Innovation, prioritization and sustainability: contemporary dilemmas of Pharmaceutical Services

Abstract

Over the last five years, articles addressing pharmaceutical services have increasingly focused on issues such as technology incorporation, funding, inequalities in access to medicines and regulatory challenges. This essay discusses the implications of focusing on innovation to the detriment of essential medicine prioritization, particularly the effects of this approach on the sustainability of the health system. First-in-class innovations do not always meet health priorities or established criteria for prioritizing medicines. From a health system perspective, innovations that genuinely address unmet health needs may be prioritized, provided their use is supported by robust evidence. However, the system needs to have the necessary structural and financial conditions and technical and workforce capacity and capability to effectively implement the technology. Ways to overcome these challenges include increasing the use of budget impact analyses and improving the regulatory framework for incorporation. To organize, or rather reorganize PS, there is an urgent need to address the dilemmas outlined in this paper.

Key words:
Health Technology and Innovation; Essential Medicines; Health Technology Assessment; Pharmaceutical Services; Unified Health System

Resumo

Nos últimos cinco anos, observa-se que os temas relacionados à Assistência Farmacêutica vêm se direcionando com maior volume e intensidade para as questões como incorporação de tecnologias, financiamento, desigualdades de acesso, desafios da regulação sanitária, dentre outros. Este ensaio pretende discutir a centralidade atribuída à inovação em detrimento da priorização de medicamentos essenciais e seus efeitos sobre a sustentabilidade do sistema de saúde. Observa-se que as inovações first-in-class nem sempre atendem às prioridades sanitárias ou aos critérios firmados para priorização. Na perspectiva do sistema de saúde, inovações que de fato abordem uma necessidade não atendida podem ser priorizadas, caso sejam respaldadas por evidências robustas. É preciso que o sistema tenha condições reais - estruturais, financeiras, e capacidades técnica e humana - de implementar adequadamente a tecnologia. Formas de superar os desafios deste descompasso são principalmente pelo incremento de análises de impacto orçamentário e do marco regulatório da incorporação. A organização, ou reorganização, da Assistência Farmacêutica depende deste enfrentamento tempestivo.

Palavras-chave:
Tecnologia e Inovação em Saúde; Medicamentos Essenciais; Avaliação de Tecnologia em Saúde; Assistência Farmacêutica; Sistema Único de Saúde

Resumen

En los últimos cinco años, los temas relacionados con los Servicios Farmacéuticos se han centrado en incorporación de tecnologías, financiación, desigualdades en el acceso, desafíos de la regulación sanitaria, entre otros. Este ensayo tiene como objetivo discutir la centralidad atribuida a la innovación en detrimento de la priorización de medicamentos esenciales y sus efectos sobre la sostenibilidad del sistema de salud. Se observa que las innovaciones first-in-class no siempre responden a las prioridades sanitarias ni a los criterios establecidos para la priorización. Desde la perspectiva del sistema de salud, pueden ser priorizadas aquellas innovaciones que aborden efectivamente una necesidad no cubierta, siempre que estén respaldadas por evidencia sólida. Es necesario albergar condiciones reales - estructurales, financieras, y con capacidades técnicas y humanas - para implementar adecuadamente la tecnología. Las formas de superar los desafíos de este desajuste incluyen principalmente el aumento de los análisis de impacto presupuestario y la adecuación del marco regulatorio para la incorporación. La organización, o reorganización, de los Servicios Farmacéuticos depende de afrontar estos retos.

Palabras clave:
Tecnología e Innovación; Medicamentos Esenciales; Evaluación de la Tecnología Biomédica; Servicios Farmacéuticos; Sistema Único de Salud

Introduction

In 2020, the Journal Ciência & Saúde Coletiva (C&SC) presented a study outlining the evolution of topics related to pharmaceutical services (PS) in articles published in the journal over the previous 25 years. This scoping review was organized into themes and called an ‘ontology’¹. The review identified core themes, including medicine utilization, management and tangential aspects of the PS cycle. The first two themes were more restricted to the organization of PS and clinical activities, while the last category encompassed secondary themes such as health technology assessment (HTA), research and development, intellectual property, registration and health regulation, global health and international cooperation.

