Phase 1 trials: dosing, vital signs and lab test monitoring

What is a phase 1 trial and what does it aim to find out?

A phase 1 trial is usually the first study of a new medicine in people. Its main aims are to find out how much of the drug is safe to give, what side effects occur, and what happens to the drug in the body, and because none of this is yet known with certainty in humans, every step of dosing and monitoring is designed with caution as the guiding principle. These trials typically involve a small number of participants, often around 20 to 50 people, and this deliberately limited size is itself a safety feature, since it keeps the number of people exposed to an unfamiliar substance as low as possible while still generating enough data to make sound decisions about the next dose^[1].

Phase 1 trials are commonly structured as dose escalation studies: the first few participants receive a very small dose. If no safety concerns arise, the next group receives a slightly higher dose. This continues, group by group, until researchers identify the dose to take forward, with each step depending entirely on the result of the one before it rather than on a fixed schedule decided in advance. Participants are recruited slowly, so even though the total number of people is small, a phase 1 trial can take a long time to complete, and this slow pace is not a sign of inefficiency but a direct consequence of waiting for each group's safety data to be fully reviewed before anyone in the next group is exposed to a new dose^[1].

In cancer research, phase 1 trials are often open to people with advanced disease who have already had all other available treatments. The trial may enrol people with different types of cancer rather than just one, since the initial focus is on how the body handles the drug and what doses are tolerable, questions that do not always require participants to share the same diagnosis. Some people taking part may benefit directly, but the main value of the trial is usually to inform future treatment options for other patients, which is an important point for anyone weighing up whether to join a study of this kind^[1].

How many people take part, and how does this compare with other phases?

The number of participants and the aims of each phase differ, which affects how monitoring is organised, since a trial designed to establish a safe dose in a handful of people naturally requires a much more intensive schedule of checks per person than a later trial comparing outcomes across hundreds or thousands of participants^[1].

Phase	Typical number of participants	Main aim	Usually randomised?
Phase 0	About 10 to 20 people	Testing a very low dose to check it is not harmful, before therapeutic testing begins	No
Phase 1	About 20 to 50 people	Finding the best dose, identifying side effects, seeing what happens to the drug in the body	No
Phase 2	Tens of people, sometimes over 100	Confirming the dose, learning more about side effects, looking at how well the treatment works	Sometimes
Phase 3	Hundreds to thousands	Comparing the new treatment with standard treatment or placebo	Usually
Phase 4	Medium to large, variable	Long-term benefits and side effects after approval	No

Data adapted from Cancer Research UK's overview of trial phases^[1].

How is the starting dose chosen?

Regulatory guidance requires the starting dose in a first-in-human trial to be set using both non-clinical safety pharmacology and toxicology data, with separate considerations depending on whether participants are healthy volunteers or patients, reflecting the fact that a dose judged tolerable in a healthy person may carry different risks or benefits in someone who is already unwell. This starting dose is deliberately conservative and well below the dose expected to produce a therapeutic effect, so that any unexpected reaction happens at the lowest possible exposure. This conservative margin is intentional: it is meant to leave a wide safety buffer between the dose actually tested first and the dose predicted, from animal data, to cause harm, and the size of that buffer is itself a subject of careful scientific judgement rather than a simple arithmetic calculation^[2].

An example from a real study protocol: a first-in-human trial of an oral drug for dystonia set the starting dose at 1 mg, in a design where 48 participants were divided into 6 dose groups of 8 people each, illustrating how even a modest total number of participants can be spread across several distinct dose levels. Within each group, 6 participants received the study drug and 2 received placebo, and the whole trial was double-blind, meaning neither participants nor clinical staff knew who received which treatment on the day of dosing, a design chosen precisely because it prevents expectation from influencing how symptoms are reported or interpreted^[3].

What is dose escalation, and how does the decision to raise the dose work?

