How do I create a data and safety monitoring plan (DSMP) for my protocol and request use of the WCM DSMB?
The WCM DSMB recommends that you first view the Investigator Initiated Trial (IIT) Template, which is available in the “Regulatory Tools and Templates” section of the Researcher’s Toolbox. Number 14 of the document, labeled, “Data and Safety Monitoring Plan,” guides you through what information needs to be included in your data and safety monitoring plan (DSMP).
Once you’ve drafted the protocol and DSMP section, the WCM DSMB is available to assist you in further refining the DSMP, including whether to incorporate the WCM DSMB into your monitoring plan. Contact the Board during the early, Clinical Study Evaluation Committee (CSEC) phase of your protocol’s regulatory review process to maximize the efficiency with which your DSMP is evaluated by CSEC, the WCM DSMB, if used, and the Institutional Review Board (IRB); however, assistance with the DSMP is not restricted to this stage.
The WCM DSMB can also be requested during the IRB review stage by selecting “Yes” in answer to the question, “Will you be using the WCM DSMB?” in the Data and Safety Monitoring Plan (DSMP) section of the eIRB application. The DSMB will be automatically notified of your request and DSMB administrators will reach out to you to schedule a presentation of your protocol to the Board. The Board will then evaluate the DSMP as the requested safety monitoring entity.
If your protocol is already underway and you wish to utilize the WCM DSMB, then before submitting an amendment to the IRB, please contact the DSMB directly at firstname.lastname@example.org. Provide a copy of the research protocol so the DSMB can evaluate whether the Board is an appropriate means of monitoring the trial. This will avoid initiating an unnecessary amendment with the IRB. If the IRB is requesting that you use the DSMB, please take the same course of action so that the DSMB is notified and can begin the process of reviewing the data and safety monitoring plan.
What can I expect when presenting at a DSMB meeting and what information do I need to include in my presentation slides?
In order to facilitate the Board’s review of DSMPs for new protocols, Principal Investigators or their designees are invited to provide a 5-minute presentation of the research protocol, either in person or by phone, followed by a brief Q&A session with Board members. This typically occurs during the course of initial DSMP review, but may also occur during the course of the trial to provide clarity when needed. PI’s utilizing the WCM DSMB are highly encouraged to present to the Board. Meeting dates, times, and locations are available here.
It is a requirement that presentation slides be provided to email@example.com at least one day in advance of the meeting. Slides provided by the WCM DSMB must be used and can be downloaded on the DSMB's site. In the case of a trial that has been ongoing, preliminary results and an overview of study conduct thus far should also be included.
When creating your slides, please be aware that each presenter is allotted 5 minutes only.
When do I submit my Periodic Report to the DSMB?
If your protocol’s DSMB review schedule is calendar based (e.g., semiannually), then you can view meeting dates and submission deadlines in advance. Please be sure not to make your submissions any earlier than is required, as the Board needs the most current and up-to-date information possible.
If your protocol’s DSMB review schedule is accrual based (e.g., after every 3 subjects are enrolled), then the PI is responsible for submitting to the DSMB as soon as the threshold has been met. This requires careful enrollment tracking on the part of the research team. The DSMB administrators will occasionally send out a survey inquiring about enrollment numbers so that it can assist research teams in tracking, but this should be considered a courtesy check-in only, rather than the sole method of tracking.
If your protocol’s DSMB review schedule is a combination of calendar-based and accrual based (e.g., every 6 months or after every 3 subjects are enrolled, whichever occurs first), then careful enrollment tracking on the part of the research team is required, as is an awareness of the DSMB’s meeting dates and submission deadlines so that a submission is made to the DSMB as soon as the threshold is met, or as soon as the designated amount of time has lapsed.
How do I submit my Periodic Report to the DSMB?
The Periodic Report is completed using the electronic Periodic Report Form (ePRF) via the REDCap system. The ePRF was designed with simplicity and efficiency in mind for all protocols that utilize the WCM DSMB for data and safety monitoring. To access and complete the ePRF:
1.) Click here to navigate to the ePRF. You can also copy and paste the following link into your browser: https://redcap.ctsc.med.cornell.edu/redcap_protocols/surveys/?s=K38L4ARET7. We recommend that you utilize Mozilla Firefox or Internet Explorer as the web browser for completing the form.
