Translation, transcultural adaptation into Brazilian Portuguese and concurrent validity of the rheumatoid arthritis assessment scale (RAKAS-13/Brazil).

BACKGROUND: Knowledge of patients about Rheumatoid Arthritis (RA) is a necessary aspect to better approach self-management support in a patient-centered manner. The research instrument known as the Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS), consisting of 13 items, is simple, reliable and reproducible, and can be applied in both clinical practice and research protocols. OBJECTIVE: This study aimed to translate and culturally adapt the RAKAS vocabulary into Brazilian Portuguese and to evaluate its concurrent validity. METHODS: The RAKAS was translated into Brazilian Portuguese and administered to 52 elderly women with RA recruited between May 2021 and May 2022. Concurrent validity was assessed using the Spearman's correlation coefficient between RAKAS and Patient Knowledge Questionnaire (PKQ). RESULTS: The participants considered RAKAS-13/BRAZIL easy to understand and did not report any doubts in answering the final version. Concurrent validity of the RAKAS-13/BRAZIL was low compared to the PKQ (ρ = 0.283, p = 0.038). CONCLUSION: The Brazilian Portuguese version of the RAKAS (RAKAS-13/BRASIL) proved to be a questionnaire that was easy and quick to administer to assess patient knowledge about Rheumatoid Arthritis, despite its low correlation with the PKQ in the present study.

Risk factors for osteoporotic hip fracture among community-dwelling older adults: a real-world evidence study.

BACKGROUND: Hip fractures in the older adults lead to increased morbidity and mortality. Although a low bone mineral density is considered the leading risk factor, it is essential to recognize other factors that could affect the risk of hip fractures. This study aims to evaluate the contribution of clinical characteristics, patient-reported outcomes, and muscle and aerobic capacity for hip fractures in community-dwelling older adults. METHODS: This is a retrospective cohort study with real world-data from subjects ≥ 60 years old attending an outpatient clinic in Minas Gerais, Brazil, from May 1, 2019, to August 22, 2022. Data about clinical characteristics (multimorbidity, medications of long-term use, sedative and or tricyclic medications, number of falls), patient-reported outcomes (self-perception of health, self-report of difficulty walking, self-report of vision problems, and self-report of falls) and muscle and aerobic capacity (calf circumference, body mass index, and gait speed) were retrieved from an electronic health record. The association of each potential risk factor and hip fracture was investigated by a multivariable logistic regression analysis adjusted for age and sex. RESULTS: A total of 7,836 older adults were included with a median age of 80 years (IQR 72-86) and 5,702 (72.7%) were female. Hip fractures occurred in 121 (1.54%) patients. Multimorbidity was associated with an increased risk of hip fracture (OR = 1.12, 95%CI 1.06-1.18) and each episode of fall increased the chance of hip fracture by 1.7-fold (OR = 1.69, 95%CI 1.52-1.80). Patient-reported outcomes associated with increased fracture risk were regular or poor self-perception of health (OR = 1.59, 95%CI 1.06-2.37), self-report of walking difficulty (OR = 3.06, 95%CI 1.93-4.84), and self-report of falls (OR = 2.23, 95%CI 1.47-3.40). Body mass index and calf circumference were inversely associated with hip fractures (OR = 0.91, 95%CI 0.87-0.96 and OR = 0.93, 95%CI 0.88-0.97, respectively), while slow gait speed increased the chance of hip fractures by almost two-fold (OR = 1.80, 95%CI 1.22-2.66). CONCLUSION: Our study reinforces the importance of identified risk factors for hip fracture in community-dwelling older adults beyond bone mineral density and available fracture risk assessment tools. Data obtained in primary care can help physicians, other health professionals, and public health policies to identify patients at increased risk of hip fractures.

