Biomarkers-Defn,Characteristics, Classificatn .pptx

Biomarkers
Various Classification
Characteristics

1. Dr D Y Patil COLLEGE OF PHARMACY, AKURDI Definition, classifications, characteristics & impact of biomarkers Guided by : Prof Pavankumar wankhade Created by : Gauri P Gawande Subject : ADVANCED PHARMACOLOGY-ii M pharm 1 st yr

2. CONTENTS Introduction Definition Characteristics Identification & Detection of Biomarkers 5. Technical validation 6. Advantages & Disadvantages 7. Classification

3. INTRODUCTION The role of biomarkers has been exponentially increasing in guiding decisions in every phase of drug development, from drug discovery and preclinical evaluations through each phase of clinical trials and into post-marketing studies. The high costs incurred when drugs fail during clinical trials has prompted interest in biomarkers as biological indicators for progress of disease, effect of therapeutic interventions, and drug-induced toxicity. Biomarkers, thus also reduce attrition of drugs during the preclinical and clinical phases of drug development, and hence, the overall cost of drug development. Biomarkers are the measures used to perform a clinical assessment such as blood pressure or cholesterol level and are used to monitor and predict health states in individuals or across populations so that appropriate therapeutic intervention can be planned.

4. BIOMARKERS B iomarker is defined as “ A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention.“ Biomarker is any indicator that is used as an index of the intensity of a disease or other physiological state in the organism. A substance that when introduced into the organism serves for the estimation of organ function or some other form of health assessment . Objective : accurately diagnosis occur. It is a measurable indicator of some biological state or condition . Measured and evaluated using blood , urine, other body fluids or soft tissues to examine normal or pathological condition . Indications of medical state observed from outside of patient which can be measured accurately .

5. CHARACTERISTICS OF BIOMARKERS Expression is significantly increased especially in the related disease condition Readily quantifiable in accessible biological fluid or clinical samples Shown to correlate with an interested outcome progression Economical, Quick and Consistent I nexpensive, reliable, consistent, easily measured, and their expression is altered under disease conditions. Should express early in the disease progression Easy to assay, less expensive and should be helpful in reducing death from cancer Gives reproducible results and multiplexing is possible for screening purpose Easily measurable in biological fluids/ clinical samples Expression is increased in related disease condition

6. Identification and detection of biomarkers:

7. Technical Validation of Biomarker Accuracy (agreement with a reference) Precision (repeatability, reproducibility) Limit of Detection (sensitivity) Interference, Cross-reactivity (specificity) Sample preparation / conditions. Performance around the cut-off Potential for carryover, cross-hybridization

8. Advantages : Objective assessment Precision of measurement Reliable, validity can be established. Less biased than questionnaires Disease mechanism often studied. Homogeneity of risk or disease Disadvantages Timing is critical Expensive (cost for analysis) Storage (longevity of samples) Laboratory errors Normal range difficult to establish Ethical responsibility

9. Classification of Biomarkers Based on Characteristics Based on Applications Based on Genetic & Molecular biology methods

10. Imaging Biomarkers: CT, PET, MRI and nuclear imaging are already widely used Medical imaging could have a great impact on slow progressing diseases, such as lymphoma, non-small cell lung cancer, Alzheimer’s disease and rheumatoid arthritis. Help monitor drug distribution, pharmacokinetics and pharmacodynamics essential for clinical trials. Advantages : non-invasive, multidimensional results, Yielding both qualitative and quantitative data Disadvantages: Exposing to radiation, high cost.  2) Molecular/ Non-imaging Biomarkers: I nvolves measurements in biological samples (plasma, serum, cerebrospinal fluid and biopsy) include nucleic acids-based biomarkers such as gene mutations or polymorphisms and quantitative gene expression molecules . L evels on which molecular biomarkers can be identified, from formation of protein to degraded products .

11. 5 ) Physiological Biomarker Ex: Pregnancy Test

12. 1 . Type 0: Natural history marker : defined as a marker of disease severity examples of type 0 markers as independent predictors of risk are the CD4' T-cell count and the HIV 1 plasma RNA level. 2. Type 1: Biological activity marker : defined as one that responds to therapy. determined in the context of early phase clinical trials. Example : Triple- drug anti retroviral combinations appeared superior to single drugs and double-drug combinations in vitro 3. Type 2: Surrogate marker of therapeutic efficacy : A “surrogate marker” can be defined as “ a laboratory measurement or physical sign that is used in therapeutic trials as a substitute for a clinically meaningful endpoint that is a direct measure of how a patient feels, functions, or survives and is expected to predict the effect of the therapy. ’’

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