Why First-In-Human studies belong in a hospital
First-in-Human (FiH) studies involve administering a new investigational medicine to humans for the first time. Experienced teams, careful monitoring and immediate access to hospital services help manage uncertainty and support informed dosing decisions.
What does this mean in practice? We spoke with our experts at Astrum’s Porto clinic about why the hospital setting matters, how teams prepare for the unexpected and what sponsors should look for in a FiH partner. Non-clinical evidence informs the study design, but cannot fully predict how a medicine will behave in humans. The clinical setting must therefore support both planned assessments and a rapid response to unexpected findings.
Safety starts before the first dose
Preparation begins long before the first dose, with the development of the study protocol.
Reviewing the investigator’s brochure and non-clinical evidence helps the team understand the medicine’s mechanism of action and potential risks. This informs the starting dose, monitoring, risk-mitigation measures, stopping rules and criteria for dose escalation.
FiH experience must be paired with practical medical expertise to interpret emerging findings and respond appropriately to unexpected situations. At Astrum, clinical pharmacology expertise and real-world clinical experience are supported by early coordination with relevant hospital teams.
Hospital access and integration matter
A hospital-integrated Phase I unit provides direct access to emergency teams, diagnostic exams, several medical specialists, intensive care and treatment facilities. This is particularly important during initial dosing and dose escalation, when human safety and tolerability data are first emerging.
Having hospital support in the same building puts the people, equipment and expertise the study team may need within easy reach.
Location alone is not enough. The unit and hospital must work as a coordinated team, with agreed emergency pathways and a shared understanding of the study schedule, expected risks and participant numbers before dosing begins.
In the Porto Phase I Unit, Astrum prepares studies in collaboration with the hospital. Teams perform emergency drills at least annually, with additional study-specific training where needed.
Sentinel dosing supports controlled progression
FiH protocols commonly use sentinel dosing: a small number of participants receive the medicine before the rest of the cohort. They are monitored for a protocol-defined period using clinical observations, laboratory tests, electrocardiograms or other targeted assessments, depending on the medicine.
The remaining participants are dosed only after the sentinel safety and tolerability data have been reviewed and no safety concerns preventing progression have been identified. This approach, together with intensive monitoring and predefined stopping rules, limits initial exposure and supports evidence-based decisions.
Expertise must translate into delivery
Early-phase protocols may require specialised pharmacodynamic assessments, cardiac monitoring or complex pharmacy preparation. Sponsors need a partner that can introduce and validate study-specific procedures, not just deliver its existing capabilities.
In one anonymised study, Astrum introduced central nervous system assessments requiring new equipment and procedures. During protocol preparation, the team sourced and validated the equipment, developed procedures and trained staff, ensuring the required assessments could be performed at the scheduled time points. This meant building the study-specific capabilities from the ground up, from writing procedures to training personnel.
Other studies have included cardiac assessments, such as Holter monitoring and ambulatory blood pressure monitoring, as well as tailored pharmacy processes for injectable products and weight-based dosing.
Why early involvement matters
Involving the clinical team during non-clinical development helps translate emerging evidence into the design of the first clinical study. It gives the FiH partner time to understand the molecule, resolve practical questions and prepare study-specific capabilities before execution.
Early collaboration also builds the open communication needed to discuss new information and adapt study delivery as the protocol evolves or new participant observations emerge.
Choosing the right First-in-Human partner
Look beyond beds and equipment. When assessing a FiH partner, ask:
1. Is the unit hospital-integrated, with rapid access to emergency care, intensive care, diagnostics and specialists?
2. Does the Principal Investigator have both clinical and research experience, particularly in FiH studies?
3. Are hospital teams prepared before dosing, and are emergency pathways tested?
4. Can the unit introduce and validate study-specific assessments?
5. Can the team provide flexible support from early planning through study delivery, with open and scientifically informed communication?
No setting removes every uncertainty from a FiH study
The aim is to anticipate risks, monitor participants closely and respond effectively to new information. Astrum’s hospital-integrated Phase I model combines experienced early-phase teams, direct access to hospital expertise and study-specific capabilities to support safe, scientifically informed study delivery.
Planning a First-in-Human program?
Speak with Astrum about building a scientifically robust and operationally practical path into the clinic.