OHSU

How does a drug become approved for use?

Phases of Studies
by Trish Kirchhoff, R.N.

A majority of the clinical trials that are conducted at the Parkinson Center of Oregon involve investigational new drugs. These investigational drugs are developed by pharmaceutical (drug) companies and have undergone years of testing in the laboratory on animal and human cells and in animal experiments. If these stages of drug testing are successful, the pharmaceutical company provides the data to the Food and Drug Administration (FDA) requesting approval to begin testing the drug in humans. This experimental drug is now called an Investigational New Drug (IND).

Clinical testing of the IND is usually conducted in successive stages or "phases" that involve a larger number of participants at each phase. These phases are defined and regulated by the FDA.

Phase I

This first phase of testing on humans is done primarily to determine drug safety. This testing is usually done with a small number (20-100) of healthy volunteers, that is, people not diagnosed with the disease being studied or with other medical complications. Studies are designed to determine what happens in a human body when the drug is given. A phase I study helps researchers decide proper dosages and looks at side effects caused by the drug. Some phase I studies can provide information on the drug's effectiveness. Phase I testing typically takes several months and about 70 percent of experimental drugs pass this initial phase of testing on humans.

Phase II

This second phase of testing is done on several hundred people diagnosed with the disease for which the drug was developed. Phase II studies test the effectiveness of the experimental drug, continue to evaluate its safety, and collect information on proper doses and dosing schedules. Phase II studies are usually "randomized," which means that one group of study participants or, on one day of a multiple day study, a "placebo"— a pill or medication that looks like the drug but does not contain any drug -- is given. Quite often, studies in phase II are "blinded" studies, meaning that both the researcher and the study participants do not know who is receiving the study drug. Only about 30 percent of experimental drugs successfully complete both phase I and II testing.

Phase III

In this phase, the drug is tested on several thousand people diagnosed with the disease to confirm its long-term effectiveness and safety and to note its less common side effects. Investigators also are able to determine the drug's effectiveness compared to commonly used treatments for the disease. This is valuable information used to establish the overall benefit/risk relationship of the drug. Most phase III studies are randomized and blinded. Studies conducted in phase III usually last several years; 70-90 percent of experimental drugs pass this phase. When a study of the drug in phase III is successfully completed, the drug company can request approval from the FDA.

Phase IV

Phase IV studies are conducted after the drug has been approved for sale by the FDA. In these studies, researchers can gather more information from "real-life conditions." These studies look at the use of the drug by a person with the disease over a longer period, at the drug effectiveness at other stages of the disease it is treating and its cost effectiveness compared to other standard drug treatments and new therapies.

Proof of Principle

Proof of principle studies, also called proof of mechanism or concept studies, are named for studies conducted on a drug that was developed for a specific purpose or disease that investigators believe could have a beneficial use for a different disease. These studies are conducted on a small number of participants. Several months are usually required to analyze the data from these studies before a dose is selected and larger trials are begun. The investigators at the PCO have gained a reputation in their field for conducting proof of principle studies, opening up new avenues for the treatment for PD.

Throughout each of these phases of studies, the investigators and drug company sponsors are monitoring individual study participants and looking at the interim data for subjects' responses to the drug. If at any time during a study a drug has proved to be ineffective or unsafe, the study may be halted.Conversely, if the drug is found to be overwhelmingly beneficial it may be approved by the FDA and released for use to the public sooner.