Step 3: Clinical Research (2023)

While preclinical research answers basic questions about a drug’s safety, it is not a substitute for studies of ways the drug will interact with the human body. “Clinical research” refers to studies, or trials, that are done in people. As the developers design the clinical study, they will consider what they want to accomplish for each of the different Clinical Research Phases and begin the Investigational New Drug Process (IND), a process they must go through before clinical research begins.

On this page you will find information on:

  • Designing Clinical Trials

  • Clinical Research Phase Studies

  • The Investigational New Drug Process

  • Asking for FDA Assistance

  • FDA IND Review Team

  • Approval

Designing Clinical Trials

Researchers design clinical trials to answer specific research questions related to a medical product. These trials follow a specific study plan, called a protocol, that is developed by the researcher or manufacturer. Before a clinical trial begins, researchers review prior information about the drug to develop research questions and objectives. Then, they decide:

  • Who qualifies to participate (selection criteria)

  • How many people will be part of the study

  • How long the study will last

  • Whether there will be a control group and other ways to limit research bias

  • How the drug will be given to patients and at what dosage

  • What assessments will be conducted, when, and what data will be collected

  • How the data will be reviewed and analyzed

Clinical trials follow a typical series from early, small-scale, Phase 1 studies to late-stage, large scale, Phase 3 studies.

What are the Clinical Trial Phases?

Watch this video to learn about the three phases of clinical trials.

Clinical Research Phase Studies

(Video) The Four Phases of Clinical Trials | Diversity in Clinical Trials | AKF

Phase 1

Step 3: Clinical Research (1)

Study Participants: 20 to 100 healthy volunteers or people with the disease/condition.

Length of Study: Several months

Purpose: Safety and dosage

During Phase 1 studies, researchers test a new drug in normal volunteers (healthy people). In most cases, 20 to 80 healthy volunteers or people with the disease/condition participate in Phase 1. However, if a new drug is intended for use in cancer patients, researchers conduct Phase 1 studies in patients with that type of cancer.

Phase 1 studies are closely monitored and gather information about how a drug interacts with the human body. Researchers adjust dosing schemes based on animal data to find out how much of a drug the body can tolerate and what its acute side effects are.

As a Phase 1 trial continues, researchers answer research questions related to how it works in the body, the side effects associated with increased dosage, and early information about how effective it is to determine how best to administer the drug to limit risks and maximize possible benefits. This is important to the design of Phase 2 studies.

Approximately 70% of drugs move to the next phase

Phase 2

Step 3: Clinical Research (2)

Study Participants: Up to several hundred people with the disease/condition.

(Video) Understanding Clinical Trials

Length of Study: Several months to 2 years

Purpose: Efficacy and side effects

In Phase 2 studies, researchers administer the drug to a group of patients with the disease or condition for which the drug is being developed. Typically involving a few hundred patients, these studies aren't large enough to show whether the drug will be beneficial.

Instead, Phase 2 studies provide researchers with additional safety data. Researchers use these data to refine research questions, develop research methods, and design new Phase 3 research protocols.

Approximately 33% of drugs move to the next phase

Phase 3

Step 3: Clinical Research (3)

Study Participants: 300 to 3,000 volunteers who have the disease or condition

Length of Study: 1 to 4 years

Purpose: Efficacy and monitoring of adverse reactions

Researchers design Phase 3 studies to demonstrate whether or not a product offers a treatment benefit to a specific population. Sometimes known as pivotal studies, these studies involve 300 to 3,000 participants.

(Video) Phases of Clinical Trial

Phase 3 studies provide most of the safety data. In previous studies, it is possible that less common side effects might have gone undetected. Because these studies are larger and longer in duration, the results are more likely to show long-term or rare side effects

Approximately 25-30% of drugs move to the next phase

Phase 4

Step 3: Clinical Research (4)

Study Participants: Several thousand volunteers who have the disease/condition

Purpose: Safety and efficacy

Phase 4 trials are carried out once the drug or device has been approved by FDA during the Post-Market Safety Monitoring

Learn more about Clinical Trials.

The Investigational New Drug Process

Drug developers, or sponsors, must submit an Investigational New Drug (IND) application to FDA before beginning clinical research.

In the IND application, developers must include:

  • Animal study data and toxicity (side effects that cause great harm) data

  • Manufacturing information

  • Clinical protocols (study plans) for studies to be conducted

  • Data from any prior human research

  • Information about the investigator

Asking for FDA Assistance

Drug developers are free to ask for help from FDA at any point in the drug development process, including:

(Video) What Are Clinical Trial Phases?

