Abstract

This study aims to describe the profile for the requested incorporation of rare disease drugs submitted to CONITEC and its recommendations, comparing the incorporation criteria employed by other HTA agencies globally. To this end, requests for the treatment of rare diseases submitted to CONITEC from July 2012 to June 2019 and its recommendations to the Brazilian Unified Health System (SUS) were included in this study. Subsequently, we compared the criteria used by CONITEC and other HTA agencies to incorporate these drugs. Sixty medicine incorporation requests to treat thirty rare diseases were submitted to CONITEC. Pharmaceutical companies made the most requests (66%). Budget impact analyses were presented in 85% of the requests and HT economic analyses in 68%. A total of 52% of the requests were incorporated into the SUS. CONITEC’s justifications for the non-incorporation were the lack of quality clinical evidence, non-cost-effective technologies, and modest clinical benefits that do not justify the high prices. International HTA agencies (CAN, UK, FR, AUS) use different criteria for rare diseases assessments. The data indicate that most of the evaluated drugs were incorporated into the SUS, and adopting different criteria to assess the incorporation of rare diseases medicines will possibly strengthen decision-making.

Key words:
Rare diseases; Health technology assessment; Unified Health System

Introduction

In Brazilian public health, Law N° 8080 was created in 1990. It established the Unified Health System (SUS) based on Universality, Comprehensiveness, and Equity¹Brasil. Lei 8080 de 19 de setembro de 1990. Dispõe sobre as condições para a promoção, proteção e recuperação da saúde, a organização e o funcionamento dos serviços correspondentes e dá outras providências. Diário Oficial da União 1990; set 20., in obeyance to Art. 196 of the 1988 Constitution health is a right for all and a duty of the State²2 Brasil. Constituição da República Federativa do Brasil. Diário Oficial [da] República Federativa do Brasil, Brasília, DF, 1988. [acessado 2020 jan 18]. Disponível em: http://www.planalto.gov.br/ccivil_03/constituicao /constituicaocompilado.htm.. Universality calls for access to health for all citizens. Equity would allow the lack of unfair, avoidable, or remediable differences in the health of populations or groups defined with social, economic, demographic, or geographic criteria³3 Brasil. Ministério da Saúde (MS). Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Ciência e Tecnologia. Política Nacional de Gestão de Tecnologias em Saúde. Brasília: MS; 2010. 47 p.. Comprehensiveness, more specifically, is the need to understand individuals as biopsychosocial beings in their essence, traversing the possibility of access to all system levels, which leads us to its more concrete practice to provide materiality to the life of services⁴4 Carnut L. Cuidado, integralidade e atenção primária: articulação essencial para refletir sobre o setor saúde no Brasil. Saude Debate 2017; 41(115):1177-1186.. Thus, Carnut⁴4 Carnut L. Cuidado, integralidade e atenção primária: articulação essencial para refletir sobre o setor saúde no Brasil. Saude Debate 2017; 41(115):1177-1186. defined comprehensiveness as a guiding principle of the SUS. It is a principle that adopts the philosophical explanation of human beings and a guideline for having become something concrete, which guides the work process.

In this context, specific access to medicines is ensured by two public health policies, the National Medicines Policy⁵5 Brasil. Ministério da Saúde (MS). Portaria GM/MS nº 3916 de 30 de outubro de 1998. Aprova a Política Nacional de Medicamentos. Brasília, DF. Diário Oficial da União, Poder Executivo, Brasília, DF, 10 de novembro de 1998. and the National Pharmaceutical Care Policy⁶6 Brasil. Conselho Nacional de Saúde. Resolução nº 338 de 6 de maio de 2004. Aprova a Política Nacional de Assistência Farmacêutica. Diário Oficial da União, Poder Executivo, Brasília, DF, 20 de maio de 2004.. However, the SUS sustainability and funding have endured some challenges in recent years. Scientific health research has produced a significant increase in alternatives for detecting, preventing, and treating diseases, but budget constraints do not allow health care systems to provide patients with all interventions⁷7 Soárez PC, Soares MO, Novaes HMD. Modelos de decisão para avaliações econômicas de tecnologias em saúde. Cien Saude Colet 2014; 19(10):4209-4222..

