Configuring the Safety Link

Safety Link is an integration between Vault CDMS and Vault Safety or between Vault CDMS and any third party Safety System via the CDMS AS2 Gateway. Enabling this integration automates the reporting of all serious adverse events (SAEs) to the chosen safety system. Organizations can configure a study to also send related (via form linking) case information, including concomitant medications, medical histories, and related adverse events, alongside the SAE, and optionally demographics items or an In Case of Death form, when that data is available. Any time a site completes or updates the SAE form, or any related forms, CDMS automatically generates a first-send or follow-up and sends it to the safety system.

The automated data transfer uses E2B in the R3 format. This provides a scalable way to send all required and complimentary case information that any safety system can parse and ingest accurately.

Safety administrators can configure this integration by mapping study design Items to the E2B R3 elements and setting the timing of the first-send and the frequency of any follow-ups. For third-party safety systems, you can provide other attributes, such as a URL and Certificate, to use with the integration.

You can configure the integration directly in the production environment, or configure it in a UAT environment for testing before exporting it and importing it into the production environment. You can also export the configuration for use in other Studies and Vaults.

Safety Link supports automated nullifications via E2B in R3 format. This is generated if the SAE Term is changed to non-serious or the form is reset. Safety Link accepts Acknowledgements from the safety system to confirm that the data was received, parsed correctly, and confirm the case status, message status, and provide error details, if any. All this data is readily available in the Safety Cases and Safety Message reports to confirm the integration status and health.

Prerequisites

A user with the Vault Owner security profile must create a connection between the CDMS and Safety vaults (if using Vault Safety), or configure a third-party Safety System.

A study designer must configure the Adverse Event form, as well as any Form Links, and create the Items for the Form using the appropriate data types. See the table below for a list of items and the required data types.


Users with the CDMS Safety Administrator standard study role can configure the Safety Link from EDC Tools > Safety Configuration by default. Users with the Vault Owner security profile can perform the enablement and connection configuration tasks.

Type Permission Label Controls
Standard Tab EDC Tools Tab

Ability to access the EDC Tools tab

Functional Permission Manage Safety Configuration

Ability to set up the Safety Clinical Data Link for a Study and map Items to their E2B elements

If your Study contains restricted data, you must have the Restricted Data Access permission to view it.

Learn more about Study Roles.


Connect to the Safety Vault

If you are using Vault Safety, a Vault Owner can follow the instructions below to connect your CDMS vault and your Safety vault. If your organization is using a third party safety system, see Connect to a 3rd Party Safety System.

Creating the Connections

First, you must connect your CDMS and Safety vaults with Vault-to-Vault Connections.

To perform the actions described below, you must be a Vault Owner in both the CDMS and Safety vaults.

Create the Connection in CDMS

  1. Navigate to Admin > Business Admin > Safety Transmission Profiles.
  2. Click + Create.
  3. For Name, enter “{Organization}SafetyVault”, for example, “VerteoPharmaSafetyVault”. Note that whitespaces aren’t allowed.
  4. For Batch Sender Identifier, enter “CDMS{CDMS Vault ID}”, for example, “CDMS50720”. You can find the Vault ID for your CDMS vault from Admin > Settings > General Settings in your CDMS vault.
  5. For Batch Receiver Identifier, enter “SAFETY{Safety Vault ID}”, for example, “SAFETY57667”. You can find the Vault ID for your Safety vault from Admin > Settings > General Settings in your Safety vault.
  6. Click Save.
  7. Click the Connection. This opens the Details page for the Connection. Click the Connection

  8. From the Actions menu, select Download Connection File. Download Connection File action

  9. In the confirmation dialog, click Download.
  10. Save the connection file to a location of your choosing.

Create the Connection in Safety

  1. Switch to your Safety vault.
  2. Navigate to Admin > Connections.
  3. Click CDMS to Safety Connection connection to open it.
  4. From the Actions menu, select Connect from File. Connect from File action

  5. Select the connection file you downloaded in your CDMS vault.
  6. Click Continue.
  7. Click Workflow Timeline to expand that section.
  8. In the Details panel, select Reassign from the Actions menu.
  9. Select your User Name.
  10. Click Save.
  11. In the Review Connection banner, click Complete.
  12. Select Approve Connection.
  13. Click Complete.

