Advanced studies—Multiple blinded products support

Summary

Multiple blinded products are supported in the case form (Enhancements 29020500, 33751893, 34736032, and 35962269)

Description

The industry has observed significant changes to the clinical trial design and methodology. In order to accommodate the evolution of clinical research, there is a need to enhance Argus Safety system to support advanced study configuration, case processing, and reporting. In this release, the system is enhanced to support multiple blinded products in the case form.

Study configuration changes

Argus Console > Business Configuration > Studies is updated to allow grouping of blinded treatment products. Configuration of blinded treatment groups is not mandatory and is available for blinded studies only.

A new button, Add blinded treatment groups, is introduced in this screen. When you click this button, a pop-up window appears, where you can configure blinded treatment groups at the study-arm-level. Each Treatment Group name must be unique. One or more blinded study products from the respective study can be associated with the Treatment Group.

When a study product is associated with a treatment group, all blinded products are expected to have an associated treatment group. In case form, you can select treatment groups that are associated with at least one blinded study product.

Treatment groups and respective blinded study products selected in the case form cannot be deleted or turned non-blinded.

Case form changes

Book-in screen

There are no changes to manual or E2B book-in screens in this release. Upon selection of Project ID, Study ID and Study Name, Case Actions > New Case > Product Name and Generic Name populates with the Study Name, as per the existing functionality.

Products tab in blinded state

New options are available in Products tab when blinded treatment groups are configured in study configuration. You must select the blinded treatment group in the new field, Treatment Group, which is mandatory and blank, by default. You can also add and delete blinded treatment group tabs using the right-click menu. Case form supports a maximum number of blinded treatment group tabs equal to the total number configured in the study configuration.

Only blinded treatment groups that are associated with at least one blinded study product in study configuration are available for selection in the case form.

When a treatment group is selected, product name as reported, product name, and generic name are updated to the format <Study Name (Treatment Group)>.

Event assessment tab

The blinded treatment groups are displayed along with study name under the Product column in the Event Assessment tab. Causality and listedness assessment can be captured for each blinded treatment group.

In Argus 8.4.3 release, the ability to assess listedness for each suspect study product in blinded cases based on their own datasheets/licenses was introduced. This is configurable in Argus Console > System Configuration > System Management (Common Profile Switches) > Case Processing > Assessments > Criteria for Event Level Assessment for Blinded Study. This functionality is maintained for each blinded treatment group:

• If Include datasheet/licenses for the default blinded study product is selected, then the system behaves as per existing functionality to evaluate and display event assessment only for single blinded product.

  Note:

  If a primary license is configured in study configuration, then event assessment is performed for the primary license product. If no primary license is configured in study configuration, then the event assessment is performed for any of the blinded product.
• If Include datasheet/licenses for all the blinded study products is selected, then the system displays all datasheets and licenses for the blinded study products associated with the blinded treatment group row as per study configuration.

Other

Case form sections and prints display the blinded treatment group(s) in the same format as shown in the Products tab > Product Name to the user based on their access rights including, but not limited to:

• PMDA tab
• Product Event Details tab
• Manual Report Scheduling dialog
• Medical Review
• Coding Review
• Case Summary
• Local labelling
• Medical Summary
• Case Form print

Blinded view

Pre-unblinding, users who do not have access to view or print unblinded information, see all blinded study products present in the case (tabs are blinded), including legacy cases where Treatment Groups were not implemented. The Treatment Group field is visible, if configured. Product name and generic name remain blinded until after the end of study unblinding.

Post-unblinding, users who do not have access to view or print unblinded information, see all study products present in the case (tabs are blinded), including legacy cases where Treatment Groups were not implemented. The Treatment Group field is visible, if configured. Product name and generic name remain blinded until after the end of study unblinding.

Legacy cases and study cases without treatment group configured

If study configuration is not updated to include treatment groups, the new Treatment Group drop-down field is not be available in the case form, and there is no impact on legacy cases and reporting.

If study configuration is updated to include treatment groups, by default, the one existing blinded product tab has a blank Treatment Group drop-down with no additional updates.

Manual unblinding

Manual unblinding in the General tab of the case form is enhanced to allow users to select one or more study products the patient received. This is not a mandatory step.

If treatment groups are configured, this dialog lists all configured treatment groups and respective study products for selection.

If treatment groups are not configured, this dialog lists all products marked as Blinded in study configuration for selection.

The system updates the product tab(s) automatically based on the study products selected in this dialog.

If no study product is selected, users are prompted to select a study product in Products > Study Drug, as per the existing functionality.

Note:

Add Study Drug option on right-click menu remains available after unblinding, as per the existing functionality.

Reporting changes

Paper reports (CIOMS I, CIOMS I Local and MedWatch)

Argus is enhanced to print more than one blinded product when a blinded report is generated for an unblinded case and multiple study products are added.

If the case is blinded and the report is set to view unblinded data, then Product Name includes <Study Name (Treatment Group) (code not broken)> for each Treatment Group. If the case is blinded and report is set to hide unblinded data, then Product Name includes <Study Name (Treatment Group) (code not broken)> for each Treatment Group. The rest of the study product fields are restricted as per existing behaviour.