Health technology assessments (HTA) and the growing demand for efficient allocation of health resources have led to the need to establish a committee to assist the Ministry of Health in decision-making, called the National Committee for the Incorporation of Technologies (CONITEC), which was created on April 28, 2011, the date on which Law No. 12.401 was enacted, defining criteria and deadlines for the incorporation of technologies in the SUS⁸8 Brasil. Lei Nº 12.401, de 28 de abril de 2011.Altera a Lei nº 8.080, de 19 de setembro de 1990, para dispor sobre a assistência terapêutica e a incorporação de tecnologia em saúde no âmbito do Sistema Único de Saúde - SUS. Diário Oficial da União, Brasília, DF, 29 de abril de 2011..

The daunting challenge for HTAs is ensuring that analyses, registrations, and availability of medicines for rare diseases (RD) are also realized⁹9 Silva EN, Sousa TRV. Avaliação econômica no âmbito das doenças raras: isto é possível? Cad Saude Publica 2015; 31(3):1-11.. The group term - rare diseases - is used to include a very heterogeneous group of disorders that can affect any system in the body. They are also called “orphan” diseases because, usually, little is known about their causes and effective therapies are still limited¹⁰10 Remuzzi G, Garattini S. Rare diseases: what's next? Lancet 2008; 371(9629):1978-1979.. Most of these diseases are genetic. They are often disabling and substantially affect life expectancy. They also impair physical and mental abilities, reducing the individual quality of life. These diseases are a significant public health issue and have been neglected for many years by health systems and pharmaceutical industries¹¹11 Schieppati A, Henter JI, Daina E, Aperia A. Why rare diseases are an important medical and social issue. Lancet 2008; 371(9629):2039-2041..

In 2012, the World Health Organization mapped between 5,000 and 8,000 rare diseases. The concept of rare diseases adopted by this group involves disease characteristics and epidemiological factors, with low prevalence determination¹²12 World Health Organization (WHO). Bulletin of the World Health Organization. Coming together to combat rare diseases. Vol. 90, Number 6, June 2012, 401-476.. Noteworthy is that the epidemiological definition varies between different countries. In Brazil, for example, in 2014, the Ministry of Health established that a rare disease is one with a prevalence below 65 per 100,000 people¹³13 Brasil. Ministério da Saúde (MS). Política Nacional de Atenção Integral às Pessoas com Doenças Raras. Portaria GM nº 199, de 30 de janeiro de 2014. [acessado 2020 jan 18]. Disponível em: http://bvsms.saude.gov.br/bvs/saudelegis/gm/2014/prt0199_30_01_2014.html.
http://bvsms.saude.gov.br/bvs/saudelegis... . The actual prevalence of these diseases is difficult to estimate, as the literature has not provided us with reliable data, showing low consistency among the information sources and low methodological quality of epidemiological studies¹⁴14 Auvin S, Irwin J, Abi-Aad P, Battersby A. The Problem of Rarity: Estimation of Prevalence in Rare Disease. Value Health 2018; 21(5):501-507..

Following extensive discussion with government agents, researchers, doctors, and patient associations, the National Policy for the Comprehensive Care of People with Rare Diseases in the SUS¹³13 Brasil. Ministério da Saúde (MS). Política Nacional de Atenção Integral às Pessoas com Doenças Raras. Portaria GM nº 199, de 30 de janeiro de 2014. [acessado 2020 jan 18]. Disponível em: http://bvsms.saude.gov.br/bvs/saudelegis/gm/2014/prt0199_30_01_2014.html.
http://bvsms.saude.gov.br/bvs/saudelegis... was promulgated in 2014, which seeks more dignified, humane, and inclusive care for those with rare diseases. One of the guiding principles of this policy is the incorporation of medicines for rare diseases and indicated within the SUS, which should result from the recommendations by government agencies from CONITEC’s assessment and approval. Based on this principle and to ensure the effectiveness of the objectives of this Policy, the first action by the Ministry of Health was a panel of experts who prioritized twelve clinical protocols for comprehensive care for people with rare diseases¹⁵15 Brasil. Ministério da Saúde (MS). Priorização de Protocolos e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Doenças Raras. No 142 Maio/2015..