The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Risk factors for osteoporotic hip fracture among community-dwelling older adults: a real-world evidence study

Abstract Background Hip fractures in the older adults lead to increased morbidity and mortality. Although a low bone mineral density is considered the leading risk factor, it is essential to recognize other factors that could affect the risk of hip fractures. This study aims to evaluate the contribution of clinical characteristics, patient-reported outcomes, and muscle and aerobic capacity for hip fractures in community-dwelling older adults. Methods This is a retrospective cohort study with real world-data from subjects ≥ 60 years old attending an outpatient clinic in Minas Gerais, Brazil, from May 1, 2019, to August 22, 2022. Data about clinical characteristics (multimorbidity, medications of long-term use, sedative and or tricyclic medications, number of falls), patient-reported outcomes (self-perception of health, self-report of difficulty walking, self-report of vision problems, and self-report of falls) and muscle and aerobic capacity (calf circumference, body mass index, and gait speed) were retrieved from an electronic health record. The association of each potential risk factor and hip fracture was investigated by a multivariable logistic regression analysis adjusted for age and sex. Results A total of 7,836 older adults were included with a median age of 80 years (IQR 72-86) and 5,702 (72.7%) were female. Hip fractures occurred in 121 (1.54%) patients. Multimorbidity was associated with an increased risk of hip fracture (OR = 1.12, 95%CI 1.06-1.18) and each episode of fall increased the chance of hip fracture by 1.7-fold (OR = 1.69, 95%CI 1.52-1.80). Patient-reported outcomes associated with increased fracture risk were regular or poor self-perception of health (OR = 1.59, 95%CI 1.06-2.37), self-report of walking difficulty (OR = 3.06, 95%CI 1.93-4.84), and self-report of falls (OR = 2.23, 95%CI 1.47-3.40). Body mass index and calf circumference were inversely associated with hip fractures (OR = 0.91, 95%CI 0.87-0.96 and OR = 0.93, 95%CI 0.88-0.97, respectively), while slow gait speed increased the chance of hip fractures by almost two-fold (OR = 1.80, 95%CI 1.22-2.66). Conclusion Our study reinforces the importance of identified risk factors for hip fracture in community-dwelling older adults beyond bone mineral density and available fracture risk assessment tools. Data obtained in primary care can help physicians, other health professionals, and public health policies to identify patients at increased risk of hip fractures.

Translation, transcultural adaptation into Brazilian Portuguese and concurrent validity of the rheumatoid arthritis assessment scale (RAKAS-13/Brazil)

Abstract Background Knowledge of patients about Rheumatoid Arthritis (RA) is a necessary aspect to better approach self-management support in a patient-centered manner. The research instrument known as the Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS), consisting of 13 items, is simple, reliable and reproducible, and can be applied in both clinical practice and research protocols. Objectives This study aimed to translate and culturally adapt the RAKAS vocabulary into Brazilian Portuguese and to evaluate its concurrent validity. Methods The RAKAS was translated into Brazilian Portuguese and administered to 52 elderly women with RA recruited between May 2021 and May 2022. Concurrent validity was assessed using the Spearman's correlation coefficient between RAKAS and Patient Knowledge Questionnaire (PKQ). Results The participants considered RAKAS-13/BRAZIL easy to understand and did not report any doubts in answering the final version. Concurrent validity of the RAKAS-13/BRAZIL was low compared to the PKQ (ρ = 0.283, p = 0.038). Conclusion The Brazilian Portuguese version of the RAKAS (RAKAS-13/BRASIL) proved to be a questionnaire that was easy and quick to administer to assess patient knowledge about Rheumatoid Arthritis, despite its low correlation with the PKQ in the present study.

Brazilian society of rheumatology methodological guide for the development of evidence-based clinical guidelines in rheumatology.

Clinical practice guidelines (CPG) are developed to align standards of health care around the world, aiming to reduce the incidence of misconducts and enabling more effective use of health resources. Considering the complexity, cost, and time involved in formulating CPG, strategies should be used to facilitate and guide authors through each step of this process. The main objective of this document is to present a methodological guide prepared by the Epidemiology Committee of the Brazilian Society of Rheumatology for the elaboration of CPG in rheumatology. Through an extensive review of the literature, this study compiles the main practical recommendations regarding the following steps of CPG drafting: distribution of working groups, development of the research question, search, identification and selection of relevant studies, evidence synthesis and quality assessment of the body of evidence, the Delphi methodology for consensus achievement, presentation and dissemination of the recommendations, CPG quality assessment and updating. This methodological guide serves as an important tool for rheumatologists to develop reliable and high-quality CPG, standardizing clinical practices worldwide.