Over the last five years (2020-2024), articles have increasingly focused on issues related to ‘macro processes’, including incorporation of technologies, financing, inequalities in access to medicines and health regulation challenges^2-13.

Considering the intersection between current issues and the secondary themes identified in the abovementioned ontology, especially HTA and developments in medicine incorporation in the country, this article reflects on three overarching issues in the current debate on PS that are central to essential medicines (or what we now consider to be essential medicines): innovation, prioritization and sustainability of health systems. To this end, we reviewed current national and international literature to inform this debate.

This essay discusses the implications of focusing on innovation to the detriment of essential medicine prioritization, particularly the effects of this approach on health system sustainability. What is considered innovation? What role does ‘innovation’ play, and how has it influenced incorporation processes? How are priorities for medicines set? What is the approach to medicine prioritization? What are the consequences of these choices for the sustainability of the health system?

Innovation

The progress made in drug therapies for various diseases in recent decades is undeniable, often changing the nature of diseases, promoting cure and contributing to increased life expectancy and sustained improvements in quality of life¹⁴. However, this progress has not encompassed all diseases, failing to include those that affect humanity the most, especially unsolved age-old problems^15,16. Nor has it been balanced across all classes of drugs, but rather carefully targeted at specific therapy niches¹⁷. Innovation dilemmas have been addressed in articles published in C&SC, albeit to a limited extent^4,7,9-11.

The key focus of pharmaceutical innovation is ‘first-in-class’ (FIC) drugs, tending to give preference to novel drugs and new therapeutic targets rather than priority health needs or traditional therapeutic gaps^15,17. The US Food and Drug Administration (FDA) approved 50 new drugs and nine new cellular and gene therapy products in 2024 for cancer, neurology, genetic disorders and cardiovascular disorders¹⁶. With regard to type of disease, there is a clear focus on rare diseases, which include cancer. Although common worldwide¹⁸, cancer encompasses an array of diseases, many of which are rare, according to existing definitions¹⁹.

This focus clearly illustrates the rationale behind innovation around the world today and behind new forms of research - platform trials, basket trials, umbrella trials, promoting ongoing trials with faster results²⁰ - and development and assessment, shortening the phases of drug development and accelerating health registration processes¹³. This accelerates the incorporation process, which is often supported by new ways of summarizing and updating evidence - such as rapid assessments, systematic reviews and network and continuous data meta-analyses - and by artificial intelligence and the production of real-world evidence derived from real-world data, without the need for comparative clinical trials¹⁷.

It is important to explore the implications of this focus on FIC in drug discovery research. For example, what do multi-target drugs, gene therapy and ‘advanced’ (cellular) therapy mean for the classification of medicines? Drugs are commonly classified by therapeutic indication, meaning that these therapies challenge our traditional understanding of pharmacology and therapeutics. From this perspective, FIC innovation may require new forms of classification, making traditional classifications such as target-based (receptor) classification and the World Health Organization’s Anatomical Therapeutic Chemical Classification, which categorizes drugs into classes and subclasses according to their pharmacological and chemical properties²¹, obsolete.

Drug classification problems also make comparative analysis studies unfeasible. If a FIC drug is essentially new, what can be compared to this ‘chemical/pharmacological/organic’ entity? After all, comparing alternative therapies to provide evidence of effectiveness and safety forms the basis of decision-making in public health. Thus, when it comes to FIC drugs, how can comparisons be made to obtain the desired clinical outcomes and inform planning and management?

Furthermore, while therapies used to be designed to modify the body’s response to disease or act on bodily processes, new therapies are designed to modify the body’s structure or genes, theoretically acting on all somatic cells. Although these therapies are not exactly individualized, they are designed to meet the needs of an extremely small group of rare disease patients¹⁸, and some therapies are used to treat single individuals. In T-cell Chimeric Antigen Receptor (CAR-T) therapy, for example, autologous T cells are extracted from the blood, genetically modified in a laboratory and injected into the patient’s blood to recognize and eliminate cancerous cells²². In the case of gene deletion, the gene ‘defect’ is diagnosed, and genome editing is proposed to improve outcomes or cure a single individual²³.

