Methodological guidelines and publications of benefit-risk assessment for health technology assessment: a scoping review.

OBJECTIVES: To map the available methodological guidelines and documents for conducting and reporting benefit-risk assessment (BRA) during health technologies' life cycle; and to identify methodological guidelines for BRA that could serve as the basis for the development of a BRA guideline for the context of health technology assessment (HTA) in Brazil. DESIGN: Scoping review. METHODS: Searches were conducted in three main sources up to March 2023: (1) electronic databases; (2) grey literature (48 HTA and regulatory organisations) and (3) manual search and contacting experts. We included methodological guidelines or publications presenting methods for conducting or reporting BRA of any type of health technologies in any context of the technology's life cycle. Selection process and data charting were conducted by independent reviewers. We provided a structured narrative synthesis of the findings. RESULTS: From the 83 eligible documents, six were produced in the HTA context, 30 in the regulatory and 35 involved guidance for BRA throughout the technology's life cycle. We identified 129 methodological approaches for BRA in the documents. The most commonly referred to descriptive frameworks were the Problem, Objectives, Alternatives, Consequences, Trade-offs, Uncertainty, Risk and Linked decisions and the Benefit-Risk Action Team. Multicriteria decision analysis was the most commonly cited quantitative framework. We also identified the most cited metric indices, estimation and utility survey techniques that could be used for BRA. CONCLUSIONS: Methods for BRA in HTA are less established. The findings of this review, however, will support and inform the elaboration of the Brazilian methodological guideline on BRA for HTA. TRIAL REGISTRATION NUMBER: https://doi.org/10.17605/OSF.IO/69T3V.

Methodological guidelines and publications of benefit-risk assessment for health technology assessment: a scoping review protocol.

BACKGROUND: Benefit-risk assessment (BRA) is used in multiple phases along the health technology's life-cycle to evaluate the balance between the benefits and risks, as it is fundamental to all stakeholders. BRA and its methodological approaches have been applied primarily in the context of regulatory agencies. However, BRA's application and extent in the context of health technology assessment (HTA) bodies remain less clear. Our goal is to perform a scoping review to identify and map methodological guidelines and publications on methods of BRA. This will be done considering the different phases of the life-cycle of health technologies to underline both the depth and extent of research concerning BRA, especially in the context of HTA. METHODS AND ANALYSIS: This scoping review protocol was developed following the framework proposed by Arksey and O'Malley, and the updated guidelines by the Joanna Briggs Institute. We will include methodological publications that provide recommendations or guidelines on methods for BRA. We will conduct electronic searches on Medline (PubMed) and EMBASE (Ovid) databases; manual searches on the main websites of HTA bodies and drug regulatory organisations; and contact experts in the field. Systematic extraction forms will be used to screen and assess the identified publications by independent assessors. We will provide a qualitative synthesis using descriptive statistics and visual tools. Results will be summarised in systematic evidence tables and comparative evidence scoping charts. ETHICS AND DISSEMINATION: This review will use data publicly available and does not require ethics approval. The results of this scoping review will contribute to scientific knowledge and act as a basis for methodologists, guideline developers and researchers for the development of BRA to inform regulatory decisions, reimbursement and coverage decision making. The results will be disseminated through peer-reviewed articles, conferences, policy briefs and workshops. TRIAL REGISTRATION NUMBER: Open Science Framework (https://doi.org/10.17605/OSF.IO/69T3V).

Evidence-based pharmacological prophylaxis recommendations for venous thromboembolism in hospitalized acutely ill medical patients: a systematic review of clinical practice guidelines.

Venous thromboembolism is a complex multifactorial disease considered the most common cause of preventable deaths in hospitalized patients. Recommendations about pharmacological venous thromboembolism prophylaxis in adult hospitalized patients are available in clinical practice guidelines for optimization of healthcare delivery and improvement of patient outcomes. We conducted a systematic review of clinical practice guidelines using ADAPTE to synthesize recommendations for pharmacological prophylaxis of venous thromboembolism in hospitalized medical patients at a medium complexity university hospital. Recommendations for pharmacological prophylaxis were extracted from seven clinical practice guidelines considered of high quality after assessment with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. These recommendations will support discussion with specialists and implementation of practices in the setting of the hospital studied.

O tromboembolismo venoso é uma doença multifatorial complexa, considerada uma causa comum de óbitos evitáveis em pacientes hospitalizados. Recomendações sobre profilaxia farmacológica de tromboembolismo venoso em pacientes adultos hospitalizados estão disponíveis em diretrizes clínicas para otimizar os cuidados à saúde e contribuir com a melhora do desfecho do paciente. Dessa forma, foi conduzida uma revisão sistemática de diretrizes clínicas utilizando a metodologia ADAPTE para sintetizar as recomendações para profilaxia farmacológica de tromboembolismo venoso em pacientes clínicos adultos hospitalizados em um hospital universitário de média complexidade. As recomendações para profilaxia farmacológica foram extraídas de sete diretrizes clínicas consideradas de alta qualidade após avaliação pelo Appraisal of Guidelines for Research and Evaluation (AGREE II). Essas recomendações servirão de apoio para discussão com especialistas e implementação de práticas dentro do contexto do hospital estudado.