Despite advances in recent years, compliance with the principles of universality, equity, and comprehensiveness in the SUS is still a challenge in light of the National Policy for the Comprehensive Care of People with Rare Diseases¹⁶16 Aith FMA. O direito à saúde e a política nacional de atenção integral aos portadores de doenças raras no Brasil. JBES 2014; 6(Supl.1):4-12.. The lack of adequate scientific evidence and the high cost of treatments hamper the inclusion of these therapies, and individuals often resort to the Judiciary to rule on the access to health products¹⁷17 Sartori Junior D, Leivas PGC, Souza MV, Krug BC, Balbinotto G, Schwartz IVD. Judicialização do acesso ao tratamento de doenças genéticas raras: a doença de Fabry no Rio Grande do Sul. Cien Saude Colet 2012; 17(10):2717-2728.^,1818 Guimarães R. Incorporação tecnológica no SUS: o problema e seus desafios. Cien Saude Colet 2014; 19(12):4899-4908.. Given this setting, rare diseases have demanded the attention of researchers and decision-makers to verify whether they should gain different assessment criteria than other diseases within the HTA⁹9 Silva EN, Sousa TRV. Avaliação econômica no âmbito das doenças raras: isto é possível? Cad Saude Publica 2015; 31(3):1-11.. Knowing that patients suffering from a rare disease is an essential part of the population, it is vital to understand the results of incorporating the technologies made available to them, compared to countries that also have consolidated HTA agencies.

This study aims to describe the profile of requests for incorporating medicines for rare diseases submitted to CONITEC and its recommendations, comparing the criteria used for including medicines for rare diseases with other globally recognized HTA agencies.

Methods

Profile of requests for incorporating medicines for rare diseases in Brazil

This is a descriptive and exploratory study carried out through surveys and quantitative analyses of requests for including medicines submitted to CONITEC and their recommendations to the SUS, from July 2012 - month and year of the onset of publications of the assessments on the website (http://conitec.gov.br/) - to June 2019 for the treatment of rare diseases.

Data regarding CONITEC’s submissions and recommendations were collected from documents made available on its website (http://conitec.gov.br/), considering the criteria established by Ordinance N° 199, of January 30, 2014, called National Policy for the Comprehensive Care of People with Rare Diseases, which considers a rare disease one that affects up to 65 people in every 100,000 individuals¹³13 Brasil. Ministério da Saúde (MS). Política Nacional de Atenção Integral às Pessoas com Doenças Raras. Portaria GM nº 199, de 30 de janeiro de 2014. [acessado 2020 jan 18]. Disponível em: http://bvsms.saude.gov.br/bvs/saudelegis/gm/2014/prt0199_30_01_2014.html.
http://bvsms.saude.gov.br/bvs/saudelegis... .

The quantitative analysis of positive or negative recommendations was performed after selecting all requests that met the definition of rare disease mentioned above. Then, the requests were presented regarding the indications of the drugs, active ingredients, applicant, year, type of study for clinical evidence, type of economic assessment, initial recommendation, recommendation after public consultation, and the result of the required inclusion. The collected data were stored and analyzed in a pre-formatted Microsoft Office Excel®365 ProPlus spreadsheet. Descriptive statistics were used, and the results were expressed as absolute or relative frequency.

Criteria used by other HTA agencies to incorporate medicines for rare diseases

We performed a comparative analysis of the criteria used by CONITEC for the incorporation of medicines for rare diseases in Brazil and by international HTA agencies. The HTA agencies of interest were chosen due to their pioneering spirit in the field and because they belong to countries whose health system is similar to the Brazilian one. They are the Pharmaceutical Benefits Advisory Committee (PBAC) of Australia, the Canadian Agency for Drugs and Technologies in Health (CADTH) of Canada, The National Institute for Health and Care Excellence (NICE) of the United Kingdom, and Haute Autorité de Santé (HAS) of France. We proceeded with a bibliographic search in the PubMed and SciELO databases, considering the search period until June 2019 and the websites of the HTA agencies mentioned above.

