Summary of Trial Design Concepts

The design of a study is a plan for outlining the activities subjects will experience and what data will be collected about them, in the course of the study, to address the study's objectives.

Nonclinical only: A study set is a collection of subjects or sources of information (REFIDs) that have a common set of parameters defined in the protocol, where those parameters include experimental parameters (e.g., diet restriction), product exposure parameters, and/or applicant-defined attributes (e.g., control-group designation). Each subject or source of information (REFID) must be assigned to 1 and only 1 study set. Each study set in an in vivo study should be assigned to a single study arm.

In vivo studies: There should be no planned parameters of interest that could further subdivide a study set. Each study set should be assigned to a single group. Each study set in an in vivo study should be assigned to a single study arm.

In vitro studies: study sets can be further subdivided into additional study sets. 

As part of the design of a study, the planned periods or phases of subjects' participation are divided into epochs. Each epoch is a period of time that serves a purpose in the study as a whole. Typically, the purpose of an epoch will be to expose subjects to a product, to prepare for such a period (e.g., screening period, wash-out period), or to gather data on subjects after exposure to a product has ended. It is possible for epochs to span multiple elements for some or all study arms.

An arm is a planned path through the study. This path covers the entire time of the study. The group of subjects assigned to a planned path is also often referred to as an "arm." Each subject is assigned to 1 and only 1 planned arm. 

Nonclinical in vitro studies only: Nonclinical in vitro studies do not typically have defined arms.

Product Impact on Individual Health only: Each planned path through the study (i.e., each arm) is divided into pieces, 1 for each epoch. Each of these pieces is called a study cell. Thus, there is a study cell for each combination of arm and epoch. Each study cell represents an implementation of the purpose of its associated epoch. For an epoch whose purpose is to expose subjects to product, each study cell associated with the epoch has an associated strategy. 

An element is a basic building block in the study design. All elements are related to planned interventions, which may involve exposure to a product or no exposure to a product, during a period of time. Elements for which the planned intervention does not involve exposure to a product could include but are not limited to screening and wash-out.

Product Impact on Individual Health only: Many studies involve a single, planned exposure within a study cell. For some studies, however, the strategy associated with a study cell involves a complex series of exposures to product. In such cases it may be important to track the component steps in a strategy operationally; analyses also might require that data be grouped by the exposure step during which it was collected. The steps within a strategy may involve different exposures to product or exposure to more than one product. When the strategy for a study cell is simple, the study cell will contain a single element, and for many purposes there is little value in distinguishing between the study cell and the element. However, when the strategy for a study cell consists of a complex series of exposures, a study cell can contain multiple elements. There may be a fixed sequence of elements, or a repeating cycle of elements, or some other complex pattern. In these cases, the distinction between a study cell and an element is very useful.

In a study or trial with multiple arms, the protocol plans for each subject to be assigned to 1 arm. The time at which this assignment takes place is often the point at which arms with common elements diverge and is referred to as a branch point. For many studies or trials, the assignment to an arm happens once so there is a single branch point. Subjects are assigned to an arm all at the same time. For other studies or trials, there may be 2 or more branches that collectively assign a subject to an arm. The process that makes this assignment may be a randomization, but this is not always the case.

The word product may be used in connection with epochs or elements, but has somewhat different meanings in each context:

• Because epochs cut across arms, an epoch involving exposure to a product is a higher-level concept that does not specify anything that differs between arms. 
• Product Impact on Individual Health only: A study cell exposure is specific to a particular arm. For example, a parallel study might have study cell exposures to two products, without any additional detail being specified. A study cell is at a relatively high level, the level at which exposures might be planned in an early conceptual draft of the study, or in the title or objectives of the study.
• An element may be fairly detailed and may be a short description of exposure to product.

Product Impact on Individual Health only: The notion of a visit—an encounter with a subject—derives from studies where subjects interact with the investigator during visits to the investigator's clinical site. However, the term is used in other studies, where a study visit may not correspond to a physical visit. For example, in a study with inpatients, time may be subdivided into visits, even though subjects are in hospital throughout the study. For example, data for a screening visit may be collected over the course of more than 1 physical visit. One of the main purposes of visits is the performance of assessments, but not all assessments need take place at clinic visits; some assessments may be performed by means of telephone contacts, electronic devices, or call-in systems. The protocol should specify what contacts are considered visits and how they are defined.