This study showed promise but clearly suffered from major methodological flaws in study design, and so the conclusions drawn are subject to careful scrutiny and review.
The first section describes the major methodological principles of clinical trial design required for a rigorous evaluation of the treatment benefit, as well as the various pitfalls or biases that could lead to erroneous conclusions.
This review analyzes the major methodological caveats related to the design and conduction of trials addressing new active drugs in patients with failed primary CNS lymphoma (PCNSL) and provides some recommendations for their therapeutic management.
The use of clinical data from subgroup analysis in a BIA analysis often suffers not only from statistical constraints, but also from that major methodological weakness that the trial was designed only for the overall trial population (e.g. the hypothesis, objective and selection of the primary clinical outcome).
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.
However, ours was the only study designed to address this specific hypothesis, and major methodological differences among studies could explain the discrepancies.
The major methodological limitation of the present study is the cross-sectional design, which does not permit causal inferences to be made.
The major methodological strength of this study is the use a randomized controlled trial design which will allow a rigorous test of the effects of RGCT with optimal internal validity.
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.
The longitudinal population-based design and a high participation rate (93% of the total aged population) are major methodological strengths of this study.