The biggest implication is the limited scope of these treatments. How can access and equity be guaranteed in the face of this narrowing down of target groups? It is now the process that is accessed rather than the product itself. The lifecycle of these technologies is shorter than that of conventional medicines, where there is continuous adoption of new drugs, improving access and lowering costs due to competition from alternative therapies until the end of the cycle when the technology is eventually replaced²⁴. With FIC drugs, adoption is the overriding interest, there is no competition, and replacement only takes place with another process aimed at the treatment of a single individual if the first one fails to fulfill the promise of cure. This logic needs to be questioned from an ethical point of view. A single individual benefits, but at the cost of how many others?²⁵ What are the (potentially substantial) implications of this type of innovation for humanity?

It is also worth noting that innovation does not necessarily guarantee effectiveness and safety. This is because of the acceleration of drug development, registration and market authorization processes. The speed of these processes does not allow for prior scrutiny of the product that is being launched, meaning that it is ‘validated’ when it comes onto the market and the population is exposed to risk. That is why around 17% of drugs launched on the market are withdrawn partially or completely (discontinued)²⁶. A study investigating the efficacy and safety of CAR-T therapy reported that clinical studies involved samples (e.g.: patients with refractory lymphoma or in partial remission) using a short follow-up period. Despite a high overall response rate, significant heterogeneity was observed, and no comparators were used, limiting the understanding of late events and real impact on survival²⁷. Furthermore, CAR-T cell therapy-associated toxicity rates vary and require experience to ensure safe management, intensive care and lifelong monitoring^28,29.

Moreover, the pace at which ‘new’ drugs enter the market is not abated by failure. When a product is withdrawn, others are waiting to take its place. The pace of market turnover poses a challenge for conventional pharmacovigilance processes, including monitoring and risk assessment.

It is also important to mention the disparities and inequities in access to FIC technologies. Innovations target a very limited audience, and it seems that developers want things to stay that way, even though lower prices could mean more people being treated, as is the case with the new diabetes and weight-loss drugs. In contrast, the rationale behind innovations for the treatment of less prevalent diseases is a focus on specific groups. The use of innovative technologies for a ‘select’ few justifies charging exorbitant prices. Companies are driven by market forces²⁵ and influence drug prescribers and patients. Right-to-health litigation is clear proof of this phenomenon. While right-to-medicines litigation plays an important role in ensuring access to medicines, it also benefits pharmaceutical companies economically³⁰. The state - the primary funder of medicines - is the last resort for people who really need medication; however, the state needs to lay a clear path for decision-making that addresses priorities.

Prioritization

Healthcare provision involves management supported by technical instruments and qualified human resources, who are often under severe strain due to health system complexities^31,32. Major issues include growing medicine needs and the high cost of new medicines, coupled with inappropriate use of medicines and health resource shortages³³.

With regard to medicines management, choices need to be made to determine which products will be made available to the population. Prioritization is a key strategy in this process to ensure equitable access and rational use of suitable treatments^32,33.

Prioritization within the health system takes place at the macro and micro level. The choices made at the macro level - for example regulation, medicine selection and incorporation, and funding - have repercussions for the entire population. The micro level is restricted to a narrower sphere that encompasses the choices of the health professionals and managers working in local health services, aimed at ensuring the rational and efficient use of medicines and available resources^2,3,31,32. It is necessary to discuss the evolution of the criteria used to define priorities for the inclusion of drugs on the essential medicines list to chart the evolution of this theme over the years and discuss the factors that determine selection.

