What is a Clinical Trial?
What is a Clinical Trial?
A clinical trial is defined by the National Institutes of Health as “a research study in which one or more humans are assigned in advance to one or more interventions to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.” Clinical trials can also be considered interventional studies, because they all contain an intervention.
In clinical trials, potential ways to treat, detect or even prevent a condition are tested. This might include investigating new drugs (ones that aren’t yet approved for use or were previously approved for other conditions), a new combination of drugs, or other new procedures/approaches to help improve a condition. Clinical trials can also evaluate other aspects of patient care, like techniques to improve symptoms or quality of life.
A well designed clinical trial is the gold-standard to prove that a treatment is safe and has an effect in improving how someone functions or is feeling.
Clinical Trials 101
This video introduces the key parts of participating in a clinical trial for Angelman syndrome. It explains common clinical trial terms and phases, then explores eligibility, enrollment, participation, and the caregiver experience. You will also learn about informed consent, participant rights, how study data and results are handled, and resources available to support families.
Standard Phases of Clinical Trials
Clinical trials are usually conducted in 4 phases.
Phases:
Phase 1
First in humans; goal is safety for a very small group of participants. Often Phase 1 studies use different dose levels of a drug to learn about the safety of these dose levels.
Phase 2
Goal is safety and does it work. A Phase 2 trial usually involves a larger number of patients (~50-300), depending on the size of the population.
Phase 3
Confirm earlier results, safety, and does it work. Sometimes called a pivotal study, Phase 3 studies might involve hundreds or even thousands of patients depending on the size of the population.
Phase 4
After FDA approval, to better understand long-term safety and benefits. Not all drugs require a Phase 4 trial.
Clinical Trials in Rare Disease
Depending on the known safety data of a drug or device or the size of the population who has the condition, some of these phases might be skipped or combined. Combined phase trials like Phase 1/2 and Phase 2/3 are fairly common in rare disease populations like Angelman syndrome
Phases:
Phase 1/2
First in humans; goal is safety for a very small group of participants
Phase 3
Pivotal study; goal is to confirm earlier results, safety and does it work for a larger group of participants
Phase 4
After FDA approval; goal is long-term safety and benefits
How Clinical Trials Work
A clinical trial is initiated by a “sponsor”, an organization/person who has authority and control over the study. Sponsors are generally the organization who funds a study and are often pharmaceutical companies involved in developing new drugs.
Sponsors are required to create a study plan, or a “protocol,” that details how a trial will be conducted.
Study protocols include:
Why the study is being done and the trial goal
Who can take part
Study design
Study treatment or procedures
Visit schedule
What researchers will measure
Safety plan and safety oversight
Privacy and data handling
How results will be analyzed
Regulatory Approval and Sponsor Responsibilities
The sponsor is responsible for ensuring the trial is conducted according to the study protocol and for seeking approvals to run the trial from regulatory agencies like the FDA (Food and Drug Administration) and ethics boards.
In the US, the sponsor generally must submit an Investigational New Drug (IND) application to the FDA before starting a trial. Outside of the US, the sponsor submits an application that is often known as a “clinical trial application.”
The regulatory agency (FDA in the US) is responsible for ensuring trials are designed to follow the laws, regulations and good clinical practice principles.
In addition to review by regulatory authorities, clinical trials must be reviewed and approved by an Ethics Committee or an “Institutional Review Board” (IRB). The ethics committee or IRB is responsible for protecting the rights and welfare of individuals in a clinical trial. One of the main responsibilities of the IRB is to review the informed consent form (ICF) to make sure it states:
- The research purpose(s) of the clinical trial
- Risks and possible benefits of participating in the trial
- Alternatives available outside of the trial
- What will happen during the trial
- How confidentiality of records will be maintained
- Who to contact with questions about the trial
- That participation in the study is voluntary and that the participant can withdraw at any time without penalty
Clinical trials typically happen at hospitals or clinics that are called “sites”. An “investigator” is typically a doctor in charge of the trial at the site. The investigator is responsible for conducting the trial, following what is set in the protocol, once all approvals are in place. The lead investigator at a site is called the principal investigator or PI. The investigator is also responsible for selecting patients for a trial per the specific criteria listed in the protocol, the inclusion and exclusion criteria. For a given clinical trial there can be one or many investigators and multiple clinical research sites enrolling patients.
How is FAST involved in clinical trials?
Accelerating or preparing for clinical trials is a key part of FAST’s approach to improving the future for all individuals living with Angelman syndrome. In FAST’s Roadmap to a Cure, this is also known as Pillar 5.
As part of that effort, FAST co-supports and leads the Angelman Syndrome Biomarkers and Outcome Measures Consortium (A-BOM), which is devoted to developing relevant and meaningful endpoints and biomarkers. For a clinical trial to show a potential treatment is effective, there must be a reliable way to measure the effect the potential treatment has on how patients feel or function, making endpoints a critical piece of clinical trials and developing a potential treatment.
FAST has also supported clinical trial infrastructure in other ways, including providing a five million dollar gift to establish the Rush Pediatric Neuroscience F.A.S.T. Center for Translational Research. This center is a dedicated environment for supporting families through clinical trials.
Another important piece of clinical trial readiness is education. FAST strongly supports clinical trial education for the AS community, to help families feel empowered to make decisions for their loved ones and to make sure AS clinicians are aware of ongoing trial opportunities. This includes webinars and sessions at Summit and other conferences, and a genetic counselor on staff to answer more specific questions. FAST also works with the researchers and companies who are developing potential treatments for AS, as a liaison to the community, ensuring that the needs and wants of AS families are considered when trials are developed.
FAST does not directly oversee any clinical trials and is not involved in choosing who can participate in a trial. In 2024, FAST announced the establishment of a drug development accelerator called AS²Bio Inc. AS²Bio was developed to help bring transformative therapeutics to those living with Angelman syndrome, by building a bridge from proof of concept studies in cells and animal models to first in human clinical trials.
Have questions about clinical trials for Angelman syndrome?
Want to talk more about clinical trials specifically for your loved one living with AS? Schedule an online or phone genetic counseling session with FAST’s Niki Armstrong. She can answer questions about genetic test results and trial eligibility, direct you to resources and trial sites for ongoing trials, and help you understand the overall clinical trial landscape in AS.
Interested in enrolling in a clinical trial?
Our new clinical trial tool can help you identify clinical trials that may be options for your loved one.
You can enter your loved one’s age, genotype, and location to see potential options for your family.
Clinical trials enroll at the site, which is typically a hospital or clinic, with the trial doctor (investigator) making decisions about who can participate based on the criteria in the protocol. You can connect directly with clinics or hospitals participating in the trial, or you can use the contact information listed in the clinical trial entry.
Choosing to participate in a clinical trial is a big decision, with many elements to weigh.
Potential benefits and risks
Consider possible improvements, side effects, and other uncertainties associated with the study intervention.
Time and travel commitment
Consider the trial’s length, number of visits, and distance to the study site.
What is known and unknown
Review the available information about the treatment, procedures, and possible outcomes.
Future care and treatment access
Ask how participation could affect future care options or access to treatments.
Talk to your loved one’s Angelman syndrome health care team about any clinical trials you are interested in. If your provider is unfamiliar with AS clinical trials, please contact FAST’s genetic counselor at genetic.counselor@cureangelman.org and she can connect you with clinics and providers who can answer your questions and support you as you consider a clinical trial.