[What conditions should the diagnosis and treatment guidelines meet, to be true clinical practice guidelines based on evidence?] / ¿Qué condiciones deben reunir las guías de diagnóstico y tratamiento para ser verdaderas guías de práctica clinica basadas en la evidencia?

The guides for diagnosis and treatment prepared by scientific medical societies constitute a very useful tool for the professional practice of the specialty. Supported by an updated bibliography, they represent material of enormous value with recommendations from experts on the various topics of the specialty. This article attempts to determine if they could be designed as "Evidence - Based Clinical Practice Guidelines" (CPG BE), for which the stages in their development and the requirements that they reviewed. The CPG BE are a "set of recommendations prepared systematically to help professionals and patients in making decisions about the most appropriate health care, selecting the most appropriate diagnostic and/or therapeutic options to address a problem of health or a specific clinical condition". Their objective is to improve the effectiveness, efficiency and safety of clinical decisions, and they can serve a basis for the development of health policies. The preparation of CPGs represents a complex process, which requires knowledge, experience and resources, both in time and money. Its robustness does not depend on who does it, but on how it is done. This implies the participation of technicians who provide the evaluation of the evidence using the GRADE method and the consideration of cost-effectiveness aspects.

Las guías de diagnóstico y tratamiento elaboradas por las sociedades científicas médicas, constituyen una herramienta muy útil para el ejercicio profesional de la especialidad. Sustentadas en bibliografía actualizada, representan un material de enorme valor con recomendaciones de los expertos en los diversos temas de la especialidad. En el presente artículo se intenta determinar si las mismas podrían ser diseñadas acercándolas lo más estrechamente posible al formato de las Guías de Práctica Clínica Basadas en la Evidencia (GPC-BE), para lo cual se revisan las etapas en su elaboración y los requisitos que deberían cumplir para ser consideradas como tales. Las GPC-BE son un "conjunto de recomendaciones elaboradas de forma sistemática para ayudar a los profesionales y a los pacientes en la toma de decisiones sobre la atención sanitaria más apropiada, seleccionando las opciones diagnósticas y/o terapéuticas más adecuadas en el abordaje de un problema de salud o una condición clínica específica". Su objetivo es mejorar la efectividad, la eficiencia y la seguridad de las decisiones clínicas, y pueden servir de base para la elaboración de políticas de salud. La elaboración de las GPC representa un proceso complejo, que requiere conocimientos, experiencia y recursos tanto en tiempo como en dinero. Su robustez no depende de quienes la realizan, sino de cómo es realizada. Ello implica la participación de técnicos que aporten la evaluación de la evidencia por el método GRADE, y la consideración de aspectos de costo-efectividad.

GADECCU 2022 Guideline for the treatment of Ulcerative Colitis. Adaptation and updating of the GETECCU 2020 Guideline. / Guía GADECCU 2022 para el tratamiento de la colitis ulcerosa. Adaptación y actualización de la Guía GETECCU 2020.

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory disease that compromises the colon, affecting the quality of life of individuals of any age. In practice, there is a wide spectrum of clinical situations. The advances made in the physio pathogenesis of UC have allowed the development of new, more effective and safer therapeutic agents. OBJECTIVES: To update and expand the evaluation of the efficacy and safety of relevant treatments for remission induction and maintenance after a mild, moderate or severe flare of UC. RECIPIENTS: Gastroenterologists, coloproctologists, general practitioners, family physicians and others health professionals, interested in the treatment of UC. METHODOLOGY: GADECCU authorities obtained authorization from GETECCU to adapt and update the GETECCU 2020 Guide for the treatment of UC. Prepared with GRADE methodology. A team was formed that included authors, a panel of experts, a nurse and a patient, methodological experts, and external reviewers. GRADE methodology was used with the new information. RESULTS: A 118-page document was prepared with the 44 GADECCU 2022 recommendations, for different clinical situations and therapeutic options, according to levels of evidence. A section was added with the new molecules that are about to be available. CONCLUSIONS: This guideline has been made in order to facilitate decision-making regarding the treatment of UC, adapting and updating the guide prepared by GETECCU in the year 2020.

Treatment of Hypercalcemia of Malignancy in Adults: An Endocrine Society Clinical Practice Guideline.