Macro level prioritization milestones in Brazil have been described in articles published in C&SC^31,34. HTA is an important strategy based on sound evidence-based criteria³⁵, which is no longer in doubt due to the work of the collegial bodies tasked with medicine selection and incorporation since 2002, such as the Technical and Multidisciplinary Committee for Updating the National List of Essential Medicines (Comare) and National Committee for the Incorporation of Technologies into the SUS (Conitec)³⁶. While the use of evidence-based criteria remains the bedrock of prioritization, there is currently a certain lack of coordination between selection/incorporation and registration processes, coverage and funding, as highlighted by Silva et al.³⁷.

On the other hand, the National List of Essential Medicines (Rename), which has historically been the primary tool for selecting the medicines provided by the country’s public health system, o Sistema Único de Saúde (SUS) or Unified Health System, has become a positive list, with incorporation dictating the inclusion of relative rather than absolute priorities, compromising funding and the public health agenda^36,38. Over the years, despite changes in the list development process, external pressures from industry, patient associations, prescribers and right-to-health litigation have caused difficulties, leading to the inclusion of medicines not registered by Brazil’s equivalent of the FDA, Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency - Anvisa). Furthermore, incorporations via simplified processes without public consultation and political and administrative interests raise transparency and independence concerns³².

A study comparing the technology incorporation process in Brazil with other countries showed that it does not include a formal stage for assessing health priorities, limiting the transparency of the process by which medicines are incorporated into the strategic plan³⁹. Differentiated assessment criteria, such as specialized programs for highly innovative technologies and structured methods for prioritizing medicines for rare diseases, have been used by countries such as the United Kingdom and Australia^4,5. In England, cost-effectiveness criteria, especially those based on costs per quality-adjusted life years (QALYs), play a central role in assessment, together with Managed Entry Agreements (MEAs), which encompass Risk Sharing Agreements (RSAs)³¹, used for medicines with a high level of clinical and financial uncertainty.

Prioritization of cancer drugs by Conitec has been guided by both clinical and economic criteria, with an emphasis on efficacy and budgetary impact; however, there is lack of clarity over the weighting of these criteria in incorporation decision-making⁸. The prioritization process, which should lead to the provision of these medicines by health services, has been hampered due to the absence of clear resource allocation criteria and unclear rules for the use of these drugs in clinical protocols and therapeutic guidelines⁹.

Despite various regulations designed to increase certainty and provide the bargaining power needed to promote the incorporation of novel therapeutic products, new prioritization criteria are still needed to address the exorbitant price of certain medicines, which challenges conventional HTA rationale, threatens the sustainability of health systems and potentially violates the principle of equity, as illustrated by the recent incorporation of gene therapy in Brazil¹⁰.

The lack of clear standardized guidelines for the practical implementation of drugs after authorization of incorporation¹¹ hampers the post-incorporation phase¹¹. The absence of a centralized and transparent price negotiation model and robust price regulation policy also leads to significant differences in incorporated medicine acquisition costs, generating regional inequities in access¹².

Conitec decisions directly affect the day-to-day functioning of PS at the micro level. The lack of rigorous technical criteria and external pressures at municipal and service level influence local essential medicines lists⁴⁰. Furthermore, the complexity of the medicine list and lack of training of prescribers and dispensers hampers rational prescribing and pharmacotherapy and contributes to inefficient management of PS³⁸.

This is because the provision of some medicines requires certain conditions, such as specialized facilities and rigorous monitoring and training, which not all services have^10,40, particularly in the case of medicines for rare diseases and cancer^4,5,9. From a day-to-day care and service perspective, complex technologies require constant monitoring of clinical outcomes to ensure safety and effectiveness, respecting the criteria endorsed at the macro level¹⁰. Effectiveness can be undermined by the absence or inadequacy of minimum technical requirements for medicines, which can adversely affect the prioritization of technologies in different contexts.

Thus, effective local implementation of macro-level decisions requires efficient management of PS, with the appropriate use of medicines requiring alignment between clinical practice in health services and incorporation policies^31,39. However, this alignment does not always occur, with the following limiting factors being observed: organizational and structural barriers and lack of focus on logistical and social aspects; limited monitoring and evaluation of outcomes after the incorporation of medicines; and lack of concrete guidelines for managers and health professionals on how to integrate priority medicines into the day-to-day functioning of local health facilities⁸.

