Introduction to master protocols : basket, umbrella, and platform trials

 

Introduction to Master Protocols

Master protocols are innovative clinical trial designs that allow for the investigation of multiple hypotheses under a single, overarching protocol. They are designed to improve efficiency, reduce costs, and accelerate the development of new treatments, particularly in the field of oncology. The three main types of master protocols are basket, umbrella, and platform trials.

1. Basket Trials

A basket trial evaluates a single targeted drug or drug combination across multiple different types of cancer or diseases. The commonality among the patients in a basket trial is a specific genetic mutation or biomarker that the drug is designed to target, rather than the location of their tumor.

  • Application: This design is highly efficient for testing drugs that target a rare genetic mutation that may appear in different types of cancer. For example, the VE-BASKET study evaluated vemurafenib in patients with various non-melanoma cancers that all shared the BRAF V600 mutation.

2. Umbrella Trials

An umbrella trial focuses on a single disease type but evaluates multiple different drugs or drug combinations. Patients with that disease are stratified into subgroups based on specific molecular or genetic markers, and each subgroup receives a different treatment tailored to its unique biomarker profile.

  • Application: This approach allows for a more efficient and comparative evaluation of several targeted therapies within a single disease area. The ALCHEMIST trial, for instance, used this design for patients with non-small cell lung cancer (NSCLC) who had either an EGFR mutation or an ALK gene rearrangement.

3. Platform Trials

A platform trial is an adaptive and often "perpetual" trial design that evaluates multiple interventions against a common control group. The key feature of a platform trial is its flexibility; it can seamlessly add new treatment arms or drop ineffective ones based on pre-specified decision rules as the trial progresses.

  • Application: This design is particularly useful for rapidly testing multiple therapies in a single disease area, as seen in trials for COVID-19 or in areas like stroke and breast cancer. The perpetual nature of the trial means it can continue to test new therapies as they become available without the need to start a new trial from scratch.






When to Use Each Trial Type

  • Use a Basket Trial when: You have a specific drug that targets a genetic mutation and you want to test its efficacy across a variety of different diseases that all have that same mutation. This is especially useful when the biomarker is rare within any single disease type.

  • Use an Umbrella Trial when: You are investigating a single disease and want to evaluate several different targeted therapies within that disease. This design allows you to stratify patients based on their molecular profiles and test which treatment works best for which subgroup.

  • Use a Platform Trial when: You want to efficiently and continuously evaluate multiple therapies for a specific disease or condition over a long period. This design is ideal for rapidly changing therapeutic landscapes, as it allows for the swift addition of new, promising drugs and the removal of ineffective ones, saving time and resources.

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