The Lilly Safety Mailing Process 1
After this presentation you will be able to: Define Safety Mailings and the type of adverse events that trigger safety mailings. Define Principal Investigator (PI) and site responsibilities for the safety mailing process. Describe the two types of site users with access to the Safety Reporting and Notification System, from now on referred to as SAFR NS. Describe how to log into SAFR NS and manage accounts. 2
So, why do we send safety mailings? ICH GCP section 5.16.2 says, The sponsor should promptly notify all concerned investigators of findings that could affect adversely the safety of subjects, impact the conduct of the trial, or alter the ERB approval/favorable opinion to continue the trial. To meet this obligation, Lilly performs a medical review of all clinical trial Serious Adverse Events (or SAEs) that are received from investigator sites. Lilly then determines which SAEs meet regulatory requirements to be distributed in an expedited manner to investigator sites. Only those that meet regulatory requirements are distributed to sites. These requirements may differ by country. 3
What is an investigator Safety Mailing? An investigator safety mailing is used to report a serious and unexpected adverse event to all the investigators on a clinical trial. Almost all safety mailings are compound-specific and not study-specific. Individual safety mailing reports are accessed through the secure SAFR NS website. Each time there is a new safety mailing for a site, Lilly electronically posts the safety mailing to the site s account in SAFR NS Sites are recognized in the SAFR NS system once a valid e-mail address and Ethics Committee approval date are entered into Lilly s clinical trial database. 4
PI responsibilities: The PI is responsible to review every safety mailing that is posted to the PI s account from the site s ERB approval date to its last patient visit. PI review of each safety mailing must be documented. There are multiple ways to accomplish this, for example: Printing the Safety Mailing Status Report (which we will cover later) and initialing and dating next to each report that has been reviewed Using a tracking log Printing and signing i each safety mailing NOTE: In general, there is no requirement that sites print and keep every safety mailing. The PI may delegate their responsibility for review. This responsibility can only be delegated to medically qualified personnel, such as a sub-investigator. This delegation must be documented. The Site Signature and Function Log or equivalent document may be used for this purpose. 5
Further Site Responsibilities: Site personnel in addition to or instead of the PI (e.g. study coordinator, regulatory coordinator) can access safety mailings in SAFR NS. The PI can transfer responsibility to retrieve safety mailings to a member of the site staff. If the PI does transfer or assign retrieval responsibilities, the person retrieving the mailings must ensure the PI or PI s delegate receives the mailings for review. Sites must have a process to ensure safety mailings are accessed and reviewed in a timely manner. The process should be clear and specify who will access SAFR NS, how often they will access the system, how the mailings will be provided to the PI or sub-investigator for review (if they do not review them on-line), and how the review of each mailing will be documented. Each person involved in the process should understand his or her responsibilities with regard to this process. It is highly recommended that sites do not rely on email notifications to alert them that a mailing is available. The site should access SAFR NS on a routine basis to check for new mailings. It is recommended this check be done at least one time per week. 6
There are two different types of site users in SAFR NS, the first type of user is the Primary Site User: There can only be one Primary Site User per site. This can either be the PI or a site staff member appointed by the PI. The Primary Site User obtains access to SAFR NS by providing their email address to their CRA for entry into Lilly s clinical trial management system. This Primary Site User s email address must be the same for all Lilly studies the PI is participating i in. For example, Dr. Jones is the PI for 5 Lilly studies. If he decides to delegate Primary Site User access, it has to be delegated to the same person across all 5 studies. The username will generally be based on the PI s first initial and last name. 7
The Delegate Site User is the second type of site user in SAFR NS : The Primary Site user can provide access for up to 5 additional site support staff members. These users are referred to as Delegate Site Users. They obtain access to SAFR NS when Primary Site User enters their first name, last name, and email address in SAFR NS. The username will be the Delegate Site User s first initial and last name Access for the Delegate Site User can be granted at compound or study level 8
The Primary Site User is responsible for maintaining Delegate Site User information during the study. Additionally, this person will be notified to complete an annual review of Delegate Site User information in SAFR NS. This review is required to comply with computer account management requirements. If this review is not completed, all Delegate Site User accounts will be deactivated. Detailed instructions for the annual review will be provided well in advance of the time the review must be completed. Primary Site Users will be sent reminders to complete this activity. 9
Changing the Primary Site User To change the Primary Site User, the site provides the email address of new Primary Site User to the CRA. Once the clinical trial management system is updated at Lilly, SAFR NS account information will be sent to the new Primary Site User. The new Primary Site User can then use this information to log into the system. 10
When accessing the SAFR NS website for the first time, the new Primary Site User must: Complete website training by accessing the Help link. Document completion of website training at the site using the usual documentation practices of the site. Transfer of this task must be documented. The Site Signature and Function Log or equivalent document can be used for this purpose 11
Accessing SAFR NS First of all, each PI will have only one SAFR NS account, regardless of how many Lilly studies the PI is involved in. Accessing the system is the same for each type of user. Access information will be sent to each user in 2 separate emails. One will include the username and the other will include the temporary password. Both emails will include the URL for the website. Once successfully logged into the system the first time, every user will be required to accept the terms of use for the website, Take a short training for website navigation (less than 5 minutes). Completion of this training is tracked within the system. And set a new password. 12
The Safety Mailing Status Report is available in SAFR NS to assist sites with management of their own local l safety mailing review process. The report includes: all the mailings the site has received which mailings have been accessed which mailings have not been accessed who accessed the mailing the first time and when 13
Safety Mailings and Ethical Review Board (ERB): Sites are responsible for sending safety mailing reports to their respective ERB, according to local regulations and the guidelines of the ERB. If the ERB does not require all safety mailings to be sent to them, it must be documented in the study binder or equivalent. In some countries (e.g in some countries in Europe), Lilly may submit safety mailing reports directly to the appropriate ERB. Additional requirements may be defined in your Letter of Agreement or local laws and regulations. 14
Managing Notifications To prevent undeliverable e-mails, the site s system administrator should be notified to set up the mail server or applications to accept e-mails from the addresses listed on the slide. Please check with your information technology department/contact for instructions. 15
We would like to finish this presentation with a reminder of some Key points: Safety mailings are sent to report certain adverse events associated with use of a drug that are both serious and unexpected. Safety mailings are accessed via the SAFR NS website Access management for the Primary Site User is managed by Lilly. A valid e-mail address must be provided to the CRA to enable access for the Primary Site User. Access management for Delegate Site Users is managed by the Primary Site User in SAFR NS. 16
All site users will receive two emails, one with the account username and one with a temporary password. The PI or PI s delegate is responsible for reviewing every safety mailing posted to his/her account in SAFR NS. This review must be documented. Routinely access SAFR NS to retrieve Safety mailings - Do not rely on email notifications! The site must send safety mailings to their ERB according to local regulations and the guidelines of the site s ERB. This completes the Lilly Safety Mailing Process training you may use this slide deck as reference during the study. Contact your CRA in case you don t know where to find it. 17