CDISC Standard Data Tabulation Module

Domain ConstructionTrial Design Domains

Presented By:Ankur SharmaBiostatistical ProgrammerPAREXEL InternationalBaltimore, MD, USA

Review

In our past presentation, we have studied about Special purpose domains and covered domains such as DM, CO, SE, SV all of which belongs to subject level domains only and do not conform to any of the three general observation class as mentioned below:

Data Classification in three general observation class.

a.) Intervention b.) Events c.) Findings

Trial Design Datasets:

Trial Design domain, such as Trial Arms (TA), Trial Elements (TE), Trial Visits (TS), Trial Summary (TS) represents information about study design and do not contain subject data.

Purpose of Trial Design domains are to provide the clear description of overall plan and design of the study basically the Clinical study report in the data form.

Trial Arms (TA)

Trial Arm has the structure of one record per planned element per arm.

Trial Arms describes the sequence of Elements in each Epoch for each Arm and thus describes the complete sequence of Elements in each arm.

It is always adviced to design trial arm the study cell level then the Element level to cover each Element to be covered in study.

STUDYID & DOMAIN

As in all other domains, we have several required variable such as:

a.) Study Identifier: Study Identifier, is the identifier number for study obtained from

protocol or study related documents b.) DOMAIN: This is two letter abbreviation for the domain TA.

ARMCD & ARM

ARMCD & ARM: Planned ARM Code, it’s a required variable and its value must be in accordance with value of ARMCD in Trial Arm (TA) dataset. By definition ARMCD defines the coded value and the structure of the drug assignment. For ex: For any 2 period crossover study, we have two drugs named as: Reference Drug (R) and Test Drug (T). As per the design of the drug plan following the period.

Continued….

Suppose for period 1, drug is assigned as Reference Drug (R) and then Test Drug (T) then ARMCD value will be R-T or RT. Similarly for period 2 the value will be in reverse order as T-R or TR and Value of ARM will be Reference-Test or Test-Reference respectively.

For any patient which is a screen failure and then ARMCD is assigned as ‘SCRNFAIL’ and ARM value is “Screen Failure”. For any patient which is not a screen failure but also not assigned to any ARMCD, its value for ARMCD be “NOTASSGN” and value for ARM be “Not Assigned”.

TAETORD

Planned Order of Elements with Arm: This represents planned order of an element in

an Arm. Its value will not be populated for the ELEMENT that are not planned for the ARM for which subject was assigned. Thus for any value of ETCD as “UNPLAN”, TAETORD should be blank.

• As per the definition of planned order of element with ARM this value is assigned in the following

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manner. For ex: if a patient is enrolled in study for Drug A vs Drug B, and assigned to get Drug A, but receives Drug B then TAETORD would be left blank for SE record for their Drug B Element.

If a subject is assigned sequence of element as A, B, C and D and instead receives A, D, B and C then its sponsors decision to decide how the visits are to be assigned and this must be described in the comments section of Define.xml.

ETCD

ETCD: Element code is the code value assigned to the variable ELEMENT. Its value can be traced from the trial design domain Trial Element (TE).

In any case if value of ELEMENT encountered is entirely different from the planned element as specified in Trial Element (TE), then this value must be replaced with the text value “UNPLAN”, since its not in accordance with the planned value of element. For ex: SCREEN, IV,ORAL, FOLLOW UP.

ELEMENT

ELEMENT: This consist the description of the Element, which usually indicates the treatment assigned during an element or if no treatment is being administered, which is the other activites that are the purpose of the period of time, such as Screening, Washout, Follow up.

As explained during the derivation of the ETCD variable explaining about situation where subject

Continued….

encounters the value of treatment which is unplanned then value of ETCD is assigned as UNPLAN, in this scenario value of variable ELEMENT should be null.

An ELEMENT is a building block for creating Study Cells and an Arm is composed of Study cells. This defines how whole drug sequence was performed.

TABRANCH

Branch: This is the expected variable. This describes the outcome of a branch decision point in the trial design for subjects in the Arm. Branch decision points takes place between Epochs and is associated with the element. For instance, if subjects are assigned to an ARM where they receive treatment A through a randomization at the end of the Element X, then value of TABRANCH for Element X would be “Randomized to A.”

