Phase 3 Clinical Trials Explained

Phase 3 Clinical Trials – Overview

Billions are spent to progress a drug to phase 3 trials, a vital phase from chemical to drug development. It focuses on efficacy and safety by collecting randomized control data on a larger number of patients with a given disease.

This phase involves confirming the drug’s efficacy, monitoring side effects, assessing the risk-benefit ratio, and determining the optimal dosage.

Phase 3 Clinical Trials – Introduction

It is necessary to perform the widest trials as most phase 2 clinical trials ending with a positive result do not succeed in phase 3. It is often due to a lack of therapeutic efficacy or serious adverse effects.

Phase 3 trials are conducted to obtain additional information and verify the new drug’s effectiveness and safety to assess the risk/benefit ratio.

This information is used in the drug’s labeling once the FDA approves it. These trials involve large-scale studies and include several hundred to thousand patients.

Phase 3 trials are Randomized Control Trials (RCTs), where the participants receive the experimental drug or placebo randomly.

The trials are double-blinded; neither the investigator nor the participant will know what the latter has received. The average duration of the trial ranges from one to four years.

A substance is considered a drug candidate or investigational drug before Phase 3; it is typically referred to as a drug throughout its development process, not only after positive Phase 3 results. It is then approved for registration and accepted by the concerned authorities. Based on valid arguments, it can be subsequently offered to prescribing physicians.

The Center for Drug Evaluation and Research (CDER), a division of the U.S. Food and Drug Administration (FDA), oversees these clinical trials.

CDER can bring a clinical on hold if the phase 3 trial design doesn’t meet its objectives or if a study is found unsafe.

Key Takeaways

  • Phase 3 trials are the third stage of clinical drug trials before a new drug can be approved for public use, followed by Phase 4 post-marketing surveillance.
  • These are randomized control trials, double-blinded, and involve large-scale participation, focusing on safety and efficacy.
  • Phase 3 trials are expensive and, therefore, have been blamed for high drug prices.

Phase 3 Clinical Trials – Methodological Bases

Phase 3 clinical trials are typically controlled and involve random assignments between control and treatment groups, and they are usually double-blind to ensure the reliability of results. It includes a sufficient number of patients. Though the modalities differ depending on the substance studies, the protocol must satisfy certain general demands.

  • Choice of scheme

The choice of the experimental scheme depends on factors such as the study’s objectives, stages, and number of participants.

The correct evaluation of the effectiveness of the drug requires comparison. The experimental scheme allows this comparison among two or more groups of patients.

The participating patients are divided randomly into two groups and receive the planned treatment throughout the trial period.

  • Randomization

Randomization is necessary and is intended to reduce bias in the choice of drugs or treatments. In this method, a patient is given treatment by chance.

Randomized clinical trials have contributed immensely to advances in patient care and serve as the standard for research.

  • Blind Studies

Implementing a blind procedure is necessary as the efficacy of treatments can be assessed. It involves two types of blinding: single-blind, where only the patient is unaware of their treatment group, and double-blind, where both the patient and the physician are unaware.

  • Statistics

The statistical tests ensure that the differences observed are meaningful. The high comparison levels contribute to the maximal probability of detecting a difference between treatments.

Phase 3 Clinical Trials – Key Elements

The several key points for phase 3 protocols include:

  • Inclusion Criteria

Want to participate in the trial? The inclusion criteria define the requirements for entering the trial. If the criteria are too vague, the patient may comprise a heterogeneous group, making it difficult to interpret trial results, thus compromising the study’s objectives.

On the other hand, if the inclusion criteria are too restrictive, finding a sufficient number of patients becomes impossible, and the results become difficult to extrapolate.

Depending on the substances studied in phase 3, several trials are conducted. During each trial, a specific population can be studied.

  • Exclusion Criteria

Exclusion or non-inclusion criteria must be indicated to eliminate patients for whom the trial represents an excessive risk. It could also represent those who would make the group too heterogeneous or those whose follow-up is uncertain.

  • Evaluation Criteria

Evaluation or judgment criteria are fundamental to attaining the study’s objective and must be chosen judiciously. They include assessment tools and outcome measurements, evaluating the safety, efficacy, and tolerability of a new treatment.

  • Adverse Effects

Adverse or clinical and biological effects should be determined concerning possible symptoms.

  • Number of Subjects Required

The number of subjects required for the trial and its length are decided before the trial begins.

Phase 3 Trial – Associated Costs and Approval Process

Phase 3 trials are extremely expensive. However, the costs may vary depending on the complexity of the study and the number of sites involved.

Drug development companies view the steep costs associated with Phase 3 trials as necessary expenses. The drug provides clinical benefits, and the successful completion of a trial raises the odds of obtaining marketing approval from the FDA for a new drug.

Drug Approval Process

Despite extensive testing, it can sometimes be difficult to evaluate a drug’s effectiveness. Clinical trials demonstrate whether the drug is working or not; however, they do not indicate the reasons.

It is also possible that the subjects on whom the drug is tested are healthier than those using the tested treatment.

After the phase 3 clinical trial, the New Drug Application (NDA) is the formal step and a comprehensive document defining the new drug’s safety and efficacy.

It includes data and analyses of the drug on animals and human body studies and its toxicology, pharmacology, dosage, and manufacturing process. NDA has to be submitted to the FDA for approval. Once approved, the new drug is then marketed in the U.S. market.


Phase 3 clinical trials are more intensive extensions of Phase 1 and Phase 2 clinical trials.

These trials determine the ultimate efficacy, safety and dosage of drugs after comparing the results. The dosage levels are modified according to the most beneficial effects while offering the least side effects.

See Also

Phase 4 Clinical Trials

Biomedical Research Grants

Current Version
April 22, 2021
Written By
Victoria Abigail Friedland
April 25, 2024
Updated By
Franco Cuevas, MD

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