The Clinical Trial Process

Overview

The process of developing and testing new drugs and medical products is lengthy and thorough. In order to ensure that new drugs are safe and effective, researchers, drug manufacturers, and the government must work together for years before the drug is made available to users. The process doesn’t end there either: even once a drug is approved and sold on the market, its safety and efficacy continue to be assessed.

An overview of the clinical drug trial process in the United States is outlined below. Resources for further reading can be found at the bottom.

Safety & Efficacy

Safety and efficacy are often used as two important features of new drugs. The significance of safety may be obvious: the drug should not have dangerous or seriously harmful side effects (some minor negative side effects are allowable). There is no point in taking a drug that solves one problem if it also creates another.

Efficacy, or how effectively a drug performs its intended purpose, is important to protect users. If drug companies were able to sell drugs that didn’t work to hopeful patients, they would be taking advantage of a vulnerable population and not contributing valuable assistance. For this reason, only drugs that have been proven to actually make patients healthier are approved.

Clinical Trials

Drug development research is initially performed in scientific laboratories. Researchers test new chemicals and compounds to determine if any of them might be useful for treating disease.

Once a potential new drug is identified based on its physical and chemical properties, it is usually tested in animals. Mice and rats are the most commonly used test species. Although their anatomy and physiology aren’t exactly the same as that of humans, they are similar enough that researchers can begin testing the safety and efficacy.

If a drug appears to be safe and effective in animals (if both aspects were tested), researchers will then begin clinical trials. Clinical trials are medical studies that help researchers find new ways to prevent, detect, or treat disease. Clinical trials are used to test new drugs in humans and prove their safety and efficacy. A study is made up of several different phases, with each phase answering particular questions and revealing more about the effects of the new drug.

Clinical Trial Phases

Clinical trials typically have four phases, which occur one after the other. Each phase includes more people than the previous phase and has slightly different goals. The phases are summarized below and described in further detail in Table 1.

• Phase I: The drug is tested for the first time in humans. Both healthy volunteers and volunteers afflicted with the disease of interest are included to test the drug’s safety.

• Phase II: The drug is tested in a larger group of people afflicted with the disease of interest with a focus on testing efficacy.

• Phase III: The drug is tested in an even larger group of afflicted volunteers to identify rare side effects, confirm efficacy, and compare the treated group with an untreated group or a group treated with a different treatment option.

• Phase IV: After the drug is approved and released, researchers continue to monitor users to ensure no rare or long-term side effects arise.

After each phase, researchers analyze the collected data, determine if the phase has met its goals and endpoints, assess whether additional data should be collected, and decide whether to proceed to the next phase.

Table 1: Clinical trial phases

Phase	Description	Participants	Length	Purpose
I	Test the drug in humans for the first time with a focus on safety	20 - 100 healthy and afflicted users	Several months	Confirm safety; determine dosing guidelines
II	Test in a larger group with a focus on efficacy	Several hundred afflicted users	Several months to several years	Assess effectiveness; identify less common side effects
III	Confirm safety and efficacy in an even larger group and compare to other treatment options	300 - 3,000 afflicted users	1 - 4 years	Confirm safety and efficacy; prove value against existing treatments (or the lack thereof)
IV	Track safety in general population after FDA approval	Several thousand afflicted users	Years	Assess safety in the general population

Protocols

When researchers are planning human testing trials, they must develop a detailed protocol and get approval from an Institutional Review Board (IRB) before proceeding with the trial. The IRB ensures that the trial is safe and fair to human participants and that the potential benefits of the study outweigh the possible risks. To further protect clinical trial volunteers, participants are monitored throughout the length of the study, are fully informed regarding all the possible risks of the study (such as side effects), and are allowed to withdraw from the study at any time.

The protocol must outline every aspect of the study including:

• The study’s specific goals and research questions

• What information will be collected

• The number of participants in each phase and which participants are eligible

• The conditions of the control group (described in Trial Designs)

• Details about tests, procedures, and treatments that will be performed

• The expected duration of each phase

• How researchers are protecting participants from risk

Trial Designs

In clinical trials, it is important to include a control group: a set of participants who don’t receive treatment or who receive a different treatment and whose results are compared against participants who do receive treatment. Users who don’t receive treatment may instead receive a placebo, an inactive treatment that appears similar to the actual treatment but does not have the same effects. For example, users in a control group may receive pills that look exactly like the tested drug but are actually made up only of sugar.

In order to ensure scientific accuracy, clinical trials are set up in particular ways to avoid bias. Bias may not be deliberate, but it is possible for researchers and participants to act in certain ways based on their expectations that make it more difficult to objectively assess the study outcomes.

For example, if participants think they are receiving treatment, they may report feeling better, even if they have only received the placebo (this is known as the placebo effect). In another example, if allowed to choose which participants are included in the control group or the treatment group, researchers may inadvertently elect to treat participants who they think are more likely to benefit from the treatment.

