WHAT IS THE EPILEPSY CONSORTIUM?

The Epilepsy Consortium is a collaboration between a number of academic medical centers and non-profit foundations devoted to development of new therapies for people suffering with epilepsy. Our aim is to identify the most effective and safest treatments, and bring them to patients as rapidly as possible.

As a result of continued research efforts, many exciting potential treatments are emerging that could represent a significant advance in epilepsy treatment. But, there is a long path between identification of a potentially useful drug, and availability of this drug to people who need it. The drug must first be demonstrated to be safe and effective. Also, studies must be done to determine which populations will benefit from treatment with the new therapy. This information is determined during clinical trials. The Epilepsy Study Consortium was created to try to ensure that the best therapies are developed, as quickly as possible. At the same time, it is our mission to make sure that clinical trials are performed in the safest way possible.

WHAT IS A CLINICAL TRIAL?

Clinical trials are carefully planned studies that will help determine important information about a new therapy. In a clinical trial, a new therapy will be used at predetermined doses, for a specific period of time, and the outcome of the therapy (usually seizure frequency and severity, and frequency of side effects) will be carefully measured. Clinical trials provide the information that will be needed for the FDA to make a decision whether the drug should be approved for use. Also, all the information that is included in the package insert will be determined from clinical trials and clinical research.

HOW IS A NEW THERAPY DISCOVERED?

Drugs are discovered in several ways. Often, new compounds will be synthesized based on an understanding about the basic mechanisms of epilepsy. At other times, a compound will be discovered based on its effect on animal models of seizures and epilepsy. The National Institutes of Health (NIH) has an active program, through which many compounds are screened for potential as epilepsy drugs. This program has contributed to the discovery of many important anti-epileptic drugs in the last two decades, including felbamate, topiramate, lamotrigine, levetiracetam, and others.

Once a new compound is identified, it must undergo a rigorous evaluation, including acute and chronic exposure in various animal species. It must be tested for its potential to produce life-threatening side effects, birth defects or mutations, or to cause cancer. Studies will be done to identify the types of seizures for which the drug may be effective, and to determine how the drug is handled by the body (metabolism). This testing is overseen by the Food and Drug Association (FDA). Only drugs that pass these studies will be tested in humans.

WHAT KIND OF CLINICAL STUDIES ARE THERE?

Phase I testing is the first exposure in man. Usually, these studies are done in normal volunteers. At first, single doses will be given. If no problems are identified, the subjects will be given multiple doses. Phase I testing will identify common side effects, and also how the drug is handled by the body, including how often the drug might need to be taken, and how high a dose might be tolerated. Usually, about 100 volunteers will be exposed during phase I testing.

Phase II testing is the first time that the drug will be given to epilepsy patients. At this stage, it will be possible for the first time to determine how effective the drug might be in controlling seizures. Since this is an early stage of testing, physicians will watch closely for improvement, or for any problems that might develop. Even though at this point there will not be definite proof that the drug will work, investigators will already have a good idea of its promise, based on animal studies.

Phase III testing will confirm that a drug is safe and effective. At this point, phase II studies will already have been completed, and some information will be available on how promising the drug looks, and what side effects might be expected.

Phase IV testing occurs after the drug is already FDA approved. This testing might be done to explore new uses for the drug, or to expose a larger population.

WHY SHOULD I OR A LOVED ONE PARTICIPATE IN A CLINICAL TRIAL?

Many people participate in a clinical trial because they want access to the newest therapies. Often, by participating in a clinical trial, a patient can obtain a new therapy up to 4 years before it will be available by prescription. This is particularly important for patients whose seizures have been difficult to control with currently available treatments.

Other people participate because they understand that new therapies will not be possible if people don’t enroll in trials. This is one way of contributing to the benefit of all patients with epilepsy and seizures.

HOW CAN I HELP THE EFFORTS OF THE CONSORTIUM TO DEVELOPE NEW THERAPIES FOR EPILEPSY:

WHAT ARE SOME COMMON TERMS USED IN CLINICAL TRIALS?

Randomization and control
In a randomized trial, subjects are assigned to one of several possible therapies by chance. Randomization ensures that the outcome of the study has not been affected by bias. Each therapy option is called an arm of the study. Studies can have two to five arms. Sometimes the arms can consist of different doses of a single drug. In some trials arms can contain different drugs. Often, patients in one arm will have no change in treatment. These patients will act as the control, against which the other arms will be compared. A control is needed, because seizure frequency might change over time by chance, and it is important to be certain that any change is truly due to effect of the drug.

Blinding
Sometimes, people will react differently if they know what treatment they are receiving. To prevent this, studies are often blinded, so that the subjects are not aware of which arm they have been randomized to. In a single-blind study, the doctor will know which arm the patient is on, but the subject will not. In a double-blind study, neither the doctor nor the subject will know. In any blinded trial, if an emergency occurs, the investigator will always be able to break the blind.

Placebo
Often, if patients who receive a drug are going to be compared to patients who are not receiving the drug, those not receiving drug will get a sugar pill, or placebo. This is done to maintain the blind, so patients will not know which arm they have been randomized to. Although the idea of being randomized to a placebo is concerning to many, it should not be. Surprisingly, in almost every trial, patients in the placebo arm show some improvement. Also, most of the time, after the trial is over, every patient, even those randomized to the placebo group, will receive drug if they want it.