In ancient times, the medical practices were accomplished with physical observation and examination of the patient. Later, with the advancements made to the field of medicinal research lead to the evolution of biomarkers which became an undeniable part of medical approaches. A biomarker is defined as a characteristic of measurement and evaluation of the progress of medical treatment in human beings. It is an excellent indicator of pathogenic processes, normal biological processes or a pharmacological response produced by the human body on account of therapeutic interventions.
FDA defines biomarker assays as a measurable endpoint for indicating a particular disease or any other physiological state of any organism. Biomarker assays are used as indicators of simple serum chemistries, cell surface protein expressions, immunochemistry, blood pressures, gene amplification, single-gene mutations etc.
Potent application of a biomarker in clinical trials –
The pharmaceutical industries today are more keen on developing high attrition rates for their drug development process. One of the key aspects here is a swift shift from test and see the approach of new drugs amongst the patients to the generation of translational biomarkers. The applicability of these biomarkers in researches has facilitated predictive evaluation of any new pharmaceutical entity in drug trials involving large scale clinical applications.
According to the FDA guidelines, the biomarkers should be developed and evaluated for safety and efficiency, predictive efficacy, pre-clinical and clinical trials involving animals and humans respectively, and lastly, serving as surrogate endpoints.
Classes of biomarkers available for testing in human clinical trials –
Clinical laboratory measurements are crucial in demonstrating both the safety and efficacy of drug studies. Here are a few classes of biomarkers that have passed the biomarker validation criteria to be employed for clinical trials –
Safety biomarkers –
The safety biomarkers are a means of critical evaluation of early toxicity during clinical development trials. Thus, it is essential that in phase 1 and 2 trials itself, optimum test criteria selection is crucial and should highly rely on the compound profile and the data obtained from the pre-clinical toxicology. Liver safety tests, renal safety tests, haematology safety tests, bone safety tests, necessary metabolite safety tests are some of the parameters that are evaluated through the use of safety biomarkers.
Efficacy biomarkers –
There is a fundamental difference between both the safety and efficacy of biomarkers. While the former one evaluates the early toxicity, the latter one helps in the characterization of a good count of treated subjects. In simpler terms, the more favourable your efficacy biomarker turns out to be, the higher efficiency of your pharmaceutical drug under evaluation. The different types of efficacy biomarkers available in the market are surrogate biomarkers, predictive biomarkers, pharmacodynamic biomarkers, and prognostic biomarkers.
An overview of biomarker validation –
By definition, biomarker validation is an open-end process where independent studies and datasets are essential for justifying every potent application of every single biomarker available in the market. Such biomarker validation processes are inclusive of open-ended evidentiary standards for biomarker characterization. The biomarker validation criteria are as follows –
- The question type for which the biomarker is designed.
- The required degree of certainty that the researcher expects out of his biomarker validation.
- Every possible assumptions or hypothesis for co-relating the clinical endpoints and changes observed during biomarker validation.