Practicalities in running early-phase trials using the time-to-event continual reassessment method (TiTE-CRM) for interventions with long toxicity periods using two radiotherapy oncology trials as examples

Table 2 Minimum recommended detail to be included in grant applications. X shows the application stage where the information is required

Information to be included	Outline (for two-stage applications) or full (where the grant application requests funding and time to design and set-up the model)	Full (where the grant application does not include time to design and set-up the model)
Reference to key TiTE-CRM literature and a brief explanation of why this design is being used, as reviewers may not have encountered it before.	X	X
Sample size. If this is not fixed, provide an upper and lower bound.	X	X
	If not confirmed, add a note to say it will be confirmed after further simulations have been undertaken.	X
Dose-limiting toxicities	X	X
Target toxicity level	X	X
Target toxicity level	X	Include justification and how this was determined.
Dose-toxicity curve		X
Number of dose levels	X	X
Number of dose levels	Include an estimate if this is not yet known.	X
Starting dose level		X
Stopping rules		X
Any restrictions on recruitment or dose escalation		X
Software or packages used to set up the model and perform simulations		X
Information on simulations to be performed	X
Information on simulations to be performed	Include details of toxicity timing and recruitment rates
Simulation results		X
Simulation results		Include details of toxicity timing and recruitment rates
How the data will be used throughout the trial to determine dose decisions		X
		Discuss the role of the safety review committee and how late toxicities will be incorporated in the trial. Explain that dose decisions are not made solely by the TiTE-CRM model.

ISSN: 1471-2288