2.) When you begin the form, you must enter the “Protocol Number” for the protocol under review prior to saving any information on the survey.
3.) If you would like to save your completed work to return to later, you may select “Save & Return Later” at the bottom of the survey. Once you select “Save & Return Later”, the survey will provide you with a Return Code. Write down, copy, or email the return code to yourself. You will need the code to continue where you left off. NOTE: Failure to write down, copy, or email the return code to yourself can result in a delay of the submission. Contact firstname.lastname@example.org if you should need assistance with the Return Code.
4.) Once you complete all required fields and have uploaded all attachments, you may select “Submit” to send the Periodic Report Form to the WCM DSMB. NOTE: You will not be able to return to the form once you submit it. Please review all data field entries for completeness and accuracy prior to submitting for review. Your finalized ePRF submission will be provided to you as a PDF when you receive your review letter from the WCM DSMB.
5.) Once you submit the report, you will be prompted to provide an email address for the confirmation email. If you do not receive a confirmation email, please contact email@example.com to confirm your submission was received.
What can I expect after a DSMB review?
PIs can expect to receive a recommendation letter from the DSMB within approximately one week of the meeting. Letters will alert the PI as to the DSMB’s recommendation and/or whether the Board requires follow-up before a determination can be made. The DSMB may recommend that the trial continue without modification, continue with modifications, be placed on an enrollment hold, or be terminated (e.g., for slow accrual; immediate safety concerns; trial clearly identifies the more efficacious treatment). Placing the trial on enrollment hold or terminating a trial is extremely rare.
If the DSMB recommends that the trial continue with modifications, the PI is asked to respond to confirm that the modification to the protocol will be made. Most often, the modification is one that alters the DSMB reporting schedule (e.g. semiannually to annually). In order to comply with the DSMB’s recommendation, the PI will need to submit an amendment to the IRB. The amendment needs to modify both the eIRB application and the research protocol.
What if I disagree with the WCM DSMB’s recommendation?
If the PI disagrees with the DSMB, s/he is invited to respond with the rationale for the disagreement. If desired, the PI can attend an upcoming DSMB meeting to discuss the issue in-person.
What are the WCM DSMB’s adverse event reporting requirements?
The WCM DSMB expects PIs to adhere to the Immediate Reporting Policy, which stipulates what adverse events need to be reported to the DSMB right away, as well as what adverse events need to be listed in the Adverse Event & IND Safety Reporting Cumulative Table when submitting a Periodic Report to the DSMB. This policy is shared with the IRB.
The DSMB also has two adverse event narrative reporting requirements that need to be followed when submitting a Periodic Report.
1) The first narrative reporting requirement is as follows:
Narratives of any adverse events that have occurred since the last Periodic Report that have resulted in the following outcomes:
• A life-threatening adverse experience
• Inpatient hospitalization
• Prolongation of existing hospitalization
• A persistent or significant disability or incapacity
• Congenital anomaly or birth defect
2) The second narrative reporting requirement is as follows:
Narratives of any adverse events that are important medical events that may not result in death, be life-threatening, or require hospitalization, but based on appropriate medical judgment require medical or surgical intervention to manage them.
Both of these requirements are listed on the Periodic Report Form.
What are some recommended administrative practices?
Send all general questions and Immediate Report submissions to the firstname.lastname@example.org listserv. This ensures your question or submission is appropriately routed.
•Whenever the DSMB recommends a modification of the protocol’s DSMB review schedule or data safety monitoring plan, update the eIRB application and research protocol with the IRB so that documents are up to date and in agreement.
•Notify the DSMB of any change in administrative contact to ensure that all DSMB requests and reminders are sent to the appropriate party.
•If your protocol has a review schedule that is threshold based, track enrollment carefully so that you remain in compliance with your DSMB review schedule. If a PI does not submit a Periodic Report in accordance with his or her protocol’s review schedule, an Immediate Report protocol deviation must be reported to the IRB and DSMB.