Methodological issues and recommendations for systematic reviews of prognostic studies: An example from cardiovascular disease

Background
Prognostic factors are associated with the risk of future health outcomes in individuals with a particular health condition. The prognostic ability of such factors is increasingly being assessed in both primary research and systematic reviews. Systematic review methodology in this area is continuing to evolve, reflected in variable approaches to key methodological aspects. The aim of this article was to (i) explore and compare the methodology of systematic reviews of prognostic factors undertaken for the same clinical question, (ii) to discuss implications for review findings, and (iii) to present recommendations on what might be considered to be 'good practice' approaches.

Methods
The sample was comprised of eight systematic reviews addressing the same clinical question, namely whether 'aspirin resistance' (a potential prognostic factor) has prognostic utility relative to future vascular events in patients on aspirin therapy for secondary prevention. A detailed comparison of methods around study identification, study selection, quality assessment, approaches to analysis, and reporting of findings was undertaken and the implications discussed. These were summarised into key considerations that may be transferable to future systematic reviews of prognostic factors.

Results
Across systematic reviews addressing the same clinical question, there were considerable differences in the numbers of studies identified and overlap between included studies, which could only partially be explained by different study eligibility criteria. Incomplete reporting and differences in terminology within primary studies hampered study identification and selection process across reviews. Quality assessment was highly variable and only one systematic review considered a checklist for studies of prognostic questions. There was inconsistency between reviews in approaches towards analysis, synthesis, addressing heterogeneity and reporting of results.

Conclusions
Different methodological approaches may ultimately affect the findings and interpretation of systematic reviews of prognostic research, with implications for clinical decision-making.

Systematic review registration: This review of systematic reviews in one medical area has been used to generate a number of recommendations for those undertaking systematic reviews of prognostic research; these include a step-wise hierarchical approach to study selection and suggested approaches for analysis (e.g. maximisation of data for meta-analysis). This work adds to and extends the growing body of methodological evidence in this field.