The New Coronavirus Pandemic and the Trend of Breast Cancer Diagnosis according to Age-Group: Total and Interrupted Time Series Study.

OBJECTIVE: There is a lack of studies evaluating the COVID-19 pandemic effect on breast cancer detection according to age-group. This study aimed to assess the pandemic impact on the trend of mammograms, breast biopsies, and breast cancer stage at diagnosis according to age-group. METHODS: This was an ecological time series study by inflection point regression model. We used data from women aged between 30 and 49, 50 and 69, and 70 years or more available in an open-access dataset of the Brazilian public healthcare system (2017-2021). We analyzed the trend of the variables in the pre-pandemic and the pandemic effect on the total time series. RESULTS: The decreasing or stationary trend of mammograms in the pre-pandemic has changed to a decreasing trend in the total time series in all age-groups. Before the pandemic, the increasing trend of breast biopsies has changed to stationary in the total time series in all age-groups. The increasing trend of tumors at stages 0 to II in the pre-pandemic has changed to decreasing or stationary in the total time series. Finally, the increasing trend of tumors at stage III or IV remained increasing in the total time series in all age-groups. CONCLUSION: The pandemic has changed the stationary or increasing trend to a decreasing or stationary trend of mammograms, breast biopsies, and tumors at stages 0 to II but has not influenced the increasing trend of tumors at stages III and IV in all age-groups.

The Negative Impact of the New Coronavirus Pandemic on the Trend of Breast Biopsies and Their Direct Costs: Interrupted Time Series Analysis.

OBJECTIVES: The overload of health services because of the COVID-19 pandemic has reduced the population's access to treatment and prevention of other diseases. This study aimed to identify whether there was a change in the trend of breast biopsies and their direct costs during the COVID-19 pandemic in a developing country's public and universal healthcare system. METHODS: This was an ecological time series study of mammograms and breast biopsies in women aged 30 years or older from an open-access data set of the Public Health System of Brazil from 2017 to July 2021. RESULTS: In 2020, there was a reduction of -40.9% in mammograms and -7.9% in breast biopsies compared with the prepandemic period. From 2017 to 2020, there was an increase in the breast biopsies ratio per mammogram (1.37%-2.55%), the percentage of Breast Imaging-Reporting and Data System (BI-RADS) IV and V mammograms (0.79%-1.14%), and the annual direct cost of breast biopsies (Brazilian Real 3 477 410.00 to Brazilian Real 7 334 910.00). In the time series, the negative impact of the pandemic was lower on BI-RADS IV to V mammograms than on BI-RADS 0 to III. There was an association between the trend of breast biopsies and BI-RADS IV to V mammography. CONCLUSIONS: The COVID-19 pandemic harmed the increasing trend of breast biopsies, their total direct costs, BI-RADS 0 to III and IV to V mammograms, observed in the prepandemic period. Furthermore, there was a tendency to screen women at a higher risk for breast cancer during the pandemic.

Brazilian society of rheumatology methodological guide for the development of evidence-based clinical guidelines in rheumatology

Abstract Clinical practice guidelines (CPG) are developed to align standards of health care around the world, aiming to reduce the incidence of misconducts and enabling more effective use of health resources. Considering the complexity, cost, and time involved in formulating CPG, strategies should be used to facilitate and guide authors through each step of this process. The main objective of this document is to present a methodological guide prepared by the Epidemiology Committee of the Brazilian Society of Rheumatology for the elaboration of CPG in rheumatology. Through an extensive review of the literature, this study compiles the main practical recommendations regarding the following steps of CPG drafting: distribution of working groups, development of the research question, search, identification and selection of relevant studies, evidence synthesis and quality assessment of the body of evidence, the Delphi methodology for consensus achievement, presentation and dissemination ofthe recommendations, CPG quality assessment and updating. This methodological guide serves as an important tool for rheumatologists to develop reliable and high-quality CPG, standardizing clinical practices worldwide.

The trend and direct costs of screening and chemotherapy treatment of breast cancer in the new coronavirus pandemic: total and interrupted time series study.

