In March 2024, the Spanish Ministry of Health published the guideline for the health economic evaluation of medicines proposed by the Advisory Committee on the Financing of Pharmaceuticals for the National Health System (CAPF, Comité Asesor para la Financiación de la Prestación Farmacéutica del Sistema Nacional de Salud).1 This guideline was developed in response to a 2023 request from the General Directorate of Pharmacy (DGF, Dirección General de Farmacia) of the Ministry of Health, aiming to provide and formalize a methodological framework for conducting and critically appraise health economic evaluations informing the introduction of innovative medicines in Spain. These evaluations can be crucial for decision-making regarding the positioning, public reimbursement, pricing, and subsequent reassessments of medicines. Furthermore, the development of this guideline was also previously recommended by CAPF.2,3 The health technology assessment (HTA) mechanisms in Spain can be contextualized and further explored in previously published documents.2,4,5 Additionally, the HTA mechanisms are currently under review by the Ministry of Health, with the publication of two related Royal Decrees, regulating HTA and price and the selective financing process, expected by the end of 2024 or the beginning of 2025.

Previous health economic evaluation guidelines have been developed in Spain,6–8 but to our knowledge, this is the first one commissioned by the Ministry of Health's Pharmacy Directorate to serve as a foundational document for the Ministry's own guideline, as part of its strategy in modifying and reforming the health technologies evaluation process.

With the aim of improving the transparency and quality of future economic evaluations of medicines, and to enhance the international dissemination of the guidelines, this article presents the official English translation of the economic evaluation guideline published on the Ministry of Health's website, to enhance access by the international community.1 In particular, the content of the guideline includes identifying and defining the sections or dimensions that a health economic evaluation must encompass, the design of a reference case, and a checklist for evaluating the methodological quality of health economic evaluations, by researchers, public health professionals, and potential decision makers. Further details on the in-depth discussions surrounding each dimension of the guidelines can be found in the original document published by CAPF in Spanish (https://www.sanidad.gob.es/areas/farmacia/comitesAdscritos/prestacionFarmaceutica/docs/20240227_CAPF_Guia_EE_definitiva.pdf).

For its development, CAPF formed an initial working group comprised of five experts (MTB, JO, FCL, LGP and LS), coordinated by one of the CAPF members (MTB). The selection criteria were based on the scientific and technical competence, the multidisciplinary composition of the group, and their expertise in health economic evaluation for informing health decision-making. The development process involved a review of previous Spanish guidelines on the subject,6–8 as well as selected international guidelines primarily from Australia, Canada, the United States, England and Wales, France, and Portugal, with a focus on the latter two.9,10 Additionally, the CHEERS 2022 statement11 and the EUnetHTA Guideline12 were considered. The first draft was reviewed by CAPF members (EA, AC, FL, AO and JPJ) and subsequently shared with a larger group of thirty-one experts, selected for their expertise and significant contributions to the field (their names are listed in the acknowledgments). We received written feedback from all these experts. Although the initial contact list of national experts was longer, no response was received from some of them. CAPF members carefully reviewed all contributions and finalized the document accordingly.

The content of the guideline was developed in several stages, as shown in Figure 1. Initially, each section or dimension was drafted by at least two members of the working group individually, followed by a peer-review of the working group members. Subsequently, the content and final form of the initial draft were determined by the working group. It was agreed to organize the content by clearly separating the definition of the reference case, the recommendations aimed at the authors conducting health economic evaluations and their reviewers, the explanation of each section, and the checklist. Following this, the document underwent a review by the CAPF, the DGF, and external experts. Finally, the CAPF completed the final version to be submitted to the DGF.

Figure 1.

Stages in the development of the proposed health economic evaluation guideline.

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The reference case delineates the methods and criteria selected for conducting health economic evaluations of medicines to support decision-making for their public funding or pricing. Table 1 reports a literal English translation of the main technical concepts of the core components of the reference case, aligning conceptual terms with those most commonly used in other international guidelines.

This reference case is accompanied by a checklist that should be utilized to evaluate the methodological quality of a health economic evaluation of medicines in Spain. This checklist can be employed during both the development and review stages of an economic evaluation analysis (see Table A.1 in online Appendix for details).

