Drug Development Process Once a compound is discovered, a major portion of its development focuses on clinical studies, which are generally categorized into four phases: Phase I Phase I typically lasts from one week to several months and involves between 20 and 100 healthy human volunteers (in clinical trials, “volunteers” are normal, healthy individuals, most often male).  The main goal during this phase of investigation is to determine a drug’s safe dosing amount in humans.  Prior to this phase, only animal and in-vitro data are available for study.  It is essential that subjects studied in Phase I are free of abnormalities or conditions that would complicate interpretation of clinical data.  However, when a drug is intended to treat certain diseases (examples include AIDS and cancer), Phase I studies are conducted in severely ill patients who have the disease. Phase II During Phase II, which can last from several months to two years, several hundred subjects are studied.  “Subjects” are individuals who participate in a clinical study, either as a recipient of the investigational product or as a control.  Investigators are seeking to determine effectiveness at a safe dose during Phase II, typically across a range of doses. This phase of the clinical trial process is typically split into two parts – Phase IIa and Phase IIb.  In Phase IIa, pilot clinical studies are conducted to evaluate efficacy and safety in selected populations of about 100-300 patients who have the disease or condition to be treated, diagnosed or prevented.  Phase IIa studies often involve hospitalized patients who can be closely monitored in order to study objectives such as dose-response, type of patient, frequency of dose and other aspects related to safety and efficacy. Studies conducted during Phase IIb usually follow IIa studies rather than occurring simultaneously.  As with Phase IIa, these studies are well-controlled evaluations of safety and efficacy in patients who have the disease or condition to be treated, diagnosed or prevented.  Phase III In Phase III, several hundred to several thousand subjects are studied to determine safety and effectiveness of the investigational drug in a large, varied population over a long time period, usually lasting from several months to four years.  This last pre-marketing drug testing stage is the comparative evaluation of the new drug versus placebo or the standard therapy.  Patients involved in these multi-center studies are ones for whom the medication is eventually intended as a medical treatment.  During Phase III’s full-scale evaluations, the new drug is tested under conditions most closely resembling those under which the drug would be used if approved for marketing.  Much of the information needed for the marketed drug’s package insert and labeling are produced during Phase III. Another aspect of Phase III studies is referred to as Phase IIIb, which occurs during a period prior to drug approval but after the completion of well-controlled studies designed to lead to marketing approval.  Phase IIIb studies usually focus on marketing or quality of life issues, or they may supplement or complete earlier studies.  They may be completed while the application for marketing approval is being prepared or reviewed. Phase IV Overarching purposes of Phase IV studies can include comparing the product to a competitor product, exploring use in additional subject sub-populations or exploring adverse experiences.  These studies may be used to evaluate formulations, dosages, durations of treatment, drug interactions and other factors.  Phase IV studies that are primarily observational or non-experimental are frequently called “post-marketing surveillance.”  Post-approval Phase IV commitment studies are conducted as a condition for a drug’s approval as the drug is introduced to the market.