Medicamentos recomendados em Protocolos Clínicos e Diretrizes Terapêuticas sob ótica da comparação com diretrizes clínicas e indicações de uso off-label
Data
2024-08-30
Autores
Dourado, Andréa da Silva 
Orientadores
Melo, Daniela Oliveira de
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A elaboração de Protocolos Clínicos e Diretrizes Terapêuticas (PCDTs) inicia em 2000 com o objetivo de suprir uma demanda ainda não atendida pelo Sistema Único de Saúde (SUS). Atualmente, é de responsabilidade da Comissão Nacional de Incorporação de Tecnologias no SUS (Conitec) auxiliar o Ministério da Saúde no processo de aprovação de PCDTs, bem como na avaliação de incorporação de tecnologias ao SUS. A publicação da Lei no 14.313/2022, que autoriza a dispensação de medicamentos com indicação de uso diferente da preconizada em bula brasileira e prevê a atualização de PCDTs de acordo com publicação de novas evidências, evidenciou dificuldades históricas associadas à priorização da elaboração e atualização desses documentos, bem como do processo de verificação e divulgação de medicamentos recomendados em PCDTs em caráter off-label. Define-se como utilização off-label aquela realizada em condições diferentes da prevista em bula cuja responsabilidade recai sob o médico prescritor. Objetivos: Verificar potenciais lacunas assistenciais e uso off-label de medicamentos a partir das recomendações sobre tratamento farmacológico previstas em PCDTs vigentes. Materiais e métodos: Foi realizada uma busca nos sites oficiais do governo federal para identificação de PCDTs vigentes e extração de informações sobre medicamentos recomendados e indicação de uso. Para cada um dos medicamentos recomendados foi realizada busca no site Consulta Anvisa para identificação da validade do registro e verificação da indicação de uso na bula – essas informações foram comparadas com o preconizado no PCDT. Para comparar recomendações de PCDTs e diretrizes clínicas internacionais, a lista de medicamentos recomendados em PCDTs foi comparada com a lista obtida a partir de recomendações de diretrizes clínicas publicadas em quatro repositórios internacionais. Resultados: Os PCDTs incluídos foram publicados entre 2002 e 2022 e reportavam 538 recomendações sobre o tratamento farmacológico. As condições mais abordadas entre PCDTs foram doenças endócrinas, nutricionais e metabólicas (n=27; 26,73%) e doenças do sistema músculo-esquelético e tecido conjuntivo (n=12;11,88%). Excluindo-se recomendações sobre medicamentos manipulados e isentos de registro, 55 (10,91%) recomendações presentes em 45 PCDTs (44,55%) estavam com situação regulatória irregular na Anvisa. Em relação às indicações off-label, 67 (66,33%) PCDTs apresentaram pelo menos uma especialidade farmacêutica recomendada em caráter off-label em relação à condição clínica tratada ou à faixa etária de utilização do medicamento, sendo que 20 PCDTs (19,81%) apresentaram 79 (7,74%) especialidades com indicação clínica distinta da prevista em bula, enquanto em 62 (59,40%) PCDTs foram identificadas 201 (44,86%) recomendações em caráter off-label para faixa etária. A população pediátrica foi a mais frequente entre as populações distintas da prevista em bula em recomendações off-label. Foram extraídas 501 recomendações de 83 diretrizes clínicas internacionais. Mais da metade das recomendações (n=220; 52,268%) foi considerada semelhante entre PCDTs e diretrizes e não foi encontrado qualquer conflito entre os documentos. Do total, 147 (34,91%) recomendações farmacológicas previstas em diretrizes clínicas internacionais não foram recomendadas em PCDTs. Conclusão: Com uma pequena proporção de especialidades farmacêuticas em situação regulatória irregular (cerca de 10%), não foram observadas lacunas assistenciais em PCDTs devido a medicamentos sem registro. A recomendação de especialidades farmacêuticas em caráter off-label foi frequente entre os PCDTs da amostra, sendo mais comum quando associada à faixa etária em comparação à indicação clínica. Mesmo com a maioria parte das recomendações de PCDTs sendo similares às de diretrizes clínicas – não sendo observados conflitos -, há muitas alternativas farmacológicas recomendadas em diretrizes que não são descritas em PCDTs.
