Using JMP Clinical for Crossover Analysis

All study information must be recorded using an ADSL data set following the ADaM standard to support multiple treatment periods.

Required Variables

The variables in ADSL required for the system to support crossover include the following:

•	Treatment Variables TRTxxP or TRTxxA : The Planned or Actual treatment for a given treatment period xx (The TRT01P , TRT02P , for example, would be the variables used to record the planned treatment for a two-period crossover analysis).

•	Timing Variables ( TRxxSDT or TRxxSDTM ) and ( TRxxEDT or TRxxEDTM ): Dates or Date/Times in numeric format indicating the start and end dates respectively for each treatment period xx .

Refer to the ADaM Implementation Guide for additional information.

JMP Clinical Reports Supporting Crossover Analysis

The software supports analysis and views for cross-over trials in the following reports.

•	Adverse Event Distribution

•	Adverse Event Incidence Screen

•	Adverse Event Severity ANOVA

•	Adverse Event Resolution Screen

•	Events Distribution

•	Events Incidence Screen

•	Findings Distribution

•	Findings ANOVA

•	Findings Time Trends

The system detects a crossover if multiple TRTxxP or TRTxxA variables exist and the associated timing variables for the xx period exist and contain values. Those values might look like the values in the Nicardipine Cross-over sample data set, shown below.

Note : For clarity, the majority of the adsl.sas7bdat columns in the screen shot below above have been hidden using the Cols > Hide/Unhide command.

In the screen shot of adsl.sas7bdat , shown above, the SAS variable names are shown. During the report analysis, when adsl.sas7bdat is merged into the relevant analysis domain (for example, AE , LB , VS ), the adsl treatment timing variables are compared to the timing variable in the domain and new variables: Treatment , Period , and Treatment (Period) are created. The values for these variables are assigned based on the value of the TRTxxP or TRTxxA and the value of the xx in the variable name when the start date of the domain record falls within the treatment period dates.

The SDTM data records for a subject can appear as shown in the portion of the VS domain ( vs.sas7bdat (SAS names are being shown)) for the Nicardipine Cross-over sample data set, shown below.

Note : For clarity, some of the vs.sas7bdat columns in the screen shot below above have been hidden using the Cols > Hide/Unhide command.

Based on comparison of the VSDTC date/time (note that SDTM follows the ISO 8601 date/time standard) with the ADSL timing date/time (numeric SAS date format), the subject records are assigned to the first treatment for Visits 1-6 and the second treatment period for Visits 7-14.

Similar analyses are done for events and intervention domains. In these domains, the timing comparisons for the record is based on the start date/time. For example, with the AE domain the AESDTC variable is used to assign the treatment period; indicating that the adverse event must START within the treatment period in order to be assigned that treatment value.

Report Results with Cross-over Analysis

A sample Nicardipine Crossover analysis is now shipped with JMP Clinical. This can be loaded (using the Settings button) from the Add Study from Folders dialog from the Clinical Starter Menu.

Analysis results and report options relevant to cross-over analysis are shown below.