Approve the Connection in CDMS

  1. Switch to your CDMS vault.
  2. Navigate to Admin > Connections.
  3. Click Vault to Vault: CDMS to Safety Connection to open the connection.
  4. Click Workflow Timeline to expand that section.
  5. In the Details panel, select Reassign from the Actions menu.
  6. Select your User Name.
  7. Click Save.
  8. In the Review Connection banner, click Complete.
  9. Select Approve Connection.
  10. Click Complete.

Safety Transmission Profile

Once you’ve connected your Safety vault to your CDMS vault, you can configure your Safety vault to accept safety cases from CDMS. To do so, you’ll create an Organization record and several supporting records. Then, you’ll create a Transmission Profile.

To perform the actions described below, you must be a Vault Owner in both the CDMS and Safety vaults.

Create an Organization, Study & Product

To create an Organization:

  1. Switch to your Safety vault.
  2. Navigate to Admin > Business Admin > Organizations.
  3. Click + Create.
  4. Select Sponsor for Type.
  5. Click Create.
  6. For Name, enter “{Organization} CDMS Vault”.
  7. For Sender Type, select Pharmaceutical Company.
  8. For Organization UID Code, enter a unique value to represent your organization.
  9. Click Save.

To create the Product and Registration:

  1. From the Organization record, click Products to expand that section.
  2. Click + Create.
  3. Select Drug for Type.
  4. Click Continue.
  5. Enter the Product Name.
  6. Click Save.
  7. Click to expand the Registrations section.
  8. Click + Create.
  9. Enter a Registration Date.
  10. For Registration Type, select Investigational New Drug (IND).
  11. For Country, select United States of America.
  12. Click Save.

To create the Study and Study Product:

  1. Navigate to Admin > Business Admin > Organizations.
  2. Click your organization’s Name to open it.
  3. Click Studies to expand that section.
  4. Click + Create.
  5. Enter a Study Number.
  6. Select Open Label for Masking. This is the only supported option in the current release.
  7. Enter the Study Name. This must be an exact match to the Study Name in the CDMS vault (study__v.name__v).
  8. Click Save.
  9. In the Study Products section, click + Create.
  10. For Type, select Drug.
  11. Click Continue.
  12. Enter a Name.
  13. For Study Product Role, select Investigational.
  14. The Product and Product Registration fields should have defaulted to the Product and Product Registration you created earlier. If not, select those.
  15. Click Save.

Create a Transmission Profile

To create a Transmission Profile:

  1. Navigate to Admin > Business Admin > Transmission Profiles.
  2. Click + Create.
  3. For Name, enter “{Organization} CDMS to {Organization} Safety”, for example, “VerteoPharma CDMS to VerteoPharma Safety”.
  4. Select your Organization.
  5. For Origin ID, enter “{Organization}{SafetyVaultID}” with no spaces, for example, “verteopharma57667”.
  6. For Destination, select your Organization.
  7. For Destination ID, enter “{Organization}{CDMSVaultID}” with no spaces, for example, “verteopharma50720”.
  8. Click Save.

Now, your Safety and CDMS vaults are ready to use the Safety Link. Configure the link for your Study and map your data items to their E2B elements from EDC Tools > Safety Configuration.

General Settings for First Send & Follow Up

Before you can map your forms to their E2B elements, you must first configure the General Settings for your Study and the safety system.