Introduction: The development of Clinical Protocols and Therapeutic Guidelines (Protocolos Clínicos e Diretrizes Terapêuticas - PCDTs) began in 2000 with the aim of meeting a demand not yet served by the Unified Health System of Brazil (Sistema Único de Saúde - SUS). Currently, it is the responsibility of the National Comitte for Health Technology Incorporation (Comissão Nacional de Incorporação de Tecnologias no SUS - Conitec) to assist the Ministry of Health of Brazil in the process of approving PCDTs and in the evaluating for the dispensing of technologies into the public health system. The publication of Law no 14.313/2022, which authorizes the incorporation of medicines with different indication from what is established in the label and define the updating of PCDTs in accordance with the publication of new evidence, highlighted historical difficulties associated with prioritizing the development and updating of these documents, as well as the publication process about off-label medicines recommended. Off-label is defined as a use carried out under conditions other than those provided for in the label, for which the responsibility lies with the prescribing doctor. Objectives: Identity potential gaps in care and off-label use of medications based on recommendations on pharmacological treatment provided for in current PCDTs. Materials and methods: A search was conducted on official federal government websites to identify current PCDTs, from which information on recommended medications and indications for use were extracted. For each of the recommended medications, a search was carried out on the Consultas Anvisa website to identify the validity of the registration and check the indication for use on the label – this information was compared with that recommended in the PCDT to map the off-label recommendation. To compare recommendations from PCDTs and clinical practice guidelines, the list PCDTs’ recommended medications was compared with the list obtained from guidelines recommendations published in four international repositories. Results: The included PCDTs were published between 2002 and 2022 and reported 538 recommendations on pharmacological treatment. The most frequently addressed conditions among PCDTs were endocrine, nutritional and metabolic diseases (n=27; 26,73%) and diseases of the musculoskeletal system and connective tissue (n=12; 11,88%). Excluding recommendations for compounded drugs and those exempt from registration, 55 (10,91%) recommendations present in 45 PCDTs (44,55%) had an irregular regulatory status at Anvisa. Regarding off-label indications, 67 (66,33%) PCDTs presented at least one pharmaceutical specialty recommended off-label in relation to the clinical condition treated or the age range of use of the medication, with 20 PCDTs (19,81%) presented 79 (7,74%) pharmaceutical specialty recommendation with a clinical indication other than that provided for in the label, while in 62 PCDTs (59,40%), 201 (44,86%) off-label pharmaceutical specialty were identified for age group. The pediatric population was the most frequent among the populations other than those foreseen in the label in off-label recommendations. In total, 501 recommendations were extracted from 83 international clinical practice guidelines. More than half of the recommendations (n=220; 52,268%) were considered similar between PCDTs and guidelines and no conflict was found between the documents. Of the total, 152 (35,59%) pharmacological recommendations provided for in clinical guidelines were not recommended in PCDTs. Conclusion: With a small proportion of pharmaceutical specialties in an irregular regulatory situation (approximately 10%), no gaps in care were observed in PCDTs due to unregistered drugs. Recommendations of off-label pharmaceutical specialties were frequent among the PCDTs in the sample, being more common when associated with the age group compared to the clinical indication. Even though most of the PCDTs recommendations are similar to those in clinical practice guidelines – no conflicts were observed – there are many pharmacological alternatives recommended in guidelines that are not described in PCDTs.
Introduction: The development of Clinical Protocols and Therapeutic Guidelines (Protocolos Clínicos e Diretrizes Terapêuticas - PCDTs) began in 2000 with the aim of meeting a demand not yet served by the Unified Health System of Brazil (Sistema Único de Saúde - SUS). Currently, it is the responsibility of the National Comitte for Health Technology Incorporation (Comissão Nacional de Incorporação de Tecnologias no SUS - Conitec) to assist the Ministry of Health of Brazil in the process of approving PCDTs and in the evaluating for the dispensing of technologies into the public health system. The publication of Law no 14.313/2022, which authorizes the incorporation of medicines with different indication from what is established in the label and define the updating of PCDTs in accordance with the publication of new evidence, highlighted historical difficulties associated with prioritizing the development and updating of these documents, as well as the publication process about off-label medicines recommended. Off-label is defined as a use carried out under conditions other than those provided for in the label, for which the responsibility lies with the prescribing doctor. Objectives: Identity potential gaps in care and off-label use of medications based on recommendations on pharmacological treatment provided for in current PCDTs. Materials and methods: A search was conducted on official federal government websites to identify current PCDTs, from which information on recommended medications and indications for use were extracted. For each of the recommended medications, a search was carried out on the Consultas Anvisa website to identify the validity of the registration and check the indication for use on the label – this information was compared with that recommended in the PCDT to map the off-label recommendation. To compare recommendations from PCDTs and clinical practice guidelines, the list PCDTs’ recommended medications was compared with the list obtained from guidelines recommendations published in four international repositories. Results: The included PCDTs were published between 2002 and 2022 and reported 538 recommendations on pharmacological treatment. The most frequently addressed conditions among PCDTs were endocrine, nutritional and metabolic diseases (n=27; 26,73%) and diseases of the musculoskeletal system and connective tissue (n=12; 11,88%). Excluding recommendations for compounded drugs and those exempt from registration, 55 (10,91%) recommendations present in 45 PCDTs (44,55%) had an irregular regulatory status at Anvisa. Regarding off-label indications, 67 (66,33%) PCDTs presented at least one pharmaceutical specialty recommended off-label in relation to the clinical condition treated or the age range of use of the medication, with 20 PCDTs (19,81%) presented 79 (7,74%) pharmaceutical specialty recommendation with a clinical indication other than that provided for in the label, while in 62 PCDTs (59,40%), 201 (44,86%) off-label pharmaceutical specialty were identified for age group. The pediatric population was the most frequent among the populations other than those foreseen in the label in off-label recommendations. In total, 501 recommendations were extracted from 83 international clinical practice guidelines. More than half of the recommendations (n=220; 52,268%) were considered similar between PCDTs and guidelines and no conflict was found between the documents. Of the total, 152 (35,59%) pharmacological recommendations provided for in clinical guidelines were not recommended in PCDTs. Conclusion: With a small proportion of pharmaceutical specialties in an irregular regulatory situation (approximately 10%), no gaps in care were observed in PCDTs due to unregistered drugs. Recommendations of off-label pharmaceutical specialties were frequent among the PCDTs in the sample, being more common when associated with the age group compared to the clinical indication. Even though most of the PCDTs recommendations are similar to those in clinical practice guidelines – no conflicts were observed – there are many pharmacological alternatives recommended in guidelines that are not described in PCDTs.