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Background: Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence-to-Decision (EtDs) frameworks are increasingly applied by health guideline developers to improve the use of evidence and transparency of health recommendations. Typically, EtDs include 12 criteria but these are flexible and EtDs have been adapted to different types of health decisions. However, developers of health recommendations struggle with the content that they should include in the EtD. The goal of this work was to provide a standardized template that facilitate the development of GRADE EtDs in health guidelines and examples for practical training.Methods: We began by establishing the need for standardized wording templates in 10 American Society of Hematology guidelines with over 250 recommendations. We drafted template wording, and examples, and sought iterative feedback from methodologists and guideline panels in this guideline and two additional guidelines. Results: We generated templates for all EtD criteria describing the type of research evidence considered, ideally based on systematic reviews, using standardized reporting of effect size, integrating the certainty of evidence and addition additional considerations. We also produced templates to inform the completion of the EtD conclusions section that includes recommendations, justification, implementation considerations, monitoring and evaluation and research priorities.Conclusion: We developed a pragmatic and useful tool to support clarity, transparency, and efficiency of the guideline EtD process.(c) 2022 Published by Elsevier Inc.

Objectives Health guidelines are a key knowledge translation tool produced and used by numerous stakeholders worldwide. Effective participation in guideline development groups or development groups is crucial for guideline success, yet little guidance exists for members of these groups. In this study, we present the Guideline Participant Tool (GPT) to support effective participation in guideline groups, in particular those using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Study Design and Setting We used a mixed methods and iterative approach to develop a tool to support guideline participation. We used the findings of a published systematic review to develop an initial list of items for considerations for guideline participants. Then, we refined this list through key informant interviews with guideline chairs, sponsors, and participants. Finally, we validated the GPT in three guideline groups with 26 guideline group members. Results The initial list of items based on 37 articles from the existing systematic review included 15 themes and 61 items for a draft tool. Ten key informant interviews helped us refine the list to include the following themes: selection of participants, guideline group process, and tool format. 26 respondents completed the validation survey from three guideline groups. Refinement of the tool ultimately generated a GPT with 33 items for participant consideration before, during, and in follow-up to guideline group meetings. Conclusion The GPT contains helpful guidance for all guideline participants, particularly those without previous guideline experience. Future research should further explore the need for additional tools to support guideline participants and identify and develop strategies for improving guideline members’ participation in guideline groups. This work will be incorporated into INGUIDE.org guideline training and credentialing efforts by the Guidelines International Network and McMaster University.

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.

Background and Objectives Outcome measures can be defined as the quality and cost targets health care organizations are trying to improve. Health-related outcomes are used to assess the effect, both positive and negative, of an intervention or treatment. To be meaningful and relevant, outcomes should ideally focus on what matters to the population to whom an intervention is applied and who may experience the outcomes. In this commentary, with a GRADE perspective in mind, we will introduce a conceptual model to address the many health care stakeholders, for example, in health technology assessment (HTA), quality assurance, systematic reviews, guidelines, and coverage decisions, who are involved in making different types of health decisions based on the same health outcomes. We will also propose and describe a method of defining core outcomes that will support reconciliation as well as harmonization across these different fields. Study Design and Setting The main focus here is on outcomes that matter most to people including patients, family members, and caregivers. We describe the hub and spokes model for core outcome sets that allows for communication and integration across different disciplines and decision makers. Ideally, the core outcomes, also called main outcomes, would be identical across these fields, including, for instance, a systematic review, an HTA, and a clinical or public health guideline. We illustrate this challenge using examples. Results We present the hub and spokes model for direct core outcome sets and describe the challenge and solution in what we call the Standardized Outcomes Linking Across StakeholdeRs (SOLAR) system approach. Judgments will have to be made regarding how directly the outcome of interest for decision makers corresponds to the intended outcome and GRADE offers it through its indirectness domain. Health outcome descriptors (HODs) provide a solution to this. Conclusion Relevant stakeholders should strive to harmonize outcome assessment for the different decision-making contexts and describe how the outcomes they use, optimally informed by systematic reviews of the importance of outcomes, relate to harmonized HODs. In the ideal world, decision makers would use the same harmonized HODs and transparently rate the degree of indirectness of the actual outcomes addressed.

