Clinical Trials

Clinical research takes place in steps; each step has a different focus. 

• Phase 0 (zero): Phase 0 trials are designed to weed out treatments that are not promising before they go on to further steps. These trials are small, typically less than 10 people, and usually focus on how a drug acts in the body and how the body reacts to it. 
• Phase I: This is usually the first step of testing in people and in healthy volunteers. Usually, a limited number of people are needed for this type of study, typically 20 to 80 people. At this point researchers are trying to answer: 
  • How much of the treatment to give? 
  • When should it be given and how often? 
  • What is the highest dose that can be given safely? 
  • How does the body react to the treatment? 
  • Are there any harmful side effects?   
• Phase II: The goal of this step is to find out whether a new approach works as intended. For example, does this drug stop seizures? Researchers also monitor people for common, short-term side effects with the therapy. Some things aren’t yet known about the treatment so risks are still present. Several hundred people at many different centers may participate in a Phase II study. 
• Phase III: If a treatment looks promising in the first two phases, it can move on to Phase III. Participants are randomly assigned to either an experimental treatment, standard treatment, or a placebo (inactive drug). Neither the patient nor the doctor can choose which treatment is received. Randomization helps to avoid bias in the study and improves the chance that the results are correct. 
  • Phase III trials provide more information about the safety of an experimental treatment and whether the standard or the experimental treatment works better and has fewer side effects. These trials usually include several hundred to several thousand people. Large trials make it easier to estimate what would happen if the experimental treatment were available to everyone with a condition. 
  • If a treatment performs well in a Phase III trial, the researchers may submit an application to the Food and Drug Administration (FDA), asking permission to make it available to the public. The FDA approval process generally takes about a year. The process is quicker for priority drugs, drugs that provide a significant advance in treatment for a life-threatening condition. The FDA tries to rule on these within six months. In other cases, it can take a few years in order to hear the final ruling. 
• Phase IV: Research may also continue even after the FDA has approved a treatment. This research, sometimes called post-marketing research, tracks side effects in people receiving the newly approved treatment. Phase IV studies aren’t required for every treatment, but the FDA can ask a manufacturer to perform a Phase IV trial to collect information on long-term safety and effectiveness. 
  • This has been done for some epilepsy drugs (i.e., Felbamate) when safety concerns were found after the drug was approved. 
  • Companies may also choose to do Phase IV research to compare their product with a competitor. 
  • Studies may also be done in new populations or seizure types that were not tested in the initial trials. Several hundred to several thousand people may take part in a Phase IV study.