  • Pre-IND application, to review FDA guidance documents and get answers to questions that may help enhance their research

  • After Phase 2, to obtain guidance on the design of large Phase 3 studies

  • Any time during the process, to obtain an assessment of the IND application

Even though FDA offers extensive technical assistance, drug developers are not required to take FDA’s suggestions. As long as clinical trials are thoughtfully designed, reflect what developers know about a product, safeguard participants, and otherwise meet Federal standards, FDA allows wide latitude in clinical trial design.

FDA IND Review Team

The review team consists of a group of specialists in different scientific fields. Each member has different responsibilities.

  • Project Manager: Coordinates the team’s activities throughout the review process, and is the primary contact for the sponsor.

  • Medical Officer: Reviews all clinical study information and data before, during, and after the trial is complete.

  • Statistician: Interprets clinical trial designs and data, and works closely with the medical officer to evaluate protocols and safety and efficacy data.

  • Pharmacologist: Reviews preclinical studies.

  • Pharmakineticist: Focuses on the drug’s absorption, distribution, metabolism, and excretion processes.Interprets blood-level data at different time intervals from clinical trials, as a way to assess drug dosages and administration schedules.

  • Chemist: Evaluates a drug’s chemical compounds. Analyzes how a drug was made and its stability, quality control, continuity, the presence of impurities, etc.

  • Microbiologist: Reviews the data submitted, if the product is an antimicrobial product, to assess response across different classes of microbes.


The FDA review team has 30 days to review the original IND submission. The process protects volunteers who participate in clinical trials from unreasonable and significant risk in clinical trials. FDA responds to IND applications in one of two ways:

  • Approval to begin clinical trials.

  • Clinical hold to delay or stop the investigation. FDA can place a clinical hold for specific reasons, including:

    • Participants are exposed to unreasonable or significant risk.

    • Investigators are not qualified.

    • Materials for the volunteer participants are misleading.

    • The IND application does not include enough information about the trial’s risks.

A clinical hold is rare; instead, FDA often provides comments intended to improve the quality of a clinical trial. In most cases, if FDA is satisfied that the trial meets Federal standards, the applicant is allowed to proceed with the proposed study.

The developer is responsible for informing the review team about new protocols, as well as serious side effects seen during the trial. This information ensures that the team can monitor the trials carefully for signs of any problems. After the trial ends, researchers must submit study reports.

(Video) The ASPro-PD phase 3 clinical trial of ambroxol: Update and Panel Discussion

This process continues until the developer decides to end clinical trials or files a marketing application. Before filing a marketing application, a developer must have adequate data from two large, controlled clinical trials.


What is stage 3 clinical trials? ›

A study that tests the safety and how well a new treatment works compared with a standard treatment. For example, phase 3 clinical trials may compare which group of patients has better survival rates or fewer side effects.

What is Phase 3 of FDA clinical trial? ›

Phase III trials

The experimental study drug or treatment is given to large groups of people. Researchers confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.

What are the main characteristics of Phase 3 clinical trials? ›

Phase III clinical trials compare the safety and effectiveness of the new treatment against the current standard treatment. Because doctors do not yet know which treatment is better, study participants are often picked at random (called randomized) to get either the standard treatment or the new treatment.

What is the difference between Phase 2 and 3 clinical trials? ›

Phase 2: Testing in a small number of patients, to assess safety, to monitor how a drug is metabolized, and to gather initial data on efficacy. Phase 3: A large trial in patients to test efficacy and safety.

How long is Phase 3 clinical trial? ›

Studies for Phase III clinical trials usually take from 1 to 4 years. This phase involves from 300 to 3,000 patients and is designed to determine the drug's long-term effects.

How long is Stage 3 clinical trial? ›

Phase 3 trials, which examine the efficacy of a treatment and monitor adverse reactions, typically last between one and four years.

What is a phase 3 and 4 of clinical trial? ›

Phase 3 is the final phase before a treatment receives FDA approval. Following FDA approval, a treatment goes through Phase 4. This phase involves the largest group of participants. It can last for several years as researchers continue to monitor the efficacy and safety of the treatment.

What is the difference between Phase 1 and Phase 3 clinical trials? ›

Phase 1 trials are the earliest phase trials and phase 3 are later phase trials. Some trials have an earlier stage called phase 0, and there are some phase 4 trials done after a drug has been licensed. Some trials are randomised. This means the people taking part are put into one of the treatment groups at random.

What are Phase I II and III clinical trials? ›

Phase I trials test if a new treatment is safe and look for the best way to give the treatment. Doctors also look for signs that cancer responds to the new treatment. Phase II trials test if one type of cancer responds to the new treatment. Phase III trials test if a new treatment is better than a standard treatment.