Factors associated with higher quality of clinical practice guidelines and their recommendations for the pharmacological treatment of depression: a systematic review.

OBJECTIVE: The objective of this study was to assess the quality of clinical practice guidelines (CPGs) for the pharmacological treatment of depression along with their recommendations and factors associated with higher quality. DESIGN: We conducted a systematic review that included CPGs for the pharmacological treatment of depression in adults. DATA SOURCES: We searched for publications from 1 January 2011 to 31 December 2021, in MEDLINE, Cochrane Library, Embase, PsycINFO, BVS and 12 other databases and guideline repositories. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included CPGs containing recommendations for the pharmacological treatment of depression in adults at outpatient care setting, regardless of whether it met the U.S. National Academy of Medicine criteria, or not. If a CPG included recommendations for both children and adults, they were considered. No language restriction was applied. DATA EXTRACTION AND SYNTHESIS: Data extraction was also conducted independently and in duplicate, a process that was validated in a previous project. The quality of the CPGs and their recommendations were assessed by three independent reviewers using Appraisal of Guidelines for Research and Evaluation (AGREE II) and Appraisal of Guidelines for Research and Evaluation-Recommendations Excellence (AGREE-REX). A CPG was considered to be of high quality if AGREE II Domain 3 was ≥60%; while their recommendations were considered high if AGREE-REX Domain 1 was ≥60%. RESULTS: Seventeen out of 63 (27%) CPGs were classified as high quality, while 7 (11.1%) had high-quality recommendations. The factors associated with higher-scoring CPGs and recommendations in the multiple linear regression analyses were 'Handling of conflicts of interest', 'Multiprofessional team' and 'Type of institution'. 'Inclusion of patient representative in the team' was also associated with higher-quality recommendations. CONCLUSIONS: The involvement of professionals from diverse backgrounds, the handling of conflicts of interest, and the inclusion of patients' perspectives should be prioritised by developers aiming for high-quality CPGs for the treatment of depression.

Guidelines' recommendations for the treatment-resistant depression: A systematic review of their quality.

INTRODUCTION: Depression is a serious and widespread mental health disorder. A significant proportion of patients with depression fail to remit after two antidepressant treatment trials, a condition named treatment-resistant depression (TRD). Clinical practice guidelines (CPGs) are instruments aimed to improve diagnosis and treatment. This study objective is to systematically appraise the quality and elaborate a comparison of high-quality CPGs with high-quality recommendations aimed at TRD. METHODS AND ANALYSIS: We searched several specialized databases and organizations that develop CPGs. Independent researchers assessed the quality of the CPGs and their recommendations using AGREE II and AGREE-REX instruments, respectively. We selected only high-quality CPGs that included definition and recommendations for TRD. We investigated their divergencies and convergencies as well as weak and strong points. RESULTS: Among seven high-quality CPGs with high-quality recommendations only two (Germany's Nationale Versorgungs Leitlinie-NVL and US Department of Veterans Affairs and Department of Defense-VA/DoD) included specific TRD definition and were selected. We found no convergent therapeutic strategy among these two CPGs. Electroconvulsive therapy is recommended by the NVL but not by the VA/DoD, while repetitive transcranial magnetic stimulation is recommended by the VA/DoD but not by the NVL. While the NVL recommends the use of lithium, and a non-routine use of thyroid or other hormones, psychostimulants, and dopaminergic agents the VA/DoD does not even include these drugs among augmentation strategies. Instead, the VA/DoD recommends ketamine or esketamine as augmentation strategies, while the NVL does not mention these drugs. Other differences between these CPGs include antidepressant combination, psychotherapy as a therapeutic augmentation, and evaluation of the need for hospitalization all of which are only recommended by the NVL. CONCLUSIONS: High-quality CPGs for the treatment of depression diverge regarding the definition and use of the term TRD. There is also no convergent approach to TRD from currently high-quality CPGs.

Critical appraisal and comparison of recommendations of clinical practice guidelines for the treatment of schizophrenia in children and adolescents: a methodological survey.

