The software ) developed by the GRADE working group was used to assess the quality of each outcome, taking into account individual study quality and the meta-analysis results. Each outcome was first examined for each of the quality elements listed and defined in Table 2. Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Table 2: Description of quality elements in GRADE for intervention studies Quality element Description Risk of bias Limitations in the study design and implementation may bias the estimates of the treatment effect. Major limitations in studies decrease the confidence in the estimate of the effect. Examples of such limitations are selection bias (often due to poor allocation concealment), performance and detection bias (often due to a lack of blinding of the patient, healthcare professional or assessor) and attrition bias (due to missing data causing systematic bias in the analysis). Indirectness Indirectness refers to differences in study population, intervention, comparator and outcomes between the available evidence and the review question. Inconsistency Inconsistency refers to an unexplained heterogeneity of effect estimates between studies in the same meta-analysis. Imprecision Results are imprecise when studies include relatively few patients and few events (or highly variable measures) and thus have wide confidence intervals around the estimate of the effect relative to clinically important thresholds. 95% confidence intervals denote the possible range of locations of the true population effect at a 95% probability, and so wide confidence intervals may denote a result that is consistent with conflicting interpretations (for example a result may be consistent with both clinical benefit AND clinical harm) and thus be imprecise. Publication bias Publication bias is a systematic underestimate or overestimate of the underlying beneficial or harmful effect due to the selective publication of studies. 