With diminishing success in drug development, manufacturers have been exploring new ways of making drug manufacturing process successful. Biomarkers play a crucial role in drug development (Bleavins, Carini, Jurima, & Rahbari, 2011). Pharmaceutical companies consider using biomarkers to increase the efficiency of new drugs. This paper explores biomarkers, their use, classifications and importance in drug development.
Biomarker has various definitions from different groups. According to Biomarkers Definition Working Group, a it is defined as an indicator in pathogenic or biological processes, which can be measured and evaluated objectively in a given intervention in therapy (Bleavins et al., 2011).
Clinical end point defines it as an indicator reflecting the feelings and functioning of a patient as well as his survival. Finally, surrogate endpoint defines biomarker, as an instrument whose intention is to substitute clinical end point (Bleavins et al., 2011).
There are three types of biomarkers: type 0, I and II. Type 0 is an indicator in diseases and correlates with given symptoms. It is concerned with risks of a given exposure. Type I shows the effects or response of a given intervention or therapy in an organism during drug development. Type II biomarkers are surrogate indicators. This means that, change in a biomarker indicates clinical end (Bleavins et al., 2011).
Biomarkers are used to measure the well-being of a person; both physical and mental. They are used to determine the state of an individual’s health (Zwierzina, 2008). In addition, they are used to measure the risks and influence of a given exposure, which can be as a result of environmental or hereditary factors.
If a disease is caused by exposure to toxins, researchers may choose to measure the level of toxin concentration in an individual’s environment. Researchers can also measure the alleged toxin in food, water, air or soil directly. As a result, they are able to ascertain the risks and susceptibility associated with a given exposure (Zwierzina, 2008).
Biomarkers are used to ascertain the severity of diseases. They can determine whether a disease is severe or not. Biomarkers are used to predict results. They are used in drug development; hence they can predict the efficacy of a new drug.
In addition, they are used in determining the most efficient type of nutrition, intervention and treatment in a patient. Imaging a biomarker assists researchers to develop efficient drugs for a given disease; through evaluation of an individual and the response to the drug (Javitt Spencer, Thaker, Winterer, & Hajós, 2008).
Post-therapy evaluation determines the efficiency of nutrition and intervention in an individual’s body. Biomarkers are used to evaluate a person’s response to therapy. Through biomarker imaging, the concentration of drugs in tissues can be measured (Javitt et al., 2008). In addition, receptor occupancy and characterization of receptors can be done to evaluate an individual’s response towards an intervention.
Biomarkers are used to monitor compliance of a drug. They are supposed to meet the intended purpose and adhere to given regulations. To determine the compliance of a drug, indicators are set in order to measure the biological activity of a drug before and after treatment.
Biomarkers are used for forensic purposes (Wagner, 2008). They are applied in various fields of science and technology to establish facts about civil law. Generally, they are used for diverse purposes in clinical development.
Different types of biomarkers are used for different purposes; hence they are unique and each has a specific purpose. For example, if a biomarker is intended to measure the effect of a drug or therapy, the response should show some correlations to the symptoms of disease (Wagner, 2008).
Biomarkers are used according to their classifications; pharmacological, toxicological and pathological biomarkers. Indicators used for pathological processes are specific and can not be used for toxicological or pharmacological processes.
In clinical care, biomarkers are classified according to their purpose (Javitt et al., 2008). Preventive biomarker identifies an individual’s risk to suffer from a certain disease. Diagnostic indicators are used to identify disease at early stages before the symptoms are noticed. Moreover, prognostic biomarkers show the possibility of disease progression in a patient as he continues with therapy.
Also, there are predictive variables which identify the response of patient to a given therapy (Zwierzina, 2008). Lastly, therapeutic indicators give the total number of responses from patients undergoing a treatment. This means that each indicator is unique and has a set purpose.
Biomarkers are identified according to their function. For example, if a researcher suspects that a disease is caused by being exposed to a certain toxin, then biomarkers (organisms) are exposed to these toxins and extend of effects is established. In oncology, the indicators for cancer are tumors and a researcher scans their sizes to determine the magnitude of an infection (Bleavins et al., 2011).
Neurologists measure the occurrence of multiple sclerosis in order to evaluate Alzheimer disease. X-ray is done to establish the impacts of muscuskeletal diseases like arthritis and fractures among others.
If the purpose of a biomarker is to measure the response of a given intervention, then an organism is subjected to a certain medicine. Different diseases have different biomarkers, for example, tumors are biomarkers for cancer (Bleavins et al., 2011).
A surrogate endpoint can be defined as an indicator which alternates a clinical endpoint. It is also known as reserve biomarker. Clinical endpoint is an indicator showing the general operation of a patient. For example, blood pressure may not affect every patient, however in clinical development, it is considered as a risk factor for diseases like stroke and heart attack (Javitt et al., 2008).
Pharmacodynamic markers are indicators used in monitoring biological impacts of a drug. They are used in decision- making during the early stages of drug development. They are used to establish doses and dosing in pre-clinical and clinical development of a drug. Pharmacodynamic marker is a reflection of pharmacologic responses (Wagner, 2008).
Surrogate end point and Pharmacodynamic are useful in drug development. Surrogate end point is not an independent marker on itself. It can be extrinsic or intrinsic. It is a substitute. Moreover, they can be used in prediction of expected clinical results in drug development process (Wagner, 2008).
The main disadvantage of surrogate end points is: they need long follow ups and they are not independent. Pharmacodynamic are induced by non-drug events and have many limitations (Bleavins et al., 2011).
One of the reasons these two biomarkers are not important in studies is surrogates are not a pathway for disease process in clinical developments. In addition, they are not sensitive to a given intervention. This means that they might give false impression about an intervention.
Surrogates are important when a given process is well- known and the results expected are certain (Bleavins et al., 2011). Validation of surrogates is somehow difficult. They are important in some clinical developments but not all. Due to these reasons, surrogate and Pharmacodynamic biomarkers are not emphasized in studies.
References
Bleavins, M. R., Carini, C., Jurima-Romet, M., & Rahbari, R. (Eds.). (2011). Biomarkers in drug development: a handbook of practice, application, and strategy. Wiley.
Javitt, D. C., Spencer, K. M., Thaker, G. K., Winterer, G., & Hajós, M. (2008). Neurophysiological biomarkers for drug development in schizophrenia. Nature Reviews Drug Discovery, 7(1), 68-83.
Wagner, J. A. (2008). Strategic approach to fit-for-purpose biomarkers in drug development. Annu. Rev. Pharmacol. Toxicol., 48, 631-651.
Zwierzina, H. (2008). Biomarkers in drug development. Annals of oncology, 19(suppl 5), v33-v37.