BACKGROUND: Hypercalcemia of malignancy (HCM) is the most common metabolic complication of malignancies, but its incidence may be declining due to potent chemotherapeutic agents. The high mortality associated with HCM has declined markedly due to the introduction of increasingly effective chemotherapeutic drugs. Despite the widespread availability of efficacious medications to treat HCM, evidence-based recommendations to manage this debilitating condition are lacking. OBJECTIVE: To develop guidelines for the treatment of adults with HCM. METHODS: A multidisciplinary panel of clinical experts, together with experts in systematic literature review, identified and prioritized 8 clinical questions related to the treatment of HCM in adult patients. The systematic reviews (SRs) queried electronic databases for studies relevant to the selected questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. An independent SR was conducted in parallel to assess patients' and physicians' values and preferences, costs, resources needed, acceptability, feasibility, equity, and other domains relevant to the Evidence-to-Decision framework as well as to enable judgements and recommendations. RESULTS: The panel recommends (strong recommendation) in adults with HCM treatment with denosumab (Dmab) or an intravenous (IV) bisphosphonate (BP). The following recommendations were based on low certainty of the evidence. The panel suggests (conditional recommendation) (1) in adults with HCM, the use of Dmab rather than an IV BP; (2) in adults with severe HCM, a combination of calcitonin and an IV BP or Dmab therapy as initial treatment; and (3) in adults with refractory/recurrent HCM despite treatment with BP, the use of Dmab. The panel suggests (conditional recommendation) the addition of an IV BP or Dmab in adult patients with hypercalcemia due to tumors associated with high calcitriol levels who are already receiving glucocorticoid therapy but continue to have severe or symptomatic HCM. The panel suggests (conditional recommendation) in adult patients with hypercalcemia due to parathyroid carcinoma, treatment with either a calcimimetic or an antiresorptive (IV BP or Dmab). The panel judges the treatments as probably accessible and feasible for most recommendations but noted variability in costs, resources required, and their impact on equity. CONCLUSIONS: The panel's recommendations are based on currently available evidence considering the most important outcomes in HCM to patients and key stakeholders. Treatment of the primary malignancy is instrumental for controlling hypercalcemia and preventing its recurrence. The recommendations provide a framework for the medical management of adults with HCM and incorporate important decisional and contextual factors. The guidelines underscore current knowledge gaps that can be used to establish future research agendas.

PARP-inhibitors for BRCA1/2-related advanced HER2-negative breast cancer: A meta-analysis and GRADE recommendations by the Italian Association of Medical Oncology.

BACKGROUND: Approximately 5-10% of unselected breast cancer (BC) patients retain a hereditary predisposition related to a germline mutation in BRCA1/2 genes. The poly-ADP ribose polymerase (PARP)-inhibitors olaparib and talazoparib have been granted marketing authorization by both FDA and EMA for adults with BRCA1/2 germline mutations and HER2-negative (HER2-) advanced BC based on the results from the phase III OlympiAd and EMBRACA trials. METHODS: The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer addressed two critical clinical questions, adopting the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Evidence to Decision framework (EtD), to develop recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related triple-negative (clinical question 1) and hormone receptor-positive (HR+)/HER2- (clinical question 2) advanced BC. RESULTS: Two studies were eligible (OlympiAd and EMBRACA). For both clinical questions, the Panel judged the benefit/harm balance probably in favor of the intervention, given the favorable impact in terms of PFS, ORR, and QoL at an acceptable cost in terms of toxicity; the overall certainty of the evidence was low. The panel's final recommendations were conditional in favor of PARP-inhibitors over single-agent chemotherapy in both HR+/HER2-and triple-negative BC. Finally, the Panel identified and discussed areas of uncertainty calling for further exploration. CONCLUSIONS: The Panel of AIOM BC Clinical Practice Guideline provided clinical recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related HER2-advanced BC by adopting the GRADE methodology.

A New Era of National Guideline Development in Saudi Arabia.

