Medical treatments, such as therapies to treat cancer, go through a multi-step process before they can be used by the general population. This process includes three phases of clinical trials, each one with its own purpose for testing the therapy.
Phase 3 is considered the last step before manufacturers apply to the U.S. Food and Drug Administration (FDA) for approval and more general use among a patient population. For this reason, phase 3 is the most critical – needing to meet the highest benchmarks for success.
By the time a treatment reaches phase 3 of the clinical trial process, it’s already shown promise. It cleared early safety tests in phase 1 and demonstrated signs of effectiveness in phase 2.
Yet, phase 3 is where it faces its most rigorous challenge: Can this treatment work better than what’s currently available, and is it safe enough to become a standard of care? This is the phase where medical innovation gets tested on a large scale – and where science and patient care truly intersect.
To catch up, read about the purpose of phase 1 clinical trials and phase 2 clinical trials.
What Is a Phase 3 Clinical Trial?
A phase 3 trial is a large-scale, late-stage study designed to confirm the effectiveness of a new treatment while continuing to monitor safety. It often involves hundreds to thousands of patients, sometimes including dozens of medical centers across multiple countries.
This phase compares the new treatment to the current standard (or to a placebo, if no standard exists) in a randomized and controlled trial. The aim is to generate statistically strong data that can support regulatory approval by agencies like the FDA or European Medicines Agency (EMA).
For example, a new immunotherapy treatment for the rare cancer mesothelioma will be tested against the current standard: chemotherapy. If immunotherapy performs better than chemotherapy – both in safety and efficacy – then there’s ground for approval.
Most phase 3 trials have two groups of people: a group receiving the tested treatment; and a group receiving a placebo or the standard of care for comparison. These groups are usually randomized to remove any potential bias in selection.
Significance of Phase 3 Trials
This is the final step before a treatment can be submitted for approval. Everything learned in phase 1 and phase 2 feeds into this moment, as phase 3 is what makes or breaks a therapy’s path to market. It determines whether a treatment has enough evidence to be made widely available.
Key reasons phase 3 trials are so important include:
- Providing conclusive data on how effective the treatment is compared to existing options
- Monitoring long-term and rare side effects in larger populations
- Help defining who benefits most from the treatment and under what conditions
- Shaping drug labeling, usage guidelines, and future insurance coverage decisions
Efficacy Versus Safety: Still a Balancing Act
Although safety is the main focus in earlier phases, it remains a critical element in phase 3. With more patients involved and longer treatment durations, this phase helps identify side effects that may not have appeared in smaller studies.
That said, effectiveness takes the lead in this phase. Researchers are testing whether the new treatment actually improves outcomes in a meaningful way – longer survival, better quality of life, faster healing or lower recurrence rates.
Endpoints in phase 3 trials are typically clinical (e.g., survival rates, disease progression, relapse) and statistically powered, meaning they’re designed to detect real differences between groups with minimal margin of error.
Enrollment Numbers in Phase 3 Clinical Trials
The size of phase 3 trials varies, but generally includes 300-3,000+ participants, depending on the disease being studied and how much statistical power is needed. For common conditions like hypertension or diabetes, numbers often climb into the thousands. However, for rare diseases such as mesothelioma, these trials are often on the smaller end, typically enrolling 150-600 patients.
Mesothelioma starts in the lining of the lungs, abdomen and heart. Only approximately 3,000 people are diagnosed in the U.S. each year, so the population size is small for clinical trials.
Factors that influence trial size include:
- The expected difference between treatment groups
- The variability of outcomes in the population
- The number of treatment arms or dosing comparisons
- How rare or common the condition is
- Regulatory requirements for approval
High Stakes of Phase 3 Clinical Trials
It’s worth noting that many therapies fail during phase 3 clinical trials despite earlier promise. The studies are long, expensive and heavily scrutinized. However, they are absolutely essential to ensuring that only the safest and most effective treatments reach the public.
By the end of a successful phase 3 study, researchers should be able to confidently answer the following questions:
- Is the new treatment more effective than current standard care or placebo?
- What are the most common and serious side effects?
- Which patients benefit the most (or the least) from this treatment?
- How does the treatment perform across different populations or subgroups (age, sex, ethnicity, etc.)?
The answers to these questions not only prove the therapy should be approved, but they also can dictate any treatment-related warnings for patients considering the therapy.
If the data is strong, the drug sponsor can submit a New Drug Application (NDA) or Biologics License Application (BLA) to regulatory agencies for potential approval and market launch.
Summary of Phase 3
Phase 3 clinical trials are the final proving ground for medical innovations. They are large, carefully designed studies that evaluate whether a new treatment really works and whether it’s safe for widespread use. The data collected here forms the foundation for regulatory approval and, ultimately, patient access.
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