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To complete an online, anonymous survey to provide your feedback about the PediDOSE study and research that uses Exception from Informed Consent (EFIC), please click here.
What is the PediDOSE study?
The Pediatric Dose Optimization for Seizures in Emergency Medical Services (PediDOSE) study is an emergency medicine study designed to evaluate if a standardized method for paramedics to administer seizure medication leads to timely delivery of the right dose. The purpose of this study is to simplify how paramedics give medication to seizing children to stop the seizure and to decrease the number of children still seizing when they arrive at the emergency department. By replacing complicated dose calculations with age-based standardized dosing, we aim to increase the number of children who receive the right amount of seizure-stopping treatment before arriving at the hospital.
Seizures in Children
Seizures are one of the most common reasons people call an ambulance, or Emergency Medical Services (EMS), for a child. Seizures that do not stop on their own can be life-threatening. Paramedics have medications to treat seizures before the child gets to the hospital. Research shows that it is harder to stop a prolonged seizure, so it is important for paramedics to be able to give the medication quickly. EMS agencies have various methods of selecting the dose and various options for the delivery method for the medication they give to a seizing child. Delays can occur when paramedics have to calculate how much medication to give and/or how to give it. Unfortunately, one-third of children transported with an active seizure when at the emergency department.
How are seizures treated?
Most EMS agencies have access to benzodiazepine medications like midazolam. These medications are commonly used to treat seizures by paramedics and by doctors in the emergency department.
How will PediDOSE affect treatment for seizures?
The purpose of this study is to simplify how paramedics give medication to seizing children in order to stop the seizure and decrease the number of children still seizing when they arrive at the emergency department. Currently, paramedics calculate the dose for midazolam based on the estimated weight of the child. EMS agencies participating in the PediDOSE study will train paramedics to give midazolam using a simplified method based on the age of the child. By replacing complicated dose calculations with age-based standardized dosing, we aim to increase the number of children who receive the right amount of seizure-stopping treatment before arriving at the emergency department.
PediDOSE will take place in 20 urban locations across the country. Participating EMS agencies will receive training on the new standardized treatment method at different times during the four years of study enrollment. Children between the ages of 6 months to 13 years who are transported by a participating EMS agency for seizures will be enrolled in the study. Researchers will record information about whether or not the children enrolled in this study received medication and if their seizure stopped. Participating EMS angencies will be randomly assigned a timeline for adpoting the standardized treatment plan over the course of the four-year study. This will allow researchers to compare the new standardized treatment plan to current methods and allow for safe implementation of the new standardized protocol.
What are the risks of study participation?
Midazolam is the benzodiazepine medication that will be used in this study. This medication are standard care for treating seizures. Like all medications, midazolam has risks. In this study, we will determine if the risks increase or decrease when using the age-based standardized dosing. EMS providers will look specifically at how breathing is affected, since respiratory depression (decreased breathing rate) is a known risk of midazolam. The goal of this study is that more children may receive the right treatment to stop their seizures early.
Will the study affect any other part of a child’s treatment for seizures?
No, after arrival at the emergency department, all decisions about how to treat a child with seizures will be made by health professionals as they normally would for any child who has had a seizure.
What if I have questions or concerns about Exception from Informed Consent (EFIC)?
We encourage you to read the EFIC section below to learn more. You can provide your anonymous feedback about the PediDOSE study and the use of EFIC for emergency research by completing the survey mentioned below.
Exception from Informed Consent (EFIC)
Ethical standards require that researchers get permission before a person can be included in a study through a process called informed consent. However, a seizure is an emergency condition that must be treated immediately. There will not be enough time to locate and talk to the person’s parent, guardian or legal representative about the study. Patients enrolled in PediDOSE will be enrolled before permission can be given. This is called “Exception from Informed Consent” (EFIC). Parents or guardians of children enrolled in this study will be notified about enrollment as soon as possible after treating the seizure.
What is Exception From Informed Consent (EFIC)?
The U.S. Food and Drug Administration (FDA) is an agency of the federal government that oversees human research protection involving medicines. The FDA has created a set of special rules, called Exception from Informed Consent (EFIC), for clinical trials that apply to critically ill patients who require emergency treatment when obtaining consent in advance is not possible or may put the patient at risk for increased harm by delaying potentially lifesaving therapies. Under some circumstances, there may not be time to obtain consent in advance from every eligible patient and, in some cases, discussing a possible option to enroll in a study may itself cause dangerous delays in a person’s care. Nonetheless, many critically ill patients could benefit from enrollment into an appropriate clinical trial. Therefore, to ensure that clinical trials can be conducted for patients in emergency situations, the FDA established rules for EFIC that require special safeguards to ensure that most people would consider the study to be ethical and appropriate. These special rules allow research studies in certain emergency situations to be conducted without obtaining consent in advance.
EFIC can only be used when:
- The person’s life is at risk, AND
- The best treatment is not known, AND
- The study might help the person, AND
- It is not possible to get permission:
- From the person because of his or her medical condition NOR
- From the person’s guardian, because there is a very short amount of time required to treat the medical problem
Before researchers can start a study using EFIC, they must provide information about the study to the community and get their feedback. If you would like to fill out a short online survey to provide your thoughts about this study, please click here.
For Medical Professionals
When seizures are not stopped quickly, they can lead to neurologic morbidity, respiratory compromise and mortality. Timely delivery of the right dose of a benzodiazepine, using an ideal route, is essential to effectively and safely treat pediatric seizures in the prehospital setting.
Paramedics currently do multi-step calculations to determine the midazolam dose for children, which may contribute to under-dosing and delayed administration of midazolam. Due to these delays and under-dosing with conventional dosing, one third of patients arrive at the emergency department still seizing.
The PediDOSE study is a multi-center, stepped-wedge design trial to compare paramedic-administered conventional and standardized dosing of midazolam for pediatric seizures in the prehospital setting. Standardized dosing eliminates calculations and utilizes an age-based dose, potentially allowing paramedics to give the right dose in a timely manner. Participants will be enrolled at 20 locations across the country over a four-year study period. Data will be collected on children, ages 6 months to 13 years, who are transported for active seizures before and after implementation of the standardized protocol. The study is funded by the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH).
If eligible, patients who are insufficiently responsive to stimuli will have a rapid response electroencephalogram (RR-EEG) device applied to their scalp to assess the primary outcome of seizing upon emergency department arrival and monitor for seizure recurrence while in the emergency department. Because seizures require immediate treatment, we anticipate that in most cases it will not be possible to obtain informed consent from patients before they are enrolled. Therefore, eligible patients will be enrolled into this trial under the U.S. Food and Drug Administration’s exception from informed consent (EFIC) requirements for emergency research (21 CFR 50.24). These special rules allow research studies in certain emergency situations to be conducted without consent. EFIC can be used only when the person’s life is at risk, the best treatment is not known, the study might help the person, and it is not possible to obtain informed consent from the patient or a legally authorized representative.
The study will not change which medications will be used in the emergency department to treat seizures; it will only modify how seizures are managed by EMS prior to arrival. Apart from the RR-EEG monitoring, which the emergency department team can choose to consider or not consider in their decision-making, all hospital-based care will be standard and determined by the treatment team per routine.
We believe that this study may help paramedics optimally treat pediatric seizures in the future with a simple and timely method if we determine that standardized dosing is more effective and equally safe when compared to conventional dosing.