Indeed, the approach devised by Schmidt and Hunter (1998), which we go on to discuss, brought a great deal of focus and discipline to the area and we agree with Guion (2011) that it must be recognized as a major methodological advance.
While we agree that some forms of lossy compression seem to be a necessity, the radical approach of discarding old data (in the hope of reproducing them later, when needed) raises major methodological doubts, as far as research applications are considered.
Based on our experience as ophthalmologists, the major methodological issue that may cause a bias is, to our opinion, the way the assessment of the visual acuity was conducted.
As one of the major methodological decisions, student-level variables were defined as fixed (e.g., gender coefficient does not differ across schools) and the intercept was defined as random (i.e., average performance varies across schools) in all eight HLM models (two for each country).
When trials that have major methodological flaws such as these are pooled, the results need to be interpreted with caution.
This study had a number of major methodological flaws such as lack of randomisation, failure to compare baseline characteristics between groups and no long term follow up.
Where possible, separate analyses were carried out for major methodological differences such as adjusted/unadjusted hazard ratios (HRs), genotyping methods, treatment, cell type and ethnicity (as determined by the International HapMap Consortium) [ 26].
Additionally, the need of improvement in major methodological aspects such as exposure characterization, symptom assessment, study design, population selection, sample size and the investigation of possible confounders has been highlighted.
The question arises whether a bias is inherent as all study designs were included and as several of the included studies have minor or major methodological weaknesses.
In this analysis, we address two major methodological issues concerning the use of caregivers as proxies for children's HRQOL measures, and the use of different HRQOL instruments across health conditions in young patients.