INTRODUCTION: The production of clinical practice guidelines (CPGs) has grown in the past years. Notwithstanding, the quality of these documents and their recommendations for the treatment of schizophrenia in children and adolescents is still unknown. OBJECTIVE: To assess the quality of the guidelines and recommendations for the treatment of schizophrenia in this population. METHODS: CPGs from 2004 to December 2020 were identified through a systematic search on EMBASE, MEDLINE, PsycINFO, PubMed, Epistemonikos, VHL, Global Index Medicus and specific CPG databases. The CPGs' quality was independently assessed by three reviewers using AGREE II and they were considered of high quality if they scored ≥60% in domains 3 and 6. The evidence classification systems were described, the quality of recommendations was assessed in pairs using AGREE-REX and the recommendations were compared. RESULTS: The database search retrieved 3182 results; 2030 were screened and 29 were selected for full-text reading. Four guidelines were selected for extraction. Two CPGs were considered of high quality in the AGREE II assessment. We described the commonly agreed recommendations for each treatment phase. The pharmacological recommendations were described in all treatment phases. Scores of AGREE-REX were lower for psychosocial recommendations. CONCLUSION: There are still few clinical studies and CPGs regarding schizophrenia in children and adolescents. The quality of the documents was overall low, and the quality of the recommendations report has much to improve. There is also a lack of transparency about the quality of the evidence and the strength of the recommendations. PROTOCOL REGISTRATION NUMBER: CRD42020164899.

Diretrizes clínicas para tratamento da depressão: análise de fatores associados à qualidade e comparação de recomendações para pacientes não respondedores e com depressão resistente / Clinical guidelines for the treatment of depression: analysis of factors associated with quality and comparison of recommendations for nonresponding patients and for patients with resistant depression

Diretrizes clínicas (DCs) de alta qualidade são importantes para a assistência efetiva de pacientes com doenças crônicas, incluindo a depressão. A depressão é um dos principais problemas de saúde mundial, sendo um dos transtornos psiquiátricos mais comumente encontrados na prática médica, afetando cerca de 300 milhões de pessoas. Além de sua natureza debilitante e onerosa, muitas vezes pode levar a desfechos graves, tal como o suicídio, principalmente em pacientes que não respondem aos tratamentos. Assim, o objetivo geral desta tese foi identificar fatores das DCs associados à qualidade metodológica desses documentos e de suas recomendações, e comparar as recomendações para duas situações de falhas da farmacoterapia: pacientes não respondedores e pacientes com depressão resistente ao tratamento (DRT). Operacionalmente, foram feitas revisões sistemáticas da literatura em bases científicas e específicas de DCs, e incluídas DCs publicadas nos últimos onze anos que contivessem recomendações para o tratamento farmacológico de adultos com depressão. Para avaliação geral das DCs, foi aplicado o instrumento AGREE II, e para avaliação específica das recomendações, o instrumento AGREE-REX. As DCs foram consideradas de alta qualidade quando pontuaram com escores maiores ou iguais a 60% (no estudo descrito no capítulo 2) e maiores ou iguais a 80% (no estudo descrito no capítulo 3) no domínio 3 (Rigor de desenvolvimento) do AGREE II. As DCs com recomendações de alta qualidade foram as que pontuaram com mais de 60% no domínio 1 (Aplicabilidade Clínica) do AGREE-REX. Das 63 DCs selecionadas, 17 (27%) apresentaram alta qualidade, e 7 (11%) apresentaram recomendações de alta qualidade. Os fatores associados à maior qualidade foram gerenciamento de conflitos de interesses, equipe multiprofissional e tipo de instituição. A inclusão de representante do paciente na equipe também foi associada a recomendações de maior qualidade. Verificou-se que a maioria das DCs concorda com a necessidade de: reavaliar o diagnóstico, a presença de comorbidades, a adesão ao tratamento, ajustar a dosagem do antidepressivo e adicionar psicoterapia como os primeiros passos para aqueles que não respondem ao tratamento antidepressivo de primeira linha. Em relação às recomendações, há falhas importantes, incluindo a não apresentação de definição padronizada de resposta adequada/inadequada/parcial, e o não estabelecimento de tempo de tratamento necessário para declarar DRT. Todas as DCs incluíram a possibilidade de substituição do antidepressivo, potencialização com outros medicamentos e combinação de antidepressivos. Todavia, três DCs não recomendaram uma sequência entre eles. Por fim, verificou-se que das 17 DCs de alta qualidade e das 7 DCs com recomendações de alta qualidade, apenas duas incluíram definição e recomendações para DRT. Não existe consenso entre as DCs de alta qualidade quanto à definição e uso do termo DRT. Não foi possível extrair uma estratégia terapêutica convergente para DRT em adultos. Os resultados obtidos reforçam a necessidade de maior foco no aprimoramento da qualidade das DCs e de suas recomendações, especialmente nos subgrupos relativos à resposta inadequada ao tratamento e a DRT, nas quais as definições não são claras