To evaluate alternative formats of summary of findings (SoF) tables for single comparison with multiple outcomes.We conducted a three-arm randomized controlled non-inferiority trial (RCT) in the following systematic review (SR) users: researchers, clinical practice guideline developers, healthcare providers, policymakers, and knowledge transfer organizations to measure understanding, accessibility, satisfaction, and preference across the current GRADE SoF, an alternative GRADE SoF, or an adapted Evidence-based Practice Center (EPC) Program SoF table.179 participants were randomized, and 129 participants completed the RCT (n=47 current GRADE, n=41 alternative GRADE, n=41 adapted EPC). Understanding the certainty of evidence and treatment effect was comparable across groups. The adapted EPC SoF table was inferior for quantifying risk and risk difference compared to the alternatives (35% correct vs85% correct). Participants reported increased satisfaction when SoF tables presented number needed to treat, anticipated absolute effect differences, and narrative syntheses for evidence that could not be meta-analyzed. Participants reported accessibility to information as significantly better in both GRADE SoF tables, when compared with the adapted EPC SoF table. Participants preferred the alternative GRADE SoF table format.The alternative GRADE SoF table is a promising format for SR users preferring a comprehensive presentation of SR results for single comparisons.

INTRODUCTION AND OBJECTIVE:The use of antibiotics before shock wave lithotripsy (SWL) varies greatly globally. Guidelines have been hampered by reliance on limited evidence summaries and data for t...

Background Study-level meta-analyses provide high-certainty evidence that heparin reduces the risk of symptomatic venous thromboembolism for patients with cancer; however, whether the benefits and harms associated with heparin differ by cancer type is unclear. This individual participant data meta-analysis of randomised controlled trials examines the effect of heparin on survival, venous thromboembolism, and bleeding in patients with cancer in general and by type.Methods In this systematic review and meta-analysis we searched MEDLINE, Embase, and The Cochrane Library for randomised controlled trials comparing parenteral anticoagulants with placebo or standard care in ambulatory patients with solid tumours and no indication for anticoagulation published from the inception of each database to January 14, 2017, and updated it on May 14, 2020, without language restrictions. We calculated the effect of parenteral anticoagulant administration on all-cause mortality, venous thromboembolism occurrence, and bleeding related outcomes through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect, adjusting for age, cancer type, and metastatic status. Interaction terms were tested to investigate effects in predefined subgroups. This study is registered with PROSPERO, CRD42013003526.Findings We obtained individual participant data from 14 of 20 eligible randomised controlled trials (8278 [79%] of 10 431 participants; 4139 included in the low-molecular-weight heparin group and 4139 in the control group). Meta- analysis showed an adjusted relative risk (RR) of mortality at 1 year of 0·99 (95% CI 0·93–1·06) and a hazard ratio of 1·01 (95% CI 0·96–1·07). The number of patients with venous thromboembolic events was 158 (4·0%) of 3958 with available data in the low-molecular-weight heparin group compared with 279 (7·1%) of 3957 in the control group. Major bleeding events occurred in 71 (1·7%) of 4139 patients in the control population and 88 (2·1%) in the low- molecular-weight heparin group, and minor bleeding events in 478 (12·1%) of 3945 patients with available data in the control group and 652 (16·6%) of 3937 patients in the low-molecular-weight heparin group. The adjusted RR was 0·58 (95% CI 0·47–0·71) for venous thromboembolism, 1·27 (0·92–1·74) for major bleeding, and 1·34 (1·19–1·51) for minor bleeding. Prespecified subgroup analysis of venous thromboembolism occurrence by cancer type identified the most certain benefit from heparin treatment in patients with lung cancer (RR 0·59 [95% CI 0·42–0·81]), which dominated the overall reduction in venous thromboembolism. Certainty of the evidence for the outcomes ranged from moderate to high.Interpretation Low-molecular-weight heparin reduces risk of venous thromboembolism without increasing risk of major bleeding compared with placebo or standard care in patients with solid tumours, but it does not improve survival.Funding Canadian Institutes of Health Research.

