Biomarker research: From bench to publication…but gasping to reach chairside.

With the increase in the research on biomarkers, their role in existence, severity and pathogenicity of periodontal disease is becoming much more clearer with number of studies being published on these biomarkers. Biomarkers are objective and quantifiable determinants of normal biological or pathogenic processes and can be measured accurately and reproducibly.[1] The use of biomarkers in diagnosis and management of periodontal diseases could add immense value to our gold standard clinical measurements on which our current clinical diagnosis is based. The use of these biomarkers can help in overcoming the limitations of various clinical measurements and indices used in diagnosis. Biomarkers have been classified into five groups based on their function in diverse disease stages: 1) Antecedent biomarkers that help in identifying the risk of developing a disease, 2) Screening biomarkers to monitoring the subclinical stage of disease, 3) Diagnostic biomarkers to diagnose, 4) Staging biomarkers to identify disease severity, and 5) Prognostic biomarkers to predict course, duration, treatment efficacy and outcome and recurrence.[1,2] Biomarkers play a critical role in prevention, diagnosis and treatment of disease. The biomarkers that have been studied widely are the biomarkers used to detect the exposure by studying the pathogen or its virulence factors (biomarkers of exposure); identify the host response as a result of exposure to infectious agent by measuring proinflammatory cytokines or other proteins (biomarkers of effect); and recognise the factors which can recognize susceptible individuals e.g., genetic biomarkers (biomarkers of susceptibility).[1,2] Endpoints in trials can be classified as either clinical or non-clinical. Biomarkers are the non-clinical endpoints. Poor selection of endpoints makes elucidation and application of findings, challenging or impossible.[3] The problem is, despite the plethora of evidence being generated by innumerable studies on biomarkers, the studies and their results do not find their way into clinical usage by developing of chairside assays. There is deficiency of confirmatory evidence in periodontal biomarker research for it to be used as chair side assays in clinical practice. This could be attributed to heterogenicity in studies, on the basis of definitions of disease and clinical endpoint used in studies, differences in subject recruitment for the studies, and disparities in sample management. Disparities in sample management could be in collection, storage and transportation methods, and variations in biochemical or microbiological techniques to study the samples.[4] Pavloum et al. mentioned four steps for chairside application of the research: (a) Preclinical exploratory studies to identify likely biomarkers. Usually the molecules having the capacity to differentiate between small samples from healthy and diseased groups is identified; (b) Development and validation of an assay to measure the biomarker of interest in an independent clinical sample; (c) Retrospective validation of the targeted biomarker in large samples that have the biological variability of the targeted population to ensure statistical precision; (d) The biomarkers that continue to show capacity to differentiate, progress to the next phase of prospective trials.[5] The development and validation of assay would require multiple studies and is a multiphase procedure. A seven point checklist especially for periodontal biomarker research has been suggested so that heterogenicities in the studies of periodontal biomarkers can be reduced for the comparability of results and chair side application of this research may be achievable.[4] This checklist provides the researchers with indispensable fundamentals checkpoints, pertinent and specific for periodontal biomarkers research.[4] The checklist talks about biological specificity of the material, clear definitions of health and disease and changes observed in the biomarker (being studied), in health and disease, recruitment of population, biomarker sampling and detection methodology, statistical values of sensitivity and specificity for the biomarker and finally interpretation.[4] With implementation of these criteria, it might become a possibility in near future, that, the wealth of information available, can be utilized in clinical practice with development of chairside assays and leading to more personalized treatment. These guidelines may be useful in streamlining the research process and reduce the clutter and research waste.