Thus, whatever the level of decision-making, it is essential to improve and strengthen these processes and complement HTA with other actions that promote effective public participation to ensure transparency, consistency and alignment between macro-level decisions and the operational reality of health services. The lack of public participation in the prioritization processes that are supposedly consolidated in the SUS is demonstrated by medicine shortages, the need for right-to-health litigation, lack of transparency in resource allocation decisions and funding shortages. It is therefore imperative to rebuild the social pact within the SUS, with a view to promoting sustainability and respect for patients’ needs.

Sustainability

SUS funding has been insufficient to meet growing health needs, with federal funding stagnating between 2010 and 2019, hampering efforts to meet Sustainable Development Goal 3 targets⁴¹. According to the Ministry of Health, funding for PS increased 1,346% between 2004 and 2024, from R$ 1.4 billion to R$ 21.9 billion⁴². But what do these figures actually mean for the sustainability of PS in the SUS?

Maybe they do not mean much, or maybe they do, but only for a short period of time. Unfortunately, the figures show that spending on alternative forms of access to medicines, predominantly claims resulting from right-to-health litigation, is growing. In some municipalities, spending in the public health system resulting from right-to-medicines litigation is equal to or greater than regular spending, depriving other areas of resources⁴³. Spending on these claims as a proportion of overall spending on PS increased from 4% in 2012 to more than 7% in 2018⁴⁴.

Drugs for rare diseases, cancer, targeted therapy and immunotherapy account for the largest proportion of this spending. The exorbitant cost of these drugs is complicated by uncertainty over the real effectiveness and benefits of numerous new therapies, which may offer only marginal gains. Although these gains may matter to individuals who wish to receive these therapies, they must be carefully weighed up when prioritizing and incorporating them into systems⁴⁵, as they could have a direct impact on sustainability in the short- to medium-term.

Price regulation plays an important role in sustainability in the short- medium- and long-term, especially when it comes to the introduction of new technologies. The market entry price should consider the technology’s life cycle, reflecting fluctuations in demand and future obsolecence⁴⁶. However, from the outset, the price should also reflect the health and social importance of the technology, which is measured according to the quality and robustness of evidence for its intended indication and level of priority as a health intervention, or its so-called ‘therapeutic value’. Ideally, only medicines of high therapeutic value should be prioritized and incorporated. These medicines indirectly foster sustainability because they have contributed to rational use since the clinical trial phase, being effective and safe and meeting the real needs of the population.

At the same time, it is essential to create mechanisms to keep drugs that the industry no longer wants to sell on the market because the price is no longer financially attractive. These medicines continue to be safe and effective and represent a lower financial burden for both the health system and individuals. This is particularly important in Brazil for two reasons: first, spending on the SUS has increased over the years, accounting for 18.2% of total health spending in 2019, which is one of the highest levels in the world; second, 87.7% of spending on medicines in the country is out-of-pocket⁴⁴.

Despite the expansion of public programs and services and the strengthening of the SUS, historical and structural obstacles, institutional legacies, and disputes over different health projects have also influenced national policy. The combination of these elements has resulted in tensions, especially over the role of healthcare in the development model, the link between healthcare and social security, the health financing model and the relationship between the public and private sectors. The expansion of public services has occurred in tandem with the growth of the private sector, forming competitive healthcare markets that compete for state and household resources, limiting the consolidation of a truly universal system and deepening social and health inequalities⁴⁷.

