Distribution Workflow Summary

The following diagram outlines the analysis performed to summarize adverse events count and percent calculations for the AE Distribution report.

Distribution Workflow Steps

Apply Domain Filters

Three parameters, Include serious adverse events only , Event Type and Offset for End of Dosing , are used to specify a domain filter.

Available options are described in the following table:

Option:	Select when you want to:
Include serious adverse events only	• Include only those event records with AESER = Y
Event Type options rely on the available Date/Time start and end variables referenced above. Options include:
All event types	• Include all events.
Pre treatment events	• Include events that occur before dosing for treated subjects. • AESDTC before RFXSTDC , for example
Treatment emergent adverse events	• Include events that occur on or after the first dose of study drug, or are flagged as treatment emergent based on AETRTEM or TRTEMFL .
On treatment events	• Include events that occur on or after the first dose of study drug and at or before the last dose of drug (+ the offset for end of dosing). • Include only events where AESDTC on or after treatment start date AND before treatment stop date. • Use the optional Offset for End of Dosing for specifying end of dosing (to account for drug half-life, for example).
Off treatment followup events	• Include events that occur after the last dose of drug (+ the offset). • Include only events where AESDTC on or after treatment start date AND before treatment stop date. • Use the optional Offset for End of Dosing for specifying end of dosing (to account for drug half-life, for example).

You can also use the Include the following adverse events: and Filter to Include Adverse Events options based on user-customized condition and/or on new/modified/stable records (when JMP Clinical snapshot comparison is being used)

Apply Subject Filters

These options filter the available subjects to use for the analysis and impact both the counts of adverse events (relevant events are considered only for subject in the analysis population) as well as for computing denominators to perform subject percent calculation.

Three parameters, Subject Filter , Additional Filter to Include Subjects and Select the population to include in the analysis , are used to specify a domain filter.

Available options are described in the following table:

Option:	Select when you want to use a:
Subject Filter	• Data set containing USUBJID values of subject to include in analysis. These data sets can be created from most of the JMP Clinical reports.
Additional Filter to Include Subjects	• General user-customized condition (enter Sex = "F" to only include females in the analysis, for example). • A percent calculation is then only generated based on demographic variable groups for subjects meeting the filtering criteria.
Select the population to include in the analysis	• Filter the subject population based on available flags in the ADSL, ADDM, or DM (and optionally SUPPDM) data tables.

Detect Crossover Study

If an ADSL table is defined and contains multiple treatment periods ( TRTxxP for example) and treatment period start/stop dates, ADSL is merged in and the corresponding treatment and period is assigned based on comparison with AESDTC .

Calculate Demographic Group Denominators

Fixed adverse event frequency/percent values are not computed and output in the results data set. Instead, the subject counts for all relevant treatment and demography variables are computed, in order to support interactive computation of AE subject percent calculations based on user filtering and selection of treatment or demographic group categories.

Note : If you want to output static AE percent tables only, the Adverse Event Report menu command should be run.

The subject counts for each value of relevant demographic variables ( Treatment , SEX , RACE , COUNTRY , SITEID , STUDYID (if not constant) are computed and then the reciprocal of the subject count is recorded in the DM or ADSL data set for merging into AE. This value can be used as a frequency weight for each subject that has a specific event to calculate the percent of subjects for that given demographic group that experience the AE.

The following example uses the Nicardipine data included with JMP Clinical.

In this example:

•	455 subjects were on Placebo.

•	The reciprocal 1/455 = .00219. This value can be used for each subject that has an AE to compute the percentage.

•	314 subject on placebo experience Vasoconstriction.

•	314 x 1/455 = 314/455 = .6901 or 69.0% of subjects on placebo experienced Vasoconstriction.

These reciprocal or frequency variables based on the demographic variable counts for each subject are computed and used when merged into the AE records table to compute percentages.

These columns are used in the distribution results dashboard to dynamically calculate percentages. Further examples are given when describing the dashboard results.

Note : If cross-over is detected, these demographic counts represent the total subjects for EACH treatment period.

Merge AE and DM/ADSL

The (filtered) AE data and the (filtered) DM or ADSL table (with computed demographic frequencies) are merged by USUBJID (and treatment period if cross-over is detected)

Optional Count Multiple Event Occurrence

The dialog contains an option to count multiple occurrences of events.

This option is turned OFF by default.

Percent calculations are performed only if this option is UNCHECKED so that when a unique event is counted only once per subject, you can interpret the frequency of AE counts as the percentage of subjects experiencing the event. The representative adverse event is chosen based on Seriousness ( AESER if exists), Severity ( AESEV ), and computed study day ( AESTDY or based on AESDTC )

Note : JMP Clinical assumes accordance with controlled terminology: "Y" to represent severe events, and "MILD", "MODERATE", "SEVERE" to select the serious, most severe event as representative.

For other events/interventions, the representative unique occurrence is chosen based on the first occurrence. The following help documentation for the Count multiple occurrences of an event per subject check box option describes the result of this option.

Box state:	Result:
Unchecked	Compute counts based on the number of subjects that had a specific intervention. Each subject contributes only one time to the occurrence count of an intervention, regardless of how many times that specific intervention might have been applied to the subject. Note : Representative intervention occurrence per subject is selected by sorting the data and taking the first intervention occurring to a subject based on Study Day.
Checked	Compute counts based on the overall counts of interventions, including multiple occurrences per subject.

Overall Subject Percent Occurrence for Each Event

This step is performed only when a unique occurrence of an event is counted (based on above check box option). This is total percent of subjects experiencing an event, calculated for each event.

For example, in the Nicardipine data , 560 of the 902 subjects in the safety population experienced vasoconstriction.

•	560/902 = 0.621 or 62.1% of all subjects had a vasoconstriction event, regardless of treatment.

After all of these steps have been completed, the STUDY_ae_xx.sas7bdat results table is used for the JMP results dashboard report.