Cohorts and Titration

Overview

A cohort is a subgroup of patients that shares a specific enrollment window, treatment arm assignment, and set of participating countries. Think of cohorts as "waves" or "batches" of patients entering the trial under defined conditions.

In Step 6 of the wizard, you can optionally configure cohorts and titration rules. Each cohort links to exactly one treatment arm and adds enrollment timing, a patient target, and country-level participation. The forecasting engine computes demand per cohort and rolls it up into totals, giving you an accurate picture of when and where kits are needed.

When to Use Cohorts

Skip cohorts if your trial enrolls all patients simultaneously under the same protocol. Most standard trials fall into this category — treatment arms alone are sufficient.

Use cohorts if:

• Phased enrollment — A safety run-in cohort enrolls first, then an expansion cohort opens once interim data is reviewed
• Dose escalation — Cohort 1 receives a low dose, Cohort 2 a medium dose, and Cohort 3 a high dose, each starting sequentially
• Adaptive designs — Interim analyses trigger changes in enrollment timing or patient targets for subsequent groups
• Regional rollout — Different cohorts enroll in different countries at different times

If you are unsure whether you need cohorts, skip them for now. You can always return to this step and enable them later.

The Step 6 Interface

When you arrive at Step 6, you see a card with two independent toggles at the top:

• Cohorts — Enables patient group management
• Titrations — Enables dose escalation/de-escalation rules

Both toggles default to off. You can enable either, both, or neither.

Neither feature is required. If your trial does not need cohorts or titration rules, leave both toggles off and continue to Step 7.

Creating Cohorts

Prerequisites

Before you can create cohorts:

• Countries (Step 1) — At least one country must be configured
• Treatment Arms (Step 5) — At least one treatment arm must be defined

If either prerequisite is missing, you will see a message directing you back to the relevant step.

Creating a Cohort

Click Create First Cohort (or Add New Cohort if cohorts already exist). An inline form opens with three sections:

Basic Information

Enrollment Period

Patient and Country Details

Cohorts auto-save after 1.5 seconds of inactivity. You can also click Save Cohort to save immediately.

Copy Cohort Configuration

When creating a new cohort and at least one cohort already exists, a Copy from... button appears. Select an existing cohort to copy its treatment arm, dates, patient count, and country selections. The cohort name is not copied — you must provide a new, unique name.

Managing Multiple Cohorts

All cohorts appear in a data table with the following columns:

Use the search bar above the table to filter cohorts by name. Click Edit to reopen the inline form, or Delete to remove the cohort (with confirmation).

Summary Statistics

Below the cohort table, a statistics bar shows four metrics:

Enrollment overflow warning: If total patients across all cohorts exceeds your recruitment target from Step 2, an amber warning banner appears. This is a warning, not a blocker — you can still proceed, but review your numbers to ensure the forecast reflects your intent.

Arm and country coverage gaps are informational only and do not prevent you from continuing.

Titration Rules

Titration is the adjustment of a patient's dose during the course of a trial. This is an advanced feature for trials with variable dosing — dose escalation, de-escalation, or pre-planned dose changes at specific visits. Most fixed-dose trials do not need titration.

Common Titration Patterns

• Escalation — Start at a lower dose, increase based on tolerability (e.g., move from 50mg to 100mg at Visit 2)
• De-escalation — Start at a higher dose, reduce if adverse events occur
• Pre-planned — Dose changes at predefined visits regardless of response

Why It Matters for Forecasting

Different dose levels typically require different kits. If 60% of patients escalate from Kit A to Kit B at Visit 3, the forecast needs to account for the changing mix of kits over time. Without titration rules, the forecast assumes patients stay on the same kit throughout.

How Titration Mode Works

Titration rules are scoped based on whether cohorts are enabled:

This is automatic — when cohorts are enabled, you define titration rules per cohort. When cohorts are disabled, you define them per treatment arm.

Prerequisites

• At least two kits must be defined in Step 3 (a "from" dose and a "to" dose)
• At least one cohort or treatment arm must exist, depending on the mode

Creating Titration Rules

Toggle Titrations to on at the top of Step 6. Each titration rule specifies a dose transition at a particular visit for a percentage of patients:

Click Add Another Rule to define additional dose transitions. You can define multiple rules for the same cohort or arm at different visits.

How Titration Affects the Forecast

• Before the titration visit: All patients use the original kit
• At and after the titration visit: The specified percentage transitions to the new kit, changing the demand mix
• Cascading transitions: If a patient escalates at Visit 3 and again at Visit 6, both transitions are reflected

Your kit demand forecast becomes visit-aware — different visits may require different quantities of each kit based on expected patient transitions.

Titration rules auto-save after 1.5 seconds of inactivity.

Disabling Features

Disabling Cohorts

If you toggle Cohorts off after creating cohorts, a confirmation dialog appears warning that all cohort data and related titration rules will be permanently removed.

Disabling Titrations

Similarly, toggling Titrations off when rules exist shows a confirmation dialog warning that all titration rules will be deleted.

Both actions are destructive and cannot be undone.

Validation Before Proceeding

Common error messages:

• "Please add at least one cohort" — Cohorts toggle is on but no cohorts exist
• "Cohort end date must be after start date" — Invalid date range
• "Cohort must have at least 1 patient" — Patient count is 0 or empty
• "Please select at least one country" — No countries assigned
• "Please select a treatment arm" — No arm selected

Tips

• Most trials do not need cohorts. Use them only for phased or dose-escalation designs. Treatment arms alone produce valid forecasts for most trials.
• Watch the summary statistics. If total cohort patients exceeds your recruitment target from Step 2, review your numbers.
• One arm can have many cohorts. Use this for dose escalation: three cohorts (low, medium, high dose) can all point to the same arm but with different timelines and kits.
• Titration is powerful but complex. Only enable it if your protocol truly requires variable dosing.
• You can edit later. Return to this step and modify cohorts or titration rules at any time. Changes are reflected in the forecast immediately.
• Country coverage is informational. Uncovered countries still receive forecasting based on treatment arm settings — cohort-specific adjustments simply will not apply to them.