This guideline is part of a reform process of the medication evaluation procedure in Spain, proposed by the CAPF.1 It is specifically designed for the evaluation of medicines, and it comes at a time of transformation in the decision-making system for medicines in the country. Its publication, at the request of the General Directorate of Pharmacy of the Ministry of Health, may be used as a first step for the implementation of explicit methodology for decision-making regarding the funding of medicines.

At a methodological level, this guideline incorporates two elements that have been infrequently included in this type of document. The first is the importance of validating decision models, both internally and externally, and the other is the need to establish a distinct dimension for the re-evaluation of decisions made from this medication evaluation process. Although authors considered that the societal perspective would be appropriate for the analysis, data requirements to use a societal perspective can be challenging, and incorporating the healthcare payer perspective, which includes all healthcare costs associated with the intervention and not just the price of medicines, would constitute a significant achievement. Additionally, the proposed guideline for medicines can be easily adapted to other health products and technologies.

It is important to note that, while the guideline on health economic evaluation represents a first step and provides an initial methodological foundation, it should be complemented by additional guidelines that delves into specific methodological aspects related to economic evaluation. In particular, guidelines on relevant added clinical benefit, efficiency thresholds, clinical and economic uncertainty analysis, and budget impact analysis are required.1

In any case, the guidelines, by itself, are merely small pieces in a complex organisational and cultural change in the field of medicine evaluation that has yet to be realised. Analyzing the efficiency of medicines requires commitment, involvement and adequate resourcing from the Ministry of Health.5 Consequently, a prioritization system should be implemented to ensure the economic evaluation is primarily used for evaluating those medicines that offer a significant additional clinical benefit. In cases where there is no clinical benefit relative to alternatives, or where the additional clinical benefit over comparators is not relevant, a cost-minimization analysis should be conducted.

A health economic evaluation guideline in the context of the incorporation of medicines and health technologies into the service portfolio of the National Health System can have multiple uses and benefits. Its primary purpose is to establish a methodological framework to systematically, transparently, and objectively evaluate the value that these medicines and technologies bring to the health system and patients. It ensures that the limited resources of the health system are used efficiently, provides a clear and consistent framework for evaluating new technologies, promotes efficient innovation, justifies and accounts for health spending to society, and provides a solid basis for negotiating prices and reimbursements with suppliers of medicines and technologies, based on evidence of their economic and clinical value.

In summary, the proposed guideline for economic evaluation of medicines represents an essential tool for health services seeking to optimize the allocation of resources, promoting interventions with the best cost-effectiveness ratio, improving the quality of care, and ensuring the long-term sustainability of the system.

Pilar Pinilla Domínguez.

The corresponding author, on behalf of the other authors guarantee the accuracy, transparency and honesty of the data and information contained in the study, that no relevant information has been omitted and that all discrepancies between authors have been adequately resolved and described.

Contributions to this research article were shared among all participating authors. The conceptualization and design of this article were carried out by all authors. The first draft of the paper was written by M. Trapero-Bertrán with help of J. Oliva, but all authors contributed substantially equally to the final version of the manuscript.

The authors are very grateful to the larger group of 31 experts who reviewed the document and sent comments to the Advisory Committee for the Financing of the Pharmaceutical Provision of the National Health System: Salvador Peiró, Fernando Antoñanzas, Almudena González, Eduardo Sánchez, Javier Rejas, Josep Darbà, Pedro Gómez, Eduardo López, José Antonio Sacristán, Cristina Valcárcel, José Manuel Rodríguez, Juan M. Cabasés, Renata Linertová, Itziar Oyagüez, Javier Mar, Antonio J. García, Laura Vallejo, Max Brosa, Miguel Ángel Casado, Pilar Pinilla, Cristina Avendaño, Javier Soto, María Dolores Fraga, Pere Ventayol, Myriam Soto, Juan Carlos Rejón, Jorge Mestre, Fernando Ignacio Sánchez, José María Abellán, Miguel Ángel Negrín and Iñaki Gutiérrez. Thank you very much to all of them.

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