The implications of biomarker evidence for systematic reviews

Background: In Evidence-Based Medicine, clinical practice guidelines and systematic reviews are crucial devices for medical practitioners in making clinical decision. Clinical practice guidelines are systematically developed statements to support health care decisions for specific circumstances whereas systematic reviews are summaries of evidence on clearly formulated clinical questions. Biomarkers are biological measurements (primarily molecular) that are used to diagnose, predict treatment outcomes and prognosticate disease and are increasingly used in randomized controlled trials (RCT). Methods: We search PubMed for systematic reviews, RCTs, case reports and non-systematic reviews with and without mentions of biomarkers between years 1990-2011. We compared the frequency and growth rate of biomarkers and non-biomarkers publications. We also compared the growth of the proportion of biomarker-based RCTs with the growth of the proportion of biomarker-based systematic reviews. Results: With 147,774 systematic reviews indexed in PubMed from 1990 to 2011 (accessed on 18/10/2012), only 4,431 (3%) are dedicated to biomarkers. The annual growth rate of biomarkers publications is consistently higher than non-biomarkers publications, showing the growth in biomarkers research. From 20 years of systematic review publications indexed in PubMed, we identified a bias in systematic reviews against the inclusion of biomarker-based RCTs. Conclusions: With the realisation of genome-based personalised medicine, biomarkers are becoming important for clinical decision making. The bias against the inclusion of biomarkers in systematic reviews leads to medical practitioners deprive of important information they require to address clinical questions. Sparse or weak evidence and lack of genetic training for systematic reviewers may contribute to this trend.