Bram Rochwerg

An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline

BACKGROUND This document updates the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guideline on idiopathic pulmonary fibrosis treatment. METHODS Systematic reviews and, when appropriate, meta-analyses were performed to summarize all available evidence pertinent to our questions. The evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and then discussed by a multidisciplinary panel. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists. RESULTS After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications to health equity, recommendations were made for or against specific treatment interventions. CONCLUSIONS The panel formulated and provided the rationale for recommendations in favor of or against treatment interventions for idiopathic pulmonary fibrosis.

Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis

IMPORTANCE Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition. OBJECTIVE To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke. DATA SOURCES We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015. STUDY SELECTION Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA). DATA EXTRACTION AND SYNTHESIS Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method. MAIN OUTCOMES AND MEASURES Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days. RESULTS Data were included from 8 trials involving 2423 patients (mean [SD] age, 67.4 [14.4] years; 1131 [46.7%] women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14-2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%) in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR, 1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI, 4.79-8.79; P < .001) but no significant difference in rates of symptomatic intracranial hemorrhage within 90 days (70 events [5.7%] vs 53 events [5.1%]; OR, 1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths [15.8%] vs 201 deaths [17.8%]; OR, 0.87; 95% CI, 0.68-1.12; P = .27). CONCLUSIONS AND RELEVANCE Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.

