Risk/Benefit Public Announcement

PUBLIC DISCLOSURE OF AN EXCEPTION TO THE REQUIREMENTS FOR INFORMED CONSENT UNDER EMERGENCY CIRCUMSTANCES FOR AN ANTI-SEIZURE RESEARCH STUDY IN MILWAUKEE COUNTY.

This announcement serves as public disclosure of an anti-seizure medication research study that will begin June 2010 by The Medical College of Wisconsin and will be performed in Milwaukee County, using the Food and Drug Administration’s (FDA) set of regulations allowing exception to informed consent under emergency circumstances. Exception to informed consent allows patients to be entered in the study without prior consent in an emergency. The study will include all adult victims determined by paramedics from the Milwaukee County Emergency Medical Services (EMS) system to be suffering from a severe or prolonged seizure. Prolonged seizure activity from any cause is a dangerous medical emergency which can result in injury or death if not stopped quickly. It has been estimated that there are between 120,000 and 200,000 cases of prolonged seizures in this country each year resulting in as many as 55,000 deaths. Seizures lasting 5 minutes or more may be defined as prolonged seizures and can produce neurological damage.

The current standard of care is to receive the anti-seizure medicine through the vein in an IV. An IV, however, may be difficult to establish in a patient who is shaking because of a seizure and may delay treatment as a result. Paramedics do not usually treat seizures with a shot in the muscle. This study, then, will evaluate two different anti-seizure medications currently used for prolonged seizures: one which is given as a shot in the muscle, the other given directly in the vein through an IV. The anti-seizure medicine for the shot is different than the anti-seizure medicine given by IV, but, both drugs have been previously shown to successfully treat prolonged seizures. It is unknown which of these two treatments stops seizures the fastest or results in the best outcome for the patient. Patients will receive both methods, a shot in the muscle and an IV, however, only one of the methods will be the actual anti-seizure medicine and the other will be a placebo. Patients will be randomized (similar to flipping a coin) with a 50:50 chance of receiving either of the anti-seizure medicines as a shot in the muscle or through the IV. After receiving the initial anti-seizure medicine, standard treatment will be given for the remainder of paramedic care.

All research contains risks. One of the risks is drowsiness or slowed breathing while being treated. This might result in a need for paramedics to support breathing by placing a tube in the lungs. Other risks are: pain, discomfort, bruising, or infection at the site of the anti-seizure shot: pain, discomfort, bruising, inflammation, or leaking of the medication into the surrounding tissue at the IV insertion site: allergic reaction (including anaphylaxis, a severe allergic reaction which can result in decreased blood pressure, airway swelling or death) to either of the two anti-seizure medications. A severe allergic reaction can occur with standard treatment or with the study medications. The risk of a severe allergic reaction in the study is not expected to be greater than standard treatment, but this will be closely monitored. Severe or prolonged seizures can result in repeat seizures despite treatment or death. The risk of repeat seizures or death is not expected to be different from standard treatment. However, these risks will be closely monitored on an ongoing basis and the study stopped if it is determined that one or the other method or medication results in higher repeat seizures, lower survival or other patient safety concerns. There may also be some unknown or unanticipated risks because of the method or medication used in this study is an attempt to advance medical knowledge. Every precaution will be taken to assure personal safety.

It is unknown which of these two treatments is better. The time it takes to stop the seizure and the outcome of patients will be closely monitored. The results of the study will help determine the treatment that results in the fastest end and the best outcome for patients with prolonged seizures in the ambulance.

The information that is obtained from this study may be useful scientifically and possibly helpful to others. The benefit that may reasonably be expected from participating in this study is shortening the time to stop a prolonged seizure and an improved outcome, but these potential benefits are not guaranteed. There are no financial risks or benefits for study participation. For this study, there are no appropriate alternative procedures that are known to be advantageous during severe or prolonged seizures. All information obtained from this study that can be identified to an individual person will remain absolutely confidential. The scientific or medical information not identifiable with a patient resulting from the study will be presented at meetings and published so that the information can be useful to others.

Usually persons in a study must be given an explanation of it and agree beforehand to participate in it. This is called “informed consent”. It is not possible to obtain informed consent from patients with prolonged seizures. They are unconscious and will suffer nerve damage or die if not treated as quickly as possible. Their families may also not be available to speak for them, and there isn’t time to describe this study before emergency treatment must be started. Under these emergency conditions, the United States Food and Drug Administration (FDA) allows studies like this to be done without first getting informed consent where there is reasonable scientific evidence to suggest a possible benefit from a new intervention. Therefore, this study will be performed under these federal regulations (21 CFR 50.24) where obtaining informed consent is not possible.

FDA regulations require public disclosure to inform the community that a research project will be done that may impact members of the local population. This disclosure must be made prior to the initiation of the study, which will begin June 2010, and continue for approximately three years. Public disclosure will also occur after the study is completed.

Interested parties with questions or concerns or information on obtaining opt-out bracelets are encouraged to contact the principal investigator, Dr. Tom P. Aufderheide, either by phone (414-805-0345), mail (Department of Emergency Medicine, 9200 W. Wisconsin Ave., Froedtert Hospital East, Pavilion 1P, Milwaukee, Wisconsin 53226 or email (taufderh@mcw.edu), or visit the WEB site at (www.mcw.edu/rampart). Feedback from the community may be used to further modify the design of the study.