Results

General analysis of incorporation requests

Sixty requests for incorporating medicines to treat 30 rare diseases to CONITEC were identified from July 2012 to June 2019 (Charts 1 and 2). It is noteworthy that in 2018, an applicant submitted an incorporation request for the treatment of uveitis. However, during its assessment, CONITEC decided on two subgroups of the disease, Active Uveitis, and Inactive Uveitis. Thus, we will analyze the 60 requests and 61 recommendations.

Most incorporation requests submitted to CONITEC were from the pharmaceutical industry (40; 66%), followed by the Ministry of Health’s Science, Technology, and Strategic Inputs - SCTIE/MS (11; 18%), and the Health Care Secretariat of the Ministry of Health - SAS/MS (6; 10%). Only a negligible portion was requested by state governments (2; 3%), the Judiciary (1; 2%), and both industry and doctor together (1; 2%). Requests were based on varying levels of clinical evidence, from case reports to systematic reviews with metanalyses. Systematic reviews became part of the dossiers more frequently from 2017 onwards.

Budget impact analyses were found in about 85% (51) of the 60 requests sent to CONITEC, while economic analyses of health technologies, such as cost-minimization, cost-effectiveness, and cost-utility, were found in 68% (41) of them. As shown in Figure 1a, eight out of the nine requests that did not present a budget impact analysis had the SAS/MS, SCTIE/MS, or state governments as applicants. Regarding the lack of economic analyses of health technologies, 17 of the 19 requests that did not show any such analysis also came from the same applicants mentioned above (Figure 1b).

The rare diseases demanded

Multiple sclerosis had the highest number of requests among the 30 rare diseases with requests for drug incorporation, namely, twelve in total (20%), and only five of these were incorporated. We can also highlight ankylosing spondylitis [5 requests (8%), 4 incorporated]; acromegaly [4 requests (7%), 1 incorporated], pulmonary arterial hypertension [4 requests (7%), 2 incorporated] and mucopolysaccharides [4 requests (7%), 4 incorporated]. The different subtypes of each disease were not considered by grouping the number of claims by disease.

CONITEC’s recommendations

Figure 2 shows the evolution of incorporation requests between July 2012 and June 2019 and the characterization of the applicants regarding CONITEC’s initial and final recommendation. Only 20 (33%) of the 61 assessments of incorporation of medicines for rare diseases had a positive initial recommendation before public consultation. However, an inversion in these numbers was observed after the public consultation, and, thus, 32 (52%) medicines received a positive recommendation and were incorporated into the SUS. We can note that the initial years (2012 and 2013) had many requests to CONITEC, both by the government and the industry, and all initial recommendations were upheld. The initial negative recommendations were reversed as of 2016 and started to recur in the following years, regardless of the applicant type.

Concerning the 12 incorporation requests with reversed decisions after the public consultation, CONITEC’s justifications for the initial negative recommendation were based on the lack of quality clinical evidence, uncertain effectiveness, not being cost-effective options vis-à-vis the options already included in the SUS, weak evidence, and modest clinical benefits that do not justify the high price. The clinical evidence presented by the applicants in these requests was, at a minimum, phase III clinical studies.

The initial negative recommendations that were reverted to positive built on the high number of contributions favoring the incorporation of medicines for rare diseases; for example, Paroxysmal Nocturnal Hemoglobinuria, which obtained 2,451 contributions. The main contributions of the public consultation were related to the presentation of new clinical studies, the availability of a generic drug on the market, the requested medicine was the only available treatment for the disease, and price negotiation with the industry.

Criteria used by international HTA agencies to incorporate medicines for rare diseases

A study by the Canadian agency CADTH¹⁹19 Pant S, Visintini S. Drugs for rare diseases: a review of national and international health technology assessment agencies and public payers' decision-making processes. Ottawa: CADTH; 2018. (Environmental scan; no 77). [acessado 2019 abr 14]. Disponível em: https://www.cadth.ca/recommendations-framework-drugs-rare-diseases-review-national-and-international-health-technology compared several HTA processes for rare diseases in some countries, including England, France, Australia, and Canada. Table 1 is an adaptation of data from the CADTH report, and the Brazil column was answered based on the bibliographic survey carried out to develop this work, with only public data from the CONITEC website itself.

