Marker methodology, with focus on time-to-event outcomes

Abstract

Introduction: A disease or medical condition is an abnormal condition of an organism that impairs bodily functions, associated with specific symptoms and signs. It may be caused by external factors, such as invading organisms, or it may be caused by internal dysfunctions, such as autoimmune diseases. In human beings, “disease” is often used more broadly to refer to any condition that causes extreme pain, dysfunction, distress, social problems, and or death to the person afflicted, or similar problems for those in contact with the person (Johnson 2002). Diseases in general, particularly chronic diseases, deprive individuals of their health and productive potential. From countries perspective, chronic diseases reduce life expectancy and ultimately economic productivity, thus depleting the quality and quantity of countries labor force (WHO 2005). Due to the need for effective, safe, and affordable pharmaceuticals to control, cure or eradicate diseases, especially those that cause high mortality and morbidity, drug regulatory agencies have been put in place to enforce a standard drug development process. The first step of the process, referred to as drug discovery, determines the target disease, develops hypothesis for a mechanism of treatment, as well as determine feasibility of producing and evaluating the selected compounds. Next comes the screening, where combination chemistry is used to obtain many possible compounds, which are tested for activity via high throughput screening. This is followed by the Pre-clinical phase, which is an animal study used to assess the safety and biological activities of the selected compound, together with lethal and normal dose levels for short and long term use. If promising results are obtained from the pre-clinical stage, a request is made to the appropriate regulatory agency to allow human exposure to the experimental drug. Upon approval from a regulatory agency, the investigational new drug is then tested and evaluated through a series of clinical trials....