Controlled research studies that test the effectiveness of new drugs. These are also called clinical pharmacology studies, clinical trials, or clinical studies. The process of taking a new drug from concept to prescription is lengthy and costly and involves many levels of research and testing. Most of these processes take place in the laboratory, making sure the new drug is as safe as possible before expanding its testing to humans. Laboratory testing is called preclinical testing. In the United States, the Food and Drug Administration (FDA) oversees drug testing and determines whether a drug is approved for clinical use (treatment of people).
Until a drug receives FDA approval, it is classified as an investigational new drug (IND). This designation imposes strict limitations on the drug’s availability and use. Drugs in the later phases of clinical testing are sometimes made available for treatment purposes under specific and limited circumstances in what is known as an expanded access protocol, as when a person who has Parkinson’s would clearly benefit from the drug but cannot qualify to participate in clinical trials.
Researchers recruit volunteers to participate in clinical pharmacology trials, which typically take place in four phases.
Phase I is the first and preliminary test of the investigational new drug in humans. These studies are generally small and intended to determine whether laboratory findings—benefits and risks—are the same in people as in test animals. Researchers look in particular for unexpected side effects that affect the drug’s safety. Nearly always, the volunteers for phase i studies are healthy individuals who have no signs or symptoms of the condition the drug is intended to treat, to provide a base of information about how an undiseased human body responds to the drug. Phase i clinical trials tend to have a short duration, often just weeks.
Phase II trials are randomized, controlled studies that involve larger groups of volunteers, who, for investigational anti-parkinson’s medications, have Parkinson’s disease. The goal in this phase is to demonstrate effectiveness in a small group and to confirm safety. The stage of disease might be narrowly defined or open, depending on the drug’s intended use. Researchers might want to test an investigational new drug’s effectiveness in early-onset Parkinson’s, for example, and so limit study enrollment to people with Parkinson’s who are younger than age 40. Phase ii clinical trials can last months to years, depending on the study’s design and the parameters researchers want to measure. Typically there are at least two groups of study participants, those who receive the investigational new drug and those who receive a standard treatment (or occasionally a placebo, an inert substance designed to look or taste like the investigational new drug). For the most objective results, studies are double-blinded—neither the researchers nor the participants know which participants are receiving the new drug and which are receiving standard treatment to prove the drug’s effectiveness for people with Parkinson’s as a whole.
Phase III trials expand the new drug’s use to a broad base of people with Parkinson’s disease, typically chosen from medical centers in different locations across the country to get a diverse selection of participants. Like phase ii trials, phase III trials are randomized and controlled, often are double-blinded, and last for several years. This is the final level of testing before the investigational new drug enters therapeutic use (if approved by the FDA), so researchers aim to account for as many variables as possible.
Phase IV studies continue to collect data after an investigational new drug receives FDA approval for marketing and use for the approved purposes. This data collection phase continues for as long as the drug is on the market.
All clinical research studies, pharmacological and nonpharmacological, follow strict guidelines and procedures to make them as safe as possible for participants. The FDA must approve and closely oversee all clinical pharmacology studies. Researchers must fully disclose all potential risks of participating in the study, and participants must sign a statement of informed consent verifying that they understand these risks and agreeing to comply with any conditions of the study. Generally research studies provide any necessary medical care related to the study during participation. some studies, especially phase i trials, pay volunteers for participation.
Because treatment options for Parkinson’s disease are less than ideal, many people with Parkinson’s are eager to participate in research studies that could result in more effective treatments. The advantage to participating in clinical pharmacology studies is that the drug being tested might provide greater relief from symptoms than do currently approved treatments. When the study ends, study participants have the knowledge to discuss with their doctors the value of continuing with the new drug. New anti-Parkinson’s medications that have caused significant improvements for many people with Parkinson’s include comt inhibitor medications and the nonergot dopamine agonist medications, drugs that received FDA approval in the 1990s.
Sometimes a clinical pharmacology trial examines a new use for a drug approved for other purposes, such as amantadine, which was originally approved as an antiviral agent. After amantadine had been in use for several years, doctors noticed that people with Parkinson’s who took the drug to prevent or shorten the course of an influenza infection also noticed significant improvement in their Parkinson’s symptoms while they were taking the amantadine. This observation opened a new avenue of research, and amantadine subsequently received formal approval for use as an anti-Parkinson’s medication. it is important to note that many drugs that have been approved for one use are commonly used off-label by physicians for other conditions; many drug firms are loathe to seek formal approval for off-label uses due to the time and expense it takes to gain formal FDA approval; doctors can already prescribe the medication off-label; and additional indications often don’t extend a firm’s exclusive rights to manufacture a drug.