Dose escalation is the process of giving progressively higher doses to successive small groups of participants, moving to the next, higher dose only once the previous dose has been reviewed and judged safe, so that the dose actually given at any point in the trial reflects everything learned from every group that came before it^[1]. Dose increases are not automatic. In the dystonia trial example, each subsequent group's dose was decided at a dedicated dose escalation meeting, after reviewing the safety data collected from the previous group. Doses could be reduced rather than increased if this was considered necessary, which shows that the process is designed to move in either direction depending on what the accumulating data actually show^[3].

In another first-in-human study of a bispecific antibody for a blood cancer, the first part of the trial was specifically dedicated to dose escalation, in order to establish an effective dose and schedule before moving into a second part where more participants received that dose, a two-part structure that separates the question of "what dose is safe and active" from the question of "how well does that dose perform in a larger group."^[4] A study combining a drug with focused ultrasound for a brain tumour tested defined combinations of drug dose (10 mg/kg and 20 mg/kg) and energy dose (200J, 400J and 800J) during its dose escalation phase, to determine the combination to carry forward, demonstrating that in some trials it is not a single variable but a pair of interacting variables that must be escalated and reviewed together^[5].

Single ascending dose versus multiple ascending dose studies

Some phase 1 studies test a single dose per participant, with different groups receiving different single doses; this design is called a single ascending dose study, and it is often chosen as the first step before any repeated dosing is attempted^[3]. An asthma study of an injectable antibody used exactly this design, with participants divided into 5 groups, each receiving a different single subcutaneous dose or placebo, allowing researchers to build up a picture of the dose-response relationship one step at a time^[6]. Regulatory guidance also addresses the separate step of moving from single-dose to multiple-dose (repeated) administration, since repeated dosing can reveal accumulation or delayed effects that a single dose would not show, and this transition is treated as its own decision point requiring fresh safety review rather than a simple continuation of the single-dose schedule^[2].

What is sentinel dosing, and why are the first participants treated differently?

Sentinel dosing means that within a dose group, one or two participants are dosed first and observed for a defined period before the remaining participants in that group receive the study drug, effectively creating a smaller safety check inside every dose group rather than relying only on comparisons between whole groups. In the dystonia trial, each group of 8 was split into cohorts of 2, 3 and 3 participants, dosed on different days, with at least 48 hours between cohorts to allow dosages to be confirmed as safe and well tolerated before the next cohort proceeded, a staggering that in practice slows down recruitment considerably in exchange for an added layer of protection^[3].

In the asthma antibody study, one placebo participant and one active-drug participant in each group were dosed before the rest of that group, and the remaining participants could only be dosed once no safety issues had been identified after 72 hours, showing that the length of the observation window before proceeding can itself vary considerably between different trials and different drugs. This staggered approach means that if an unexpected reaction occurs, it affects the smallest possible number of people before dosing is paused, which is precisely the point of building sentinel cohorts into the design in the first place^[6].

What vital signs and physical checks are monitored during a phase 1 trial?

Participants in a phase 1 trial can expect to have regular observations recorded, including blood pressure and pulse, alongside careful recording of any side effects and when they occur, since the exact timing of a symptom relative to dosing is often as important to researchers as the symptom itself. Participants often spend more time in hospital during a phase 1 trial compared with later phases, because of this intensive monitoring schedule, which reflects how much still remains unknown about the drug at this early stage compared with later phases of testing^[1].

In the asthma antibody study, assessments included medical history, heart monitoring, adverse event monitoring, vital signs, physical examination, blood and urine tests, and an asthma-specific questionnaire, across a 4-day inpatient period followed by up to 40 weeks of post-dose follow-up visits, a combination that shows how safety monitoring in these trials extends well beyond the days immediately surrounding dosing^[6]. In the bispecific antibody study for blood cancer, safety assessments specifically included physical examination, vital signs, clinical laboratory tests, a performance-status scale (which measures how well a participant can carry out daily activities), electrocardiograms of the heart, and adverse event monitoring, a broad set of checks reflecting the fact that a drug acting on the immune system can affect many different organ systems at once^[4].

