How Case Assessment Expectedness is Generated

Vault Safety assesses expectedness for each Case Assessment through generated Expectedness records.

About Expectedness

An Expectedness record identifies whether the MedDRA Term on a Case Adverse Event is considered expected on the corresponding Product Family, Product, Local, Study, or Study Product Datasheet. Depending on your Admin’s configuration, Vault can:

Generate Expectedness records for blinded Study Products on Cases for double-blinded clinical trial Studies without Study Arms.
Copy the rationale for adverse event expectedness evaluations from the Datasheet to Case Assessment Expectedness and Localized Case Assessment records.

Expectedness records are generated for each of the following Datasheet sources associated with the Case Product in the Case Assessment. See Expectedness Evaluations for Clinical Trial Study Cases for special considerations based on Datasheet type.

Source	Expectedness Generation
Product Family Datasheet	If an assessment's Case Product inherits a Datasheet from the Product Family record, an Expectedness record is generated for the Datasheet.
Product Core Datasheet	If an assessment's Case Product has a Core Datasheet, an Expectedness record is generated for the Core Datasheet.
Study Core Datasheet	When the assessment's Case Product is of the type Study Product, and if the Study Product Role is Investigational, an Expectedness record is generated for the Study's Core Datasheet. If no Study Core Datasheet is available, Vault considers the Product Core Datasheet when evaluating Expectedness.
Local Datasheets	Expectedness records are generated for each Case Product Registration with a Local Datasheet. Admins can configure Local Datasheets to inherit listed events from the Core Datasheet.
Study Product Datasheet	When the assessment's Case Product is of the type Study Product, and if the Study Product Role is Investigational, an Expectedness record is generated for the Study Product Datasheet. Admins can configure Study Product Datasheets to inherit listed events from the Study Core Datasheet.

All Expectedness records are linked to the source Datasheet and the latest version of the referenced datasheet document in Vault Library.

Note:

When assessing Combination Products, the Case expectedness is based on the drug or biologic constituent. The device constituent expectedness is not assessed.
For blinded Cases associated with double-blinded Studies, Expectedness records are not generated while the Study Product is blinded, therefore roll-ups do not occur. In this scenario, when the Case Product is unblinded Expectedness records are generated and roll-ups occur.

How Expectedness is Evaluated

When evaluating whether a Case Adverse Event is expected in relation to a Case Product’s Datasheet, Vault first checks whether the event MedDRA matches a term on the Datasheet. To be considered a match, the term must be listed on or fall under the hierarchy of a term on the Datasheet. Then, Vault performs a number of checks based on the precise expectedness and conditional expectedness settings on the Datasheet.

Review the following sections to see how Vault Safety evaluates a MedDRA term without specified demographics, with specified demographics, and for Clinical Trial Study Cases.

Expectedness Evaluations Without Demographics

The following flowchart illustrates how Vault Safety evaluates Case Assessment Expectedness. The green components show the precise expectedness evaluation, while the orange components show the conditional expectedness evaluation:

The following table outlines the different expectedness scenarios, based on the Datasheet settings and MedDRA Criteria settings for the event term:

Term Matched on Datasheet?	Datasheet		MedDRA Criteria		Case Assessment Expectedness
Term Matched on Datasheet?	Precise Expectedness Enabled?	Unexpected Seriousness Criteria	Expectedness	Seriousness Exclusion	Case Assessment Expectedness
Yes	N/A	Blank	Expected ¹	Blank	Yes
Yes	N/A	N/A²	Expected	Yes: not matching ³	Yes
Yes	N/A	Yes: not matching ³	Expected	Blank	Yes
Yes	N/A	N/A²	Expected	Yes: matching ³	No
Yes	N/A	Yes: matching ³	Expected	Blank	No
Yes	N/A	N/A	Unexpected	N/A	No
No	No	N/A	N/A	N/A	No
No	Yes	N/A	N/A	N/A	Blank
1. If "Expectedness" is not defined, the value defaults to Expected.
2. When "Seriousness Exclusion" is defined on a MedDRA Criteria record, this setting takes precedence and the Datasheet's "Unexpected Seriousness Criteria" setting is ignored.
3. Matching refers to whether the Case Adverse Event has one (1) or more Seriousness values that match a Seriousness condition defined on the Datasheet or MedDRA Criteria.

Expectedness Evaluations With Demographics

Expectedness evaluations in Vault Safety support age and sex criteria. This enables creating more precise Product Datasheets for adverse events that affect specific demographics.

When matching patient details to MedDRA Criteria terms on Datasheets, Vault prioritizes the Expected/Unexpected Event Terms record with the most details. For example, if a Datasheet includes the same MedDRA Criteria term, once with sex as the only demographic detail and once with sex and age range specified, Vault matches Case Adverse Events using the second, more detailed, record.