Background\ud Oncology guidelines suggest using the Khorana score to select ambulatory cancer patients receiving chemotherapy for primary venous thromboembolism (VTE) prevention, but its performance in different cancers remains uncertain.\ud \ud Objective\ud To examine the performance of the Khorana score in assessing 6‐month VTE risk, and the efficacy and safety of low‐molecular‐weight heparin (LMWH) among high‐risk Khorana score patients.\ud \ud Methods\ud This individual patient data meta‐analysis evaluated (ultra)‐LMWH in patients with solid cancer using data from seven randomized controlled trials.\ud \ud Results\ud A total of 3293 patients from the control groups with an available Khorana score had lung (n = 1913; 58%), colorectal (n = 452; 14%), pancreatic (n = 264; 8%), gastric (n = 201; 6%), ovarian (n = 184; 56%), breast (n = 164; 5%), brain (n = 84; 3%), or bladder cancer (n = 31; 1%). The 6‐month VTE incidence was 9.8% among high‐risk Khorana score patients and 6.4% among low‐to‐intermediate‐risk patients (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1‐2.2). The dichotomous Khorana score performed differently in lung cancer patients (OR 1.1; 95% CI, 0.72‐1.7) than in the group with other cancer types (OR 3.2; 95% CI, 1.8‐5.6; Pinteraction = .002). Among high‐risk patients, LMWH decreased the risk of VTE by 64% compared with controls (OR 0.36; 95% CI, 0.22‐0.58), without increasing the risk of major bleeding (OR 1.1; 95% CI, 0.59‐2.1).\ud \ud Conclusion\ud The Khorana score was unable to stratify patients with lung cancer based on their VTE risk. Among those with other cancer types, a high‐risk score was associated with a three‐fold increased risk of VTE compared with a low‐to‐intermediate risk score. Thromboprophylaxis was effective and safe in patients with a high‐risk Khorana score.

Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings. Methods We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047. Findings Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] −10·2%, 95% CI −11·5 to −7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; pinteraction=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD −14·3%, −15·9 to −10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; pinteraction=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD −10·6%, 95% CI −12·5 to −7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings. Interpretation The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance. Funding World Health Organization.

Objective: To evaluate how and to what extent health equity considerations are assessed in World Health Organization (WHO) guidelines. Study Design and Setting: We evaluated WHO guidelines published between January 2014 and May 2019. Health equity consider-ations were assessed in relation to differences in baseline risk, importance of outcomes for socially disadvantaged populations, inclusion of health inequity as an outcome, equity-related subgroup analysis, and indirectness in each recommendation. Results: We identified 111 WHO guidelines, and 54% (60 of 111) of these used the Evidence to Decision (EtD) framework. For the 60 guidelines using an EtD framework, the likely impact on health equity was supported by research evidence in 28% of the recommendations (94 of 332). Research evidence was mostly provided as differences in baseline risk (23%, 78/332). Research evidence less frequently addressed the importance of outcomes for socially disadvantaged populations (11%, 36/332), considered indirectness of the evidence for socially disadvantaged populations (2%, 5/332), considered health inequities as an outcome (2%, 5/332) and considered differences in the magnitude of effect in relative terms between disadvantaged and more advantaged populations (1%, 3/332). Conclusion: The provision of research evidence to support equity judgements in WHO guidelines is still suboptimal, suggesting the need for better guidance and more training. (c) 2020 Elsevier Inc. All rights reserved.

Background Guidelines and quality indicators (for example as part of a quality assurance scheme) aim to improve health care delivery and health outcomes. Ideally, the development of quality indicators should be grounded in evidence-based, trustworthy guideline recommendations. However, anecdotally, guidelines and quality assurance schemes are developed independently, by different groups of experts who employ different methodologies. We conducted an extension and update of a previous systematic review to identify, describe and evaluate approaches to the integrated development of guidelines and related quality indicators. Methods On May 24th, 2019 we searched in Medline, Embase and CINAHL and included studies if they reported a methodological approach to guideline-based quality indicator development and were published in English, French, or German. Results: Out of 16,034 identified records, we included 17 articles that described a method to integrate guideline recommendations development and quality indicator development. Added to the 13 method articles from original systematic review we included a total 30 method articles. We did not find any evaluation studies. In most approaches, guidelines were a source of evidence to inform the quality indicator development. The criteria to select recommendations (e.g. level of evidence or strength of the recommendation) and to generate, select and assess quality indicators varied widely. We found methodological approaches that linked guidelines and quality indicator development explicitly, however none of the articles reported a conceptual framework that fully integrated quality indicator development into the guideline process or where quality indicator development was part of the question formulation for developing the guideline recommendations. Conclusions In our systematic review we found approaches which explicitly linked guidelines with quality indicator development, nevertheless none of the articles reported a comprehensive and well-defined conceptual framework which integrated quality indicator development fully into the guideline development process.