The brain tumour combination study likewise listed frequency and severity of adverse events, dose-limiting toxicities, laboratory testing, vital signs, electrocardiographic assessment, and neurologic and physical examinations as its core safety assessments, with the addition of neurologic examination reflecting the specific concern of treating a tumour located in the brain^[5].

What laboratory tests are done, and why so often?

Participants can expect frequent blood tests in a phase 1 trial, because researchers need to track how the body absorbs, processes and eliminates the drug over time, information that cannot be gathered any other way than by taking repeated samples at carefully chosen intervals after dosing^[1]. This tracking of drug levels in blood and urine over time, known as the pharmacokinetic profile, is one of the primary purposes of a phase 1 study, and the resulting data feeds directly back into decisions about whether and how to escalate the dose further^[3].

In the dystonia trial, participants resided in the study unit for 6 days after dosing before a follow-up visit 7 to 14 days later, a schedule built around collecting these serial blood and urine samples, and this length of inpatient stay illustrates how much of the burden of a phase 1 trial for participants comes not from the dose itself but from the sheer density of the monitoring that surrounds it^[3]. In the asthma study, blood tests also tracked levels of eosinophils (a type of white blood cell linked to airway inflammation) and other disease-relevant markers, in addition to standard safety bloods, giving researchers an early signal of biological activity alongside the basic safety picture^[6].

Imaging and tissue samples alongside blood tests

Some early-phase studies extend laboratory monitoring beyond blood and urine. In phase 0 studies specifically, participants may have extra scans and give extra blood or tissue samples (biopsies) so researchers can determine whether the drug reaches its intended target in the body, a question that is distinct from, and often asked before, the question of what dose is safe^[1]. In the brain tumour combination study, MRI scans were scheduled at defined treatment cycles to evaluate tumour response, alongside the standard laboratory and vital-sign checks, so that changes in the tumour itself could be tracked in parallel with the drug's safety profile^[5].

Who reviews the safety data between dose groups?

Before any dose increase, the safety data from the current dose group is reviewed at a dedicated meeting. This review determines whether the next group can proceed to a higher dose, stay at the same dose, or move to a lower dose, and it is this review, rather than any pre-set timetable, that ultimately controls the pace at which the trial moves forward^[3]. This step-by-step review is why phase 1 trials, despite enrolling relatively few participants, can take many months or longer to complete, since no group can begin until the previous group's results have been fully assessed^[1].

Regulatory guidance sets out that trial sponsors and investigators must have strategies in place to identify and reduce risk throughout a first-in-human trial, covering the overall design of the protocol as well as the specific criteria used to decide on dose escalation, so that the rules for moving between doses are established and agreed before the trial begins rather than improvised as it proceeds^[2].

What should you report immediately if you are taking part?

Trial protocols require that any side effect a participant experiences is carefully recorded, along with the exact time it occurred, so that it can be linked back to the dose given and reviewed before the next step of the trial, which is why timely and accurate reporting by participants themselves is such a central part of how these studies are kept safe^[1]. If you are taking part in a phase 1 trial, you should tell the study team about any new symptom, however minor it seems, as soon as it appears, rather than waiting for your next scheduled visit, because a symptom that seems trivial to you may be exactly the signal researchers need to catch before deciding on the next dose^[6].

• Any new physical symptom (for example dizziness, rash, nausea, palpitations) — even if it seems minor or unrelated to the study drug^[1];
• Changes noticed between scheduled visits, if you are sent home between assessments rather than staying as an inpatient^[3];
• Any other medication you start taking, since concomitant medicines are recorded and reviewed as part of trial safety monitoring^[7];
• Missed or delayed follow-up visits, since the post-dose observation period (which can extend to many weeks) is part of how long-term safety is assessed^[6].

How are early-phase protocols designed to avoid disruptive changes once a trial starts?

