Table 2.

Examples of the use of randomisation in early-phase dose-confirmation trials.

Clinical Setting	Prior/available data	Assumptions
Paediatrics	Extrapolating from completed adult studies	Drug profile in adults has been established and it is safe. Paediatric patients are expected to tolerate the treatment as well as or better than the adult patients. This has been true with most cytotoxic therapies, whether this is true for novel classes is uncertain.
Paediatrics	Extrapolating from ongoing adult studies	Drug’s safety profile in paediatrics and adults is unknown. Paediatric patients are expected to tolerate the treatment as well as or better than the adult patients and this will be tested.
Combination Regimens	Experimenting at the MTD of each drug individually and 1–2 levels below	Combination of the MTDs of each single agent is expected to be tolerable and this is to be confirmed.
Emerging evidence	Obtaining reliable control estimates on safety parameters	Historical data and data from ongoing trial are anticipated to be in agreement and this will be monitored.

MTD maximum tolerated dose.