To protect from this bias, control and treatment groups are usually randomized; researchers do not get to choose who receives the treatment or the placebo, rather each participant is assigned at random. Clinical trials are also usually blinded: those involved do not know who is receiving treatment and who is receiving the placebo until after the study is over. In single-blinded studies, the researchers know which participants are receiving treatment but the participants don’t. In double-blinded studies, neither the researchers nor the participants know who is receiving treatment.

FDA Review & Approval

The Food & Drug Administration (FDA) is responsible for making the final decision on drug approvals and is involved in every step of the clinical trial process. Teams at the FDA are also available to provide advice regarding clinical trial design and data analysis.

Before clinical trials begin, the researchers and manufacturer must submit an Investigational New Drug (IND) application to the FDA. The IND application includes manufacturing information, clinical protocols, any existing data, and investigator information. The team that reviews the IND application consists of specialists in different scientific fields and has 30 days to approve the application. If the application is approved, clinical trials can begin.

Once Phase III of the clinical trial is completed, the researchers and the manufacturer submit a New Drug Application (NDA) to the FDA. This application includes data showing that the drug is safe and effective and requests permission to bring the new drug to market. The NDA contains all the data from the clinical trials, as well as proposed labeling, safety updates, drug abuse information, patent information, IRB compliance information, and directions for use. Drug pricing is not discussed during the clinical trial process.

The FDA has 10 months to review the NDA, during which the team reviews the application, assesses the provided data, and visits the clinical trial sites. The review team may also request additional studies or data to be provided. Once their assessment is complete, the team decides whether the drug should be approved. If the review team has additional questions or concerns, they may also gather an FDA Advisory Committee, which is an external panel of experts who also assess the data and make their recommendation. The FDA is not required to accept the Advisory Committee’s recommendation, but they often do.

Once the drug is approved, the manufacturer can bring the drug to market, and Phase IV begins.

Timelines

In order to thoroughly assess the safety and efficacy of new drugs, the process of bringing a new drug to market takes years and costs millions of dollars. Typically, a drug will be in development and testing for 12-15 years before it is released to market. The median cost of developing a new drug in the U.S. is $985 million. Many potential new drugs don’t even make it all the way through the process with only 70% of drugs advancing past Phase I, 33% advancing past Phase II, and 25-30% advancing past Phase III.

Not all drugs make it through the clinical trial process. If the drug cannot be proved safe or effective at any point, it will not advance to the next stage of testing.

Rare Conditions

Since drug development is so time intensive and expensive, drug companies want to ensure that developing a new drug is worthwhile for their business. Drugs that treat rare conditions won’t have as many users, so companies may be less interested in focusing on these products, knowing they won't earn as much money, even if the drug does get approved. For this reason, there are several benefits given to drugs developed for rare conditions in order to incentivize their development.

Some of these incentives also apply to drugs that treat a serious condition without existing treatment to allow patients to receive life-saving care more quickly.

Orphan Drug Designation

“Orphan Drugs” are drugs that are used to treat rare diseases and conditions (diseases that affect fewer than 200,000 people). If a drug is approved for Orphan Drug status, the manufacturer receives exclusivity for seven years, meaning no other companies can make the drug, so the initial developer receives all the business for that drug.

Accelerated Approval

Accelerated Approval allows promising therapies for serious or life-threatening conditions to come to market more quickly. Accelerated Approval uses a “surrogate endpoint”, which essentially means that researchers just have to prove that the drug appears to be working, even if it hasn’t been shown to be fully effective. Researchers still have to prove the drug fully effective eventually, but the drug can be sold to patients in the meantime (the label will indicate that the drug received Accelerated Approval).

Fast Track & Breakthrough Therapy

When drugs are Fast Tracked, they can be approved more quickly by also considering earlier human data or animal data that was collected prior to the clinical trials. Drugs are considered a Breakthrough Therapy and are eligible for Fast Track approval if they treat a serious medical condition that doesn’t have other existing treatment options or if the preliminary research shows significant improvement over existing treatments.

Priority Review

The FDA is obligated to take action on all new drug applications within 10 months. However, drugs that can significantly improve treatment, diagnosis, or prevention of serious conditions may qualify for Priority Review, and the FDA will assess the application within 6 months.

Summary

The drug approval process is lengthy and involved. Although the system is specifically designed to protect patients and ensure they are receiving the care they need, the process can also be frustrating both for manufacturers and patients who are eager for access to life-saving treatment. Incentives like those mentioned above have helped expedite the process in certain circumstances, however, the system is likely to continue to evolve in the future in order to help patients receive safe treatment in a timely manner.

Sources

• “Advisory Committees Give FDA Critical Advice and the Public a Voice.” U.S. Food & Drug Administration. FDA, 2025.

• “Development & Approval Process | Drugs.” U.S. Food & Drug Administration. FDA, 2025.

• "FDA Drug Approval Process." Drugs.com. Drugs.com, 2024.

• “How Clinical Trials Work.” National Heart, Lung, and Blood Institute. NIH, 2022.

• “The Drug Development Process.” U.S. Food & Drug Administration. FDA, 2025.