Saudi Arabia's ambitious Vision 2030 project was launched in 2016 as a strategy for economic development and national growth, with 11 Vision Realization Programs put in charge of its implementation. The backbone of its Transformation Program for the Health Sector has been the definition of a new Model of Care aiming to deliver 42 coordinated interventions across 6 Systems of Care, with the development of clinical guidelines identified as a key cross-cutting intervention to foster the use of national, evidence-based practices across KSA, reduce care variation, and promote accountable care. This article provides an overview of the history, progress to date, and future outlook of the recently initiated National Guidelines Center in Saudi Arabia, established in collaboration between the Health Holding Company and the Saudi Health Council represented by its National Center for Evidence-based Medicine. The lessons learnt from previous guideline initiatives are grouped under the Center's design principles of high quality, relevance, practical implementation, and sustainability. Aspects setting the project apart from previous endeavors have been its focus on extensive engagement with key stakeholders in the Saudi guideline ecosystem, the co-development of evidence-based recommendations with aligned key performance measures, and the implementation of guideline recommendations in the clinical workflow via integrated electronic order sets. Nine activity streams aim to enable the Center to take its place among the leading regional and global guideline developing organizations and to optimally support clinicians and patients, Saudi Arabia's health sector transformation, and the work of guideline communities worldwide.

Inclusion of Platinum Agents in Neoadjuvant Chemotherapy Regimens for Triple-Negative Breast Cancer Patients: Development of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Medical Oncology (AIOM).

In the absence of identified therapeutic targets, chemotherapy is the main systemic treatment option for triple-negative breast cancer (TNBC). The achievement of a pathological complete response (pCR) after neoadjuvant chemotherapy leads to good outcome, whereas patients not achieving a pCR are at high risk of relapse. Various trials have evaluated the inclusion of platinum in neoadjuvant chemotherapy regimens for TNBC, leading to non-univocal results. The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on Breast Cancer developed a clinical recommendation on the addition of platinum to anthracycline/taxane-based neoadjuvant chemotherapy for TNBC by using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology and the Evidence to Decision framework (EtD). Five studies were eligible. The panel identified the following outcomes of benefit: pCR (critical), disease/event-free survival (DFS/EFS, critical), and overall survival (OS, critical). The panel identified febrile neutropenia (critical), serious adverse events (critical), anemia grade 3-4 (important), thrombocytopenia grade 3-4 (important) as outcomes of harms. The probability of pCR was higher in the platinum-based chemotherapy group versus control group (RR = 1.45, 95%CI 1.28-1.64); however, no impact on long-term outcome was observed. Neoadjuvant treatment regimens containing platinum resulted in a non-significant increase in the risk of febrile neutropenia and in a significant increase in the risk serious adverse events, G3-G4 anemia and G3-G4 thrombocytopenia: 11.3% versus 0.8%, RR = 15.66 (95%CI 6.38-38.44). The panel judged uncertain/favorable the benefit/harms balance. The panel's final recommendation was conditional in favor of the inclusion of platinum in anthracycline/taxane-based neoadjuvant regimens for TNBC.

Adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive early breast cancer: evidence evaluation and GRADE recommendations by the Italian Association of Medical Oncology (AIOM)

Premenopausal women with hormone receptor-positive early breast cancer are candidates for adjuvant endocrine therapy, as recommended by the major international guidelines. To date, adjuvant endocrine options for premenopausal women include tamoxifen with or without ovarian function suppression (OFS) or an aromatase inhibitor with OFS. Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed, and the results of randomised clinical trials have been reported over the last years. Despite this evidence, the optimal algorithm for endocrine therapy for premenopausal women with hormone receptor-positive early stage invasive breast cancer shows open questions regarding the role of OFS in addition to tamoxifen and the optimal use of hormonal agents. The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer applied the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology on three critical questions on the choice of the adjuvant hormonal therapy in premenopausal breast cancer patients to summarise available evidence and to create recommendations to help physicians in their clinical practice.

GRADEing the un-GRADE-able: a description of challenges in applying GRADE methods to the ethical and implementation questions of pediatric organ donation guidelines.

Good practice statements (GPSs) have been proposed by the GRADE working group as a way of avoiding the inappropriate characterization of evidence as low quality in support of strong recommendations justified by indirect evidence. This commentary examines how the GPS methodology was applied to the development of a recent guideline for pediatric deceased donation after circulatory determined death. This guideline was informed by a broad body of indirect literature and addressed a variety of social, legal, and ethical questions in addition to several implementation issues. While the resulting document contained a vast majority of GPS (63 as opposed to seven actionable GRADEd recommendations), we maintain that this application was appropriate to develop recommendations within the GRADE framework. This commentary explores how GPS may be applied in this context and explores whether a new classification of recommendations focused on these types of issues may be appropriate.

Adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive early breast cancer: Evidence evaluation and GRADE recommendations by the Italian Association of Medical Oncology (AIOM).

Premenopausal women with hormone receptor-positive early breast cancer are candidates for adjuvant endocrine therapy, as recommended by the major international guidelines. To date, adjuvant endocrine options for premenopausal women include tamoxifen with or without ovarian function suppression (OFS) or an aromatase inhibitor with OFS. Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed, and the results of randomised clinical trials have been reported over the last years. Despite this evidence, the optimal algorithm for endocrine therapy for premenopausal women with hormone receptor-positive early stage invasive breast cancer shows open questions regarding the role of OFS in addition to tamoxifen and the optimal use of hormonal agents. The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer applied the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology on three critical questions on the choice of the adjuvant hormonal therapy in premenopausal breast cancer patients to summarise available evidence and to create recommendations to help physicians in their clinical practice.

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a complex disease with new drugs becoming available in the past years. There is a need for a reference tool compiling current data to aid professionals in treatment decisions. OBJECTIVES: To develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS. METHODS: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients-Intervention-Comparator-Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. RESULTS: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. CONCLUSION: The present guideline will enable homogeneity of treatment decisions across Europe.

Evidence-Based Guidelines for Fatigue Risk Management in Emergency Medical Services.

BACKGROUND: Administrators of Emergency Medical Services (EMS) operations lack guidance on how to mitigate workplace fatigue, which affects greater than half of all EMS personnel. The primary objective of the Fatigue in EMS Project was to create an evidence-based guideline for fatigue risk management tailored to EMS operations. METHODS: Systematic searches were conducted from 1980 to September 2016 and guided by seven research questions framed in the Population, Intervention, Comparison, Outcome (PICO) framework. Teams of investigators applied inclusion criteria, which included limiting the retained literature to EMS personnel or similar shift worker groups. The expert panel reviewed summaries of the evidence based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The panel evaluated the quality of evidence for each PICO question separately, considered the balance between benefits and harms, considered the values and preferences of the targeted population, and evaluated the resource requirements/needs. The GRADE Evidence-to-Decision (EtD) Framework was used to prepare draft recommendations based on the evidence, and the Content Validity Index (CVI) was used to quantify the panel's agreement on the relevance and clarity of each recommendation. CVI scores for relevance and clarity were measured separately on a 1-4 scale to indicate consensus/agreement among panel members and conclusion of recommendation development. RESULTS: The EtD framework was applied to all 7 PICO questions, and the panel created 5 recommendations. PICO1: The panel recommends using fatigue/sleepiness survey instruments to measure and monitor fatigue in EMS personnel. PICO2: The panel recommends that EMS personnel work shifts shorter than 24 hours in duration. PICO3: The panel recommends that EMS personnel have access to caffeine as a fatigue countermeasure. PICO4: The panel recommends that, EMS personnel have the opportunity to nap while on duty to mitigate fatigue. PICO5: The panel recommends that EMS personnel receive education and training to mitigate fatigue and fatigue-related risks. The panel referenced insufficient evidence as the reason for making no recommendation linked to 2 PICO questions. CONCLUSIONS: Based on a review of the evidence, the panel developed a guideline with 5 recommendations for fatigue risk management in EMS operations.

ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in the decision-making process. METHODS: This guideline has been developed using the GRADE methodology and following the recently updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. An exhaustive literature search up to December 2016 was performed for each question and the evidence is presented narratively and, when possible, combined in a meta-analysis using a random-effects model. The quality of evidence for each outcome was rated into four categories - very high, high, low and very low - according to the risk of bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro) software (Version 3.6). The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panellists was reached by use of the modified nominal group technique. RESULTS: A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at the time of publication. A total of 20 recommendations were agreed by the guideline working group members after three rounds of consensus.

The Implementation of Targeted Temperature Management: An Evidence-Based Guideline from the Neurocritical Care Society.