High-quality clinical practice guidelines (CPGs) are important for treating patients with chronic diseases such as depression. Depression is a major health concern worldwide, affecting approximately 300 million people. It is one of the most prevalent psychiatric disorders in medical practice. It is not only debilitating and costly but can also lead to tragic consequences such as suicide, particularly in patients who do not respond to treatment. The objective of this thesis was to identify CPGs factors associated with the methodological quality of these documents and their recommendations. Furthermore, this thesis aimed to compare the recommendations in two pharmacotherapy failure situations: inadequate response to treatment and treatment-resistant depression (TRD). Systematic literature reviews were conducted on scientific and CPG-specific databases. Reviews were also conducted on CPGs published in the last eleven years that included recommendations for pharmacological treatment of adults with depression. The AGREE II instrument was used for the CPGs general assessment, while the AGREE-REX instrument was used specifically to assess their recommendations. CPGs were considered high quality if they achieved a score of at least 60% in the study mentioned in Chapter 2 and a score of at least 80% in the study mentioned in Chapter 3 in the AGREE II, rigour of development domain. The CPGs with high-quality recommendations were those that scored greater than 60% in Domain 1 (Clinical Applicability) of the AGREE-REX. Of the 63 selected CPGs, 17 (27%) were high quality, and 7 (11.1%) had recommendations of high quality. Factors associated with higher quality were conflict of interest management, multi-professional team, and type of institution. Inclusion of a patients representative on the team was associated with higher quality recommendations. Most CPGs agreed with the need to reassess diagnoses, comorbidities, and treatment adherence. They also agreed on adjusting antidepressant dosage and providing psychotherapy as a first step for patients who do not respond to first-line antidepressant treatment. There are significant shortcomings in the recommendations. In particular, the lack of a standardized definition of adequate, inadequate, or partial response to treatment and the lack of clarity surrounding the duration of treatment required to establish TRD. All CPGs included the possibility of antidepressant substitution, potentiation with other drugs, and a combination of antidepressants. However, three CPGs did not recommend a preferred sequence for these interventions. Finally, of the 17 high-quality CPGs and the 7 CPGs with high-quality recommendations, only two included definition and recommendations for TRD. There is no consensus among the high-quality CPGs regarding the definition and use of the term TRD. Ultimately, finding a convergent therapeutic strategy for TRD in adults was not possible. These results highlighted the need to focus more on improving the quality of CPGs and their recommendations, especially in the subgroups related to inadequate response to treatment and TRD, where definitions are unclear

Evidence-based pharmacological prophylaxis recommendations for venous thromboembolism in hospitalized acutely ill medical patients: a systematic review of clinical practice guidelines / Recomendações baseadas em evidências científicas de profilaxia farmacológica para tromboembolismo venoso em pacientes hospitalizados com doenças agudas: uma revisão sistemática de diretrizes clínicas

Abstract Venous thromboembolism is a complex multifactorial disease considered the most common cause of preventable deaths in hospitalized patients. Recommendations about pharmacological venous thromboembolism prophylaxis in adult hospitalized patients are available in clinical practice guidelines for optimization of healthcare delivery and improvement of patient outcomes. We conducted a systematic review of clinical practice guidelines using ADAPTE to synthesize recommendations for pharmacological prophylaxis of venous thromboembolism in hospitalized medical patients at a medium complexity university hospital. Recommendations for pharmacological prophylaxis were extracted from seven clinical practice guidelines considered of high quality after assessment with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. These recommendations will support discussion with specialists and implementation of practices in the setting of the hospital studied.

Resumo O tromboembolismo venoso é uma doença multifatorial complexa, considerada uma causa comum de óbitos evitáveis em pacientes hospitalizados. Recomendações sobre profilaxia farmacológica de tromboembolismo venoso em pacientes adultos hospitalizados estão disponíveis em diretrizes clínicas para otimizar os cuidados à saúde e contribuir com a melhora do desfecho do paciente. Dessa forma, foi conduzida uma revisão sistemática de diretrizes clínicas utilizando a metodologia ADAPTE para sintetizar as recomendações para profilaxia farmacológica de tromboembolismo venoso em pacientes clínicos adultos hospitalizados em um hospital universitário de média complexidade. As recomendações para profilaxia farmacológica foram extraídas de sete diretrizes clínicas consideradas de alta qualidade após avaliação pelo Appraisal of Guidelines for Research and Evaluation (AGREE II). Essas recomendações servirão de apoio para discussão com especialistas e implementação de práticas dentro do contexto do hospital estudado.

