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Biomarkers are indicators used for measuring, characterizing and evaluating normal biological functioning or pathogenic processes or even responses to treatment. Physicians, drug developers, device developers, regulatory agencies, consider these imaging biomarkers very important for treatment decisions, for approving drugs, to define the efficacy of a drug, its therapeutic benefits, safety and the determination of the extent of off-target responses. When imaging biomarkers are used in a clinical trial, its cost is approximately 15% of the cumulative budget of the entire clinical trial. However, using an imaging biomarker in a clinical research requires addressing several issues satisfactorily. Among the issues to be addressed, first is the standardization of imaging interpretation which should be done to the greatest level possible that is, to minimize bias in a study it is necessary to reduce inter- and intra- reader variability. The next issue to be addressed is the necessity of top notch computing facilities that has the capability of storage, management and analysis of large volume of data that is generated through the imaging modalities. In most scenarios, clinical data from all the sites should essentially be assessed, interpreted, analyzed and for these setting up a core central lab is deemed ideal. However, there have been critical issues like the core labs may take much time to respond and also to handle discrepancies from the participating sites further leading to bias. These issues can be reduced by standardizing and bringing in more expertise in each step of the trial, thus helping the sponsors to access and review imaging biomarker data fairly quickly. Thus making the data available in near real time and allowing sponsors to make positive or negative decision faster and at the same time better designs to collect data can be implemented effectively. This will further help to employ the same imaging biomarker in the all phases of a clinical trial. Imaging biomarkers can be differentiated in many ways. But one of the most useful classification that is more relevant to clinical trials is to differentiate biomarkers that show “evidence of mechanism”, “evidence of principle” or “evidence of efficacy” that depend on their interaction with the target that is intended or a pathway modification subsequent to an interaction with the target. Biomarker for the later classification is called as surrogate endpoints. These surrogate endpoints replaces clinical endpoints. The clinical endpoints are basically those biomarkers that highlight how patients feel, functions or survives for example mortality, duration of patients stay in the intensive care unit etc. Although clinical endpoints have intrinsic value to the patient, it becomes difficult to quantify and these data cannot be collected until much after exposure to a drug or a factor that may be of high risk to the patient. Surrogate endpoints however, help to identify biomarker changes much earlier in the disease process and can be measured with a better precision as compared to clinical endpoints. Surrogates for example viral DNA levels, reduction in cholesterol, controlling blood sugar have been used; imaging biomarkers have also been used as surrogates. Sometimes the above mentioned surrogates may also be used as imaging biomarkers as it has not been established so far by the regulatory agencies which surrogates can or cannot be an imaging biomarker. However, for any given study that uses biomarkers have to be approved by the regulatory agency as an imaging biomarker. Development of an imaging biomarker involves analytic and clinical validation as highly critical step which is done by the regulatory agencies for any given trial using biomarker as an endpoint. For analytical validation the regulatory authority will ensure complete imaging equipment evaluation, standardizing the procedure, production and measurement of imaging phantoms, sensitivity to variability between subjects and progression of disease. Regulatory authorities will also pay much attention to the reconstruction and segmentation algorithm for imaging. For clinical validation the regulatory authorities will ensure that the association between the imaging biomarker and the clinical endpoint is reliable and that the use of it as a surrogate endpoint will impact cost effectiveness in a favourable way. Imaging modalities like PET – Positron Emission Tomography and/or MR – Magnetic Resonance has the capability of combining molecular and morphological imaging that can give novel tools for imaging biomarker. Apart from this PET imaging uses radiotracers which can be a potential imaging biomarker. There is much potential in using imaging biomarkers as clinical endpoints. Thus using imaging biomarkers will help early elimination of drugs that’s less promising and at the same time assist in rapid deployment of new drugs that can be successful. Clinnovo is a clinical innovation company. It is pioneer CRO industry in India. Clinnovo offers professional clinical research course , clinical data management course , SAS and imaging training. Clinnovo has been serving different bio-pharma industries across the world with excellence and high quality. For more information contact at +91 9912868928, 040 64635501
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