Fluid Resuscitation in Sepsis: A Systematic Review and Network Meta-analysis

Resuscitation with crystalloids compared with colloids for critically ill patients has been evaluated in large randomized, controlled trials (16) and meta-analyses (713). One meta-analysis(10) including 74 trials reported no difference in mortality between critically ill patients resuscitated with crystalloids and albumin (relative risk [RR], 1.01 [95% CI, 0.93 to 1.10]), hydroxyethyl starch (HES) (RR, 1.10 [CI, 0.91 to 1.32]), gelatin (RR, 0.91 [CI, 0.49 to 1.72]), or dextran (RR, 1.24 [CI, 0.94 to 1.65]). Another meta-analysis (8) reported that resuscitation with an albumin-containing solution in patients with sepsis may decrease mortality compared with solutions containing no albumin (RR, 0.82 [CI, 0.67 to 1.00]). Recent evidence suggests that starches, compared with other fluids and regardless of molecular weight, may be associated with acute kidney injury in the general population of critically ill patients and in those with sepsis (5, 11, 1315). A recent large pragmatic trial comparing colloids (mostly starches) with crystalloids (mostly 0.9% sodium chloride) suggested a 90-day mortality benefit with colloids (RR, 0.92 [CI, 0.86 to 0.99]) (16). Crystalloids can be characterized on the basis of tonicity and electrolyte content. The presence of an organic anion (for example, lactate, acetate, or gluconate) and correspondingly lower chloride content that more closely resembles the composition of plasma suggest that a crystalloid is balanced (for example, Ringer lactate and acetate solutions) (17). The most commonly used crystalloid, normal saline (0.9% sodium chloride), is far from normal, with a pH much less than 7.0 and a supraphysiologic chloride content of 154 mmol/L (18, 19). Compared with a balanced crystalloid solution, normal saline predisposes patients to hyperchloremic metabolic acidosis, decreased renal blood flow to the glomerulus, and impaired smooth-muscle contractility (20). Investigators have not done randomized, controlled trials (RCTs) comparing balanced and unbalanced crystalloids. However, 1 large beforeafter study of critically ill patients showed that balanced versus unbalanced fluid solution was associated with a lower incidence of acute kidney injury (8.4% vs. 14%; P< 0.01) and renal replacement therapy (6.3% vs. 10%; P= 0.05) but no differences in hospital mortality (18). Colloids include natural compounds, such as albumin, and synthetic compounds of HES, gelatin, or dextran. Expansion of plasma volume increases in proportion to the osmotic or oncotic potential, and colloids theoretically require less volume than crystalloids to achieve equivalent hemodynamic effect (19). Limitations of colloids include development of acute kidney injury and coagulation disorders with starches (14) and albumin creates risk for exposure to blood products (19). Another important consideration is the biochemical properties of the crystalloid solution in which the colloid is dissolved. For example, the chloride concentrations in HES may vary between 154 mmol/L (Voluven, Fresenius Kabi) and 118 mmol/L (Tetraspan, B. Braun Medical) (21). Whether any of these fluid properties translate into a survival advantage remains unclear, particularly regarding the optimal fluid for resuscitation in patients with sepsis. Fluid resuscitation, in addition to antibiotics and source control, is a cornerstone of initial management of sepsis (22). However, fluid management in patients with sepsis varies widely in practice (16, 23, 24). Meta-analyses of fluid resuscitation have been limited by not focusing on patients with sepsis (7, 9, 10), not considering electrolyte composition (5, 8, 10, 11), considering only 2 or 3 categories of fluid (25), not including direct and indirect comparisons in the same model, and omission of recent large RCTs(35, 16). Therefore, we did a network meta-analysis (NMA) considering direct and indirect comparisons of all types of fluid resuscitation tested in RCTs in patients with severe sepsis and septic shock, focusing on the effect of these interventions on mortality. Methods Data Sources and Searches This review was done using a predefined protocol. Initially, we searched MEDLINE (1948 to December 2012), EMBASE (1980 to December 2012), ACP Journal Club (1991 to December 2012), the Cochrane Central Register of Controlled Trials, HealthSTAR, the Allied and Complementary Medicine Database, and CINAHL. We updated the MEDLINE and EMBASE searches in August 2013 and March 2014. We screened previously published meta-analyses for relevant citations. Supplement 1 presents the search terms used. Supplement 1. WinBUGS Code for NMA Six reviewers working in 3 pairs screened the titles and abstracts to determine potential eligibility, and entries identified by any reviewer proceeded to the full-text eligibility review. Pretested eligibility forms were used for full-text review, which was also done in duplicate. A third adjudicator helped to resolve disagreements through consensus. Study Selection We selected parallel-group RCTs, including factorial designs, but excluded quasi-randomized and crossover trials. We excluded all studies published by Dr. Joachim Boldt because of suspected lack of integrity (26, 27). We did not apply restrictions on language or publication date. We included studies that involved adult (aged 16 years) critically ill patients with severe sepsis or septic shock as defined by the investigators and who required fluid resuscitation (defined as the administration of a bolus of intravenous fluid exceeding the amount required for maintenance or replacement fluids). We included studies with mixed critically ill populations whenever separate data for patients with sepsis were available. We excluded studies in which most patients had the systemic inflammatory response syndrome secondary to other causes (such as burn, pancreatitis, and trauma) without a clear sepsis subgroup and those focusing on patients after elective surgery. Interventions studied included any fluid or fluid strategy used for resuscitation compared with another fluid or fluid strategy. We excluded studies in which the primary goal was to assess short-term hemodynamic response. Our outcome was 90-day mortality or, if not available, 30-day, intensive care unit, or hospital mortality, whichever was longest. Data Extraction Pairs from the same 6 reviewers abstracted data in duplicate. Another clinician reviewed disagreements, and consensus was reached by discussion. We contacted authors of primary publications for missing or unclear information. Risk of Bias Independently and in duplicate, reviewers assessed risk of bias using a modified version of the Cochrane Collaboration assessment tool (28, 29). We judged each included study as having low, probably low, probably high, or high risk of bias for randomization-sequence generation, randomization concealment, blinding, incomplete data, selective reporting, and free of other bias (including intention-to-treat analysis). The overall rating of risk of bias for each study was the lowest rating for any of the criteria (Appendix Table). Appendix Table. Risk of Bias, by Study Data Synthesis and Analysis Our analysis classified fluids as crystalloids (divided into balanced and unbalanced solutions) and colloids (divided into albumin, gelatin, and low- and high-molecular-weight HES [threshold molecular weight, 150000 kDa]). We considered fluid balanced if it contained an anion of a weak acid (buffer) and its chloride content was correspondingly less than in 0.9% sodium chloride (21). The relevant analyses were a 4-node NMA (crystalloids vs. albumin vs. HES vs. gelatin), a 6-node NMA (crystalloids vs. albumin vs. HES vs. gelatin, with crystalloids divided into balanced or unbalanced and HES divided into low or high molecular weight), and a conventional direct frequentist fixed-effects meta-analytic comparison of crystalloids versus colloids. To calculate direct estimates of treatment effect for each pair of treatments in the 4- and 6-node networks, we did a frequentist fixed-effects meta-analysis. We reported the results as odds ratios (ORs) and corresponding 95% CIs. We evaluated heterogeneity by estimating the variance between studies (chi-square test and I 2 statistic) (30, 31). Using a Bayesian framework, we did 4- and 6-node fixed-effects NMAs for each treatment. We reported the results as ORs and corresponding 95% credibility intervals (CrIs), which are the Bayesian analogue of 95% CIs(32). The ORs reported are relative effects of compared fluids. The models are based on 80000 iterations with a burn-in of 40000 and a thin of 10. We used a random seed and vague priors. We assessed nonconvergence on the basis of BrooksGelmanRubin plots (33). We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess confidence in estimates of effect (quality of evidence) associated with specific comparisons, including estimates from direct, indirect, and final NMAs (Supplement 2) (34). Our confidence assessment addressed risk of bias, incoherence, imprecision, inconsistency, indirectness, and publication bias. Supplement 2. GRADE Confidence Explanations for All Point Estimates The starting point for confidence in direct and indirect estimates was high. However, indirect estimates were potentially rated down for intransitivity (that is, differences in patients, co-interventions, or settings that could lead to effect modification and thus a misleading comparison of fluid management strategies). We inferred confidence in indirect estimates by examining the connecting loops associated with the particular comparison. The confidence rating chosen was the lowest of the direct estimates contributing to the indirect comparison. For example, consider a comparison of A versus B that is informed by comparisons of A versus C and B versus C. If A versus C was rated as high confidence and B versus C as moderate confidence, the overall indirect confidence rating was ini

