---

Introduction

Enrollment describes how patients join the study over space and time. In order to adapt to the level of available data, 4C Supply® supports different enrollment methods ranging from strongly simplified to highly granular. The simplest, lowest detail approach is to use a single, static value in the Site Groups table. The other methods use a detailed enrollment table, which captures input as patients per month, with respect to the enrollment level.

---

Enrollment Levels

The enrollment level defines how enrollment details defined in the specification will be interpreted.

To define an enrollment level, a column with header Enrollment Level must included in the Demand Configuration table, which accepts values:

• Site (default)

• Region

• Cohort

By setting an enrollment level, users can specify that enrollment rates should be interpreted as:

• patients per site per month (default)

• patients per region per month

• patients per cohort per month

Site level enrollment

If the enrollment level is not defined or if it is defined as Site, 4C Supply® will evaluate specified enrollment rates as patients per site per month. Enrollment must be specified either:

• Statically, using the Site Groups table (enrollment rate of each active site in the corresponding site group in every period) - or -

• Dynamically, using an Enrollment table (enrollment rate of each active site in the corresponding site group in the corresponding period).

If the enrollment level is specified as Site and an Enrollment table is used, the column headers in this table must be specified as site groups (matching the site groups defined in the Site Groups table). If the Enrollment table column headers are not specified as site groups, an error message is shown.

Region level enrollment

If the enrollment level is set to Region, 4C Supply® specification will evaluate enrollment rates as patients per region per month.

If the enrollment level is set to region, enrollment must be specified using an Enrollment table (enrollment rate of the corresponding region in the corresponding period). If the enrollment level is set to region and enrollment is defined in the site groups table, a warning message is shown.

When using region-level enrollment and an Enrollment table, column headers in this table must be specified as regions. If column headers are not specified as regions, an error message is shown.

Note: If the enrollment level is set to Region and multiple site groups are specified per region, the individual site groups will show some variability in their enrollment.

Cohort level enrollment

If the enrollment level is set to Cohort, 4C Supply® specification will evaluate enrollment rates as patients per cohort per month.

If the enrollment level is set to cohort, enrollment must be specified using an Enrollment table (enrollment rate of the corresponding cohort in the corresponding period). If the enrollment level is set to cohort and enrollment is defined in the site groups table, a warning message is shown.

When using cohort-level enrollment and an Enrollment table, column headers in this table must be specified as cohorts. If column headers are not specified as cohorts, an error message is shown.

---

Using the Site Groups table

Enrollment can be defined in the site groups table. In this case, different enrollment rates can be applied for each site group which are the same for each enrollment period.

If enrollment is specified in the same specification in the site groups table and in an enrollment table, an error message is shown.

Using the Enrollment table

Enrollment can be defined in a dedicated Enrollment table. In this case, different enrollment rates can be applied:

• for each cohort,

• for each site group or region and

• for each enrollment period.

In studies without cohorts:

• If enrollment level is site: there must be a column for each site group in the enrollment table

• If enrollment level is region: there must be a column for each region in the enrollment table

In studies with cohorts:

• If enrollment level is cohort: there must be a column for each cohort in the enrollment table

• If enrollment level is site: there must be a column for each cohort and site group in the enrollment table

• If enrollment level is region: there must be a column for each cohort and region in the enrollment table

If any of the columns specified above are missing, no enrollment will be forecasted for the corresponding site group, region, cohort, cohort / site group combination, cohort / region combination.

Note: If enrollment is defined in an enrollment table for a scenario with cohorts and the enrollment table column headers do not specify the cohort, an error with the following message is shown:

Examples

Note the table caption does not change with the level, for all versions of the table the caption should be: Enrollment table

Site Group level enrollment

Region level enrollment

Cohort level enrollment

Region level enrollment with Cohorts

Site level enrollment with Cohorts

Period Start Date

Defines the start date of each enrollment period. Must be a valid date. If an invalid entry is made, a warning message is shown.

In forecast calculations with RTSM data extract, the series of period start dates specified in 4C Supply® defines when further enrollments are forecasted to occur.

• If a period occurs before the extract date, then 4C Supply® will not consider the associated enrollment in the forecast calculation.

• If a period occurs after the extract date, then 4C Supply® will consider the associated enrollment in the forecast calculation.

Enrollment rate

Defines the number of patients forecasted to be enrolled in each cohort, site, or region per month. Enrollment rates are always interpreted as patients per site cohort/site/region per month; even if the periods are days and exact dates are specified as period start dates. To model enrollment per day, enter 30 times the intended enrollment rate per day. This will be interpreted as the enrollment rate per month, so the result will be the intended enrollment rate per day.

Blank cells before the first enrollment rate entry are interpreted as zero. Empty cells below an enrollment rate entry are interpreted to be the same value as the cell above.

To ensure enrollment does not continue past a certain date for any given cohort, site, or region, enter a row with 0 in the cell.

Example:

Explanation: enrollment will stop on 31-Mar-2024 when the table on the left is used. Enrollment will continue indefinitely when the table on the right is used; the rate will stay the same, 2 patients per month for Site Group A, and 1 patient per month for Site Group B. Enrollment will continue until the cap has been reached when 0 values are not used to truncate the table.

In forecast calculations with RTSM data extract, the combination of cohort and site group or region specified in 4C Supply® for an enrollment period is the combination of cohort and site group or region where further enrollment is forecasted to occur in the associated period. If enrollment is forecasted to occur in a combination of cohort and site group or region that does not exist, a forecast calculation error is shown.