Table 2 Definitions of terminology used

Subgroup

The term “subgroup” describes an analysis of a subset of participants (e.g., selected set of individuals with specific patient characteristics within an individual study or across studies in the case of individual patient data meta-analyses).

“Subgroup analyses are often performed to identify characteristics within the study population that are associated with greater benefit from the intervention, with no benefit, or even with harm” [37].

Subpopulation

The term “subpopulation” describes a specific group of individuals with common patient characteristics (e.g., race/ethnicity, age, risk factors) that is the target of an intervention or a policy recommendation.

“If a subpopulation may not benefit from the therapy, it is important to identify the subpopulation and verify this finding in an appropriate clinical trial” [37].

Clinical heterogeneity

Variability between studies in the populations enrolled, the active interventions and comparison interventions they receive, or selection and timing of measured outcomes [3, 7].

Patient characteristics

• Socio-demographics

• Baseline risk

Study characteristics

• Intervention

• Comparators

• Outcome measurement

Methodological heterogeneity

Variability in study design and conduct that can lead to differences in measured intervention effects due to non-comparability or bias [3, 7].

Risk of bias

• Study design

• Study conduct

• Study analysis

Statistical heterogeneity

Measured variability in observed intervention effects between studies that are greater than would be expected due to chance (random error) [3, 7].

Statistical tests

• I ²

• Cochran’s Q test

Within study

The term “within study” refers to the framework in which comparisons or analyses are conducted; in this case, researchers are examining the variation or impact of factors (e.g., populations, interventions, outcomes) within one study or trial.

"In single trials, the comparison [between subgroups] is always within studies: that is, the two groups of patients (e.g., the older and younger) or the two alternative ways of administering the intervention (e.g., higher and lower doses) were assessed in the same RCT" [26].

Between study

The term “between study” refers to the framework in which comparisons or analyses are conducted; in this case, researchers are examining the variation or impact of factors (e.g., populations, interventions, outcomes) across multiple studies or trials.

"The inference regarding the effect is, however, limited because this was a between study rather than a within study comparison. As a result there are a number of competing explanations for the observed differences between the high- and low-dose studies” [26].

Study level

The term “study level” is used to describe the unit of inquiry or data source being considered by systematic reviewers; in this case, data from a single study or trial are evaluated.

"The ideal way to study causes of true variation is within rather than between studies. In most situations however, we will have to make do with a study level investigation \and hence need to be careful about adjusting for potential confounding by artefactual factors such as study design features" [51].

Body of evidence level

The term “body of evidence level” is used to describe the unit of inquiry or data source being considered by systematic reviewers; in this case, data from a group of studies are evaluated.

"Systematic review and guideline authors use this [GRADE] approach to rate the quality of evidence for each outcome across studies (i.e., for a body of evidence)" [52].