Phase III studies usually involve 500 to 5000 patients, and patient demographics should as far as possible be representative of the population in which the new drug will ultimately be used. 15 years to take a drug from laboratory discovery to FDA approval. Out of every 5-10 000 compounds evaluated pre-clinically, only five enter clinical trials, and of these only one gains regulatory approval. More information on the efficacy, safety and mechanism of action should be sought from early-stage clinical trials to minimize late-stage attrition. Medical imaging has an enlarging role in new drug development. This progress is ex229 (compound 991) driven by several factors, including the growing technical capabilities of imaging methods and the increasing focus by drug developers on chronic diseases. The application of medical imaging in pharmaceutical clinical trials involves its use to determine disease predisposition; to identify likely responder patients; to diagnose lesions and evaluate their severity; and to monitor therapy effects and follow-up. Considerable emphasis has also been placed on linking pre-clinical imaging and clinical data in order to increase the success rate of clinical trials(1). Pre-clinical imaging in appropriate disease animal models can contribute to the identification of new imaging biomarkers, whereby histological correlation can be obtained. It is anticipated that greater use of imaging during pre-clinical stages will facilitate better translation from animal models to human subjects. In this article some basic principles of new drug development are explained and unique aspects of study design for clinical trials with an imaging component are ex229 (compound 991) ex229 (compound 991) discussed. The main emphasis is on the application of medical imaging in therapeutic drugs trials; however, many principles may be equally applicable to the development of novel imaging contrast agents and radiopharmaceuticals. == New drug clinical development process == A new drug can be a small inorganic molecule or a complex organic molecule such as an antibody. Drug discovery involves the identification of a target (eg, an enzyme or a receptor), and the design and optimization of a drug to interact with it. Preclinical studies conducted in animals are typically used to demonstrate the safety and effectiveness of a new drug. If promising, the new product then proceeds to clinical trials in human subjects, a process that usually involves multiple stages commonly known as phases(2),(3). Thus drug discovery and development can be broken down into preclinical drug discovery (approx. 6.5 years), Phase I testing (approx. 1.5 years), Phase II testing (approx. 2 years), Phase III testing (approx. 3.5 years), and FDA approval (approx. ex229 (compound 991) 1.5 years). The aim of phase I trials is principally to study pharmacokinetics and initial tolerability in humans. Where possible, the duration and dose dependency of the drug effect is explored. To avoid the confounding influence of other diseases, medications and age, phase I studies usually start with young, healthy volunteers. With some types of drug, such as some cancer drugs which carry a significant risk of adverse effects, patients for whom there may be a therapeutic benefit are recruited. To assess tolerability, a dose-ranging schedule may be applied in which successive volunteers are exposed to increasing drug doses. Phase I studies typically involve 50 to 150 subjects. Phase II trials study the safety and effectiveness of the drug in cases with the indication in question, and seek to identify the optimum dosage schedule. Phase II studies, which typically involve 100 to 200 subjects, can also investigate the pharmacological differences between patients and healthy volunteers. The phase III study is the most extensive phase of development. Its purpose is to confirm the effect, tolerability and safety of the new drug compared Rabbit Polyclonal to Aggrecan (Cleaved-Asp369) with standard therapy (or placebo), and to prove the correct dose in cases with the indication in question. Phase III studies usually involve 500 to 5000 patients, and patient demographics should as far as possible be representative of the population in which the new drug will ultimately be used. Phase IIIb studies are not.