Phase of investigation | Quality of evidence | Downgrade if: | Upgrade if: |
---|---|---|---|
Explanatory research aimed to understand prognostic pathways (phase 3 explanatory study) and explanatory research aimed to confirm independent associations between potential prognostic factor and the outcome (phase 2 explanatory study) | High | Study limitations: | Moderate or large effect: |
- Serious limitations when most evidence is from studies with moderate or unclear risk of bias for most bias domains | - For meta-analysis: pooled effect is moderate or large, | ||
- Very serious limitations when most evidence is from studies with high risk of bias for almost all bias domains | - For narrative summary: moderate or large similar effect is reported by most studies | ||
Inconsistency: | Exposure-gradient response | ||
Unexplained heterogeneity or variability in results across studies with differences of results not clinically meaningful. This may be supported by: | - For meta-analysis: gradient is present between analyses for factors measured at different doses | ||
- For meta-analysis: significant heterogeneity detected by test of heterogeneity and large I2 value. | - For narrative summary: possible gradient exists within and between primary studies | ||
- For narrative summary: variations in effect estimates across studies with points of effect on either side of the line of no effect, and confidence intervals showing minimal overlap | |||
Indirectness: | |||
Outcome prediction research or explanatory research aimed to identify associations between potential prognostic factors and the outcome (phase 1 explanatory study) | Moderate | The study sample, the prognostic factor, and/or the outcome in the primary studies do not accurately reflect the review question | |
Imprecision: | |||
- For meta-analysis: (1) insufficient sample size and (2) no precise estimate of the effect size in the meta-analysis: confidence interval is excessively wide and overlaps the value of no effect and contain values implying that the factor plays an important role in protecting or putting the individual at risk | |||
 | Low | - For narrative summary: within-study imprecision: (1) sample size justification is not provided and there are less than 10 outcome events for each prognostic variable (for dichotomous outcomes) OR there are less than 100 cases reaching endpoint (for continuous outcomes), and (2) no precision in the estimation of the effect size within each primary study, AND | |
Very low | |||
- Across study imprecision: there are few studies and small number of participants across studies. | |||
Publication bias: | |||
 | We recommend downgrading unless: | ||
 |  | - The value of the risk/protective factor in predicting the outcome has been repetitively investigated, ideally by phase 2 and 3 studies |  |