Outcome measures can be defined as the quality and cost targets health care organizations are trying to improve. Health-related outcomes are used to assess the effect, both positive and negative, of an intervention or treatment. To be meaningful and relevant, outcomes should ideally focus on what matters to the population to whom an intervention is applied and who may experience the outcomes. In this commentary, with a GRADE perspective in mind, we will introduce a conceptual model to address the many health care stakeholders, for example, in health technology assessment (HTA), quality assurance, systematic reviews, guidelines, and coverage decisions, who are involved in making different types of health decisions based on the same health outcomes. We will also propose and describe a method of defining core outcomes that will support reconciliation as well as harmonization across these different fields.The main focus here is on outcomes that matter most to people including patients, family members, and caregivers. We describe the hub and spokes model for core outcome sets that allows for communication and integration across different disciplines and decision makers. Ideally, the core outcomes, also called main outcomes, would be identical across these fields, including, for instance, a systematic review, an HTA, and a clinical or public health guideline. We illustrate this challenge using examples.We present the hub and spokes model for direct core outcome sets and describe the challenge and solution in what we call the Standardized Outcomes Linking Across StakeholdeRs (SOLAR) system approach. Judgments will have to be made regarding how directly the outcome of interest for decision makers corresponds to the intended outcome and GRADE offers it through its indirectness domain. Health outcome descriptors (HODs) provide a solution to this.Relevant stakeholders should strive to harmonize outcome assessment for the different decision-making contexts and describe how the outcomes they use, optimally informed by systematic reviews of the importance of outcomes, relate to harmonized HODs. In the ideal world, decision makers would use the same harmonized HODs and transparently rate the degree of indirectness of the actual outcomes addressed.

Additional file 1. Appendix A. Search strategies. Appendix B. List of predefined organizations for manual search. Appendix C. Screening forms. Appendix D. Data abstraction forms.

BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization. (PROSPERO: CRD42020178187).

Background: Coronavirus disease 2019 (COVID-19) is spread person to person by virus through close contact The optimal person-person distance and use of facemas

Background:Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality.Objective:These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery.Methods:ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.Results:The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2).Conclusions:For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.

Background: Although several tools to evaluate the credibility of health care guidelines exist, guidance on practical steps for developing guidelines is lacking. We systematically compiled a comprehensive checklist of items linked to relevant resources and tools that guideline developers could consider, without the expectation that every guideline would address each item. Methods: We searched data sources, including manuals of international guideline developers, literature on guidelines for guidelines (with a focus on methodology reports from international and national agencies, and professional societies) and recent articles providing systematic guidance. We reviewed these sources in duplicate, extracted items for the checklist using a sensitive approach and developed overarching topics relevant to guidelines. In an iterative process, we reviewed items for duplication and omissions and involved experts in guideline development for revisions and suggestions for items to be added. Results: We developed a checklist with 18 topics and 146 items and a webpage to facilitate its use by guideline developers. The topics and included items cover all stages of the guideline enterprise, from the planning and formulation of guidelines, to their implementation and evaluation. The final checklist includes links to training materials as well as resources with suggested methodology for applying the items. Interpretation: The checklist will serve as a resource for guideline developers. Consideration of items on the checklist will support the development, implementation and evaluation of guidelines. We will use crowdsourcing to revise the checklist and keep it up to date.

Objective Summary of findings (SoF) tables present results of systematic reviews in a concise and explicit format. Adopted by many review groups including the Cochrane Collaboration and the Agency for Healthcare Research and Quality (AHRQ), optimal understanding of SoF table may be influenced by the type of information being conveyed and objectives or preferences of the end user. This study aims to compare three SoF table formats in terms of understanding, accessibility, satisfaction and preference with systematic review users. Methods The primary objective of this three-arm randomised controlled non-inferiority trial is to investigate whether an alternative Grading of Recommendations Assessment, Development and Evaluation (GRADE) SoF table or Evidence-based Practice Center SoF table is non-inferior to the current GRADE SoF table in the understanding of the information presented to systematic review users, particularly for descriptive findings. Researchers, clinical practice guideline developers, policy-makers or knowledge transfer professionals will be recruited. Data will be collected electronically at baseline and after randomisation. Non-inferiority would be declared if the difference in the proportion of participants who understand the information displayed in the alternative SoF table is 10% or less. Ethics and dissemination The Hamilton Integrated Research Ethics Board reviewed this protocol. The findings from this study will be disseminated through a publication in a peer-reviewed journal. Trial registration number NCT02813941.