Why do most clinical trials never go to Stage 3? ›

In summary, the main three reasons for drug failure during phase 3 of clinical trials is often due to a lack of supporting data around efficacy, safety and commercial viability. Without proof of efficacy and safety, a drug cannot be approved for market use.

What are 2 benefits to using a phase III trial? ›

Hope that something in the new trial may give the patient a better treatment option. And, if not them, that the treatment or the results of that trial will help other patients in the future. Another benefit is the chance to participate in new research and potentially receive a new drug.

How long does FDA approval take after Phase 3? ›

Following successful completion of a Phase 3 trial, a New Drug Application (NDA) can be submitted to the FDA to request review for approval. The FDA will then take 6-10 months to review all of the data submitted and either accept or deny the NDA.

What are Phase 4 clinical trials? ›

Listen to pronunciation. (fayz … KLIH-nih-kul TRY-ul) A type of clinical trial that studies the side effects caused over time by a new treatment after it has been approved and is on the market.

What happens after Phase 3 trials? ›

After successful Phase 3 trials, data gathered in clinical trials is sent to the FDA (and/or other governing bodies around the world) for review and approval. The FDA looks at all the data from the three phases of clinical trials to determine if an investigational product should be sold to consumers.

What are the 4 types of clinical trials? ›

Types of clinical trials
  • Pilot studies and feasibility studies.
  • Prevention trials.
  • Screening trials.
  • Treatment trials.
  • Multi-arm multi-stage (MAMS) trials.
  • Cohort studies.
  • Case control studies.
  • Cross sectional studies.
Feb 1, 2022

What is the average cost of a Phase 3 clinical trial? ›

The average cost of phase 1, 2, and 3 clinical trials across therapeutic areas is around $4, 13, and 20 million respectively. Pivotal (phase 3) studies for new drugs approved by the Food and Drug Administration (FDA) of the United States cost a median of $41,117 per patient.

What is a good sample size for a Phase 3 clinical trial? ›

After incorporating the prior information of the treatment effects, the sample size for a Phase III clinical trial could be E ( m 2 ) for a given power p, or m2 for a given ASP. In the cases of diluted treatment effects, we recommend the uniform and truncated normal prior distributions for the treatment effects.

Which phase of clinical trials is the longest? ›

Phase IV clinical trials happen after the FDA has approved medication. This phase involves thousands of participants and can last for many years. Investigators use this phase to get more information about the medication's long-term safety, effectiveness, and any other benefits.

What are the 3 phases of FDA approval? ›

Phases of Clinical Trials
  • Phase 1 Clinical Trial. The purpose of Phase 1 is to ensure that the treatment is safe in humans and to determine how and where it distributes within the body. ...
  • Phase 2 Clinical Trial. ...
  • Phase 3 Clinical Trial. ...
  • Monitoring Post-FDA Approval.
Sep 2, 2021

What does a Phase 2 3 trial mean? ›

Listen to pronunciation. (fayz … KLIH-nih-kul TRY-ul) A study that tests how well a new treatment works for a certain type of cancer or other disease and compares the new treatment with a standard treatment.

What is an NIH Phase III clinical trial? ›

What NIH defines as a Phase 3 trial is, a broadly-based perspective investigation that compares two or more interventions. A Phase 3 trial often is aimed at generating evidence that may lead to a consideration in a change in health policy or standard of care.” – Dawn Corbett.

What is Phase 3b vs Phase 4? ›

Once a manufacturer applies for marketing approval on a drug, all subsequent research that is not conducted in-line with the product approval is termed Phase IIIB and all subsequent research that is conducted in-line with the product approval is called Phase IV.

What are the 4 phases of drug development? ›

Drug development can be divided into four phases: discovery, preclinical studies, clinical development and market approval. The image below provides an overview of the process, including an estimated timeline for each step.

What is the difference between Phase 3 and Phase 4 clinical trials? ›

Phase 3 is the final phase before a treatment receives FDA approval. Following FDA approval, a treatment goes through Phase 4. This phase involves the largest group of participants. It can last for several years as researchers continue to monitor the efficacy and safety of the treatment.

What are the 3 types of clinical trials? ›

Types of clinical trials
  • Interventional trials aim to find out more about a particular intervention, or treatment. ...
  • Observational studies aim to find out what happens to people in different situations. ...
  • Feasibility studies are designed to see if it is possible to do the main study.
Feb 1, 2022


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2. Phase 3 and 4 trial||Clinical Research||Trial master file||Clinical trial
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