Clinical Trials in Children with Intractable Epilepsy

Clinical trials are conducted to allow safety and efficacy data to be collected for health interventions (e.g., drugs, diagnostics, devices, therapy protocols). These trials can take place only after satisfactory information has been gathered on the quality of the non-clinical safety, and Health Authority/Ethics Committee approval is granted in the country where the trial is taking place.

Some examples of what a clinical trial may be designed to do:

  • Assess the safety and effectiveness of a new medication or device on a specific kind of patient (e.g., patients who have been diagnosed with intractable epilepsy)
  • Assess the safety and effectiveness of a different dose of a medication than is commonly used (e.g., 10 mg dose instead of 5 mg dose)
  • Assess the safety and effectiveness of an already marketed medication or device for a new indication, i.e. a disease for which the drug is not specifically approved
  • Assess whether the new medication or device is more effective for the patient’s condition than the already used, standard medication or device (“the gold standard” or “standard therapy”)
  • Compare the effectiveness in patients with a specific disease of two or more already approved or common interventions for that disease (e.g., Device A vs. Device B, Therapy A vs. Therapy


Participating in a clinical trial

Phase 0 and Phase I drug trials seek healthy volunteers. Most other clinical trials seek patients who have a specific disease or medical condition.

Locating trials

ICE Alliance will keep updated list of clinical trials under “Research” that are recruiting children based on the website and submission of clinical trial information by investigators.  You may also browse the website to find clinical trials.   However, many clinical trials will not accept participants who contact them directly to volunteer as it is believed this may bias the characteristics of the population being studied. Such trials typically recruit via networks of medical professionals who ask their individual patients to consider enrollment.  Speak to your child’s neurologist if a clinical trial is of  interest, he or she may be able to refer you.  Self referral is welcomed in many cases where a child has a rare disease. 


Clinical trials involving new drugs are commonly classified into four phases. Each phase of the drug approval process is treated as a separate clinical trial. The drug-development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV are ‘post-approval’ studies.

Pre-clinical studies

Pre-clinical studies involve test tube and animal or cell culture experiments using wide-ranging doses of the study drug to obtain preliminary efficacy, toxicity and pharmacokinetic information. Such tests assist pharmaceutical companies to decide whether a drug candidate has scientific merit for further development as an investigational new drug.

Phase 0

Phase 0 is a recent designation for exploratory, first-in-human trials conducted in accordance with the United States Food and Drug Administration’s (FDA) 2006 Guidance on Exploratory Investigational New Drug (IND) Studies. Phase 0 trials are also known as human microdosing studies and are designed to speed up the development of promising drugs or imaging agents by establishing very early on whether the drug or agent behaves in human subjects as was expected from preclinical studies.

Phase I

Phase I trials are the first stage of testing in human subjects. Normally, a small (20-100) group of healthy volunteers will be selected. This phase includes trials designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. Phase I trials also normally include dose-ranging, also called dose escalation, studies so that the appropriate dose for therapeutic use can be found. The tested range of doses will usually be a fraction of the dose that causes harm in animal testing. Phase I trials most often include healthy volunteers. However, there are some circumstances when real patients are used, such as patients who have terminal cancer or HIV and lack other treatment options.

Phase II

Once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger groups (20-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients. When the development process for a new drug fails, this usually occurs during Phase II trials when the drug is discovered not to work as planned, or to have toxic effects.

Phase II studies are sometimes divided into Phase IIA and Phase IIB.

  • Phase IIA is specifically designed to assess dosing requirements (how much drug should be given).
  • Phase IIB is specifically designed to study efficacy (how well the drug works at the prescribed dose(s)).

Phase III

Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current ‘gold standard’ treatmentIt is common practice that certain Phase III trials will continue while the regulatory submission is pending at the appropriate regulatory agency. This allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase. Other reasons for performing trials at this stage include attempts by the sponsor at “label expansion” (to show the drug works for additional types of patients/diseases beyond the original use for which the drug was approved for marketing), to obtain additional safety data, or to support marketing claims for the drug. Studies in this phase are by some companies categorized as “Phase IIIB studies.

While not required in all cases, it is typically expected that there be at least two successful Phase III trials, demonstrating a drug’s safety and efficacy, in order to obtain approval from the appropriate regulatory agencies such as FDA (USA), or the EMA (European Union), for example.

Phase IV

Phase IV trial is also known as Post Marketing Surveillance Trial. Phase IV trials involve the safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives permission to be sold.


Clinical trials are closely supervised by appropriate regulatory authorities. All studies that involve a medical or therapeutic intervention on patients must be approved by a supervising ethics committee before permission is granted to run the trial. In the U.S., this body is called the Institutional Review Board (IRB).

To be ethical, researchers must obtain the full and informed consent of participating human subjects. (One of the IRB’s main functions is ensuring that potential patients are adequately informed about the clinical trial.) If the patient is unable to consent for him/herself, researchers can seek consent from the patient’s legally authorized representative.