Withholding versus Continuing Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers before Noncardiac Surgery: An Analysis of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN Prospective Cohort.

Background: The effect on cardiovascular outcomes of withholding angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in chronic users before noncardiac surgery is unknown. Methods: In this international prospective cohort study, the authors analyzed data from 14,687 patients (including 4,802 angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users) at least 45 yr old who had in-patient noncardiac surgery from 2007 to 2011. Using multivariable regression models, the authors studied the relationship between withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and a primary composite outcome of all-cause death, stroke, or myocardial injury after noncardiac surgery at 30 days, with intraoperative and postoperative clinically important hypotension as secondary outcomes. Results: Compared to patients who continued their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, the 1,245 (26%) angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users who withheld their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the 24 h before surgery were less likely to suffer the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1,245 [12.0%] vs. 459/3,557 [12.9%]; adjusted relative risk, 0.82; 95% CI, 0.70 to 0.96; P = 0.01) and intraoperative hypotension (adjusted relative risk, 0.80; 95% CI, 0.72 to 0.93; P < 0.001). The risk of postoperative hypotension was similar between the two groups (adjusted relative risk, 0.92; 95% CI, 0.77 to 1.10; P = 0.36). Results were consistent across the range of preoperative blood pressures. The practice of withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was only modestly correlated with patient characteristics and the type and timing of surgery. Conclusions: Withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers before major noncardiac surgery was associated with a lower risk of death and postoperative vascular events. A large randomized trial is needed to confirm this finding. In the interim, clinicians should consider recommending that patients withhold angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 24 h before surgery.

