What is a Biomarker? From its Discovery to Clinical Application

What is a Biomarker? From its Discovery to Clinical Application The term biomarker in medicine most often stands for a protein measured in the circulation (blood) whose concentration indicates a normal or a pathological response of the organism, as well as a pharmacological response to the applied therapy. From a wider perspective, a biomarker is any indicator that is used as an index of the intensity of a disease or other physiological state in the organism. This means that biomarkers have a very important role in medical research and practice providing insight into the mechanism and course of a disease. Since a large number of biomarkers exist today that are used for different purposes, they have been classified into: 1) antecedent biomarkers, indicating risk of disease occurrence, 2) screening biomarkers, used to determine a subclinical form of disease, 3) diagnostic biomarkers, revealing an existing disease, 4) staging biomarkers, that define the stage and severity of a disease, and 5) prognostic biomarkers, that confirm the course of disease, including treatment response. Regardless of their role, their clinical significance depends on their sensitivity, specificity, predictive value, and also precision, reliability, reproducibility, and the possibility of easy and wide application. For a biomarker to become successful, it must undergo the process of validation, depending on the level of use. It is very important for every suggested biomarker, according to its purpose or its nature, to possess certain characteristics and to meet the strict requirements related to sensitivity, accuracy and precision, in order for the proper outcome to be produced in the estimation of the state for which it is intended. Finally, the development of guidelines for biomarker application is very important, based on well defined and properly conducted assessments of biomarker determination, providing the means by which research is translated into practice and allowing evidence based on facts to promote the clinical application of new biomarkers. Šta je Biomarker? Od Otkrića Do Kliničke Primene Izrazom biomarker u medicini se označava najčešće protein izmeren u cirkulaciji (krvi) čija koncentracija ukazuje na normalan ili patološki odgovor u organizmu, kao i na farmakološki odgovor na primenjenu terapiju. Šire gledano biomarker je bilo koji pokazatelj koji se koristi kako indikator intenziteta nekog oboljenja ili drugog fiziološkog stanja u organizmu. To znači da biomarkeri imaju veoma značajnu ulogu u medicinskim istraživanjima i primeni jer omogućavaju sagledavanje mehanizma i toka bolesti. Pošto danas postoji veliku broj biomarkera koji se koriste u različite svrhe izvršena je njihova podela na: 1) antecedentne biomarkera, koji ukazuju na rizik od nastanka bolesti, 2) »screening« biomarkere, kojima se utvrđuje subklinička forma bolesti, 3) dijagnostičke biomarkere, koji otkrivaju postojeću bolest, 4) »staging« biomarkere, koji definišu stadijum i težinu bolesti i 5) prognostičke biomarkere, koji potvrđuju tok bolesti, uključujući i odgovor na terapiju. Bez obzira na ulogu koju imaju, njihov klinički značaj zavisi od njihove osetljivosti, specifičnosti, prediktivne vrednosti, zatim preciznosti, pouzdanosti, reproducibilnosti, kao i mogućnosti jednostavne i široke primene. Da bi biomarker bio uspešan mora proći kroz put validacije zavisno od nivoa upotrebe. Veoma je značajno da svaki predloženi biomarker zavisno od namene ili njegove prirode ima odgovarajuće karakteristike i da ispunjava stroge zahteve koji se odnose na osetljivost, tačnost i preciznost kako bi se postigao odgovarajući ishod za procenu stanja za koji je namenjen. Shodno navedenom više istraživačkih cenatara i grupa predložilo je način i uputstva za evaluaciju biomarkera uzimajući u obzir prognostičke prema diajgnostičim modelima. Konačno, veoma je značajna izrada uputstava (Guidelines) za primenu biomarkera koja su zasnovana na dobro definisanim i sprovedenim procenama određivanja nekog biomarkera, na koji način su dobijena dobra sredstva putem kojih su preneta istraživanja u praksu a dokazi zasnovani na činjenicama potpomažu kliničku primenu novih biomarkera.