When matching based on sex, if the Case specifies the Patient’s sex, Vault matches to MedDRA Criteria terms on the Datasheet that include that sex if such a record exists. If the MedDRA Criteria term appears on the Datasheet without a specified sex, Vault matches if all other criteria match the details on the Case.

When matching based on age, Vault matches the Patient’s age to the age range of the adverse event on the Datasheet using the following priority order:

Age at Onset calculated using the Onset date of the Case Adverse Event and the Date of Birth in the Patient section. If those values are not available, Vault maps from the manually populated Age at Onset in the Patient section.
If the Age at Onset value uses Decades as the unit, Vault considers both the lower and upper bounds of the decade when evaluating expectedness. For example, if the patient’s age is entered using 2 in the Number field and Decade in the Unit field, indicating they are between 10–20 years old, and the adverse event on the Datasheet is expected only for patients with an age range of 2–12 years old, Vault considers this adverse event unexpected since the upper bound of the decade (age 20) is outside the expected age range.
Age Group based on the Age Group Controlled Vocabulary type. When matching is based on Age Group, the Patient Age Group must fall entirely within the age range on the Datasheet. The following table provides examples of when Vault matches the Patient Age Group to the age range of the adverse event on the Datasheet.

Patient Age Group (Controlled Vocabulary Age Range)	Datasheet Age Range	Expectedness Match?
Child (2–11 years old)	Age Range Start: 2 years Age Range End: 20 years	Matched
Adolescent (12–17 years old)	Age Range Start: 5 years Age Range End: 15 years	Not matched
Adolescent (12–17 years old)	Age Range Start: 5 years Age Range End: 20 years	Matched
Adult (18–64 years old)	Age Range Start: 35 years Age Range End: 55 years	Not matched
Elderly (65+ years old)	Age Range Start: 60 years Age Range End: blank	Matched

Expectedness Evaluations for Clinical Trial Study Cases

If your Admin has enabled Agency-Based Auto-Expectedness for Clinical Trial Study Cases, Vault may calculate expectedness on Clinical Trial Study Cases based on the Onset date of Case Adverse Events or the New Info Date on Cases, depending on the Agency’s expectedness setting.

When an Agency is configured to base Clinical Trial expectedness evaluations on Onset dates, Vault also considers whether the Onset date of a Case Adverse Event is within the MedDRA Term’s active date range on the Datasheet. Onset dates outside this range are considered unexpected. If the MedDRA Term on the Datasheet does not include an Active End Date, the term is considered to be expected to the present day. If there is no Active Start Date or Active End Date, the term is always considered expected. If the Onset date is blank on the Case Adverse Event, Vault uses the Receipt Date on the Case for the evaluation.

Note: If your Admin has not enabled Agency-Based Auto-Expectedness for Clinical Trial Study Cases, Vault calculates expectedness using Case Adverse Event Onset date and uses the logic described above.

When an Agency is configured so Vault calculates expectedness based on New Info Dates, Vault calculations do not consider the active date range of the MedDRA Term. If a Clinical Trial Study has at least one (1) Study Registration with an Agency set to this evaluation basis, when an Inbox Item is promoted to a Case, Vault creates Expectedness records as follows:

One (1) Expectedness record based on New Info Date for each applicable Product Core Datasheet and Local Datasheet for the Product referenced by the Study Product
Two (2) Expectedness records, one (1) based on New Info Date and the other based on Onset date, for each applicable Study Core Datasheet and Study Product Datasheet.

When promoting Inbox Items to Follow-up Cases, Vault recalculates all Expected values where the Expectedness record is based on New Info Date. Where Expected values are based on Onset date or have been overridden, Vault copies the values to Follow-up Cases and does not recalculate Expected values.

Manual Record Creation

If you manually create an Expectedness record related to a Study Core Datasheet or Study Product Datasheet, Vault populates the Based On field with “Onset Date”. For any Agency associated with a Study Registration that is configured to base expectedness on “New Info Date”, Vault also creates Expectedness records with the Based On field set to “New Info Date”. For both record types, Vault sets the Expected (status) field to “Overridden”.

For any other manually created Expectedness records, Vault sets the Based On field to “New Info Date” and the Expected (status) field to “Overridden”.

If you manually create a Case Product record for a non-Study Product, Vault generates Expectedness records for the Product Core Datasheet and Local Datasheet only.

Additional Considerations

Vault does not automatically update the basis of expectedness evaluations in the following instances:

For in-progress Clinical Trial Study Cases created before your Admin configured the Agency-Based Auto-Expectedness for Clinical Trial Study Cases feature
When merging an Inbox Item to an in-progress Clinical Trial Study Case created before your Admin configured the feature
If your Admin changes the basis of expectedness evaluations for an Agency. For example, if your Admin updates an Agency’s evaluation basis from “New Info Date” to “Onset Date”.