Because early-phase trials evolve as safety data accumulates, researchers and regulators have worked on designing "integrated" protocols from the outset, aiming to reduce the number of substantial modifications needed once dosing is already underway, since frequent formal amendments can slow a trial down and add administrative burden at exactly the point when momentum in safety review matters most. This kind of forward planning, including how different participant groups are defined in advance, is intended to keep dose-escalation decisions predictable for everyone involved, including participants, who benefit from knowing in general terms how the trial is expected to progress even before their own dose group is reached^[8].

When should you contact the study team or your own doctor?

Contact the study team straight away if you notice any new or worsening symptom after dosing, rather than waiting for your next scheduled visit, since the trial's safety monitoring depends on timely reporting and a delay of even a day or two can make it much harder to link a symptom clearly to the dose that caused it^[1]. If you are unsure whether a symptom is related to the study drug or to something else entirely, it is still appropriate to report it to the study team, who can then decide whether further assessment or review by your own doctor is needed, rather than trying to make that judgement yourself^[6].

You should also ask the study team in advance what the plan is if you need to attend an emergency department or see another doctor during the trial, so that the study drug and its known effects can be communicated to any other clinician treating you, since an emergency clinician unfamiliar with the trial protocol may otherwise have no way of knowing what substance you have recently been given^[4].

Summary

A phase 1 trial is built around a simple sequence: start at a very low, carefully calculated dose, treat a small number of participants first under close observation, review the safety data, and only then decide whether to move to a higher dose, and every other feature of the trial's design, from sentinel dosing to the frequency of blood tests, exists to support this basic cycle^[2]. Vital signs, blood and urine tests, and in many trials heart tracings and imaging, are repeated on a fixed schedule so that any warning sign is caught early and linked to the exact dose that caused it, which is what allows the next dose decision to be made on solid evidence rather than guesswork^[4].

If you are considering taking part in a phase 1 trial, ask the study team directly about the starting dose, how dose increases will be decided, what sentinel dosing arrangements apply to your group, and what symptoms you must report immediately, since understanding these details in advance can make the intensity of the monitoring schedule far less daunting^[3]. This information should be part of the consent process before you agree to take part, so that you go into the trial with a realistic picture of what will be asked of you and why^[1].

This article is for general information only and does not replace individual medical advice. If you are considering joining a clinical trial or have symptoms during one, speak to the study team or your treating doctor.

1. [1] Cancer Research UK | Phases of clinical trials (accessed 2 June 2026) — https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/what-clinical-trials-are/phases-of-clinical-trials
2. [2] European Medicines Agency. Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products, Rev. 1. EMEA/CHMP/SWP/28367/07 Rev. 1. 20 July 2017. (accessed 2 June 2026) — https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-strategies-identify-and-mitigate-risks-first-human-and-early-clinical-trials-investigational-medicinal-products-revision-1_en.pdf
3. [3] Health Research Authority. A Phase I, Single Ascending Dose Study of HTL0014242 in Healthy Adults (accessed 2 June 2026) — https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/a-phase-i-single-ascending-dose-study-of-htl0014242-in-healthy-adults/
4. [4] Health Research Authority. 88549968MPN1001 (accessed 2 June 2026) — https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/88549968mpn1001/
5. [5] Cleveland Clinic. Study Explores Optimal Dosage of Novel Combination Therapy for Recurrent Glioblastoma (accessed 2 June 2026) — https://consultqd.clevelandclinic.org/study-explores-optimal-dosage-of-novel-combination-therapy-for-recurrent-glioblastoma
6. [6] Health Research Authority. GSK3511294 – first doses in humans (accessed 2 June 2026) — https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/gsk3511294-first-doses-in-humans/
7. [7] University Hospital Southampton NHS Foundation Trust. ACCORD-2: A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study — Master Protocol. 22 April 2020. (accessed 2 June 2026) — https://www.uhs.nhs.uk/Media/Southampton-Clinical-Research/COVID-19/ACCORD/ACCORD-2-master-protocol.pdf
8. [8] https://pmc.ncbi.nlm.nih.gov/articles/PMC12883952/