Inferential and Operational Seamless Phase 2/3 Clinical Trial Designs: What Are They, How Are They Different, and Why Use Them?

Clinical trials are a critical part of the drug development process. They are used to assess the safety and efficacy of new treatments, and to gather data that can be used to support regulatory approval.

Traditionally, following a successful Phase 1 (First in Human) study, clinical trials programs usually move sequentially to the next two phases: Phase 2 and then Phase 3. Phase 2 trials are typically mid-size (larger than Ph1 but smaller than Ph3) and focused on assessing safety and dose-finding. Phase 3 trials are larger and focused on comparing the new treatment to the standard of care.

In recent years, there has been a growing interest in conducting seamless Phase 2/3 clinical trials. These trials combine the two phases into a single trial, which can offer a number of advantages.

Advantages of Seamless Phase 2/3 Trials

There are several advantages to conducting seamless Phase 2/3 clinical trials. These include:

• Reduced development time and cost: Seamless trials can reduce development time and cost by eliminating the need to conduct a separate phase 2 trial.
• Improved efficiency: Seamless trials can improve efficiency by allowing for more efficient patient recruitment and data collection.
• Increased statistical power: Seamless trials can increase statistical power by pooling data from both phases 2 and 3 (see Inferentially Seamless Trials below). This can lead to more reliable results and a greater chance of regulatory approval.
• Enhanced patient benefit: Seamless trials can enhance patient benefit by providing patients with access to a new treatment sooner.

Types of Seamless Phase 2/3 Trials

There are two main types of seamless phase 2/3 clinical trials: inferentially seamless trials and operationally seamless trials.

Inferentially Seamless Trials

Inferentially seamless trials use data from both Phases 2 and 3 in the final analysis. This means that the results of the Phase 2 trial are used to inform the design of the Phase 3 trial, and the results of the Phase 3 trial are used to confirm the findings of the Phase 2 trial.

Operationally Seamless Trials

Operationally seamless trials do not use data from both Phases 2 and 3 in the final analysis. Instead, the two phases are conducted as a single trial, but the data from the two phases are analyzed separately.

Which Type of Seamless Trial is Right for You?

The decision of whether to use an inferentially seamless trial or an operationally seamless trial depends on a number of factors, including the specific objectives of the trial, the availability of data, and regulatory requirements. One of the important issues with running an inferentially seamless trial is minimizing bias and Type I error of pooling Phase 2 data that has been viewed and assessed with the Phase 3 data. You will need to design your study to minimize this potential bias.

In summary, seamless Phase 2/3 clinical trials offer a number of advantages over traditional two-phase separate Phase 2 and Phase 3 trials. They can reduce development time and cost, improve efficiency, increase statistical power, and enhance patient benefit.