Available Settings

Setting Default Description
Send Adverse Events to Safety System No Setting this field to Yes enables Safety Link for your Study. Vault will not begin sending Safety Cases until this is set to Yes, even if the other configuration is complete.
Safety System -- Select the Safety System you want to send your Safety Cases to. The available options are the configured Transmission Profiles.
Reporter -- Select None or Principal Investigator. If you choose Principal Investigator, Vault uses the Principal Investigator assigned to the Site. This is the value for the Reporter field on the Safety Case.
Investigational Product Blinded No Select Yes if your Investigational Product is blinded. This blinds the Date of Birth and Sex E2Bs on Patient Characteristics and Date of Death on In Case of Death. This inserts the E2B ID G.k.2.5 with the value “true”. If set to No, this E2B isn’t included in the XML file.
First Send E2B Schedule 3 hours Select an Interval. This is the amount of time after form submission that CDMS will send the collected data to the safety system.
Follow-up E2B Schedule Once every 3 days Select an Interval. This is the amount of time after a user saves changes to a form that CDMS will send a follow-up to the safety system.
Null Flavor for Coding None

Select how to handle null values for coding, “None” or “99999999”. If you choose “None”, CDMS doesn’t include the E2Bs below in the Safety Case. If you choose “99999999”, CDMS sends “99999999” as the value for the E2Bs below.

Coding E2Bs:

  • SAE - E.i.2.1b: Reaction / Event (MedDRA code)
  • AE - E.i.2.1b: Reaction / Event (MedDRA code)
  • MH - D.7.1.r.1b: Medical History (disease / surgical procedure / etc.) (MedDRA code)

Configure General Settings

To configure your general settings:

  1. Navigate to your Study in Tools >EDC Tools.
  2. Open Safety Configuration.
  3. Click Edit.
  4. Click General Settings to expand that section.
  5. Select Yes for Send Adverse Events to Safety System.
  6. Select your Safety System.
  7. Select None or Principal Investigator for Reporter. This is the value sent for Reporter to the safety system.
  8. Optional: If you want to blind the Investigational Product, select Yes for Investigational Product Blinded. Otherwise, leave this set to No.
  9. For First Send E2B Schedule, select an Interval. This is the amount of time after form submission that CDMS will send the collected data to the safety system.
  10. For Follow-up E2B Schedule, select an Interval. This is the amount of time after a user saves changes to a form that CDMS will send a follow-up to the safety system.
  11. Click Save.

General Settings filled for Safety Configuration

Send Multiple SAEs per Safety Case

You can configure Safety Link to send multiple SAEs in a single Safety Case. For example, if a Subject was hospitalized for a heart attack, and then they had a stroke while in the hospital, you can send the SAE data for both the heart attack and the stroke in the same Safety Case.

In Data Entry, if the AE is marked as Serious, Vault generates a Safety Case. If the E2B IDs for the Term are inside a repeating Item Group, then every instance of that repeating Item Group is treated as a unique SAE within one Safety Case.

To send multiple SAEs, ensure that your Form meets the design requirements, then set Allow Multiple SAEs per Case to Yes in the Serious Adverse Events section.

Study Design Requirements

To send multiple SAEs in one Safety Case, you must use a repeating Item Group for your AE Term item and the related Items. Site users can create an instance of the repeating Item Group for each SAE to be included in the Safety Case.

All Items except for those listed below must be within the repeating Item Group. The following E2B Items can reside in another, non-repeating Item Group:

  • G.k.8: Action(s) Taken with Drug
  • H.1: Case Narrative Including Clinical Course, Therapeutic Measures, Outcome and Additional Relevant Information
  • H.2: Reporter’s Comments

E2B Mapping

Once you’ve finished the General Settings, you can configure which Forms you want to use and map data items to their corresponding E2B elements.

Serious Adverse Events

To map your Serious Adverse Event form for E2B:

  1. Click Edit if you aren’t already in Edit mode.
  2. Click Serious Adverse Events to expand that section.
  3. Select the Serious Adverse Event Form.
  4. Select the Item Indicating Seriousness.
  5. Enter the Item Value Indicating Seriousness. This must be an exact match.
  6. Optional: To allow the send of multiple SAEs in a single Safety Case, select Yes for Allow Multiple SAEs per Case. Otherwise, leave this set to No. Allow Multiple SAEs per Case set to Yes

  7. Select the Item for each SAE Field that you include in your form. Note that the Item must have the correct data type. See the table below for a list of Items and their expected Data Type.
  8. Select Required for First Send to require that a value be entered on that Item for CDMS to send the SAE to the safety system.
  9. Click Save.