We observe that only NICE uses the six criteria adopted in the assessment, although it does not define the exact prevalence of a rare disease. Among the others, only PBAC has a differentiated process for submitting a request for inclusion for rare diseases. All four international HTA agencies use as criteria different considerations regarding economic assessments. It is worth noting that only England and Brazil report being willing to enter into risk-sharing agreements with technology applicants.

Discussion

Given the data presented in this study and considering that until the beginning of the publications of the evaluations by CONITEC, most drugs for rare diseases attended by the SUS treated only the symptoms²⁰20 Associação da Indústria Farmacêutica de Pesquisa (Interfarma). Doenças Raras: A urgência do acesso à saúde. São Paulo: Interfarma; 2018. [acessado 2019 abr 14]. Disponível em: https://www.interfarma.org.br/public/files/biblioteca/doencas-raras--a-urgencia-do-acesso-a-saude-interfarma.pdf., an important advance can be seen in the way in which patients with rare diseases are treated. Most technologies evaluated between July 2012 and June 2019 by CONITEC were orphan drugs that could interfere with disease progression.

The National Policy for the Comprehensive Care of People with Rare Diseases guided paths and goals for prioritizing some clinical protocols and therapeutic guidelines (PCDT)¹³13 Brasil. Ministério da Saúde (MS). Política Nacional de Atenção Integral às Pessoas com Doenças Raras. Portaria GM nº 199, de 30 de janeiro de 2014. [acessado 2020 jan 18]. Disponível em: http://bvsms.saude.gov.br/bvs/saudelegis/gm/2014/prt0199_30_01_2014.html.
http://bvsms.saude.gov.br/bvs/saudelegis... . Based on the need to accelerate the arrival of orphan drugs created after this 2014 Policy¹³13 Brasil. Ministério da Saúde (MS). Política Nacional de Atenção Integral às Pessoas com Doenças Raras. Portaria GM nº 199, de 30 de janeiro de 2014. [acessado 2020 jan 18]. Disponível em: http://bvsms.saude.gov.br/bvs/saudelegis/gm/2014/prt0199_30_01_2014.html.
http://bvsms.saude.gov.br/bvs/saudelegis... , the National Health Surveillance Agency (ANVISA) stipulated a procedure for the registration of orphan drugs under RDC N° 205/17: drugs registered through pre-established criteria would be prioritized with a period of up to 365 days to be marketed.²¹ Then, the way the Brazilian health system addresses diseases takes shape gradually. Among other factors, there may be a causal relationship between the rising number of incorporation requests from 2017 and this new setting for rare diseases, as occurred in the U.S. after introducing incentives and legislation (Orphan Drug Act)²²22 Drummond MF, Wilson D, Kanavos P, UbelP. Assessing the economic challenges posed by orphan drugs. Int J Technol Assess Health Care 2007; 23(1):36-42.^,2323 US Food and Drug Administration. Orphan Drug Act of 1983. Pub L. Nº 97-414, 96 Stat. 2049. 4 January 1983. Retrieved 27 October 2015. [acessado 2019 abr 14]. Disponível em: https://www.govinfo.gov/content/pkg/STATUTE-96/pdf/STATUTE-96-Pg2049.pdf.
https://www.govinfo.gov/content/pkg/STAT... .

With the advances through Policies and Resolutions, patients could be treated by the health system in a more dignified manner. There is, then, an attempt to enforce two of the three SUS¹Brasil. Lei 8080 de 19 de setembro de 1990. Dispõe sobre as condições para a promoção, proteção e recuperação da saúde, a organização e o funcionamento dos serviços correspondentes e dá outras providências. Diário Oficial da União 1990; set 20. principles: equity, since patients who suffer from rare conditions should have the same opportunity to receive treatment as other patients with more frequent disorders²²22 Drummond MF, Wilson D, Kanavos P, UbelP. Assessing the economic challenges posed by orphan drugs. Int J Technol Assess Health Care 2007; 23(1):36-42.; and universality, including this group of patients in public health policies. On the other hand, due to the difficulty of organizing a system that can take care of the patient in its entirety, whether in rare or more prevalent diseases²⁴24 Aith F, Bujdoso Y, Nascimento PR, Dallari S. Os princípios da universalidade e integralidade do SUS sob a perspectiva da política de doenças raras e da incorporação tecnológica. R Dir Sanit 2014; 15(1):10-19., comprehensiveness is still one of the desired aspects.

