Reporting of prognostic markers: current problems and development of guidelines for evidence-based practice in the future

Abstract

Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome (e.g. recurrence of disease), and are important tools in the management of cancer and many other diseases. Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because (sometimes conflicting) evidence relating to markers is often published across a number of studies. To investigate the practicality of this approach, an empirical investigation of a systematic review of tumour markers for neuroblastoma was performed; 260 studies of prognostic markers were identified, which considered 130 different markers.The reporting of these studies was often inadequate, in terms of both statistical analysis and presentation, and there was considerable heterogeneity for many important clinical/statistical factors. These problems restricted both the extraction of data and the meta-analysis of results from the primary studies, limiting feasibility of the evidence-based approach.Guidelines for reporting the results of primary prognostic marker studies in cancer, and other diseases, are given in order to facilitate both the interpretation of individual studies and the undertaking of systematic reviews, meta-analysis and, ultimately, evidence-based practice. General availability of full individual patient data is a necessary step forward and would overcome the majority of problems encountered, including poorly reported summary statistics and variability in cutoff level, outcome assessed and adjustment factors used. It would also limit the problem of reporting bias, although publication bias will remain a concern until studies are prospectively registered. Such changes in practice would help important evidence-based reviews to be conducted in order to establish the most appropriate prognostic markers for clinical use, which should ultimately improve patient care.

A Systematic Review of Molecular and Biological Tumor Markers in Neuroblastoma

“…Type of treatment and method of marker measurement were not recorded but both would have added additional heterogeneity to that already noted. A more in-depth evaluation of these reporting problems, together with recommendations for improvement, are provided elsewhere (15).…”

“…Availability of full IPD, including all of the exact values of all markers assessed and subgroup information (e.g., age and stage of disease), from each paper would facilitate such assessments in the future (15). Ideally, large multicenter studies should also be initiated to assess the benefits of using chromosome 17q and the other important prognostic markers, both individually and in combination, to improve strategies for the stratification of children with neuroblastoma for therapy.…”

“…For those researchers studying prognostic tumor markers, Altman and Lyman (29) have proposed important guidelines for both conducting and evaluating prognostic factor studies that should be considered. We have also provided guidelines for improved statistical reporting of primary studies to facilitate the evaluation and comparison of individual markers, identify the additional benefits of using combinations of markers, and ultimately allow important evidence-based reviews to be made (15). In particular, presentation of the HR with some measure of precision (e.g., 95% CI) and availability of IPD, either in the paper or on the internet (30), are both highly desirable.…”

REporting recommendations for tumour MARKer prognostic studies (REMARK)

“…The reporting guidelines proposed in this paper build upon earlier suggestions (Altman and Lyman, 1998;Gion et al, 1999;Altman, 2001a, b;Riley et al, 2003a) as well as educational publications (McShane and Simon, 2001;Biganzoli et al, 2003;Schumacher et al, 2005). They recommend elements and formats for presentation with the objectives of facilitating evaluation of the appropriateness and quality of study design, methods, analyses, and improving the ability to compare results across studies.…”

“…Such reporting deficiencies are increasingly being highlighted by systematic reviews of the published literature on particular markers or cancers (Brundage et al, 2002;Mirza et al, 2002;Riley et al, 2003aRiley et al, , b, 2004Burton and Altman, 2004;Popat et al, 2004).…”