Low-Risk Antenatal Care Enhanced by Telemedicine: A Practical Guideline Model / Atenção ao pré-natal de baixo risco potencializada por telemedicina: Diretriz clínica prática

Abstract Objective To develop a protocol for hybrid low-risk prenatal care adapted to Brazilian guidelines, merging reduced face-to-face consultations and remote monitoring. Methods The PubMed, Embase, and Cochrane Library databases were systematically searched on telemedicine and antenatal care perspectives and adaptation of the low-risk prenatal care protocols recommended by the Ministry of Health and by the Brazilian Federation of Gynecology and Obstetrics Associations. Results Five relevant articles and three manuals were included in the review, for presented criteria to develop this clinical guideline. We identified, in these studies, that the schedule of consultations is unevenly distributed among the gestational trimesters, and ranges from 7 to 14 appointments. In general, the authors propose one to two appointments in the first trimester, two to three appointments in the second trimester, and two to six appointments in the third trimester. Only three studies included puerperal evaluations. The routine exams recommended show minimal variations among authors. To date, there are no validated Brazilian protocols for prenatal care by telemedicine. The included studies showed that pregnant women were satisfied with this form of care, and the outcomes of interest, except for hypertensive diseases, were similar between the groups exposed to traditional and hybrid prenatal care. Conclusion The presented guideline comprises the Ministry of Health recommendations for low-risk prenatal care and reduces exposure to the hospital environment and care costs. A randomized clinical trial, to be developed by this group, will provide real-world data on safety, effectiveness, satisfaction, and costs.

Resumo Objetivo Desenvolver uma diretriz clínica híbrida para atendimento pré-natal de baixo risco, mesclando consultas presenciais e remotas por telemedicina, adapta às recomendações brasileiras. Métodos Revisão sistemática da literatura nas bases de dados PubMed, Embase e Cochrane e adaptação dos protocolos de atenção ao pré-natal de baixo risco preconizados pelo Ministério da Saúde e pela Federação Brasileira das Associações de Ginecologia e Obstetrícia. Resultados Cinco artigos relevantes e três manuais foram incluídos na revisão por preencherem critérios para o desenvolvimento desta diretriz clínica. Nos estudos incluídos, identificou-se que o cronograma de consultas se distribui de forma desigual entre os trimestres gestacionais, variando entre 07 e 14 encontros. De forma geral, os autores propõem uma a duas consultas no primeiro trimestre, duas a três consultas no segundo trimestre e duas a seis consultas no terceiro trimestre. Somente três estudos incluíram avaliações puerperais. A rotina de exames preconizada apresenta mínimas variações entre os autores. Até o momento, não existem protocolos brasileiros validados para atendimento pré-natal por telemedicina. Os estudos incluídos evidenciaram a satisfação das gestantes em relação a esta forma de atendimento, e os desfechos de interesse, excetuando doenças hipertensivas, foi semelhante entre os grupos expostos ao pré-natal tradicional e ao pré-natal híbrido. Conclusão A diretriz apresentada contempla as recomendações do Ministério da Saúde para atendimento pré-natal de gestantes de baixo risco, reduz a exposição ao ambiente hospitalar e os custos de atendimento. Seu emprego em um ensaio clínico randomizado, a ser desenvolvido por este grupo, proporcionará dados de mundo real, relativos à segurança, efetividade, satisfação e custos.

Low-Risk Antenatal Care Enhanced by Telemedicine: A Practical Guideline Model.

OBJECTIVE: To develop a protocol for hybrid low-risk prenatal care adapted to Brazilian guidelines, merging reduced face-to-face consultations and remote monitoring. METHODS: The PubMed, Embase, and Cochrane Library databases were systematically searched on telemedicine and antenatal care perspectives and adaptation of the low-risk prenatal care protocols recommended by the Ministry of Health and by the Brazilian Federation of Gynecology and Obstetrics Associations. RESULTS: Five relevant articles and three manuals were included in the review, for presented criteria to develop this clinical guideline. We identified, in these studies, that the schedule of consultations is unevenly distributed among the gestational trimesters, and ranges from 7 to 14 appointments. In general, the authors propose one to two appointments in the first trimester, two to three appointments in the second trimester, and two to six appointments in the third trimester. Only three studies included puerperal evaluations. The routine exams recommended show minimal variations among authors. To date, there are no validated Brazilian protocols for prenatal care by telemedicine. The included studies showed that pregnant women were satisfied with this form of care, and the outcomes of interest, except for hypertensive diseases, were similar between the groups exposed to traditional and hybrid prenatal care. CONCLUSION: The presented guideline comprises the Ministry of Health recommendations for low-risk prenatal care and reduces exposure to the hospital environment and care costs. A randomized clinical trial, to be developed by this group, will provide real-world data on safety, effectiveness, satisfaction, and costs.

