Addressing Challenges When Applying GRADE to Public Health Guidelines: A Scoping Review Protocol and Pilot Analysis

This is a protocol for a scoping review that aims to determine how guideline authors using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach have addressed previously identified challenges related to public health. The Joanna Briggs Institute (JBI) methodology for scoping reviews will be followed. We will search and screen titles of guidelines for all languages published in 2013–2021 in: the GIN library, BIGG database, Epistemonikos GRADE guidelines repository, GRADEpro Database, MAGICapp, NICE and WHO websites. Two reviewers will independently screen full texts of the documents identified. The following information will be extracted: methods used for identifying different stakeholders and incorporating their perspectives; methods for identification and prioritization of non-health outcomes; methods for determining thresholds for decision-making; methods for incorporating and grading evidence from non-randomized studies; methods for addressing concerns with conditional recommendations in public health; methods for reaching consensus; additional methodological concerns; and any modifications made to GRADE. A combination of directed content analysis and descriptive statistics will be used for data analysis, and the findings presented narratively in a tabular and graphical form. In this protocol, we present the pilot results from 13 identified eligible guidelines issued between January and August 2021. We will publish the full review results when they become available.

Photobiomodulation for the Treatment of Primary Headache: Systematic Review of Randomized Clinical Trials

The purpose of this study was to evaluate the efficacy and safety of photobiomodulation as an adjuvant treatment for primary headache. A systematic review of randomized clinical trials was performed. For such, electronic searches were performed in the MEDLINE, Embase, Cochrane Library, LILACS, PEDro, PsycInfo, Clinicaltrials.gov., and WHO/ICTRP databases, with no restrictions imposed regarding language or year of publication. We included studies that assessed any photobiomodulation therapy as an adjuvant treatment for primary headache compared to sham treatment, no treatment, or another intervention. The methodological assessment was conducted using the Cochrane Risk of Bias tool. The certainty of the evidence was classified using the GRADE approach. Four randomized clinical trials were included. Most of the included studies had an overall high risk of bias. Compared to sham treatment, photobiomodulation had a clinically important effect on pain in individuals with primary headache. Despite the benefits reported for other outcomes, the estimates were imprecise, and the certainty of the evidence was graded as low. These findings are considered insufficient to support the use of photobiomodulation in the treatment of primary headache. Randomized clinical trials, with higher methodological quality, are needed to enhance the reliability of the estimated effects.

Moving From Evidence To Decisions in Guidelines: An Analysis of Guidance Documents

Background The process of moving from evidence to decisions (EtD) represents a cornerstone within guideline development methods. Little is known about the processes used by organizations in charge of guideline development and what criteria they consider when formulating recommendations. Objective To identify and describe the processes suggested for the formulation of healthcare recommendations in health care guidelines available in guidance documents. Methods We searched in spring 2020 the Guidelines International Network (G-I-N) website, MEDLINE, and The Cochrane Methodology Register to retrieve guidance documents published in the last decade by organizations dedicated to guideline development. Pairs of researchers independently selected and extracted data about the characteristics of the guidance document, including explicit or implicit recommendation-related criteria and processes considered, as well as the use of frameworks. We conducted both descriptive and bivariate analyses. Results We included 68 guidance documents, published mostly by scientific societies (58%). Most of the organizations reported a system for grading the strength of recommendations (88%), half of them being the GRADE approach. Two out of three guidance documents (66%) proposed the use of a framework to guide the EtD process. We identified 14 recommendation-related criteria. The GRADE Evidence to Decision (GRADE-EtD) framework was the most often reported framework (19 organizations, 42%), whereas 20 organizations (44%) proposed their own multi-criteria frameworks. Using any EtD framework was related with a more comprehensive set of recommendation-related criteria compared to no framework, especially for criteria like values, equity, and acceptability. A similar association was observed between the GRADE-EtD framework and either no framework or another EtD frameworks. Conclusion The use of systematic and structured processes for moving from evidence to decisions is still limited among international organizations. The use of EtD frameworks facilitates the inclusion of relevant recommendation criteria. Among the structured frameworks, the GRADE-EtD framework offers the most comprehensive perspective for evidence-informed decision-making processes. More complete and detailed reporting in the guidance documents is warranted.

Perspectives of patients and consumers on the use of generic medicines

INTRODUCTION Access to medicines constitutes a public health challenge worldwide. Promoting utilization of generic medicines is one of the strategies that has been proposed to optimize pharmaceutical spending and thus allow greater coverage. However, its use is not yet widespread enough. This study seeks to explore the perspectives and acceptability to the use of generic medicines from patients and consumers. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a evidence synthesis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified four systematic reviews that together include 47 primary studies, of which one corresponds to a randomized trial. A low rate of patients or consumers has a negative perception regarding generic medicines, including dimensions such as risk, quality, safety, risk of adverse effects, among others.

Radiosurgery for brain oligometastases in lung cancer

INTRODUCTION Brain metastases are a common problem in oncology patients, especially in lung cancer. The usual treatment for cerebral oligometastases is whole brain radiation therapy. Given the persistent poor prognosis of this disease, other therapeutic alternatives such as stereotactic radiosurgery have been considered. However, there is no clarity regarding the effectiveness of its addition. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified 17 systematic reviews including seven studies overall, of which four were randomized trials. All trials assessed patients with brain oligometastases, but none of them included exclusively lung cancer population. We concluded that it is not possible to clearly establish whether radiosurgery decreases neurological functionality, cognitive impairment, mortality or serious adverse effects, as the certainty of the existing evidence has been assessed as very low.