BACKGROUND: The COVID-19 pandemic has overloaded the healthcare systems of many countries and reduced the population's access to treatment and prevention of other diseases. This study aims to assess whether the COVID-19 pandemic has negatively interfered with the trend and the direct costs of screening and chemotherapy treatment of breast cancer in a public and universal healthcare system. METHOD: This was an ecological time series study using an open database of a public and universal health system from 2017 to 2021. RESULTS: In 2020, there was a 41% reduction in the coverage rate of breast cancer screening in women aged 50 to 69 years (about 1 million mammograms missed). The total direct cost of breast cancer screening reduced proportionally to the number of tests (BRL 67 million). On the other hand, the cost of chemotherapy treatment was higher in 2020, both in advanced (BRL 465 million) and localized (BRL 113 million) diseases. In the time series, mammograms' trend and direct costs changed from stationary to decreasing after the COVID-19 pandemic. The trend of direct costs with chemotherapy treatment for the advanced disease has been increasing and has not changed after the COVID-19 pandemic. On the other hand, in the case of localized disease, there was a trend toward reducing direct costs after the pandemic. CONCLUSION: After COVID-19, there was a downward trend in breast cancer screening and its direct costs, an upward trend in chemotherapy costs for advanced disease, and a downward trend in chemotherapy costs for localized disease.

Impact of COVID-19 pandemic on patients with rheumatic diseases in Latin America.

The objective of our study was to describe knowledge, attitudes and practices of Latin-American rheumatology patients regarding management and follow-up of their disease during COVID-19 pandemic. A cross-sectional observational study was conducted using a digital anonymous survey. Rheumatic patients ≥ 18 years from non-English-speaking PANLAR countries were included. Our survey included 3502 rheumatic patients living in more than 19 Latin-American countries. Median age of patients was 45.8(36-55) years and the majority (88.9%) was female. Most frequently self-reported disease was rheumatoid arthritis (48.4%). At least one anti-rheumatic treatment was suspended by 23.4% of patients. Fear of contracting SARS-Cov2 (27.7%) and economic issues (25%) were the most common reasons for drug discontinuation. Self-rated disease activity increased from 30 (7-50) to 45 (10-70) points during the pandemic. Communication with their rheumatologist during the pandemic was required by 55.6% of patients, mainly by telephone calls (50.2%) and social network messages (47.8%). An adequate knowledge about COVID-19 was observed in 43% of patients. Patients with rheumatic diseases in Latin America were negatively affected by the COVID-19 pandemic. An increase in self-rated disease activity, a reduction in medication adherence, and hurdles for medical follow-up were reported. Teleconsultation was perceived as a valid alternative to in-person visits during the pandemic.

Impact of COVID-19 Pandemic on Rheumatology Practice in Latin America.

OBJECTIVE: To describe the effect of the coronavirus disease 2019 (COVID-19) pandemic on Latin American rheumatologists from a professional, economic, and occupational point of view. METHODS: We conducted an observational cross-sectional study using an online survey sent to rheumatologists of each non-English-speaking country member of the Pan American League of Rheumatology Associations (PANLAR). A specific questionnaire was developed. RESULTS: Our survey included 1097 rheumatologists from 19 Latin American countries. Median (IQR) age of respondents was 48 (40-59) years and 618 (56.3%) were female. Duration of practice since graduation as a rheumatologist was 17 years, and 585 (53.3%) were aged < 50 years. Most rheumatologists worked in private practice (81.8%) and almost half worked in institutional outpatient centers (55%) and inpatient care (49.9%). The median number of weekly hours (IQR) of face-to-face practice before the pandemic was 27 (15-40) hours, but was reduced to 10 (5-20) hours during the pandemic. Telehealth was used by 866 (78.9%) respondents during the pandemic. Most common methods of communication were video calls (555; 50.6%), telephone calls (499; 45.5%), and WhatsApp voice calls (423; 38.6%). A reduction in monthly wages was reported by 946 (86.2%) respondents. Consultation fees also were reduced and 88 (8%) rheumatologists stated they had lost their jobs. A reduction in patient adherence to medication was reported by nearly 50% of respondents. Eighty-one (7.4%) rheumatologists received a COVID-19 diagnosis and 7 (8.6%) of them were hospitalized. CONCLUSION: The COVID-19 pandemic has reshaped rheumatology practice in Latin America and has had a profound effect on rheumatologists' behaviors and clinical practice.