OBJETIVO: Desenvolver uma diretriz clínica híbrida para atendimento pré-natal de baixo risco, mesclando consultas presenciais e remotas por telemedicina, adapta às recomendações brasileiras. MéTODOS: Revisão sistemática da literatura nas bases de dados PubMed, Embase e Cochrane e adaptação dos protocolos de atenção ao pré-natal de baixo risco preconizados pelo Ministério da Saúde e pela Federação Brasileira das Associações de Ginecologia e Obstetrícia. RESULTADOS: Cinco artigos relevantes e três manuais foram incluídos na revisão por preencherem critérios para o desenvolvimento desta diretriz clínica. Nos estudos incluídos, identificou-se que o cronograma de consultas se distribui de forma desigual entre os trimestres gestacionais, variando entre 07 e 14 encontros. De forma geral, os autores propõem uma a duas consultas no primeiro trimestre, duas a três consultas no segundo trimestre e duas a seis consultas no terceiro trimestre. Somente três estudos incluíram avaliações puerperais. A rotina de exames preconizada apresenta mínimas variações entre os autores. Até o momento, não existem protocolos brasileiros validados para atendimento pré-natal por telemedicina. Os estudos incluídos evidenciaram a satisfação das gestantes em relação a esta forma de atendimento, e os desfechos de interesse, excetuando doenças hipertensivas, foi semelhante entre os grupos expostos ao pré-natal tradicional e ao pré-natal híbrido. CONCLUSãO: A diretriz apresentada contempla as recomendações do Ministério da Saúde para atendimento pré-natal de gestantes de baixo risco, reduz a exposição ao ambiente hospitalar e os custos de atendimento. Seu emprego em um ensaio clínico randomizado, a ser desenvolvido por este grupo, proporcionará dados de mundo real, relativos à segurança, efetividade, satisfação e custos.

Recommendations for the pharmacological treatment of treatment-resistant depression: A systematic review protocol.

INTRODUCTION: Depression is a serious and widespread mental health disorder. Although effective treatment does exist, a significant proportion of patients with depression fail to respond to antidepressant treatment trials, a condition named treatment-resistant depression. Efficient approach should be given this condition in order to revert the burden caused by depression. Clinical practice guidelines (CPGs) are evidence-based health promotion instruments to improve diagnosis and treatment. CPGs recommendations for treatment-resistant depression must be trustworthy. The objective of the proposed study is to systematically identify, appraise the quality of CPGs for the treatment of depression and elaborate a synthesis of recommendations for treatment-resistant depression of CPGs considered to be of high quality and with high quality recommendations. METHODS AND ANALYSIS: We will search the databases of organizations, such as PubMed, Embase, Cochrane Library, PsycInfo, and the Virtual Health Library, and organizations that develop CPGs. Three independent researchers will assess the quality of the CPGs and their recommendations using the AGREE II and AGREE-REX instruments, respectively. Given the identification of divergences and convergences as well as weak and strong points among high quality CPGs, our work may help developers, clinicians and eventually patients. ETHICS AND DISSEMINATION: No ethical approval is required for a systematic review, as no patient data will be used. The research results will be disseminated in conferences and submitted to a peer reviewed journal.

Quality of clinical practice guidelines for inadequate response to first-line treatment for depression according to AGREE II checklist and comparison of recommendations: a systematic review.

OBJECTIVE: To assess similarities and differences in the recommended sequence of strategies among the most relevant clinical practice guidelines (CPGs) for the treatment of depression in adults with inadequate response to first-line treatment. DATA SOURCES: We performed a systematic review of the literature spanning January 2011 to August 2020 in Medline, Embase, Cochrane Library and 12 databases recognised as CPGs repositories. CPGs quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). STUDY SELECTION: The eligibility criteria were CPGs that described pharmacological recommendations for treating depression for individuals aged 18 years or older in outpatient care setting. We included CPGs considered of high-quality (≥80% in domain 3 of AGREE II) or recognised as clinically relevant. DATA EXTRACTION: Two independent researchers extracted recommendations for patients who did not respond to first-line pharmacological treatment from the selected CPGs. RESULTS: We included 46 CPGs and selected 8, of which 5 were considered high quality (≥80% in domain 3 of AGREE II) and 3 were recognised as clinically relevant. Three CPGs did not define inadequate response to treatment and 3 did not establish a clear sequence of strategies. The duration of treatment needed to determine that a patient had not responded was not explicit in 3 CPGs and was discordant in 5 CPGs. Most CPGs agree in reassessing the diagnosis, assessing the presence of comorbidities, adherence to treatment, and increase dosage as first steps. All CPGs recommend psychotherapy, switching antidepressants, and considering augmentation/combining antidepressants. CONCLUSION: Relevant CPGs present shortcomings in recommendations for non-responders to first-line antidepressant treatment including absence and divergencies in definition of inadequate response and sequence of recommended strategies. Overall, most relevant CPGs recommend reassessing the diagnosis, evaluate comorbidities, adherence to treatment, increase dosage of antidepressants, and psychotherapy as first steps. PROSPERO REGISTRATION NUMBER: CRD42016043364.

Pharmacological treatment of depression: A systematic review comparing clinical practice guideline recommendations.

