TAP) study group. Brown MM. de Jong PT. Díaz-Varela M. Hollands H. Arch Ophthalmol 2001. Termoterapia transpupilar en neovascularización subretiniana oculta secundaria a degeneración macular asociada a la edad. McIntosh SB. Mitchell P. 77: 617-622. Ceballos M. Sádaba Echarri LM. 88: 982-987. 10: 215-225. Jonasson F. The cost-effectiveness of photodynamic therapy for fellow eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Friedman DS. 3. Wang JJ. Mitchell P. 11. Sasaki H. Drugs Aging 2001. 121: 379-385. Primeros resultados. Foran S. Verteporfin In Photodynamic Therapy Study Group. O'Colmain B. Hopley C. 88: 212-217. double-masked. Arch Ophthalmol 2000. 8. 119: 171-180. 204 ARCH SOC ESP OFTALMOL 2006. Congdon N. Bressler NM. et al. Brown MM. Salkeld G. 118: 47-51. Arnarsson A.MUSLERA E. Farber MD. Ophthalmic Epidemiol 2003. Klaver CC. 18: 405-467. Maguire A. García Layana A. Foran S. randomized clinical trial. Smith W. 15. Risk factors for age-related macular degeneration: Pooled findings from three continents. Sharma S. Sánchez Tocino H. Bressler NM. 16. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult no classic choroidal neovascularization--verteporfin in photodynamic therapy report 2. 106: 2239-2247. randomized. Arch Ophthalmol 2003. Assink J. 20. Juberías Sánchez JR. 12. Prieto L. Am J Ophthalmol 2001. 4. 5. Klein R. Klein R. 10: 267-277. 16: 334-343. Oliva G. Mitchell P. McCarty C. 19. 13. Br J Ophthalmol 2004. Photodynamic therapy with verteporfin is effective. et al. et al. 131: 541-560. Arch Soc Esp Oftalmol 2002. 14. 108: 697-704. 10. double-masked trial on radiation therapy for neovascular age-related macular degeneration (RAD study). Sharma S. Ophthalmology 1999. 21. Muslera-Canclini E. Radiation Therapy for Age-related Macular Degeneration. Brown GC. O'Colmain BJ. 122: 477-485. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap Report 2. Ophthalmology 2001. Utility values and age-related macular degeneration. Causes and prevalence of visual impairment among adults in the United States. et al. Klein BE. 108: 2051-2059. Kistler J. Informe Técnico realizado por la Agència d’Avaluació de Tecnologia y Recerca Mèdiques. 18: 233-241. ¿Qué es una tecnología sanitaria eficiente en España? Gac Sanit 2002. 6. McCulloch D. Cienfuegos S. Mitchell P. Moreno Montañes J. Rev Calidad Asistencial 2003. Age-related macular degeneration: cost-of-illnes issues. 2. National Registry for the Blind in Israel: estimation of prevalence and incidence rates and causes of blindness. Sasaki K. Aduriz-Lorenzo P. 121 :658-663. 122: 564-572. Wang JJ. A prospective. Barcelona: Agència d’Avaluació de Tecnologia y Recerca Mediques. Hyde C. Munoz B. et al. External beam irradiation of subfoveal choroidal neovascularization complicating agerelated macular degeneration: one-year results of a prospective. Oneill C. 9. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Arch Ophthalmol 2004. 2002. REFERENCES 1. Effects of verteporfin therapy on contrast sensitivity: Results From the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) investigation-TAP report No 4. Klaver CC. Sheils W. Shah GK. Leibach DB. Brown GC. Br J Ophthalmol 2004. Tomany SC. Ophthalmic Epidemiol 2003. Sacristan JA. Salinas Alamán A. Causes of visual impairment in two older population cross-sections: the Blue Mountains Eye Study. Arch Ophthalmol 2003. Rubin GS. Cost utility of photodynamic therapy for predominantly classic neovascular age related macular degeneration. 119: 198-207. Prevalence of age-related macular degeneration in the United States. Jamison J. Smith W. Ophthalmology 2001. Peto T. Oliva J. 18. Retina 2002.