Risk Factors for Venous Thromboembolism in Severe COVID-19: A Study-Level Meta-Analysis of 21 Studies

Venous thromboembolism (VTE) in patients with COVID-19 in intensive care units (ICU) is frequent, but risk factors (RF) remain unidentified. In this meta-analysis (CRD42020188764) we searched for observational studies from ICUs reporting the association between VTE and RF in Medline/Embase up to 15 April 2021. Reviewers independently extracted data in duplicate and assessed the certainty of the evidence using the GRADE approach. Analyses were conducted using the random-effects model and produced a non-adjusted odds ratio (OR). We analysed 83 RF from 21 studies (5296 patients). We found moderate-certainty evidence for an association between VTE and the D-dimer peak (OR 5.83, 95%CI 3.18–10.70), and length of hospitalization (OR 7.09, 95%CI 3.41–14.73) and intubation (OR 2.61, 95%CI 1.94–3.51). We identified low-certainty evidence for an association between VTE and CRP (OR 1.83, 95% CI 1.32–2.53), D-dimer (OR 4.58, 95% CI 2.52–8.50), troponin T (OR 8.64, 95% CI 3.25–22.97), and the requirement for inotropic drugs (OR 1.67, 95% CI 1.15–2.43). Traditional VTE RF (i.e., history of cancer, previous VTE events, obesity) were not found to be associated to VTE in COVID-19. Anticoagulation was not associated with a decreased VTE risk. VTE RF in severe COVID-19 correspond to individual illness severity, and inflammatory and coagulation parameters.

Abstract 1122‐000144: Experiences and Strategies Developing an Evidence‐Based Clinical Guideline for Ischemic Stroke in a Middle‐income Setting

Introduction : Developing an evidence‐based clinical practice guideline in a middle‐income country is challenging. After a discussion with the stakeholders, we identified and prioritized the need for a clinical guideline about ischemic stroke in our country. We defined stakeholders to anyone who has an interest in the recommendations of the guideline, including patients' representatives, practitioners, policy/decision makers, commissioners of guidelines and other end users. Methods : We developed an evidence‐based guideline using the Grades of Recommendation, Assessment, Development, and Evaluation System (GRADE) approach with a multidisciplinary team including independent methodologists, local and international clinical experts. Systematic step‐by‐step search strategy was used. Four clinical guidelines were identified, quality of development of these guidelines was evaluated using the Appraisal of Guidelines for Research & Evaluation (AGREE II) tool. In the absence of a systematic review in the guideline to answer the clinical question, we proceeded to search for primary studies. The certainty of evidence was classified according to the GRADE system, as high, moderate, low, and very low. Recommendations were classified according to strength, as strong or conditional, and to direction, as in favor or against. Applicability and acceptability were evaluated by the stakeholders and patient’s representatives. External validation by national and international experts in the field was performed. Results : Eight clinical questions related to diagnosis, management, and early rehabilitation for ischemic stroke were formulated. Evidence from systematic reviews and meta‐analysis for every clinical question was discussed, an update was made when needed, and finally, twenty‐eight trustworthy recommendations (8 strong and 20 conditional) were developed. Also, thirty‐eight good practice points and two flowcharts were developed. Conclusions : In a setting with limited resources a high‐quality clinical guideline could be developed using good quality data from the systematic reviews found in previous guidelines. The GRADE approach could be very useful to contextualize the available evidence, making the process feasible and efficient.

Anti-hypertensive drugs deprescribing: an updated systematic review of clinical trials

Background Polypharmacy is defined as the prescription of at least 5 different medicines for therapeutic or prophylactic effect and is a serious issue among elderly patients, who are frequently affected by multi-morbidity. Deprescribing is one of the proposed approaches to reduce the number of administered drugs, by eliminating those that are inappropriately prescribed. The aim of this systematic review is to provide an updated and systematic assessment of the benefit-risk profile of deprescribing of anti-hypertensive drugs, which are among the most commonly used drugs. Methods MEDLINE, EMBASE and The Cochrane Library were searched for studies assessing the efficacy and safety of anti-hypertensive drugs deprescribing in the period between January, 12,016 and December, 312,019. The quality of randomized clinical trials (RCTs) was assessed using the GRADE approach for the evaluation of the main outcomes. The risk of bias assessment was carried out using the Cochrane risk-of-bias tool. Results Overall, two RCTs were identified. Despite summarized evidence was in favor of anti-hypertensive deprescribing, the overall risk of bias was rated as high for each RCT included. According to the GRADE approach, the overall quality of the RCTs included was moderate regarding the following outcomes: systolic blood pressure < 150 mmHg after 12 weeks of follow-up, quality of life, frailty and cardiovascular risk. Conclusions This updated systematic review of the efficacy and safety of anti-hypertensive treatment deprescribing found two recently published RCTs, in addition to the previous guideline of the National Institute for Health and Care Excellence (NICE). Evidence points towards non-inferiority of anti-hypertensive deprescribing as compared to treatment continuation, despite the quality of published studies is not high. High quality experimental studies are urgently needed to further assess the effect of deprescribing for this drug class in specific categories of patients.