Background: Parenteral anticoagulants may improve outcomes in patients with cancer by reducing the risk of venous thromboembolism (VTE) and through a direct anti-tumour effect. Study-level meta-analysis indicates a reduction in VTE and provide moderate certainty that a small survival benefit exists; it is unclear if patients with specific cancers benefit more or less. Utilizing data from randomized controlled trials (RCT), this individual participant data meta-analysis examines the impact of heparin on survival, VTE and major bleeding in oncological patients randomized to low-molecular weight heparin (LMWH) or no LMWH. Methods: We performed a comprehensive systematic search for all RCTS (last search date March 2017) and contacted authors and sponsors to obtain individual participant data of patients with solid cancers and no other indication for prophylactic or therapeutic anticoagulation. We utilized the GRADE approach to evaluate the certainty of evidence and produce an evidence profile. All analyses followed the intention-to-treat principle. We calculated the impact on mortality through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We adjusted the analysis for age, cancer type and metastasis status. To investigate whether intervention effects vary by predefined subgroups, including type of cancer, we tested interaction terms in the statistical model. Results: A total of 18 RCTs (n=10,041 participants) were eligible for inclusion and we obtained data from 82.4% of the participants (13 RCTs, n=8,278; n=4,139 for LMWH and n=4,139 for no LMWH). The meta-analysis revealed an adjusted relative risk of mortality within one year of 0.99 (95% CI: 0.95, 1.03) and a hazard ratio of 0.97 (95% CI: 0.82, 1.14) after one year. The relative risk for VTE was 0.58 (95% CI: 0.48, 0.71), 0.57 (95% CI: 0.44, 0.74) for symptomatic deep vein thrombosis and 0.58 (95%CI: 0.44, 0.77) for symptomatic pulmonary embolism, separately. For every 1,000 patients treated, approximately 16 fewer would experience symptomatic DVT and 16 fewer would experience any PE. The adjusted relative risk for major bleeding throughout trial duration was 1.24 (95% CI: 0.91, 1.69; P=0.17). Subgroup analysis, by cancer type, of VTE occurrence throughout trial duration identified lung cancer OR=0.52 (95% CI: 0.39, 0.68; P Conclusion: LMWH reduces risk of VTE without increasing risk of bleeding but does not improve survival across all patients. Funding: Canadian Institutes of Health Research knowledge synthesis grant, KRS 126594 Registration: International Prospective Register for Systematic Reviews (PROSPERO), CRD42013003526. Disclosures Schünemann: Canadian Institutes of Health Research: Research Funding. Crowther: Alexion: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Leo Pharma: Research Funding; Pfizer: Honoraria; Portola: Consultancy; Shinogi: Consultancy. Macbeth: Pfizer: Other: Provision of Dalteparin for FRAGMATIC trial; Cancer Research UK: Research Funding. Griffiths: Pfizer: Consultancy, Other: Comment: I run an academic clinical trials unit, have received educational/investigator intiated research grants from companies that make these heparin agents. As consultant > 3 years ago, advised Pfizer on clinical trial designs unrelated to this study., Research Funding. Van Es: Pfizer: Employment, Other: Comment: Dr. van Es reports personal fees from Pfizer as a member of their advisory board. These fees are unrelated to this project.. Streiff: Roche: Research Funding; Portola: Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding. Ageno: BMS-Pfizer: Consultancy, Honoraria; Bayer AG: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria. Bozas: PharmaMar: Honoraria. McBane: Bristol Myers Squibb: Other: Research grant for cancer associated VTE. Maraveyas: Bayer: Other: Personal fees and conference attendance; Bristol-Myers Squibb: Other: Grants and personal fees; Leo Pharma: Other: Grants, personal fees and conference attendance; Pfizer: Other: Personal fees. Loprinzi: Bristol Myers: Other: Grant - unrelated to this project; Janssen: Other: Grant - unrelated to this project.