Assessing the process and outcome of the development of practice guidelines and recommendations: PANELVIEW instrument development.

BACKGROUND: Guideline recommendations may be affected by flaws in the process, inappropriate panel member selection or conduct, conflicts of interest and other factors. To our knowledge, no validated tool exists to evaluate guideline development from the perspective of those directly involved in the process. Our objective was to develop and validate a universal tool, the PANELVIEW instrument, to assess guideline processes, methods and outcomes from the perspective of the participating guideline panellists and group members. METHODS: We performed a systematic literature search and surveys of guideline groups (identified through contacting international organizations and convenience sampling of working panels) to inform item generation. Subsequent groups of guideline methodologists and panellists reviewed items for face validity and missing items. We used surveys, interviews and expert review for item reduction and phrasing. For reliability assessment and feedback, we tested the PANELVIEW tool in 8 international guideline groups. RESULTS: We surveyed 62 members from 13 guideline panels, contacted 19 organizations and reviewed 20 source documents to generate items. Fifty-three additional key informants provided feedback about phrasing of the items and response options. We reduced the number of items from 95 to 34 across domains that included administration, training, conflict of interest, group dynamics, chairing, evidence synthesis, formulating recommendations and publication. The tool takes about 10 minutes to complete and showed acceptable measurement properties. INTERPRETATION: The PANELVIEW instrument fills a gap by enabling guideline organizations to involve clinicians, patients and other participants in evaluating their guideline processes. The tool can inform quality improvement of existing or new guideline programs, focusing on insight into and transparency of the guideline development process, methods and outcomes.

Clinical practice guidelines in Brazil - developing a national programme.

In Brazil, governmental and non-governmental organisations develop practice guidelines (PGs) in order to optimise patient care. Although important improvements have been made over the past years, many of these documents still lack transparency and methodological rigour. In order to conduct a critical analysis and define future steps in PG development in Brazil, we carried out a structured assessment of strengths, weaknesses, opportunities and threats (SWOT analysis) for the development of a national guideline programme. Participants consisted of academia, methodologists, medical societies and healthcare system representatives. In summary, the PG development process has improved in Brazil and current investments in methodological research and capacity-building are ongoing. Despite the centralised processes for public PGs, standardised procedures for their development are not well established and human resources are insufficient in number and capacity to develop the amount of trustworthy documents needed. Brazil's capacity could be strengthened and initial efforts have been made such as the adoption of standards proposed by world-renowned institutions in PG development and enhancement of the involvement of key stakeholders. Further steps involve the alignment between health technology assessment and PG processes for synergy and the development of a national network to promote the interaction between groups involved in the development of PGs. The lessons learned from this paper could be used to foster debate on guideline development, especially for countries facing similar threats on this topic.

Brazilian recommendations on the safety and effectiveness of the yellow fever vaccination in patients with chronic immune-mediated inflammatory diseases.

BACKGROUND: In Brazil, we are facing an alarming epidemic scenario of Yellow fever (YF), which is reaching the most populous areas of the country in unvaccinated people. Vaccination is the only effective tool to prevent YF. In special situations, such as patients with chronic immune-mediated inflammatory diseases (CIMID), undergoing immunosuppressive therapy, as a higher risk of severe adverse events may occur, assessment of the risk-benefit ratio of the yellow fever vaccine (YFV) should be performed on an individual level. Faced with the scarcity of specific orientation on YFV for this special group of patients, the Brazilian Rheumatology Society (BRS) endorsed a project aiming the development of individualized YFV recommendations for patients with CIMID, guided by questions addressed by both medical professionals and patients, followed an internationally validated methodology (GIN-McMaster Guideline Development). Firstly, a systematic review was carried out and an expert panel formed to take part of the decision process, comprising BRS clinical practitioners, as well as individuals from the Brazilian Dermatology Society (BDS), Brazilian Inflammatory Bowel Diseases Study Group (GEDIIB), and specialists on infectious diseases and vaccination (from Tropical Medicine, Infectious Diseases and Immunizations National Societies); in addition, two representatives of patient groups were included as members of the panel. When the quality of the evidence was low or there was a lack of evidence to determine the recommendations, the decisions were based on the expert opinion panel and a Delphi approach was performed. A recommendation was accepted upon achieving ≥80% agreement among the panel, including the patient representatives. As a result, eight recommendations were developed regarding the safety of YFV in patients with CIMID, considering the immunosuppression degree conferred by the treatment used. It was not possible to establish recommendations on the effectiveness of YFV in these patients as there is no consistent evidence to support these recommendations. CONCLUSION: This paper approaches a real need, assessed by clinicians and patient care groups, to address specific questions on the management of YFV in patients with CIMID living or traveling to YF endemic areas, involving specialists from many areas together with patients, and might have global applicability, contributing to and supporting vaccination practices. We recommended a shared decision-making approach on taking or not the YFV.

