First-in-human (FIH) trials represent the initial instance a new drug, medical device, or other treatment is administered to people. These studies are a foundational step in bringing new therapies to the public. They bridge the gap between extensive laboratory research and broader clinical evaluation, providing initial insights into how a new intervention behaves within the human body. This early stage of medical research focuses on understanding preliminary responses and setting the stage for subsequent, larger studies.
The Road to a Human Trial
Before any new treatment can be tested in humans, it undergoes extensive preclinical research. This phase involves laboratory studies, often referred to as in vitro (“within the glass”), which utilize cell cultures and tissues to evaluate a drug’s initial effects and potential toxicity. These studies are inexpensive and efficient, providing robust results on a large scale.
Following in vitro work, the drug candidate moves to in vivo (“within the living”) testing, involving animal models such as rodents, dogs, or primates. This stage assesses the drug’s safety, efficacy, and potential side effects within a complex biological system, mimicking conditions expected in human trials. Toxicity studies examine responses to increasing doses, while activity studies assess the drug’s ability to address the target disease in animals.
Once sufficient preclinical data demonstrating reasonable safety and potential effectiveness are gathered, the developer must submit an Investigational New Drug (IND) application to regulatory bodies like the U.S. Food and Drug Administration (FDA). This application summarizes all preclinical findings, details the drug’s manufacturing information, and outlines the proposed plan for human trials. The FDA then has a 30-day period to review the IND for safety, ensuring research subjects are not exposed to unreasonable risks before allowing clinical trials to proceed.
Objectives and Design
The primary objective of a first-in-human trial is to assess the safety and tolerability of the new treatment in people. Researchers carefully monitor participants for any adverse effects, which are undesirable or unintended responses to the investigational product. This initial safety evaluation helps determine if the drug causes unacceptable harm at various dose levels.
A common approach to safety assessment is through dose-escalation studies, which involve administering progressively higher doses of the treatment to small groups of participants. A very low dose, determined from preclinical data, is given to the first group of subjects. If that dose is well-tolerated, the next group receives a slightly higher dose, and this process continues until a maximum tolerated dose (MTD) is identified or the maximum planned dose is reached.
Beyond safety, FIH trials also investigate pharmacokinetics (PK) and pharmacodynamics (PD). Pharmacokinetics describes what the body does to the drug, including how it is absorbed, distributed, metabolized, and eliminated over time. This involves measuring drug concentrations in blood samples at specific intervals after administration. Pharmacodynamics, on the other hand, examines what the drug does to the body, such as its biological effects or how it interacts with its intended target. These secondary objectives help determine a safe and effective dosage range for later-phase studies and provide early insights into the treatment’s potential activity.
Participant Involvement and Safeguards
Participants in first-in-human trials are healthy volunteers without serious medical conditions. Their participation allows researchers to understand the treatment’s safety and how the human body processes it without interference from existing diseases or medications. For certain high-risk treatments, such as some chemotherapy drugs, patients with the specific condition who cannot benefit from standard therapies may be recruited instead.
Ethical and safety protocols are in place to protect individuals participating in these early-phase studies. Informed consent is central to participant protection. Before enrollment, potential subjects receive a detailed document explaining the study’s purpose, procedures, potential risks, anticipated benefits, alternative treatments, and their right to withdraw at any time. This information is presented in easily understandable language to ensure a voluntary and informed decision.
All clinical trials involving human subjects must undergo review and approval by an Institutional Review Board (IRB) or an Independent Ethics Committee (IEC). This diverse committee, composed of medical professionals, scientists, and community members, ensures the study design is ethical, risks are minimized, and participant welfare is prioritized. The IRB also provides ongoing oversight throughout the trial, reviewing any protocol changes and reports of adverse events to continuously monitor participant safety.
From Trial to Treatment
A successful first-in-human trial is an important step, but it marks only the initial step in a drug development pipeline. The data gathered from FIH studies, particularly on safety, tolerability, pharmacokinetics, and pharmacodynamics, are analyzed to make an informed “go/no-go” decision about whether to proceed with further development. This decision involves evaluating the balance between potential benefits and identified risks, considering the investment required for subsequent phases.
If the data support continued development, the treatment progresses to Phase 2 clinical trials. These studies involve a larger group of patients with the target disease, typically several dozen to a few hundred. The primary goal of Phase 2 is to assess the treatment’s efficacy, or how well it works, while continuing to monitor safety.
Should Phase 2 trials demonstrate promising efficacy and an acceptable safety profile, the treatment advances to Phase 3. This phase involves large-scale studies with hundreds to thousands of patients, often comparing the new treatment to existing standard therapies or a placebo. Phase 3 trials provide extensive data on long-term safety and effectiveness across a diverse patient population, which is required for regulatory approval before the treatment can be made available to the general public.