Clinical Research Basics
How First-in-Human Cardiovascular Trials Are Conducted Safely
First-in-human (FIH) trials are an essential — and carefully governed — step in bringing new cardiovascular therapies to patients. They are also among the most demanding studies a research site can run.
What is a first-in-human trial?
A first-in-human (sometimes called first-in-man or FIH) study is the first time a new investigational therapy is administered to human participants. For drugs and biologics this is typically a Phase 1 study; for devices it is often the first clinical evaluation following bench and preclinical animal testing.
What happens before a first-in-human trial?
- Extensive preclinical pharmacology and toxicology studies
- Investigational New Drug (IND) submission to the FDA for drugs/biologics, or an Investigational Device Exemption (IDE) for devices
- FDA review of the proposed protocol, manufacturing, and safety data
- Institutional Review Board (IRB) review of the protocol, consent form, and site qualifications
- Site qualification visits by the sponsor and CRO
What safety measures are built into FIH trials?
- Cautious dose-escalation schemes (often single-ascending then multiple-ascending dose)
- Intensive in-clinic monitoring during and after dosing
- Pre-specified pause and stopping rules tied to safety signals
- Independent Data Safety Monitoring Boards (DSMBs) for many studies
- Continuous adverse event reporting to the sponsor, IRB, and FDA
How are FIH sites selected?
Sponsors select sites based on Principal Investigator experience, prior FIH performance, infrastructure, regulatory track record, and the ability to enroll the right patient population safely. FIH cardiovascular trials require advanced cardiac imaging, on-site procedural capability, and a research staff trained in high-acuity protocols.
Why does FIH experience matter to patients?
FIH trials offer access to novel therapies for serious cardiovascular conditions long before they would otherwise be available. The combination of an experienced site, a thoughtful protocol, and intensive oversight is what makes that access responsible.
References
Frequently asked questions
What does first-in-human (FIH) mean?
FIH refers to the first time an investigational therapy is studied in human participants, after extensive preclinical work and FDA/IRB review.
Are first-in-human trials safe?
FIH trials use cautious dosing, intensive monitoring, and pre-specified stopping rules. Risks vary by therapy and are described in the informed consent document. They are reviewed by the FDA and an IRB before any participant is enrolled.
Who can participate in a first-in-human trial?
Eligibility depends entirely on the protocol. Many cardiovascular FIH trials enroll patients with serious or treatment-resistant conditions who meet specific clinical and safety criteria.
How are first-in-human sites chosen?
Sponsors select sites based on Principal Investigator experience, infrastructure, regulatory record, and the ability to enroll and monitor patients safely.
Where are FIH trials conducted?
At specialized clinical research sites with the right infrastructure. Amavita Research conducts FIH cardiovascular trials at its affiliated ambulatory surgery center in Miami.
What is the difference between FIH and Phase 1?
For drugs, the first Phase 1 study is typically also the FIH study. For devices, the FIH study is the first clinical use after bench and animal testing, and may not be labeled with a phase number.