TATRANS

Transition Rule: This variable again is the expected variable. As per the definition for TATRANS, if the trial design allow any subject to move to other Element than the next one in the sequence, then that condition which allows the subject to do so, populates the value for variable TATRANS. For ex: Subject was assigned to following Element sequence

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Such as Screening, Drug A, IV, Drug B and because of any reason possibly any adverse event or may be change in the position in the crossover study subjected to new Element as following Screening, Drug A, Washout then that particular condition which in the above said case is patient suffered adverse event or changed to another study period is TATRANS value.

EPOCH

EPOCH: It’s the value of the visit associated with the Element in the planned sequence of the ARM for which the subject is assigned.

For ex: if ETCD is SCREEN, then value of EPOCH is SCREEN. If ETCD is IV then EPOCH is FIRST TREATMENT or whichever value of treatment is assigned.

Trial Elements (TE)

Trial Elements domain contains all the information regarding the Elements that are included in the study and subjects are assigned to it.

In the TE domain, important thing to note that there are no gaps between Element, as one Element the other starts right after that.

TESTRL

Rule for Start of Element: This variable identifies the event that

marks the transition into this Element. For Elements that involves the treatment is usually the start of treatment.

• Important thing to remember is to assign the start rule to element carefully. In case of non treatment element such as Washout and

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Screening, Trial Element start rule will be defined as 24 or 48 hour after the last dose of drug for the proceeding treatment element or Epoch. Rule can also be defined by a decision making activity such as enrollment or randomization. Since its element based variable so its not necessarily needs to match the TA domain.

TEENRL

Trial Element End Rule: Trial Element End rule basically accounts

for the condition which describes how any subject moved out or completed the Element it was assigned to. It can depend on the condition how Element was achieved. For ex: if a patient in oncology for ending of a rest study rule would be explained as follows:

Continued….

15 days after start of Element and after WBC values have recovered.

End rule must be described disregarding the ARM and just be referring to the Trial Element.

TEDUR

Trial Element Duration: Trial Element duration variable must

be populated for every record where TEENRL is populated. This variable must be presented in ISO 8601 format as specified, its value such as P6W is equivalent to TEENRL of “6 Weeks after start of element”.

Trial Visit

Trial Visits domain describes the planned visit in a trial. These visits basically are described in VISIT, VISITNUM, and VISITDY.

Trial visit has the structure of “One record per planned Visit per Arm”.

Assumption for populating variables such as ARMCD in this domain is if all the visits are

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Same for all of the ARM, then ARMCD variable doesn’t need to be populated.

But in any case, if visits are same for couple of ARM values and different for the others than ARMCD should be populated for each record, even though it will be creating duplicate records.

VISITNUM & VISIT

VISITNUM: Visit Number is the numerical sequence provided to the visit according to the study related document, may be from protocol or codebook.

VISIT: Visit is defined as the textual presentation of the numeric visit defined as per protocol defining each visit. For ex: if VISITNUM is 1 then VISIT is assigned as SCREENING.

VISITDY

Planned Study Day of Visit: Planned study day of visit as per the

definition is the visit planned by the study protocol to follow and its numeric in nature.

For ex: Planned study day structure for any study is defined as: 1, 2, 3,4,8,29, which explains as the treatment period starts from the Visit 1 and goes till Visit 8, and further non treatment day 29.

ARMCD & ARM

As explained in the previous slides.

TVSTRL

Trial Visit Start Rule: Rule describing when the Visit starts, in

relation to the sequence of Elements. For ex: for Screening visit rule would be stated as Start of the Screening Epoch. For visit 1 rule would be stated as when the visit 1 was started, if suppose Visit 1 is after next day of Screening then rule will be 1 day after Screen Epoch. TVSTRL is a required variable.

TVENRL

• Trial Visit End Rule: This the rule describing the end of the

visit in relation with the sequence of the element. This rules will be based upon when the trial element completes. For ex: if Screening visit ends in 4 hrs for every subject, then TVENRL will be 4 hrs after Start of Visit. TVENRL is a permissible variable.