Role of Biomarkers for Drug Development in Cardiovascular Disorders

The cardiovascular therapeutic area is complex and includes a number of overlapping diseases. In the past, low-cost biomarkers, such as blood pressure and cholesterol measurements were used. However, they do not address issues such as plaque stability and size. Many new biomarkers have been discovered in recent years (see Chap. 15). Many of these are bases for diagnostic tests and there have potential uses in drug discovery and development. There is need for better diagnostic tests including those encompassing metabolic syndrome - a constellation of disorders including cardiovascular diseases, diabetes, and obesity. Other clinical biomarkers for cardiovascular diseases will include intravascular ultrasound, and in vivo tests for plaque composition and stability using imaging. Biomarkers will be important for development of personalized therapies for cardiovascular disorders.

Role of Biomarkers for Drug Development in Neurological Disorders

The ideal biomarker for CNS drug development should recognize the mechanism of action of a potential new therapy (mechanism-based biomarker) and the relation between biomarker endpoint and intervention should have a biologically plausible explanation. Biomarker endpoints need to be investigated in both animals and humans, as the extrapolation of animal models of disease to human pathology is often uncertain. Validation process is required for a better definition of the biomarker sensitivity, specificity, positive and negative predictive value, accuracy, likelihood ratio of positive and negative tests, discriminant validity, sensitivity to change and to treatment difference.

Improvements in biomarker-based drug discovery in neurological disorders will take place first in diseases without satisfactory treatment, e.g. neurodegenerative disorders, schizophrenia, and pain. The biology of these diseases is not well understood, and the phenotype is complex. This hampers the biomarker discovery and development process, but there is promise in case of Alzheimer’s disease to assess the benefit of treatment using imaging and other biomarker techniques (see Chap. 14). Complex diseases, such as schizophrenia and depression, to be most difficult, with biomarker applications developing at a later date.

Neuroimaging is a key biomarker that provides a unique bridge from the laboratory to the clinic in CNS drug development as quantitative biomarkers as surrogate efficacy measures are often lacking and clinical trial endpoints can be confounded by high placebo response. It can be used preclinically to select candidate drug molecules during drug discovery and clinically to facilitate proof of concept testing and optimization of resources through prioritization of decision making during the development of new therapeutics.

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