Sustainability faces some other ominous challenges. Technological dependence and the lack of domestic production of technologies that meet real health needs places the country in the hands of external producers and distributors and changes in the international context⁴⁸. A diverse range of factors can hamper medicine provision and force governments to look for alternatives - that are often more expensive, less adequate, and carry uncertainty about their quality - or endure shortages, resulting in gaps in essential medicines. These factors include: difficulties in active pharmaceutical ingredient (IFA) production in countries like China and India, which are the largest manufacturers of these inputs; problems with trade routes due to wars or geopolitical tensions or interruptions in supply chains due to shortcomings in the country chain or limitations in international bodies⁴⁹; obstacles to authorization for health products by international bodies or Anvisa; and sudden spikes in national or localized demand driven by health emergencies or disasters, resulting in shortages.

Sustainability depends not only on medicine funding but also on having the right structural conditions in place to ‘cushion’ variations in supply and demand. Affordability to the health system is one of the core criteria for selecting essential medicines. This increasingly applies to rich countries, who also do not have the luxury to spend precious resources on non-essential medicines³³.

If these criteria are not met, gaps in supply, and therefore treatment, are inevitable. Overburdening the system with expensive - or even cheap - alternative therapeutic options, therapies of dubious effectiveness, or treatments supported by a robust evidence base at prices that make provision unsustainable, makes maintaining a stable timely supply unfeasible, ultimately undermining the health system, which is the current reality in the SUS.

Sustainability is directly linked to innovation and prioritization. Excellent new innovations that save lives and improve quality of life are desirable and should receive the same level of priority as older safe and effective medicines. It is also important to take into account the environmental impact of medicines, including pollution, waste and health risks, giving priority to less environmentally harmful alternatives⁵⁰.

Given the importance of these issues, this topic, which is still in its infancy in the pages of C&SC, is likely to gain prominence in the debate surrounding PS in coming years. Finally, it is worth highlighting three core principles that underpin the sustainability of PS. First, it is important to ensure that resources are allocated to both innovations and older safe medicines, maintaining a continuous and stable supply. Second, a life-cycle approach needs to be adopted, addressing the risks associated with long-term use of new technologies. Third, it is essential to recognize that everyone with a proven health need has the same right to access technology, meaning that access must be equitable.

Final considerations

From a health system perspective, innovations that genuinely address unmet health needs may be prioritized, provided their use is supported by robust evidence. However, the existence of evidence or the lack of therapeutic options for a given indication are not the sole criteria for prioritizing a given technology. The system needs to have the necessary structural and financial conditions and technical and workforce capacity and capability to effectively implement the technology. Otherwise, the potential of the adopted technology will not be fully harnessed and, worse still, the investment could be in vain.

Attempting to harness the full potential and effectiveness of a technology is an ethical imperative. After all, all new medicines have an opportunity cost, ultimately depriving other technologies and alternatives of resources due to limited funding.

However, there are ways to overcome these challenges, one of which is to increase the use of budget impact analyses during the incorporation process to provide managers with quality data for decision-making. Another is to improve the regulatory framework for incorporation, for a number of reasons: (i) to ensure ongoing monitoring of incorporated innovations and, first and foremost, patient protection; (ii) to promote ongoing rather than ad hoc priority setting, while monitoring the technology horizon; (iii) to be able to judge the therapeutic value of incorporated technologies in relation to price; (iv) to enable the implementation of reimbursement mechanisms based on therapeutic outcomes and technology performance, facilitating divestment; (v) to integrate diagnosis and treatment processes to ensure that treatments for which a diagnosis is not available are not adopted, which is a prerequisite for the timely use of technology; and finally, (vi) to facilitate the production of sound evidence to enable effective monitoring and vigilance and promote transparency in access to and appropriate use of technologies.

Prioritization processes tend to be reactive rather than proactive: we do not anticipate problems, rather we wait for them to occur and then take action. To organize, or rather reorganize PS, there is an urgent need to address these dilemmas, and RCSC provides a critical forum to advance this important contemporary debate.

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• Chief editors:
  Maria Cecília de Souza Minayo, Romeu Gomes, Antônio Augusto Moura da Silva, Vania de Matos Fonseca

Publication Dates

• Publication in this collection
  06 Oct 2025
• Date of issue
  Sept 2025

History

• Received
  15 June 2025
• Accepted
  16 June 2025
• Published
  18 June 2025