Brazilian recommendations on the safety and effectiveness of the yellow fever vaccination in patients with chronic immune-mediated inflammatory diseases

Abstract Background: In Brazil, we are facing an alarming epidemic scenario of Yellow fever (YF), which is reaching the most populous areas of the country in unvaccinated people. Vaccination is the only effective tool to prevent YF. In special situations, such as patients with chronic immune-mediated inflammatory diseases (CIMID), undergoing immunosuppressive therapy, as a higher risk of severe adverse events may occur, assessment of the risk-benefit ratio of the yellow fever vaccine (YFV) should be performed on an individual level. Main body of the abstract: Faced with the scarcity of specific orientation on YFV for this special group of patients, the Brazilian Rheumatology Society (BRS) endorsed a project aiming the development of individualized YFV recommendations for patients with CIMID, guided by questions addressed by both medical professionals and patients, followed an internationally validated methodology (GIN-McMaster Guideline Development). Firstly, a systematic review was carried out and an expert panel formed to take part of the decision process, comprising BRS clinical practitioners, as well as individuals from the Brazilian Dermatology Society (BDS), Brazilian Inflammatory Bowel Diseases Study Group (GEDIIB), and specialists on infectious diseases and vaccination (from Tropical Medicine, Infectious Diseases and Immunizations National Societies); in addition, two representatives of patient groups were included as members of the panel. When the quality of the evidence was low or there was a lack of evidence to determine the recommendations, the decisions were based on the expert opinion panel and a Delphi approach was performed. A recommendation was accepted upon achieving ≥80% agreement among the panel, including the patient representatives. As a result, eight recommendations were developed regarding the safety of YFV in patients with CIMID, considering the immunosuppression degree conferred by the treatment used. It was not possible to establish recommendations on the effectiveness of YFV in these patients as there is no consistent evidence to support these recommendations. Conclusion: This paper approaches a real need, assessed by clinicians and patient care groups, to address specific questions on the management of YFV in patients with CIMID living or traveling to YF endemic areas, involving specialists from many areas together with patients, and might have global applicability, contributing to and supporting vaccination practices. We recommended a shared decision-making approach on taking or not the YFV.

The biosimilars journey: current status and ongoing challenges.

Biosimilar products are already approved and marketed in several countries. The Food and Drug Administration has approved ten different biosimilars, and the European Medicines Agency has approved 40. Even though this scenario has provided important experience with biosimilar products, there are still challenges and unanswered questions. Up to now, a good amount of knowledge has been gathered in order to support the importance of the totality of evidence and the construction of a biosimilarity exercise for regulatory approval. In addition, the extrapolation of indications has been proved viable when a careful analysis is performed. The models for clinical trials and the use of the most sensible populations have been extensively discussed, and there is apparent homogeneity in manufacturer choices for study designs. However, some challenges remain. The lack of regulatory harmony, especially concerning naming, the marketed intended copies, the interchangeability, and the biosimilars in orphan diseases are some of those and are the focus of discussion in this review.

Development of rapid guidelines: 3. GIN-McMaster Guideline Development Checklist extension for rapid recommendations.