However, if you promote an Inbox Item for a Clinical Trial Study to a Follow-up Case, Vault automatically recalculates expectedness values on the Follow-up Case based on Agency settings.

Study Product Placeholder Expectedness

If your Admin has configured your Vault to isolate blinded clinical trial information and enabled Datasheet Expectedness for Blinded Study Products, you can associate all Datasheets on a double-blinded clinical trial Study without Study Arms with its Study Product Placeholders. This allows Medical Reviewers to access all relevant values from associated Datasheets, supporting comprehensive assessments during blinded Case reviews.

Vault generates Study Product Placeholder expectedness as follows:

For each blinded Case Product and Adverse Event combination, Vault generates a Case Assessment, Case Assessment Result, and Expectedness record based on each Datasheet associated with the Study Product Placeholder. These records have the Blinding Type set to Blinded. For information on expectedness roll-ups at the Case-level, see How Expectedness Rolls Up to Case Expectedness and Listedness.
If you change the Expected value on a blinded Expectedness record, Vault updates the Expected (status) field to Overridden.

If the Case is unblinded, Vault generates unblinded Case Assessment, Case Assessment Result, and Expectedness records based on Datasheets for the unblinded Case Product. The Blinding Type on these records is Unblinded. Vault does not alter the blinded records. For information on switching between the blinded and unblinded views, see Isolate Blinded Clinical Trial Information.

Recalculate Expectedness

To recalculate expectedness:

On the applicable clinical trial study Case, for each Case Assessment, delete all existing Expectedness records.
In the All Actions menu, select Generate Assessments.

For more information on generating Case Assessments for Clinical Trial Study Cases, see Generate Assessments.

How-To Videos: Understanding Expectedness Evaluations

Watch our quick video tutorials on Understanding Expectedness Evaluations and Understanding Precise Expectedness Evaluations.

When is Expectedness Evaluated

Expectedness is evaluated upon Case creation and aggregate report generation. Expectedness is re-evaluated when any of the following related fields are updated on a Case record:

Case Assessment
Case Adverse Event
Case Product
Case Patient Sex
Case Patient Age (including Date of Birth, Age at Onset, or Age Group)

For Clinical Trial Study Cases, expectedness is also re-evaluated when the related Case Adverse Event Onset date is updated. If your Admin has enabled Datasheet Expectedness for Blinded Study Products, Vault also re-evaluates expectedness when you modify the Blinded Name field on a Case Product.

When re-evaluating expectedness, Vault replaces the previous system-generated Case Assessment Expectedness records with new records.

Note: Case Assessment Expectedness records with an Overridden status are not deleted and do not get re-created, unless an associated Product or Adverse Event is updated.

The following table provides more information:

Object	Conditions
Case	Expectedness is evaluated upon Case promotion. For Follow-Up Cases, Case Assessment Expectedness records are copied from the previous Case version. Expectedness is not recalculated unless the Case Adverse Event Seriousness or MedDRA Term (Event MedDRA) changed in the new version. For Clinical Trial Study Cases, Expectedness is also recalculated if the Adverse Event Onset Date is changed. Note: To evaluate expectedness for an E2B-imported Case, products in the E2B file must be matched to a preconfigured Company Product. Expectedness is not evaluated for the Imported Case object type.
Case Assessment	Expectedness is evaluated when a Case Assessment is created or updated.
Case Adverse Event	Expectedness is evaluated when a Case Adverse Event related to a Case Assessment is created or either of the following fields are modified: MedDRA Term (Event MedDRA) Seriousness
Case Product	Expectedness is evaluated when a Case Product with a Drug Role of Suspect, Interacting, or Drug Not Administered related to a Case Assessment is created or the linked Product or Study Product are updated. Note: To include Case Products with the Drug Role of Drug Not Administered when evaluating Expectedness, your Admin must have enabled Extend Definition of Suspect to Drug Not Administered. Otherwise, Expectedness evaluations consider only Case Products with the Suspect or Interacting Drug Role. If your Admin has enabled Datasheet Expectedness for Blinded Study Products, Vault also re-evaluates expectedness when you modify the Blinded Name field.
Case Product Indication	Expectedness is evaluated when an Indication under the Case Product related to a Case Assessment is created or the Indication (Reported) field is updated.
Case Patient Sex	Expectedness is evaluated when the Case Patient's Sex is added, changed, or deleted.
Case Patient Age	Expectedness is evaluated when any of the following age-related fields on the Case are added, updated, or deleted: Date of Birth Age at Onset Age Group Adverse Event Onset