To continue our effort in unpacking the heavily scientific, and sometimes daunting, jargon that is used throughout the Angelman syndrome community, this week we will clarify terms often used in clinical trials.
First and foremost, what is a clinical trial? A clinical trial is a study that tests an intervention such as a drug or surgical device/procedure in a disorder to determine its safety and efficacy (how well it works for the intended purpose) in humans. Clinical trials typically consist of three parts: 1. Phase 1 designed to test safety, 2. Phase 2 designed to evaluate both safety and efficacy, 3. Phase 3 designed to confirm safety and efficacy in a large group of people. Less commonly, there is a 4th part or “Phase 4” that happens after an intervention is approved for use by patients and involves potential follow-up studies to understand more about how the drug works in other groups not included in the initial studies or to answer other questions (for example, can you dose the drug less often and still get good results). Typically, in the rare disorder space, there is often overlap between each phase because there are less patients to enroll in trials and sometimes an opportunity to shorten the overall development timeline because the need for therapies is so great.
Clinical studies can be either interventional or observational. Interventional clinical trials are studies that evaluate the safety and efficacy of a therapeutic for a disorder. We can remind ourselves of this by looking at the name “interventional” and think – to intervene with disorder progress. Observational studies are research projects that evaluate characteristics and disorder progression over time but do not include the use of an intervention. Similarly, we can remember this by looking at the term “observational” and think – to observe a disorder.
In clinical trials, groups of individuals that are tested and evaluated for the duration of that trial are called treatment groups. These groups can be made up of individuals who are receiving the therapeutic and a control group, or comparison group to measure the effect of the therapeutic. A placebo group is a type of control group made up of the individuals who do not receive the therapeutic but instead receive an inactive medicine (for example maybe a sugar pill) that is meant to look like the treatment. Often times studies are “blinded” and this means you do not know if the participant has been assigned to the treatment group or the control group.
If a clinical trial is recruiting for either treatment or control groups, it will be listed as recruiting at clinicaltrials.gov.
To understand if an investigational therapeutic is effective at addressing characteristics of a disorder, appropriate measures of important symptoms of a disorder must be used or even developed to evaluate change before and after the intervention. For example, in clinical trials of people with seizure disorders, a diary is commonly used to count how many and which type of seizures an individual had before and after they took a treatment. This help to understand if they had less seizures when they used the investigational treatment than they typically had before. Last week we discussed outcome measures, or tests used to determine if a therapeutic had some sort of effect in an individual. Often, these outcome measures are listed as endpoints in a clinical trial, where investigators predict the expected change in these outcomes at the end of the study. Endpoints can also include biomarkers, a type of measure of processes within the body like a blood test or an EEG. Advances in biomarker identification in AS are ongoing and could potentially include measures such as elevated delta power in EEG recordings, EEG-related sleep information, UBE3A in cerebrospinal fluid levels, etc.
These are some of the most frequent terms associated with clinical trials and if you would a more in-depth explanation please watch the linked talk “Clinical Trial Basics: What Parents Need to Know About Trial Participation” given by Jennifer Panagoulias at the 2022 Science Summit and Gala.