BACKGROUND: Practice guidelines require a substantial investment of resources and time, often taking between 1 and 3 years from conceptualisation to publication. However, urgent situations require the development of recommendations in a shorter timeframe. In this third and final article in the series exploring challenges and solutions in developing rapid guidelines (RGs), we propose guiding principles for the development of RGs. METHODS: We utilised the Guideline International Network-McMaster Guideline Development Checklist (GDC) as a starting point for elements to consider during RG development. We built on those elements using the findings from a systematic review of guideline manuals, a survey of international organisations conducting RGs, and interviews of guideline developers within WHO. We reviewed initial findings and developed an intermediate list of elements, as well as narrative guidance. We then invited experts to validate the intermediate list, reviewing for placement, brevity and redundancy. We used this iterative process and group consensus to determine the final elements for RG development guidance. RESULTS: Our work identified 21 principles within the topics of the Guideline International Network-McMaster GDC to guide the planning and development of RGs. Principles fell within 15 of the 18 checklist topics, highlighting strategies to streamline and expedite the guideline development process. CONCLUSIONS: We defined principles to guide the development of RGs, while maintaining a standardised, rigorous and transparent process. These principles will serve as guidance for guideline developers responding to urgent situations such as public health urgencies. Integration of these principles within currently disseminated guideline development standards will facilitate the use of those tools in situations necessitating RG recommendations.

Development of rapid guidelines: 2. A qualitative study with WHO guideline developers.

BACKGROUND: Situations such as public health emergencies and outbreaks necessitate the development and publication of high-quality recommendations within a condensed timeframe. For example, WHO has produced examples of and guidance for the development of rapid guidelines (RGs). However, more information is needed to understand the experiences and perceptions of guideline developers. This is the second of a series of three articles addressing methodological issues around RGs. This study describes the perceptions and experiences of guideline developers at WHO about RGs. METHODS: We conducted interviews consisting of open- and closed-ended questions with guideline developers at WHO. Our analysis described the definition and rationale of RGs, the differences from regular guidelines with regard to timelines from topic definition until publication, barriers to identifying the evidence and the lack of a standard methodology to develop RGs. RESULTS: We interviewed 10 participants, the majority of whom were comfortable with the current WHO definition of RGs. Most stated that the rationale for developing RGs should be in response to new evidence about efficacy, cost-effectiveness or safety. Respondents differed with regards to the amount of time RGs should take. While the majority of participants agreed that guidelines should be based on a systematic review, this step in the process was considered the most time and resource intensive. Challenges for developing RGs included limited personnel and financial resources as well as the lack of evidence. Facilitators, in turn, that may improve RG development include additional financial and personnel resources as well as the use of virtual meetings. CONCLUSIONS: While our study suggests a strong need and rationale for the development of RGs, standardisation of timelines and guidance on panel composition, peer-review process, conduct of meetings and sources of permissible evidence require further research.

Development of rapid guidelines: 1. Systematic survey of current practices and methods.

BACKGROUND: Guidelines in the healthcare field generally should contain evidence-based recommendations to inform healthcare decisions. Guidelines often require 2 years or more to develop, but certain circumstances necessitate the development of rapid guidelines (RGs) in a short period of time. Upholding methodological rigor while meeting the reduced development timeframe presents a challenge for developing RGs. Our objective was to review current practices and standards for the development of RGs. This is the first of a series of three articles addressing methodological issues around RGs. METHODS: We conducted a systematic survey of methods manuals and published RGs to identify reasons for the development of RGs. Data sources included existing guideline manuals, published RGs, Trip Medical Database, MEDLINE, EMBASE and communication with guideline developers until February 2018. RESULTS: We identified 46 guidelines that used a shortened timeframe for their development. Nomenclature describing RGs varied across organisations, wherein the United States Centers for Disease Control and Prevention produced 'Interim Guidelines', the National Institute for Health and Care Excellence in the United Kingdom developed 'Short Clinical Guidelines', and WHO provided 'Rapid Advice'. The rationale for RGs included response to emergencies, rapid increases in cases of a condition or disease severity, or new evidence regarding treatment. In general, the methods to assess the quality of evidence, the consensus process and the management of the conflict of interest were not always clear. While we identified another 11 RGs from other institutions, there was no reference to timeframe and reasons for conducting a RG. The three organisations mentioned above provide guidance for the development of RGs. CONCLUSIONS: There is a lack of standardised nomenclature and definitions regarding RGs and there is inconsistency in the methods described in manuals and in RG. It is therefore important that all RGs provide a detailed and transparent description of their methods in order for readers and end-users to be able to assess their quality and validate their findings.