If the case is unblinded and report is reviewed to view unblinded data, then Product Name displays the unblinded product, as per the existing behaviour. If the case is unblinded and the report is set to hide unblinded data, then Product Name includes <Study Name (Treatment Group) (code not broken)> for each Treatment Group. The rest of the study product fields are restricted as per the existing behaviour.

For more details, refer to CIOMS I, CIOMS I Local and MedWatch mapping documents.

Expedited report scheduling

Expedited report scheduling considers the existence of multiple treatment groups for report scheduling. You can also schedule report for any of the blinded products in the case.

E2B export (all profiles)

There are no changes in the mapping logic for E2B(R3) reports based on the Treatment Group configuration. Data populated in the MEDICINALPRODUCT[G.k.2.2] element of the Blinded E2B(R3) reports is the data available in the Product Name field that contains <Study Name (Treatment Group)>.

The mapping logic for E2B(R2) reports (ICH, EMA, FDA 2.1, and FDA 2.2) is revised to populate all the blinded products (from the study configuration) based on the Treatment Group selected in the case form.

For more details, refer to the following documents:

• ArgusInterchange844_E2B (R3) Export Mappings
• ArgusInterchange844_E2B (R2) 2.1 Export Mappings.xlsx
• ArgusInterchange844_E2B (R2) 2.2 Export Mappings.xlsx

.

E2B(R3) import

When a study is configured with Treatment Groups, import of ICSRs is as follows:

During initial import:

• Product Name and Generic Name are populated with Study Name.
• Company Drug Code is populated as Study Drug.
• Treatment Group is not populated.
• Dosage and Causality are copied from the respective drug block of ICSR.
• If there are more blinded products in ICSR than configured in the Study, then the excessive blinded products are added as non-study products.

During follow-up import:

• If the treatment groups are selected for blinded products in the case, then the system compares the blinded products in ICSR with the blinded products in the case by matching the primary keys (as present in PK element CSV that can be downloaded from Interchange Mapping screen) associated with the parent element as Drug. Blinded product data from incoming ICSR is updated to the respective blinded products of the case.
• If the blinded product data from incoming ICSR does not match with the primary keys associated with parent element drug, then the blinded product is inserted to the case and data is populated as per the previous point.
• If the number of blinded products present in ICSR exceeds the number of blinded products configured in the study, then the system imports the excess products as non-study products.
• If the treatment groups are not specified for blinded products in the case, then the system includes ICSR in failed report section with an error indicating that the Treatment Groups are not specified for blinded products in the case.

When the study is not configured with Treatment Group, import of ICSR is as follows:

• If the incoming initial ICSR has multiple blinded products with no Treatment Groups, then the blinded products are imported with product name as study name. If there are more blinded products in ICSR than configured in the study, then the excessive blinded products are added as non-study products.
• If the incoming follow-up ICSR has multiple blinded products with no Treatment Groups, then the existing blinded products present in the case are updated. If there are more blinded products in ICSR than configured in the study, then the excessive blinded products are added as non-study products.

PMDA E2B(R2, R3) import

There are no changes to the PMDA E2B(R2, R3) import mappings. The system creates a single blinded product on initial and follow-up ICSR import.

E2B(R2) import

There are no changes to the E2B(R2) import mappings. The system creates a single blinded product on initial and follow-up ICSR import.

Periodic reports

The line listing sections of the following reports prints multiple blinded study drugs as available in the case with blinded information, when it is generated with the Blinded Line listing check box as checked:

• PSUR
• CTPR
• CIOMSLL
• Case listing

Product Name prints the data present in the Product Name field of the Product tab. Therefore, if a Treatment Group is selected for a blinded study product, then the Treatment Group that was populated in the Product Name field within parentheses is printed in these reports.

The blinded column of the summary tabulation of the following reports counts an event only once for cases that have multiple blinded products:

• CTPR (native)
• DSUR (BIP)
• PBRER (native)
• PBRER (BIP)

The cumulative tabulation prints a list event counts pertaining individual blinded products present in the case. However, total of adverse event for this report counts the event once per case.

There is no change on the IND or NDA reports since the product name is not populated in these reports.

There is no change in the CDA report, if the product name is used in the row or column selection.

Argus Unblinding Advanced updates

To perform end of study unblinding (EOSU) from Argus Unblinding Advanced screen, you select the study product(s) that the patient received for each unique treatment code. This selected product(s) is added as study drug in the case after unblinding, as per the existing functionality.

The Argus Unblinding Advanced screen is enhanced to display the treatment group along with the existing study product name list.

• When Treatment Groups are configured:

  After study product(s) selection in the profile and successful execution in update mode, during unblinding of case, the system checks the respective Treatment Group(s) and updates the blinded product tabs in Case Form as per study configuration. The system does not allow duplicate selection of treatment code: Product Name (Treatment Group) combination, as per existing functionality.

• When Treatment Groups are not configured:

  No change in existing functionality.

  Note:

  Treatment Code in the EOSU profile is not directly related to the Treatment Groups defined in Argus Console. Treatment code in EOSU is derived from the PRD file that is loaded.

Argus Unblinding Lite updates

Argus Unblinding Lite is updated to exclude studies with the Treatment Group configuration and display only Study IDs without treatment groups.

For more details, refer to the ArgusSafety8.4.4_CaseForm_Console_Updates_Summary.xls.