We should highlight that, while most incorporation requests submitted to CONITEC have a favorable decision, access to treatment may be more difficult than expected. Logistics, distribution, and supply problems are frequent in specialized component pharmacies, impacting the availability and, thus, the treatment of medicine users²⁵25 Blatt CR, Campos CMT, Becker IRT.Assistência Farmacêutica no Brasil: Política, Gestão e Clínica. Logística de medicamentos. Cap. 3, Vol. IV, Santa Catarina: Editora UFSC; 2016..

The fundamental issue when discussing this topic is the budgetary impact of such incorporations to the system since these are medicines for a limited number of patients and generally have high manufacturing and sale costs. According to estimates by the Ministry of Health published by Interfarma²⁰20 Associação da Indústria Farmacêutica de Pesquisa (Interfarma). Doenças Raras: A urgência do acesso à saúde. São Paulo: Interfarma; 2018. [acessado 2019 abr 14]. Disponível em: https://www.interfarma.org.br/public/files/biblioteca/doencas-raras--a-urgencia-do-acesso-a-saude-interfarma.pdf., in 2016 alone, the Federal Government’s spending on lawsuits reached BRL 1.3 billion, up 23% from the previous year.

The participation of orphan drugs in these expenses through the courts already represents 90% of the total cost, and half of the most legalized medicines in 2016 were for the treatment of rare diseases²⁰20 Associação da Indústria Farmacêutica de Pesquisa (Interfarma). Doenças Raras: A urgência do acesso à saúde. São Paulo: Interfarma; 2018. [acessado 2019 abr 14]. Disponível em: https://www.interfarma.org.br/public/files/biblioteca/doencas-raras--a-urgencia-do-acesso-a-saude-interfarma.pdf.. Thus, there is already a high expenditure on acquiring medicines for this group of diseases by the Federal Government, besides the lack of predictability in the allocation of resources, lower bargaining power with industries, and a reduced number of benefited patients. Given this scenario, incorporating these drugs into the SUS could bring more significant control over expenses with lawsuits and enable treatment to more patients.

The comparison of criteria used by international HTA agencies makes it clear that the way a rare disease is evaluated is a current issue and still requires maturation. No matter how much the country invests in health, it is impossible to pay everything for all⁷7 Soárez PC, Soares MO, Novaes HMD. Modelos de decisão para avaliações econômicas de tecnologias em saúde. Cien Saude Colet 2014; 19(10):4209-4222.. For this reason, debating more effective ways to evaluate new technologies besides the cost-effectiveness and budget impact methodology is crucial. As observed in the five HTA agencies included in this work, differentiated criteria (using utilitarian principles less and considering both the vulnerability of the affected population and the society’s position regarding this inclusion) and setting priorities may be the most indicated way to evaluate medicines for rare diseases⁸8 Brasil. Lei Nº 12.401, de 28 de abril de 2011.Altera a Lei nº 8.080, de 19 de setembro de 1990, para dispor sobre a assistência terapêutica e a incorporação de tecnologia em saúde no âmbito do Sistema Único de Saúde - SUS. Diário Oficial da União, Brasília, DF, 29 de abril de 2011. and, thus, improve access to medicines for this very different population. Also, some new specific programs to evaluate medicines for rare diseases are emerging in Europe to cope with the challenging setting of more significant political pressure for more transparency in the HTA processes²⁶26 Novaes HMD, Soárez PC. Doenças raras, drogas órfãs e as políticas para avaliação e incorporação de tecnologias nos sistemas de saúde. Sociologias 2019; 21(51):332-364., such as the Patient and Clinician Engagement (PACE) Meeting and the decision-making program by the Scottish Medicines Consortium (SMC), the National Institute for Health and Clinical Excellence (NICE) highly specialized technology program in England, and a European initiative, the Mechanism of Coordinated Access (MoCA)²⁷27 Nicod E, Annemans L, Bucsics A, Lee A, Upadhyaya S, Facey K. HTA programme response to the challenges of dealing with orphan medicinal products: process evaluation in selected European countries. Health Policy 2019; 123(2):140-151..