Depression affects over 300 million individuals worldwide and is responsible for most of the 800,000 annual suicides. Clinical practice guidelines (CPGs) for treatment of depression, founded on scientific evidence, are essential to improve patient care. However, economic and sociocultural factors may influence CPG elaboration, potentially leading to divergences in their recommendations. Consequently, we analyzed pharmacological recommendations for the treatment of depression from the most relevant CPGs. We included four CPGs with scores ≥ 80% for Domain 3 (rigor of development) on the Appraisal of Guidelines for Research and Evaluation and two other commonly used CPGs. The recommendations, their strengths, and the level of evidence were extracted from each CPG by two independent researchers and grouped as follows: (1) general recommendations for the pharmacological treatment for depression (suicide risk, acute treatment, continuation and maintenance phases, and treatment discontinuation); (2) treatment of non-responsive or partially responsive patients; and (3) treatment for subtypes of depression (chronic, psychotic, catatonic, melancholic, seasonal, somatic, mixed, and atypical). Only 50% of CPGs included recommendations for the risk of suicide associated with pharmacotherapy. All CPGs included serotonin selective reuptake inhibitors (SSRIs) as first-line treatment; however, one CPG also included agomelatine, milnacipran, and mianserin as first-line alternatives. Recommendations for depression subtypes (catatonic, atypical, melancholic) were included in three CPGs. The strength of recommendation and level of evidence clearly differed among CPGs, especially regarding treatment augmentation strategies. We conclude that, although CPGs converged in some recommendations (e.g., SSRIs as first-line treatment), they diverged in cardinal topics including the absence of recommendations regarding the risk of suicide associated with pharmacotherapy. Consequently, the recommendations listed in a specific CPG should be followed with caution.

Factors Associated With High-Quality Guidelines for the Pharmacologic Management of Chronic Diseases in Primary Care: A Systematic Review.

Importance: As the rate of publication of new and sometimes conflicting medical research increases, clinicians rely heavily on clinical practice guidelines (CPGs) to inform practice. However, CPGs are of widely variable quality, and there are no existing objective measures to rate the quality of CPGs. Objective: To systematically assess 421 CPGs for the management of common noncommunicable diseases in primary care using the validated Appraisal of Guidelines for Research and Evaluation Instrument, version II (AGREE-II) tool and elucidate the factors associated with quality of CPGs. Evidence Review: MEDLINE, Embase, the Cochrane Library, and 12 websites for CPGs were searched for CPGs for the management of common noncommunicable diseases in primary care published between January 1, 2011, and August 30, 2017. The assessment of the quality of CPGs was performed by 3 appraisers using the 6 domains of the AGREE-II instrument. A multiple logistic regression was performed to identify factors associated with quality of CPGs. Findings: Of the 421 CPGs reviewed, 23.5% (99) were classified as high quality. Among included guidelines, clarity of presentation (70%) and scope and purpose (61%) had the highest median AGREE-II scores. The domains with the lowest median scores were applicability (22%) and rigor of development (33%). Factors associated with high-quality CPGs included having more than 20 authors (odds ratio, 9.08; 95% CI, 3.35-24.62), development at governmental institutions (odds ratio, 10.38; 95% CI, 2.72-39.60), and reporting funding (odds ratio, 10.34; 95% CI, 4.77-22.39). Year of publication, region, guideline version, and scope were not associated with quality among included CPGs. Conclusions and Relevance: Primary care professionals and policymakers should be aware that CPGs in primary care are of widely variable quality, with less than 25% of included CPGs rated as high quality. High-quality CPGs were associated with a higher number of authors, governmental institutions, and the report of funding. Region of origin was not associated with quality of CPGs, which suggests that the improvement of the quality of CPGs should be an international concern.

Clinical practice guidelines for surgical antimicrobial prophylaxis: Qualitative appraisals and synthesis of recommendations.

RATIONALE, GOALS, AND OBJECTIVES: Clinical practice guidelines (CPGs) for preoperative care have been developed for surgical antimicrobial prophylaxis (SAP). The objective of this study was to synthetize recommendations for SAP based on best-evaluated CPGs. METHODS: A systematic literature search for documents related to SAP, published between January 2011 and December 2016, was conducted on MEDLINE (PubMed), EMBASE, and specific CPG websites. Three reviewers independently assessed the rigour of development and editorial independence of CPGs based on domains 3 and 6 of the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. CPGs with domain 3 scores of 50% and greater were selected for synthesis of recommendations. Two reviewers independently extracted CPG recommendations from among these documents. A third reviewer performed the synthesis of recommendations. RESULTS: The search retrieved 363 documents, of which 29 CPGs were appraised using AGREE II. Only eight (28%) scored 50% and greater in domain 3. Most CPGs addressed topics related to preoperative care, including SAP. No conflicting recommendations were found, and most recommendations were based on clinical practice. The only recommendation for which there was a difference among CPGs was with respect to the time to initiate the administration of antibiotics (1 hour before or close to the time of the surgical incision). Four CPGs provide recommendations that demonstrate concern about inadequate SAP prolongation. CONCLUSION: Several CPGs for SAP were developed without the desired methodological rigour or transparency. Synthesis of recommendations for best-evaluated CPGs provides a broad approach owing to the complementarity of the recommendations.