If you selected Yes for Allow Multiple SAEs per Case, you must select an Item for E.i.1.1a (Reaction / Event as Reported by the Primary Source in Native Language) E2B first. Vault will only enable the other E2Bs (except for those listed below) for item selection after you select an item for E.i.1.1a. Both E.i.1.a and the other E2Bs must be inside a repeating Item Group.

The following E2Bs remain enabled, as they do not need to be in a repeating Item Group for multiple SAEs:

  • G.k.8: Action(s) Taken with Drug
  • H.1: Case Narrative Including Clinical Course, Therapeutic Measures, Outcome and Additional Relevant Information
  • H.2: Reporter’s Comments

However, if you don’t have E.i.1.1a mapped to an Item, Vault disables these rows.

If H.1 and H.2 are in a repeating Item Group, and there is more than one instance of that Item Group for the SAE, Vault concatenates the values for each, separating them with a space. The concatenation order is based on the item group Sequence Number, in ascending order. The character limits apply to the concatenated text, not individual items.

</tbody> </tbody>
E2B ID E2B Element Data Type
E.i.1.1a Reaction / Event as Reported by the Primary Source in Native Language Text (250)
E.i.3.1 Term Highlighted by the Reporter Number (1)
E.i.3.2a Results in Death Boolean
E.i.3.2b Life Threatening Boolean
E.i.3.2c Caused / Prolonged Hospitalization Boolean
E.i.3.2d Disabling / Incapacitating Boolean
E.i.3.2e Congenital Anomaly / Birth Defect Boolean
E.i.3.2f Other Medically Important Condition Boolean
E.i.4 Date of Start of Reaction/Event (value) Datetime
E.i.5 Date of End of Reaction/Event (value) Datetime
E.i.6a Duration of reaction/event (value) Number (5)
E.i.6b Duration of reaction/event (unit) Text (50)
E.i.7 Outcome of Reaction/Event at the Time of Last Observation Number (1)
G.k.8 Action(s) Taken with Drug Number (1)
G.k.9.i.2.r.3 Result of Assessment Text (60)
G.k.9.i.4 Did Reaction Recur on Re-administration? Number (1)
H.1 Case Narrative Including Clinical Course, Therapeutic Measures, Outcome and Additional Relevant Information Text (100,000)
H.2 Reporter's Comments Text (200,000)

Adverse Events

You can elect to include related Adverse Events in the SAE ICSR. Note that you must have a Form Link between the Serious Adverse Event form and the Adverse Event form.

To include a related Adverse Event:

  1. Click Edit if you aren’t already in Edit mode.
  2. Click Adverse Events to expand that section.
  3. Select Yes for Include Related Adverse Events in the SAE ICSR..
  4. Select the AE Form. If this is a different Form from the Serious Adverse Event form, continue with the following steps. Otherwise, click Save.
  5. Select the Item for each AE Field that you include in your form. Note that the Item must have the correct data type. See the table below for a list of Items and their expected Data Type.
  6. Click Save.
E2B ID E2B Element Data Type
E.i.1.a Reaction / Event as Reported by the Primary Source in Native Language Text (250)
E.i.3.2a Results in Death Boolean
E.i.3.2b Life Threatening Boolean
E.i.3.2c Caused / Prolonged Hospitalization Boolean
E.i.3.2d Disabling / Incapacitating Boolean
E.i.3.2e Congenital Anomaly / Birth Defect Boolean
E.i.3.2f Other Medically Important Condition Boolean
E.i.4 Date of Start of Reaction/Event (value) Datetime
E.i.5 Date of End of Reaction/Event (value) Datetime
E.i.7 Outcome of Reaction/Event at the Time of Last Observation Number (1)

Concomitant Medications

To include Concomitant Medications:

  1. Click Edit if you aren’t already in Edit mode.
  2. Click Concomitant Medications to expand that section.
  3. Select Yes for Include Concomitant Medication.
  4. Select the Concomitant Medications Form.
  5. Select the Item for each CM Field that you include in your form. Note that the Item must have the correct data type. See the table below for a list of Items and their expected Data Type.
  6. Click Save.
E2B ID E2B Element Data Type
G.k.11 Additional Information on Drug (free text) Text (2000)
G.k.2.2 Medicinal Product Name as Reported by the Primary Source Text (250)
G.k.2.3.r.3a Strength (number) Number (10)
G.k.2.3.r.3b Strength (unit) Text (50)
G.k.2.4 Identification of the Country Where the Drug Was Obtained Text (2)
G.k.4.r.10.1 Route of Administration (free text) Text (60)
G.k.4.r.1a Dose (number) Number (8)
G.k.4.r.1b Dose (unit) Text (50)
G.k.4.r.2 Number of Units in the Interval Number (4)
G.k.4.r.3 Definition of the Time Interval Unit Text (50)
G.k.4.r.4 Date and Time of Start of Drug Datetime
G.k.4.r.5 Date and Time of Last Administration Datetime
G.k.4.r.7 Batch / Lot Number Text (35)
G.k.4.9.1 Pharmaceutical Dose Form (free text) Text (60)
G.k.7.r.1 Indication as Reported by the Primary Source Text (250)

Medical History

To include Medical History:

  1. Click Edit if you aren’t already in Edit mode.
  2. Click Medical History to expand that section.
  3. Select Yes for Include Medical History
  4. Select the Medical History Form.
  5. Select the Item for each MH Field that you include in your form. Note that the Item must have the correct data type. See the table below for a list of Items and their expected Data Type.
  6. Click Save.
E2B ID E2B Element Data Type
D.7.1.r.2 Start Date Datetime
D.7.1.r.3 Continuing Boolean
D.7.1.r.4 End Date (value) Datetime
D.7.1.r.5 Comments Text (2000)
D.7.1.r.6 Family History Boolean
D.7.2 Text for Relevant Medical History and Concurrent Conditions (not including reaction / event) Text (10,000)

Patient Characteristics

To include Patient Characteristics:

  1. Click Edit if you aren’t already in Edit mode.
  2. Click Patient Characteristics to expand that section.
  3. Select the Patient Characteristics Event Group. This is the Event Group containing the Form with the patient characteristics data items.
  4. Select the Patient Characteristics Event. This is the Event containing the Form with the patient characteristics data items.
  5. Select the Patient Characteristics Form.
  6. Select the Item for each Patient Characteristics Field that you include in your form. Note that the Item must have the correct data type. See the table below for a list of Items and their expected Data Type.
  7. Click Save.
E2B ID E2B Element Data Type
D.2.1 Date of Birth (value) Datetime
G.2.2a Age at time of onset of reaction/event (number) Number (5)
G.2.2b Age at time of onset of reaction/event (unit) Text (50)
D.5 Sex Number (1)

In Case of Death

To include data from an In Case of Death form:

  1. Click Edit if you aren’t already in Edit mode.
  2. Click In Case of Death to expand that section.
  3. Select the In Case of Death Event Group. This is the Event Group containing the In Case of Death form.
  4. Select the In Case of Death Event. This is the Event containing the In Case of Death form.
  5. Select the In Case of Death Form.
  6. Select the Item for each In Case of Death Field that you include in your form. Note that the Item must have the correct data type. See the table below for a list of Items and their expected Data Type.
  7. Click Save.
E2B ID E2B Element Data Type
D.9.1 Date of Death Datetime
D.9.2.r.2 Reported Cause(s) of Death Text (250)
D.9.3 Was Autopsy Done? Boolean
D.9.4.r.2 Autopsy-determined Cause(s) of Death Text (250)

External Labs

To include data from External Labs:

  1. Click Edit if you aren’t already in Edit mode.
  2. Click External Labs to expand that section.
  3. For Include External Labs, select Yes.
  4. Select the External Labs Form.
  5. Select the Item for each field that you include in your form. Note that the Item must have the correct data type. See the table below for a list of Items and their expected Data Type.
  6. Click Save.
E2B ID E2B Element Data Type
F.r.1 Test Date Datetime
F.r.2.1 Test Name Text (250)
F.r.3.1 Test Result (code) Number (1)
F.r.3.2 Test Result (value / qualifier) Number (50)
F.r.3.3 Test Result (unit) Text (50)
F.r.3.4 Result Unstructured Data (free text) Text (2000)
F.r.4 Normal Low Value Text (50)
F.r.5 Normal High Value Text (50)
F.r.6 Comments (free text) Text (2000)
F.r.7 More Information Available Boolean

