Table 1 Investigational medicinal product/dose
Adaptive study design category | Adaptive features | Boundaries |
|---|---|---|
Dosing regimen | 1. Dosing regimens may be determined or adapted in accordance with pharmacokinetic (PK), pharmacodynamic (PD), safety and tolerability data (as applicable) collected up to the decision making time-point. | 1. Maximum starting dose |
The term dosing regimen includes (1) the dose level administered, (2) the frequency of dosing and (3) the duration of dosing, i.e. the number of doses administered. Accordingly these can be adjusted individually or in combination. | 2. Maximum dose or exposure increment for each dose/exposure escalation step | |
2. The number of dosing regimens investigated may be adjusted. | 3. Maximum (mean) exposure | |
4. Minimum/maximum dosing frequency | ||
5. Minimum/maximum treatment duration | ||
6. Permissibility of dosing regimen adaptation within and/or between cohorts | ||
7. Minimum/maximum number of dosing regimens to be investigated, safety and tolerability permitting | ||
8. Dose/exposure relationships between discrete parts of umbrella protocols (e.g. between SAD and MAD parts). | ||
Sentinel/sub groups | 3. The number and size of sentinel/sub-groups groups within a dosing regimen may be adaptable | 1. Mandatory sentinel groups for selected dosing regimens/study parts |
2. Maximum sentinel/sub-group group size; maximum number of study participants receiving IMP at any one time | ||
3. Minimum time to elapse between sentinel/sub-groups of a dosing regimen | ||
IMP formulation/mode of administration | 4. Adaptable use of different IMP formulations or modes of administration | 1. Formulation/administration characteristics and requirements |
2. Exposure limits (see adaptive feature 1) |