Official ERS/ATS clinical practice guidelines: Noninvasive ventilation for acute respiratory failure

Noninvasive mechanical ventilation (NIV) is widely used in the acute care setting for acute respiratory failure (ARF) across a variety of aetiologies. This document provides European Respiratory Society/American Thoracic Society recommendations for the clinical application of NIV based on the most current literature. The guideline committee was composed of clinicians, methodologists and experts in the field of NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology for each actionable question. The GRADE Evidence to Decision framework in the guideline development tool was used to generate recommendations. A number of topics were addressed using technical summaries without recommendations and these are discussed in the supplementary material. This guideline committee developed recommendations for 11 actionable questions in a PICO (population–intervention–comparison–outcome) format, all addressing the use of NIV for various aetiologies of ARF. The specific conditions where recommendations were made include exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, de novo hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliation, post-operative care, weaning and post-extubation. This document summarises the current state of knowledge regarding the role of NIV in ARF. Evidence-based recommendations provide guidance to relevant stakeholders. ERS/ATS evidence-based recommendations for the use of noninvasive ventilation in acute respiratory failure http://ow.ly/NrqB30dAYSQ

How safe is gelatin? A systematic review and meta-analysis of gelatin-containing plasma expanders vs crystalloids and albumin

Gelatin is a widely used synthetic colloid resuscitation fluid. We undertook a systematic review and meta-analysis of adverse effects in randomized and nonrandomized studies comparing gelatin with crystalloid or albumin for treatment of hypovolemia. Multiple databases were searched systematically without language restrictions until August 2015. We assessed risk of bias of individual studies and certainty in evidence assessment by the Grading of Recommendations Assessment, Development, and Evaluation approach. Sixty studies were eligible, including 30 randomized controlled trials, 8 nonrandomized studies, and 22 animal studies. After gelatin administration, the risk ratios were 1.15 (95% confidence interval, 0.96-1.38) for mortality, 1.10 (0.86-1.41) for requiring allogeneic blood transfusion, 1.35 (0.58-3.14) for acute kidney injury, and 3.01 (1.27-7.14) for anaphylaxis. Well-performed nonrandomized trials found increased rates of hospital mortality and acute kidney injury or renal replacement therapy in the gelatin intervention periods. Between 17% and 31% of administered gelatin was taken up extravascularly. The mean crystalloid-to-colloid ratio was 1.4. Gelatin solutions increase the risk of anaphylaxis and may be harmful by increasing mortality, renal failure, and bleeding possibly due to extravascular uptake and coagulation impairment. Until well-designed randomized controlled trials show that gelatin is safe, we caution against the use of gelatins because cheaper and safer fluid alternatives are available.

Advances in the GRADE approach to rate the certainty in estimates from a network meta-analysis

This article describes conceptual advances of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group guidance to evaluate the certainty of evidence (confidence in evidence, quality of evidence) from network meta-analysis (NMA). Application of the original GRADE guidance, published in 2014, in a number of NMAs has resulted in advances that strengthen its conceptual basis and make the process more efficient. This guidance will be useful for systematic review authors who aim to assess the certainty of all pairwise comparisons from an NMA and who are familiar with the basic concepts of NMA and the traditional GRADE approach for pairwise meta-analysis. Two principles of the original GRADE NMA guidance are that we need to rate the certainty of the evidence for each pairwise comparison within a network separately and that in doing so we need to consider both the direct and indirect evidence. We present, discuss, and illustrate four conceptual advances: (1) consideration of imprecision is not necessary when rating the direct and indirect estimates to inform the rating of NMA estimates, (2) there is no need to rate the indirect evidence when the certainty of the direct evidence is high and the contribution of the direct evidence to the network estimate is at least as great as that of the indirect evidence, (3) we should not trust a statistical test of global incoherence of the network to assess incoherence at the pairwise comparison level, and (4) in the presence of incoherence between direct and indirect evidence, the certainty of the evidence of each estimate can help decide which estimate to believe.

