Introduction

Titration describes the dose level changes forecasted to occur during the patient journey in the trial.

Notes

Specification of titrations can occur using sentences or using visit action titration. If visit action titration is used, then titration specification using sentences is ignored.

If different titration rates should be modeled per region, visit action titration must be used.

Titration specification using sentences

Syntax

There are [total number of dose levels] dose levels in this study: [dose level 1, dose level 2, … and dose level n].

Patients in cohort [cohort 1, cohort 2, … and cohort n], treatment arm [treatment arm 1, treatment arm 2, … and treatment arm n] on dose level [dose level 1, dose level 2, … and dose level n], visit [visit 1, visit 2, … and visit n] can titrate to [dose level] with a [percentage] chance, to [dose level] with a [percentage] chance, … or remain on [dose level] with a [percentage] chance.

Example

There are two dose levels in this study: DL_L, DL_H.

Patients on dose level DL_L, visit V2, V3, V4 and V5 can titrate to DL_H with a 5% chance or remain on DL_L with a 95% chance.

Patients on dose level DL_H visit V3, V4 and V5 can titrate to DL_L with a 5% chance or remain on DL_H with a 95% chance.

Titration events

Definition

Defines at which visit and for which patients a titration can occur. Titration events are characterized by

• cohort,

• treatment arm,

• titration level and

• visit.

In forecast calculations with RTSM data extract, if a titration event is specified in 4C Supply®, then the corresponding titration rate will be considered in the forecast calculation for future visits of existing and forecasted patients.

Rules

Cohorts specified for titration events must match a cohort specified in the cohorts table. If an invalid entry is made, no error will be raised, but the titration specification will apply to all cohorts.

Treatment arms specified for titration events must match a treatment specified in the randomization specification. If an invalid entry is made, no error will be raised, but the titration specification will apply to all treatment arms.

Titration levels specified for titration events must match a specified titration. If an invalid entry is made, no error will be raised, but the titration specification will apply to all titration levels.

Visits specified for titration events must match a visit code specified in the visit schedule. If an invalid entry is made, no error will be raised, but the titration specification will apply to all visits.

In forecast calculations with RTSM data extract, if the titration events specified in 4C Supply® do not match the real future titration events (for which the RTSM extract often contains valuable data), the demand and supply forecasts can be incorrect.

Titration probability

Definition

Defines the percentage of patients forecasted to titrate at a titration event.

In forecast calculations with RTSM data extract, the titration probability specified in 4C Supply® is the assumed titration probability of existing and forecasted patients which is considered in the forecast calculation.

Rules

Must be a valid percentage value. If an invalid entry is made, an error with the following message is shown:

Must be a value between 0% and 100%. If an out-of-range entry is made, an error with the following message is shown:

If the titration probability specified in 4C Supply® does not match the real future titration probability (for which the RTSM extract often contains valuable data), the demand and supply forecasts can be incorrect.