Síntese de recomendações: um recurso para subsidiar o processo de adaptação de guia de prática clínica para o tratamento farmacológico da depressão / Summary of recommendations: a resource to support the process of adaptation of the clinical practice guidelines for the pharmacological treatment of depression

A depressão é um dos maiores problemas de saúde pública do século XXI. Guias de prática clínica (GPCs) estão disponíveis para o tratamento da depressão e têm como objetivo fornecer a melhor e mais recente evidência disponível para os cuidados dos pacientes. Visando reduzir a duplicação de esforços e realizar a adequação de GPC ao contexto local o objetivo desta pesquisa é sintetizar as recomendações de GPCs de alta qualidade sobre o tratamento farmacológico da depressão em adultos na atenção primária. Foram realizadas as etapas busca sistemática dos GPCs, avaliação e seleção dos GPCs de melhor qualidade, e elaboração da síntese de recomendações de acordo com o preconizado no método ADAPTE. Foram considerados os GPCs com recomendações para o tratamento farmacológico da depressão em adultos em atenção primária, em língua inglesa, portuguesa ou espanhola, publicados a partir de 2011. Para a avaliação da qualidade dos GPCs, foi utilizado o Appraisal of Guidelines for Research & Evaluation II (AGREE II) sendo considerados de alta qualidade os GPCs com 80% ou mais no domínio "rigor metodológico". As características associadas à alta qualidade dos GPCs foram analisadas por meio do teste estatístico de Fisher. A extração das recomendações foi realizada de modo independente por dois avaliadores e estas foram organizadas em tópicos. Dos 28 GPC avaliados apenas cinco (18%) foram considerados de alta qualidade. A realização de revisão sistemática e da revisão externa e a aplicação de consenso formal foram características associadas à alta qualidade. Na síntese, além dos GPCs de alta qualidade, foram incluídos 2 GPCs muito empregados na prática clínica. Constatou-se que a maioria dos GPCs traz recomendações concordantes e complementares. Quase todos os GPCs recomendam o uso de inibidores seletivos de recaptação de serotonina como primeira escolha de tratamento. Uma das principais divergências é a recomendação de agomelatina, milnaciprano e mianserina por um dos GPCs como opção de primeira linha de tratamento. A pesquisa demonstra que a qualidade dos GPCs está aquém do desejável, tal qual evidenciado em outros estudos. A elaboração da síntese de recomendações permitiu evidenciar que há um GPC que se destacou por recomendar o uso de medicamentos considerados pouco eficazes na depressão. Considerando que a maioria das recomendações eram concordantes e os GPCs complementavam-se, essa síntese pode contribuir para que sejam realizadas discussões e adaptações locais, favorecendo a elaboração de novos GPCs que possam atender às necessidades de distintos grupos de usuários e demandas regionais

Depression is one of the most significant public health problems of the 21st century. Clinical practice guidelines (CPGs) are available for treating depression and are used for providing the best and latest evidence available for patient care. To avoid the duplication of effort and allow the adequacy of CPGs to regional healthcare networks, the objective of this study is to summarise the recommendations of high-quality CPGs on the pharmacological treatment of depression in adults in the primary healthcare network. The stages of this study were the systematic search of CPGs, analysis and selection of high-quality CPGs, and summarisation of the recommendations according to the ADAPTE guidelines. The CPGs published in English, Portuguese, and Spanish since 2011 with recommendations for the pharmacological treatment of depression in adults in the primary healthcare network were considered. The Appraisal of Guidelines for Research & Evaluation II (AGREE II) was used to evaluate the quality of CPGs. CPGs with a score of >=80% in the domain 'methodological rigour' were considered high-quality. The factors associated with high quality were analysed using Fisher's exact test. The recommendations were extracted independently by two evaluators and organised into topics. Of the 28 evaluated CPGs, five (18%) were considered high-quality. The inclusion of systematic reviews and external reviews and the application of formal consensus were associated with high quality. In addition to high-quality CPGs, two CPGs commonly used in clinical practice were included in the summary. The recommendations provided by most CPGs were consistent and complementary. Almost all CPGs recommended using selective serotonin reuptake inhibitors as the first choice of treatment. One of the main divergences was the recommendation of agomelatine, milnacipran, and mianserin by one CPG as a first-line treatment option. The quality of CPGs was below desirable, and this result was corroborated by other studies. The analysis of the recommendations indicated that one CPG advised using medications with low efficacy in treating depression. Provided that most suggestions were concordant and the CPGs were complementary, this summary may contribute to local discussions and adaptations and promote the development of new CPGs that meet the needs of different user groups and regional demands