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. 2020 Jun 5;2020(6):CD012906. doi: 10.1002/14651858.CD012906.pub2
Items (1) All‐cause mortality (2) Serious adverse events (3) Health‐related quality of life (4) Cardiovascular mortality (5) Non‐fatal myocardial infarction (6) Non‐fatal stroke (7) End‐stage renal disease
Trial limitations
(risk of bias)a Was random sequence generation used (i.e. no potential for selection bias)? NA Unclear NA NA NA NA NA
Was allocation concealment used (i.e. no potential for selection bias)? Unclear
Was there blinding of participants and personnel (i.e. no potential for performance bias) or outcome not likely to be influenced by lack of blinding? Yes
Was there blinding of outcome assessment (i.e. no potential for detection bias) or was outcome measurement not likely to be influenced by lack of blinding? Yes
Was an objective outcome used? Yes
Were more than 80% of participants enrolled in trials included in the analysis (i.e. no potential reporting bias)?e Yes
Were data reported consistently for the outcome of interest (i.e. no potential selective reporting)? No (↓)
No other biases reported (i.e. no potential of other bias)? No (↓)
Did the trials end up as scheduled (i.e. not stopped early)? Yes
Inconsistencyb Point estimates did not vary widely? NA
To what extent did confidence intervals overlap (substantial: all confidence intervals overlap at least one of the included studies point estimate; some: confidence intervals overlap but not all overlap at least one point estimate; no: at least one outlier: where the confidence interval of some of the studies do not overlap with those of most included studies)? NA
Was the direction of effect consistent? NA
What was the magnitude of statistical heterogeneity (as measured by I²) ‐ low (I² < 40%), moderate (I² 40% to 60%), high I² > 60%)? NA
Was the test for heterogeneity statistically significant (P < 0.1)? NA
Indirectness Were the populations in included studies applicable to the decision context? Highly applicable
Were the interventions in the included studies applicable to the decision context? Highly applicable
Was the included outcome not a surrogate outcome? Yes
Was the outcome timeframe sufficient? Sufficient
Were the conclusions based on direct comparisons? Yes
Imprecisionc Was the confidence interval for the pooled estimate not consistent with benefit and harm? NA
What is the magnitude of the median sample size (high: 300 participants, intermediate: 100 to 300 participants, low: <100 participants)?e Low (↓)
What was the magnitude of the number of included studies (large: >10 studies, moderate: 5 to 10 studies, small: < 5 studies)?e Small (↓)
Was the outcome a common event (e.g. occurs more than 1/100)? NA
Publication biasd Was a comprehensive search conducted? Yes
Was grey literature searched? Yes
Were no restrictions applied to study selection on the basis of language? Yes
There was no industry influence on studies included in the review? Unclear
There was no evidence of funnel plot asymmetry? NA
There was no discrepancy in findings between published and unpublished trials? NA
aQuestions on risk of bias are answered in relation to the majority of the aggregated evidence in the meta‐analysis rather than to individual trials
bQuestions on inconsistency are primarily based on visual assessment of forest plots and the statistical quantification of heterogeneity based on I²
cWhen judging the width of the confidence interval it is recommended to use a clinical decision threshold to assess whether the imprecision is clinically meaningful
dQuestions address comprehensiveness of the search strategy, industry influence, funnel plot asymmetry and discrepancies between published and unpublished trials
eDepends on the context of the systematic review area
(↓): key item for potential downgrading the quality of the evidence (GRADE) as shown in the footnotes of the 'Summary of finding' table(s); GRADE: Grading of Recommendations Assessment, Development and Evaluation; NA: not applicable.