Assessment of the extent of unpublished studies in prognostic factor research: a systematic review of p53 immunohistochemistry in bladder cancer as an example.

OBJECTIVES: When study groups fail to publish their results, a subsequent systematic review may come to incorrect conclusions when combining information only from published studies. p53 expression measured by immunohistochemistry is a potential prognostic factor in bladder cancer. Although numerous studies have been conducted, its role is still under debate. The assumption that unpublished studies too harbour evidence on this research topic leads to the question about the attributable effect when adding this information and comparing it with published data. Thus, the aim was to identify published and unpublished studies and to explore their differences potentially affecting the conclusion on its function as a prognostic biomarker. DESIGN: Systematic review of published and unpublished studies assessing p53 in bladder cancer in Germany between 1993 and 2007. RESULTS: The systematic search revealed 16 studies of which 11 (69%) have been published and 5 (31%) have not. Key reason for not publishing the results was a loss of interest of the investigators. There were no obviously larger differences between published and unpublished studies. However, a meaningful meta-analysis was not possible mainly due to the poor (ie, incomplete) reporting of study results. CONCLUSIONS: Within this well-defined population of studies, we could provide empirical evidence for the failure of study groups to publish their results that was mainly caused by loss of interest. This fact may be coresponsible for the role of p53 as a prognostic factor still being unclear. We consider p53 and the restriction to studies in Germany as a specific example, but the critical issues are probably similar for other prognostic factors and other countries.