Clinical Trial Phases: From Preclinical Research to Phase 4
Clinical trials are carefully designed research studies conducted to evaluate the safety, effectiveness, and appropriate use of medical treatments, such as medications, biologics, vaccines, or medical devices.
Each phase of clinical research reviewed by the Institutional Review Board (IRB) and designed to answer specific scientific and safety questions before moving forward. The IRB is a group of experts that work together to ensure that the research study is safe and ethical for participants. By doing this it helps to protect the participants, ensure ethical conduct, and generate reliable data that both healthcare professionals and patients can trust.
Preclinical research
What is preclinical research?
Preclinical research includes studies conducted:
- In laboratories
- In animal models
These studies are required to assess whether a treatment is reasonably safe to move into human testing.
What is evaluated during preclinical research?
Preclinical studies help researchers understand:
- Basic safety and toxicity
- How the treatment behaves in the body (absorption, distribution, metabolism, and elimination)
- Potential target organs for side effects
- Early signals of biological activity or effectiveness
- An appropriate starting dose for first-in-human studies
These data are essential for regulatory review. In the United States, preclinical results are submitted to the Food and Drug Administration (FDA), as part of an Investigational New Drug (IND) application before Phase 1 can begin.
Phase 1: Assessing Safety in Humans
Primary focus: Safety, tolerability, and dosing
Phase 1 trials are usually the first studies conducted in humans. They typically involve a small number of participants, which may include healthy volunteers or patients, depending on the condition being studied.
During Phase 1, researchers evaluate:
- How safe the treatment is at different dose levels
- How the body processes the treatment
- Common side effects
- The safest dose range for further study
Why Phase 1 matters:
A treatment must demonstrate an acceptable safety profile before it can be studied in larger populations.
Phase 2: Evaluating Effectiveness and Continued Safety
Primary focus: Preliminary effectiveness and ongoing safety evaluation
Phase 2 trials enroll a larger group of participants, usually individuals who have the condition being studied.
Researchers assess:
- Whether the treatment shows signs of effectiveness
- Continued safety and side effect monitoring
- Optimal dosing and treatment schedules
- Meaningful clinical outcomes (endpoints)
Why Phase 2 matters:
This phase helps determine whether the treatment is promising enough to justify larger, more definitive studies.
Phase 3: Confirming Benefits and Monitoring Risks at Scale
Primary focus: Confirming effectiveness and comparing to standard treatments
Phase 3 trials involve hundreds or thousands of participants and are often conducted at multiple research sites.
These studies are designed to:
- Confirm the treatment’s effectiveness
- Compare it to standard of care or placebo, when appropriate
- Identify less common or longer-term side effects
- Collect data needed for IRB approval
Why Phase 3 matters:
Phase 3 trials provide the strongest evidence regulators rely on to determine whether a treatment’s benefits outweigh its risks for a specific population.
Phase 4: Post-Approval and Real-World Monitoring
Primary focus: Long-term safety and real-world use
Phase 4 studies take place after a treatment has been approved and is available to patients.
These studies may evaluate:
- Long-term safety
- Rare side effects
- Effectiveness in broader, real-world populations
- New ways to use the treatment
Why Phase 4 matters:
Ongoing research ensures continued patient safety even after approval and helps refine how treatments are used in everyday clinical practice.
Why Clinical Trials Follow This Phased Approach
Clinical trials are conducted in phases to:
1. Protect participant safety
Each step limits risk by ensuring sufficient safety data before exposing larger populations.
2. Generate reliable scientific evidence
Different phases answer different questions, building a complete understanding of a treatment’s risks and benefits.
3. Meet ethical and regulatory standards
All phases are conducted under Good Clinical Practice (GCP) guidelines, which prioritize participant rights, safety, and data integrity.
References and Sources:
MedlinePlus Magazine. Is a Clinical Trial Right for You?
https://magazine.medlineplus.gov/article/is-a-clinical-trial-right-for-you
National Institutes of Health (NIH). NIH Clinical Research Trials and You: The Basics.
https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics
U.S. Food and Drug Administration (FDA). Drug Development Process.
https://www.fda.gov/patients/drug-development-process
U.S. Food and Drug Administration (FDA). Investigational New Drug (IND) Application.
https://www.fda.gov/drugs/investigational-new-drug-ind-application
International Council for Harmonisation (ICH). ICH E6(R3) Good Clinical Practice Guideline.
https://database.ich.org/sites/default/files/ICH_E6%28R3%29_Step4_FinalGuideline_2025_0106.pdf
National Heart, Lung, and Blood Institute (NHLBI). How Clinical Trials Work.
https://www.nhlbi.nih.gov/research/clinical-trials/how-studies-work