Understanding comprehensiveness as a principle that permeates decision-making and guarantees the right to health, some crucial questions emerge: are drug incorporations being carried out based on criteria that consider health needs and the perspective of comprehensiveness? Is it possible to provide comprehensive care to patients with rare diseases using current health technology assessment criteria? An initial, albeit complex path for decision-makers could be identifying the value factors they deem relevant for each decision, the preferences of the groups involved, which value propositions support the decisions, and the construction of a consensus among all the parts²⁶26 Novaes HMD, Soárez PC. Doenças raras, drogas órfãs e as políticas para avaliação e incorporação de tecnologias nos sistemas de saúde. Sociologias 2019; 21(51):332-364.^,2828 Paulden M, Stafinski T, Menon D, McCabe C. Value-based reimbursement decisions for orphan drugs: a scoping review and decision framework. Pharmacoeconomics 2015; 33(3):255-269.^,2929 BaickerK, Chandra A. Evidence-based health policy. N Engl J Med 2017; 377:2413-2415.. Therefore, making the work process more transparent and participatory is necessary to facilitate collective decisions considering minority and even individual perspectives without compromising majority groups. This would allow differentiating the still widely used criteria for both high and low prevalence diseases.

In three of the 12 requests in which there was an inversion in the initial recommendation, CONITEC justified the final positive recommendation after public consultation as follows: scientific evidence concerning rare diseases must be analyzed differently when compared to high disease prevalence. Likewise, there was a need to monitor these patients so that the treatment results are monitored and documented, found in the reports of Mucopolysaccharidosis IVa and VI³⁰30 Comissão Nacional de Incorporação de Tecnologias no SUS (CONITEC). Relatório 412- Galsulfase para a terapia de reposição enzimática de longo prazo, em pacientes com diagnóstico confirmado de mucopolissacaridose tipo VI (deficiência de N-acetilgalactosamina 4-sulfa). 2018. [acessado 2019 abr 20]. Disponível em: http://conitec.gov.br/images/Relatorios/2018/Recomendacao/Relatorio_Galsulfase_MPS_VI.pdf.
http://conitec.gov.br/images/Relatorios/... ^,3131 Comissão Nacional de Incorporação de Tecnologias no SUS (CONITEC). Relatório 411 - Alfaelosulfase para pacientes com mucopolissacaridose tipo IVa (Síndrome de Morquio A). 2018. [acessado 2019 abr 20]. Disponível em: http://conitec.gov.br/images/Relatorios/2018/Relatorio_Alfaelosulfase_MPS_IVa.pdf.
http://conitec.gov.br/images/Relatorios/... . Also, the decision was reconsidered upon compliance with provisionally established criteria for rare diseases - Paroxysmal Nocturnal Hemoglobinuria report³²32 Comissão Nacional de Incorporação de Tecnologias no SUS (CONITEC). Relatório nº 413 - Eculizumabe para o tratamento da Hemoglobinúria Paroxística Noturna. 2018. [acessado 2019 abr 20]. Disponível em: http://conitec.gov.br/images/Relatorios/2018/Relatorio_Eculizumabe_HPN.pdf.
http://conitec.gov.br/images/Relatorios/... .

Conclusion

The setting of rare diseases has changed in the Brazilian public health system since the establishment of CONITEC. We cannot deny the advances achieved that have already been observed from the data in this study, in which most medicines (52%) that CONITEC has evaluated in the last seven years have been incorporated into the SUS. However, there are still challenges and opportunities in Brazil and countries whose HTA agencies were pioneers; such is the topic’s relevance and timeliness. Countries like England and Australia, for example, already have significant differentiated criteria in their HTA agencies. On the other hand, limited health resources and the economic-political setting are points of attention and difficulty in the country. However, so that advances are not slowed down, it is crucial to bring to the light of conscience the Federal Government’s spending, above all, with judicialization. This point, associated with differentiated criteria and relevant value factors for rare diseases, besides policies with well-defined objectives, will possibly strengthen decision-making and provide more significant potential for patients to access life-changing treatments.

References

Publication Dates

History