Withholding Pantoprazole for Stress Ulcer Prophylaxis in Critically Ill Patients: A Pilot Randomized Clinical Trial and Meta-analysis*

Introduction: A decreased frequency of upper gastrointestinal bleeding and a possible association of proton pump inhibitor use with Clostridium difficile and ventilator-associated pneumonia have raised concerns recently. The Reevaluating the Inhibition of Stress Erosions Pilot Trial determined the feasibility of undertaking a larger trial investigating the efficacy and safety of withholding proton pump inhibitors in critically ill patients. Methods: In 10 ICUs, we randomized adult ICU patients anticipated to be mechanically ventilated for greater than or equal to 48 hours to receive 40 mg of IV pantoprazole daily or placebo. We excluded patients who had acute or recent gastrointestinal bleed, used dual antiplatelet agents, had a medical condition requiring proton pump inhibitor treatment, or had already received more than one dose of acid suppression daily. Patients, families, clinicians, and research staff were blinded. We conducted a systematic review and meta-analysis of similar trials. Main Results: Ninety-one patients (49 pantoprazole and 42 placebo) from 10 centers in Canada, Saudi Arabia, and Australia were enrolled. All feasibility goals were met: 1) recruitment rate was 2.6 patients per month; 2) consent rate was 77.8%; and 3) protocol adherence was 97.7%. Upper gastrointestinal bleeding developed in 6.1% of patients in the pantoprazole group and 4.8% in the placebo group (p = 1.0). Ventilator-associated pneumonia developed in 20.4% of patients in the pantoprazole group and 14.3% in the placebo group (p = 0.58). C. difficile was identified in 4.1% pantoprazole patients and in 2.4% placebo patients (p = 1.0). We meta-analyzed five trials (604 patients) of proton pump inhibitors versus placebo; there was no statistically significant difference in the risk of upper gastrointestinal bleeding, infections, or mortality. Conclusions: Our results support the feasibility of a larger trial to evaluate the safety of withholding stress ulcer prophylaxis. Although the results are imprecise, there was no alarming increase in the risk of upper gastrointestinal bleeding; the effect of proton pump inhibitors on ventilator-associated pneumonia and C. difficile remain unclear.

Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017.

Objective: To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients. Participants: A multispecialty task force of 16 international experts in critical care medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine. Design/Methods: The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members. Results: The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of < 9 &mgr;g/dL) after cosyntropin (250 &mgr;g) administration and a random plasma cortisol of < 10 &mgr;g/dL may be used by clinicians. We suggest against using plasma-free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using IV hydrocortisone < 400 mg/day for ≥ 3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO2 < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence). Conclusions: Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.

Using patient values and preferences to inform the importance of health outcomes in practice guideline development following the GRADE approach

BackgroundThere are diverse opinions and confusion about defining and including patient values and preferences (i.e. the importance people place on the health outcomes) in the guideline development processes. This article aims to provide an overview of a process for systematically incorporating values and preferences in guideline development.MethodsIn 2013 and 2014, we followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to adopt, adapt and develop 226 recommendations in 22 guidelines for the Ministry of Health of the Kingdom of Saudi Arabia. To collect context-specific values and preferences for each recommendation, we performed systematic reviews, asked clinical experts to provide feedback according to their clinical experience, and consulted patient representatives.ResultsWe found several types of studies addressing the importance of outcomes, including those reporting utilities, non-utility measures of health states based on structured questionnaires or scales, and qualitative studies. Guideline panels used the relative importance of outcomes based on values and preferences to weigh the balance of desirable and undesirable consequences of alternative intervention options. However, we found few studies addressing local values and preferences.ConclusionsCurrently there are different but no firmly established processes for integrating patient values and preferences in healthcare decision-making of practice guideline development. With GRADE Evidence-to-Decision (EtD) frameworks, we provide an empirical strategy to find and incorporate values and preferences in guidelines by performing systematic reviews and eliciting information from guideline panel members and patient representatives. However, more research and practical guidance are needed on how to search for relevant studies and grey literature, assess the certainty of this evidence, and best summarize and present the findings.