Treatment

To include data from a Treatment form:

  1. Click Edit if you aren’t already in Edit mode.
  2. Click Treatment to expand that section.
  3. For Include Treatment Form, select Yes.
  4. Select the Treatment Form.
  5. Enter the Treatment Name.
  6. Select the Item Indicating Treatment Administered.
  7. Enter the Item Value Indicating Treatment Administered.
  8. Select the Item for each Treatment field that you include in your form. Note that the Item must have the correct data type. See the table below for a list of Items and their expected Data Type.
  9. Click Save.
E2B ID E2B Element Data Type
G.k.10.r Additional Information on Drug (coded) (repeat as necessary) Number (2)
G.k.11 Additional Information on Drug (free text) Text (2000)
G.k.2.3.r.3a Strength (number) Number (10)
G.k.2.3.r.3b Strength (unit) Text (50)
G.k.2.4 Identification of the Country Where the Drug Was Obtained Text (2)
G.k.4.r.10.1 Route of Administration (free text) Text (60)
G.k.4.r.10.2a Route of Administration TermID Version Date / Number Text (60)
G.k.4.r.10.2b Route of Administration TermID Number (3)
G.k.4.r.1a Dose (number) Number (8)
G.k.4.r.1b Dose (unit) Text (50)
G.k.4.r.2 Number of Units in the Interval Number (4)
G.k.4.r.3 Definition of the Time Interval Unit Text (50)
G.k.4.r.4 Date and Time of Start of Drug Datetime
G.k.4.r.5 Date and Time of Last Administration Datetime
G.k.4.r.6a Duration of Drug Administration (number) Number (5)
G.k.4.r.6b Duration of Drug Administration (unit) Text (50)
G.k.4.r.7 Batch / Lot Number Text (35)
G.k.4.r.8 Dosage Text Text (2000)
G.k.4.r.9.1 Pharmaceutical Dose Form (free text) Text (60)
G.k.4.r.9.2a Pharmaceutical Dose Form TermID Version Date / Number Text (60)
G.k.4.r.9.2b Pharmaceutical Dose Form TermID Text (60)
G.k.5a Cumulative Dose to First Reaction (number) Number (10)
G.k.5b Cumulative Dose to First Reaction (unit) Text (50)
G.k.6a Gestation Period at Time of Exposure (number) Number (3)
G.k.6b Gestation Period at TIme of Exposure (unit) Number (10)
G.k.7.r.1 Indication as Reported by the Primary Source Text (250)
G.k.8 Action(s) Taken with Drug Number (1)
G.k.9.i.2.r.3 Result of Assessment Text (60)
G.k.9.i.3.1a Time Interval between Beginning of Drug Administration and Start of Reaction / Event (number) Number (5)
G.k.9.i.3.1b Time Interval between Beginning of Drug Administration and Start of Reaction / Event (unit) Text (50)
G.k.9.i.3.2a Time Interval between Last Dose of Drug and Start of Reaction / Event (number) Number (5)
G.k.9.i.4 Did Reaction Recur on Re-administration? Number (1)

Export & Import Safety Configuration

You can export the Safety Configuration from a study environment and import it into another environment, for example, in the case that you configure the Safety Integration in your UAT environment and then want to move it into your production environment. You can also use this feature to copy the configuration from one Study to another, but the Forms and Items must be an exact match between the two studies for this to work.

Export the Safety Configuration

  1. Navigate to the source study environment in Tools > EDC Tools.
  2. Open Safety Configuration.
  3. From the Actions menu, select Export. Export action

  4. Save the output JSON file in your chosen location.

Import the Safety Configuration

  1. Navigate to the source study environment in Tools > EDC Tools.
  2. Open Safety Configuration.
  3. From the Actions menu, select Import. Import action

  4. Click Select a File. Import dialog

  5. Select your Safety Config JSON file.
  6. Click Import. Import button