In the 1980s, the first economic evaluation studies in the Spanish healthcare field were published1. Since then, numerous pharmacoeconomic analyses have been conducted and published in Spain. A simple search in PubMed, using the terms “Cost-effectiveness” and “Spain”, yields (January 13, 2025) 3,544 references. As is often the case with new techniques, the first hurdle that had to be overcome at national and international level was the need to standardize pharmacoeconomic studies. In this regard, several guidelines have been published in Spain over the years, including the Economic Evaluation for Clinicians series2 and various unofficial guidelines that represented a considerable advance in this regard, one of which was published in 20103. The first official Spanish guide was developed in the Catalonia region in 20144.
After this brief historical review of the economic analysis of medicines in Spain, we should ask ourselves what the role of such analyses should be in the general context of the evaluation of medicines. The effects of medicines on the health of patients can be measured by three basic parameters: efficacy (demonstrated by randomized clinical trials), effectiveness in clinical practice (which should be demonstrated by pragmatic clinical trials, rather than by observational or “real-life” studies, which are very common today) and, finally, the efficiency of the new medicine, analyzed by economic studies, mainly cost-effectiveness or cost-utility. In this sense, economic analyses should be considered not only as a necessary step in obtaining the price and reimbursement of the new medicine, but also and above all, as the last stage in the development of a new drug. In order for the doctor to be able to choose the most appropriate treatment, he needs to have not only the efficacy and safety data, but also to know the efficiency of the various treatment options.
According to Royal Decree-Law 16/2012, of April 20, on urgent measures to ensure the sustainability of the National Health System: “The financing of medicines and health products in the National Health System is one of the great current challenges. Austerity in public spending, essential at all times, has become an urgent objective. Therefore, it is necessary, more than ever, that financing decisions be governed by the criteria of scientific evidence of cost-effectiveness and by economic evaluation, with consideration of the budgetary impact, in which a price scheme associated with the real value that the medicine or health product contributes to the system is taken into account”5. This was the first legal text that made official the need for economic analysis of medicines in Spain, despite the fact that this need was tacitly accepted since the 1980s.
Recently, the Spanish Ministry of Health has published two draft Royal Decrees: one on the financing and pricing of medicines6 and another on the assessment of health technologies7, both currently in prior public consultation. It also published a proposal for a guide to the economic evaluation of medicines8.
The proposed guideline8 includes what has been indicated in previously published guides. However, it insists on considering cost-utility analyses (cost per Quality-adjusted life-years [QALY] gained) to be preferable to cost-effectiveness analyses (cost per Life-years [LY] gained). This approach would be questionable in practice, given that in many cases there are no utility studies carried out in Spain, so that those carried out in other European countries with a similar socioeconomic level must be used. This preference for cost-utility studies could, however, result in more utility studies being carried out in Spain, which would be very positive. In any case, we consider that both results (cost per QALY or LY gained) are equally important when determining the efficiency of a new drug, so the most appropriate thing would be – whenever possible – to estimate both in pharmacoeconomic analyses.
Another debatable aspect of the proposed guideline8 would be the one related to the performance of probabilistic sensitivity analyses. This is an issue that, surprisingly, has been dragging on since the beginning of pharmacoeconomic evaluation. The probabilistic analysis (generally performed by means of a second-order Monte Carlo simulation) should not be a sensitivity analysis but the base case of the economic evaluation, since it provides a mean result, a 95% confidence interval of that mean and the probability that the most effective drug is cost-effective compared to the least effective, according to a willingness to pay per QALY or LY gained. In our opinion, the base case should be probabilistic, so that uncertainty can be adequately assessed, and univariate sensitivity analyses should be performed (using tornado diagrams) to establish which variables condition the result.
About the Authors
Carlos Rubio-Terrés, MHE, MPharmacol, BSc
Carlos Rubio Terrés is Director of HEALTH VALUE, Health Economics & Research of Outcomes Consulting, in Madrid, Spain. Over the past three decades he has held various positions in the Instituto de Salud Carlos III (Madrid), the Ministry of Health (Madrid), the Committee for Proprietary Medicinal Products (CPMP), (Brussels), and in a number of pharmaceutical companies (Lederle, Wyeth, Aventis). He has published 289 articles in peer-reviewed journals and book chapters.
Darío Rubio-Rodríguez, MHE, BCom
Darío Rubio Rodríguez is a Senior Consultant on Market Access and Pharmacoeconomics at Omakase Consulting SL, in Madrid. Previously he was a Senior Consultant on Pharmacoeconomics at Health Value SL, in Madrid. He has published 84 articles in peer-reviewed journals.
References:
- Badia X. La evaluación económica en el sector sanitario: revisión de los estudios españoles y apuntes para el futuro. Revisiones en salud pública. 1991; 2: 107-17.
- Prieto L, Sacristán JA, Antoñanzas F, Rubio-Terrés C, Pinto JL, Rovira J, por el Grupo ECOMED. Análisis coste-efectividad en la evaluación económica de intervenciones sanitarias. Medicina Clínica 2004; 122: 505-10.
- López J, Oliva J, Antoñanzas F, García-Altés A, Gisbert R, Mar J, et al. Propuesta de guía para la evaluación económica aplicada a las tecnologías sanitarias. Gac Sanit. 2010; 24: 154–70.
- Puig-Junoy J, Oliva-Moreno J, Trapero-Bertrán M, Abellán-Perpiñán JM, Brosa-Riestra M y Servei Català de la Salut (CatSalut). Guía y recomendaciones para la realización y presentación de evaluaciones económicas y análisis de impacto presupuestario de medicamentos en el ámbito del CatSalut. Generalitat de Catalunya. Departament de Salut. Servei Català de la Salut: Barcelona, 2014.
- Real Decreto-ley 16/2012, de 20 de abril, de medidas urgentes para garantizar la sostenibilidad del Sistema Nacional de Salud y mejorar la calidad y seguridad de sus prestaciones. BOE Nº 98, de 24 de abril de 2012.
- Proyecto de Real Decreto por el que se regulan los procedimientos de financiación y precio de los medicamentos. Available at URL: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.sanidad.gob.es/gl/normativa/docs/CPP_RD_PRECIO_MED.pdf (access: 14/01/2025).
- Proyecto de Real Decreto por el que se regula la evaluación de tecnologías sanitarias. Available at URL: https://www.sanidad.gob.es/normativa/audiencia/docs/DG_54_24_Solicitud_informacion_publica_RD_EVALUACION_TECNOLOGIAS_SANITARIAS.pdf (access: 14/01/2025).
- Comité Asesor para la Financiación de la prestación Farmacéutica del SNS. Guía de Evaluación Económica de Medicamentos. Ministerio de Sanidad, 2023. Available at URL: https://www.sanidad.gob.es/areas/farmacia/comitesAdscritos/prestacionFarmaceutica/docs/20240227_CAPF_Guia_EE_definitiva.pdf (access: 14/01/2025).