Master Protocols provide a framework to simultaneously evaluate more than one investigational drug and/or more than one disease type within the same study and under a common (master) protocol. For example, a single investigational drug or drug combination could be evaluated for multiple cancer types (Basket trial design) as a part of a Phase-2 trial with further confimatory trials planned for cancer types that show benefit with the investigational drug.
Another example is that of Umbrella trial design where multiple drugs or combinations of drugs are evaluated for a particular disease against a common control arm. Yet another type of trial design within a master protocol is the Platform trial design where multiple drugs or combination of drugs are evaluated for multiple related disease type, for example, multiple biomarker-defined subpopulations within the same cancer type. In this case further investigation of drugs showing little promise can be halted while new drugs can be added into the pool.
There are several statistical challenges that have to be dealt with in setting up a trial under a master protocol. The major ones being adaptive (data-driven) decision rules in dropping/graduating/increasing sample size for a disease type and/or therapies - also the use of shared information; seamless (both operationally and inferentially) extensions for promising therapies; and the problem of multiplicity (testing of multiple hypotheses, multiple interim looks, etc.).
Our statisticians can help in setting up the trial design and ironing out the statistical details for such protocols. They can also help with interim analyses and decision making. Our experience in this area includes:
- A platform trial design for a COVID therapeutic trial.
- A seamless phase-1/2 dose escalation and dose finding oncology trial evaluating multiple single agents and their combinations.
- A Basket, Master protocol adaptive design for a rare indication with nutraceuticals.