Phase III trials involve the use of an investigational product on a larger population with the disease or condition (usually 300 to several thousand). Once the dose has been determined and the safety profile on both healthy volunteers and patients with the targeted condition looks promising, phase III studies will be done to confirm the dose, efficacy and safety as well as compare the effectiveness of the product with current approved drugs that target the same condition.  

Patient Selection

• Inclusion Criteria: Phase III trials aim to confirm the efficacy and safety of a new intervention identified in earlier phases. Inclusion criteria are carefully defined to ensure that the study population is representative of the target patient population. Criteria may include age, gender, disease severity, previous treatment history, and other relevant factors.
• Exclusion Criteria: Exclusion criteria are set to eliminate factors that might confound the study results or pose risks to participants. Common exclusions include the presence of other serious medical conditions, use of certain medications, or allergies.
• Diversity Considerations: Efforts are made to include a diverse patient population to ensure that the results can be generalized to a broader demographic.

Design of Phase III Trials

• Randomized Controlled Trials (RCTs): Phase III trials are typically randomized, meaning participants are assigned to different treatment groups randomly. This helps control for confounding variables and increases the reliability of the study findings.
• Blinding: Double-blind, placebo-controlled designs are often employed to minimize bias. This means that neither the participants nor the investigators know who is receiving the experimental treatment and who is receiving a placebo or standard treatment until the end of the study.
• Sample Size: Determining an adequate sample size is crucial for the statistical power of the trial. This is calculated based on factors such as the expected effect size, variability, and significance level.

Endpoints of Phase III Trials

• Primary Endpoints: These are the main outcomes used to evaluate the efficacy of the intervention. They are typically chosen based on their clinical relevance and the ability to demonstrate the treatment’s effectiveness.
• Secondary Endpoints: These are additional outcomes that provide more comprehensive information about the intervention’s effects, safety, and tolerability.
• Surrogate Endpoints: In some cases, surrogate endpoints may be used as a substitute for a clinical endpoint. However, their validity and ability to predict clinical benefit must be well-established.

Ethical Considerations

• Informed Consent: Participants must provide informed consent before being enrolled in the trial. They should be fully informed about the study’s purpose, procedures, potential risks, and benefits.
• Independent Review Boards (IRBs): Each study must be approved by an IRB, an independent body that ensures the protection of participants’ rights, safety, and well-being.
• Data Monitoring Committees (DMCs): DMCs may be established to regularly review interim data to ensure participant safety and the scientific integrity of the trial.
• Publication and Reporting: There is an ethical obligation to publish and report the results of clinical trials, regardless of the outcomes. This helps prevent publication bias and ensures that the scientific community and the public have access to all relevant information.

References

• International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). ICH Harmonised Guideline: Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2). Current Step 4 version dated 9 November 2016. database.ich.org/sites/default/files/E6_R2_Addendum.pdf
• World Health Organization (WHO). Guidelines for good clinical practice (GCP) for trials on pharmaceutical products. who.int/medicines/areas/quality_safety/safety_efficacy/gcp1.pdf