Experimental Design (TA and TE)

This contains the Trial Design datasets that describe the planned design of the study, and provide the representation of study product in its most granular components, as well as the representation of all sequences of these components as descripted in the protocol.. The TA and TE datasets are interrelated, and they provide the building blocks for the development of actual subject-level information included in the Demographics (DM), and Subject Elements (SE) domain. 

This section includes example trials, which illustrate the development of the TA and TE dataset. 

The core of the Trial Design Model is the TA dataset. For each arm of the trial, the TA dataset contains 1 record for each occurrence of an element in the path of the arm.

Although the TA dataset has 1 record for each trial element traversed by subjects assigned to the arm, it is generally more useful to work out the overall design of the trial at the study cell level first, then to work out the elements within each study cell, and finally to develop the definitions of the elements that are contained in the Trial Elements (TE) table.

When working out the design of a trial, it is generally useful to draw diagrams such as those mentioned in ICH E3. The protocol may include a diagram that can serve as a starting point. Such a diagram can then be converted into a trial design matrix that displays the study cells and which in turn can be converted into the TA dataset.

This section uses example trials of increasing complexity to illustrate the concepts of trial design. For each example trial, the process of working out the TA table is illustrated by means of a series of diagrams and tables, including:

• A diagram showing the branching structure of the trial in a “study schema” format such as might appear in a protocol

• A diagram that shows the “prospective” view of the trial (i.e., the view of those participating in the trial). This is similar to the study schema view in that it usually shows a single pool of subjects at the beginning of the trial, with the pool of subjects being split into separate treatment groups at randomizations and other branches. Such diagrams include the epochs of the trial, and, for each group of subjects and each epoch, the sequence of elements within each epoch for that treatment group. The arms are also indicated on these diagrams.
• A diagram that shows the “retrospective” view of the trial (i.e., the view of the analyst reporting on the trial). This style of diagram looks more like a matrix; it is also more like the structure of the TA dataset. The retrospective view is arm-centered and shows, for each study cell (epoch/arm combination) the sequence of elements within that study cell. It can be thought of as showing, for each arm, the elements traversed by a subject who completed that arm as intended.
• If the trial is blinded, a diagram that shows the trial as it appears to a blinded participant
• A trial design matrix, an alternative format for representing most of the information in the diagram that shows arms and epochs, and which emphasizes the study cells
• The TA dataset

The Trial Elements (TE) dataset contains the definitions of the elements that appear in the Trial Arms (TA) dataset. An element may appear multiple times in the TA table because it appears either (1) in multiple arms, (2) multiple times within an arm, or (3) both. However, an element will appear only once in the TE table.

Each row in the TE dataset may be thought of as representing a "unique element" in the same sense of "unique" as a CRF template page for a collecting certain type of data referred to as "unique page." For instance, a CRF might be described as containing 87 pages, but only 23 unique pages. By analogy, the trial design matrix in Example Trial 1 (see Section 7.2.1, Trial Arms) has 9 study cells, each of which contains 1 element, but the same trial design matrix contains only 5 unique elements, so the TE dataset for that trial has only 5 records.

An element is a building block for creating study cells, and an arm is composed of study cells. Or, from another point of view, an arm is composed of elements; that is, the trial design assigns subjects to arms, which comprise a sequence of steps called elements.

Trial elements represent an interval of time that serves a purpose in the trial and are associated with certain activities affecting the subject. “Week 2 to week 4” is not a valid element. A valid element has a name that describes the purpose of the element and includes a description of the activity or event that marks the subject's transition into the element as well as the conditions for leaving the element.

Example 1 should be reviewed before reading other examples, as it explains the conventions used for all diagrams and tables in the examples.