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Clinical Trial or Clinical Study - Definition Any investigation in human subjects intended to discover or verify the clinical, pharmacokinetic (study of the processes of bodily absorption, distribution, metabolism, and excretion of compounds and medicines), and/or other pharmacodynamic (study of interactions between drugs and living structures) effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), with the object of ascertaining its safety and/or efficacy. The terms "clinical trial" and "clinical study" are synonymous.
Testing of Experimental Drugs in Humans Before a medication can be sold over the counter or with a prescription, it must undergo rigorous testing. The process by which new medications are tested so they can ultimately be marketed to treat various diseases is as follows: |
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1. Development of a Compound Chemists in a laboratory develop compounds with a certain chemical structure that the scientists believe may function in humans to alleviate certain symptoms in a disease, or perhaps even cure it. |
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2. Pre-clinical Testing To prove that the compound works as is hypothesized (assumed) and does not produce any negative side effects, it is first thoroughly tested in animals (i.e., mice, rats, dogs and monkeys). This stage of testing is commonly referred to as the "pre-clinical" stage. The purpose of these animal studies is to prove that the drug is not carcinogenic (causes cancer), mutagenic (causes mutations), or teratogenic (causes malformations), and to understand how the drug is absorbed and excreted. Once a pharmaceutical company proves that the compound appears to be safe, and possibly effective in animals, the company will provide this information to the Food and Drug Administration (FDA) requesting approval to begin testing the compound (experimental drug) in humans via an Investigational New Drug (IND) application. |
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3. Clinical Trials/Studies in Humans The clinical testing (investigation) of experimental drugs (previously unproven in humans, therefore "experimental") in humans is normally done in three phases (Phase I, II and III) with more and more people included in each subsequent phase. Before moving to the next phase of development the data are carefully analyzed to ensure the experimental drug is at least safe and well tolerated. After successful completion of Phase I-III testing, a company will submit the results of all of the studies to the FDA to obtain a New Drug Approval (NDA). Once the FDA grants a company with a NDA, the company can market the drug (medication) to the public. Additional testing (post-marketing or late phase III/phase IV) to look at the long-term safety continues. |
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Phase I studies are primarily concerned with the drug's safety, and are the first time the drug is tested in humans. These studies are typically done in a small number of healthy volunteers (20-100), usually in a hospital setting where they can be closely watched and treated should there be any side effects. These volunteers are usually paid for their participation and for the most part tend to be men (approximately 30 years of age on average). The purpose of these studies is to determine how the experimental drug is absorbed, metabolized, and excreted in humans. Additionally, they seek to determine what types of side effects occur as the dosage of the drug is increased. Any beneficial effects of the drug are also noted. The HSG is not involved in Phase I testing of experimental drugs. However, it is during Phase I testing that the HSG begins to collaborate with a pharmaceutical company to plan Phase II and III clinical trials in HD. |
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Once an experimental drug has been proven to be safe and well tolerated in healthy volunteers, it must be tested in the patients that have the disease or condition that the experimental drug is expected to improve/cure. In addition to ensuring that the experimental drug is safe and effective in the patient population of interest, Phase II studies are also designed to evaluate the effectiveness of the drug. The second phase of testing may last from several months to a few years and may involve up to several hundred patients. Most Phase II studies are well controlled, randomized trials. That is, one group of patients (subjects) receives the experimental drug, while a second "control" group receives a standard treatment or placebo. Placement of the subject into the drug treatment or placebo group is by random chance (as if by the flip of a coin). Often these studies are "double-blinded", that is, the patient nor the researchers (investigator, coordinator, etc.) know who is getting the experimental drug. Additionally, Phase II studies are often designed to determine the correct dosage, that is the dosage with the least number of side effects that is most effective. These are often referred to as dose-ranging studies. In general, the purpose of Phase II studies is to provide the pharmaceutical company and the FDA with comparative information about the relative safety of the experimental drug, the proper dosage needed to treat the condition, and the drug's effectiveness. Only about one-third of experimental drugs successfully complete both Phase I and Phase II testing. The HSG has been involved in the Phase II testing of a number of experimental drugs for HD.
In a Phase III study, an experimental drug is tested in several hundred to several thousand patients with the disease/condition of interest. Most Phase III studies continue to be randomized and blinded. The large-scale testing provides the pharmaceutical company as well as the FDA with a more thorough understanding of the drug's effectiveness, benefits/risks, and range/severity of possible adverse side effects. Phase III studies typically last several years. Seventy to 90 percent of drugs that enter Phase III studies successfully complete this phase of testing.
4. Marketing of New Drugs After successful completion of Phase I-III testing, a company submits the results of all of the studies to the FDA to obtain a New Drug Application (NDA). Once the FDA grants a company with a NDA, the company can market the drug (medication) to the public. Additional testing (post-marketing or late phase III/phase IV) to look at the long-term safety continues.
5. What about Natural Remedies? HD patients and families are often interested in natural treatments of Huntington's disease. It is important to understand that "natural" products may not be subjected to the kind of rigorous testing outlined above prior to marketing the product. Therefore scant data are available for the safety or effectiveness of these products specifically in HD. |