BACKGROUND: Targeted temperature management (TTM) is often used in neurocritical care to minimize secondary neurologic injury and improve outcomes. TTM encompasses therapeutic hypothermia, controlled normothermia, and treatment of fever. TTM is best supported by evidence from neonatal hypoxic-ischemic encephalopathy and out-of-hospital cardiac arrest, although it has also been explored in ischemic stroke, traumatic brain injury, and intracranial hemorrhage patients. Critical care clinicians using TTM must select appropriate cooling techniques, provide a reasonable rate of cooling, manage shivering, and ensure adequate patient monitoring among other challenges. METHODS: The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacotherapy to form a writing Committee in 2015. The group generated a set of 16 clinical questions relevant to TTM using the PICO format. With the assistance of a research librarian, the Committee undertook a comprehensive literature search with no back date through November 2016 with additional references up to March 2017. RESULTS: The Committee utilized GRADE methodology to adjudicate the quality of evidence as high, moderate, low, or very low based on their confidence that the estimate of effect approximated the true effect. They generated recommendations regarding the implementation of TTM based on this systematic review only after considering the quality of evidence, relative risks and benefits, patient values and preferences, and resource allocation. CONCLUSION: This guideline is intended for neurocritical care clinicians who have chosen to use TTM in patient care; it is not meant to provide guidance regarding the clinical indications for TTM itself. While there are areas of TTM practice where clear evidence guides strong recommendations, many of the recommendations are conditional, and must be contextualized to individual patient and system needs.

Critical concepts, practice recommendations, and research perspectives of pixantrone therapy in non-Hodgkin lymphoma: a SIE, SIES, and GITMO consensus paper.

OBJECTIVES: In this paper, we present a review of critical concepts and research perspectives and produce recommendations on the optimal use of pixantrone in non-Hodgkin lymphoma (NHL) by group discussion from an expert panel appointed by the Italian Society of Hematology and the affiliate societies, Società Italiana di Ematologia Sperimentale and Gruppo Italiano Trapianto di Midollo Osseo. METHODS: Recommendations were produced using the Delphi process. Scientific evidence on pixantrone efficacy was analyzed using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology in the areas where at least one randomized trial was published. The following key issues were addressed for practical recommendations: pixantrone monotherapy in aggressive relapsed or refractory non-Hodgkin B-cell lymphomas and toxicity risk management in patients candidates to pixantrone. RESULTS AND CONCLUSIONS: After a balanced and value-oriented discussion, the panel agreed that the benefit/risk profile was in favor of pixantrone in the treatment of adult patients with multiply relapsed or refractory aggressive NHL B-cell lymphomas. Pixantrone was deemed to be contraindicated in patients with uncontrolled cardiovascular disease. Despite a low rate of cardiotoxicity of pixantrone reported in clinical trials, the panel recommended that all patients receiving pixantrone should undergo periodical cardiac monitoring.

The role of Cochrane reviews in informing international guidelines: a case study of using the Grading of Recommendations, Assessment, Development and Evaluation system to develop World Health Organization guidelines for the psychosocially assisted pharmacological treatment of opioid dependence.

BACKGROUND AND AIMS: The World Health Organization (WHO), and a growing number of other organizations, have adopted the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system in order to both assess the quality of research evidence and develop clinical practice guidelines. In 2009 WHO published a guideline on psychosocially assisted pharmacological treatment of opioid dependence, based on the results of Cochrane Reviews summarized using the GRADE methodology. The main features of this system are an a priori definition of outcomes and their relevance, and distinction between the quality of evidence (also referred to as confidence in the estimate of intervention effect) and the strength of recommendations. We consider how successful this approach has been. ANALYSIS AND EVIDENCE: We discuss the merits and limitations of using Cochrane Reviews and GRADE framework in developing guidelines in the field of drug addiction. In 2009 a panel of multi-disciplinary international experts identified 15 clinical questions and eight relevant outcomes. Cochrane reviews were available for each clinical question and four outcomes. The panel formulated 15 recommendations. Eight recommendations were classified as strong, two of which were based on high-quality evidence and three on very low-quality evidence. For example, the strong recommendation to use methadone in adequate doses in preference to buprenorphine was based on high-quality evidence, while the strong recommendation not to use the combination of opioid antagonists with heavy sedation in the management of opioid withdrawal was based on low-quality evidence. CONCLUSIONS: An explicit stepwise process of moving from evaluation of the quality of evidence to the definition of the strength of recommendations is important in providing practical and clear clinical guidance for practitioners and policy-makers in addiction.