Clinical trials are an important part of the process of developing new drugs and treatments. They are conducted in three main phases: phases 1 to 3.Phase 1 trials are the earliest phase trials and phase 3 are later phase trials. In some cases, there is an earlier stage called phase 0, and there are also phase 4 trials that are done after a drug has been authorized. Phase I trials focus mainly on establishing the safety and dose range of a new drug in about 20 to 100 healthy volunteers.
The way the human body absorbs, distributes, metabolizes, and excretes a drug is called pharmacokinetics. This is determined by frequent blood draws (usually in a hospital setting) to check the level of the drug in the blood plasma. Phase I studies may involve risks even if an investigational drug has passed the preclinical phase of testing. Volunteers in these studies are often compensated for their time and effort, as they may not receive any benefit from participating.
Although generally conducted with healthy volunteers, phase I trials can also be conducted with patients with serious or terminal illnesses, such as those with AIDS or cancer. A phase I trial takes several months to complete, and around 70 percent of experimental drugs pass this initial phase of testing. Phase II studies determine the effectiveness of an experimental drug in a particular disease or condition in approximately 100 to 300 volunteers. This phase can last from several months to two years.
A phase II trial answers the question: Does drug X improve disease Y? A secondary objective of a phase II trial is to determine the therapeutic dose level and dosing frequency. This answers the questions: How much drug X works best for disease Y (1 mg, 2 mg, or 3 mg)? and Does drug X work better in disease Y if taken once or twice a day? Most phase II studies are randomized, meaning that subjects are randomly assigned (by chance and not by choice) to receive the experimental drug, a standard treatment, or a placebo (an inactive, harmless substance). Those who receive the standard treatment or the placebo are called a control group. Randomized phase II studies are often double-blind, meaning that both the subject and the doctor do not know what treatment is being used.
Blinding prevents any unscientific influence on study results that may be due to knowledge of the treatment. In a single-blind study, only the subject is unaware of the treatment used. Because more patients receive treatment in phase II studies than in phase I studies, there are more opportunities to observe and collect information about side effects. Subjects in a phase II trial may benefit from participating if they receive active treatment. Approximately 33 percent of experimental drugs that pass phases I and II will move on to phase III.
Phase III studies are conducted in several centers with several hundred or several thousand patients for whom the drug is intended. Massive drug testing provides a continuous generation of data about the safety and effectiveness of a drug. As in phase II, most phase III studies are randomized and blinded. Phase III trials provide most of the information needed for the package leaflet and labeling of a drug, once it has been approved by the FDA. A drug in this phase can be studied for several years and can be one of 25 to 30 percent that passes phases I, II, and III.
Once a phase III study is complete, a pharmaceutical company can apply for FDA approval to market the drug. This is called a New Drug Application (NDA). The NDA contains all the scientific data that the company has collected throughout the phases of all the trials. A clinical trial generally consists of four phases: Phase 0, Phase 1, Phase 2, and Phase 3.Each phase helps to advance the study step by step. The purpose of a clinical trial could be to study a drug, therapy, or method to prevent or detect a disease. As long as clinical trials are carefully designed, reflect what developers know about a product, protect participants, and meet federal standards, developers have ample room for maneuver when designing clinical trials. This is called “repurposing” a drug, and sometimes this can shorten the clinical trial or allow phase 2 clinical trials to accelerate because the safety profile was already tested in an earlier clinical trial.
As developers design their clinical study they will consider what they want to achieve in each of the different phases of clinical research and begin their New Drug Research (IND) process before clinical research begins. Drug developers or sponsors must submit an investigational new drug (IND) application to the FDA before starting clinical research. Before starting a clinical trial researchers review previous information about the drug to develop research questions and objectives. Researchers design clinical trials to answer specific research questions related to a medical product. The process protects volunteers participating in clinical trials from unreasonable and significant risks in clinical trials.