Clinical Research Operations

Submitting a Report to the Safety Monitoring Committee (SMC)

Purpose: To identify the process for submitting reports to the Safety Monitoring Committee (SMC). 

Step 1:  Determine if a protocol meets the criteria for submitting to the SMC

Criteria for determining whether protocol has to be reviewed by SMC:

The SMC will meet quarterly to review any studies that meet the requirements for SMC review. Protocols that meet the criteria for SMC review will be reviewed initially as soon as possible after their annual NCI-IRB continuing review date.   Subsequently, each protocol will be reviewed as close to annually as the quarterly meeting schedule permits or more frequently as may be required by the SMC.

The criteria for review are listed below:

• All NCI CCR multi-institutional treatment protocols for which the NCI CCR is the coordinating site, unless the study has already a designated Data and Safety Monitoring Board (DSMB) or equivalent. These studies will be monitored across the sites for unusual, significant toxicities that are related to the investigational agents being used.    Note: The SMC will not monitor a CTEP-sponsored protocol if this is the only SMC qualifying criteria for the protocol.
• All protocols using gene transfer or gene therapy methodology. Monitoring of these protocols will focus on unusual toxicities specific to gene therapy.
• All protocols that the CCR believes require special attention due to high public interest or public perception of risk or potential conflict of interest. These include studies where the PI or an AI holds a patent on any agent being used in the protocol. For these protocols, the review will focus on unusual, significant toxicities that are related to the investigational agents being used, as well as on the potential perception of a conflict of interest regarding issues such as the continuing study relevance vs. PI benefit.
• All protocols that are deemed by the IRB to pose potentially very high risk to patients.    (Please note that stem cell transplant protocols are no longer automatically being reviewed by the SMC.)

Notification:
The PI will receive email notification from Susan McMullen of the due date for submission of the SMC report.  Usually, notification is sent out 2 months prior to the review date. 
Note: If there is no protocol related treatment and no protocol related toxicity within the review period, then, the PI or proxy should contact Susan McMullen to let her know.

Format:
Follow the template for the SMC report.

Data to be obtained:
The following information should be collected from the research team and then complied into the SMC report:
Note: See the template below. Some requested information may not apply.

• Accrual to date by year per treatment arm – table format
• Tabulation of all grade 3 or greater expected or unexpected adverse events that have an attribution of “possibly,” “probably”, or “definitely” related to the research by treatment arm and by study site since study initiation – table format
• For multi-institutional trials: frequency of monitoring and completeness of data submission by participating sites
• Any commercial sponsorships, payments, royalties, or CRADAs (include #) associated with the protocol.
• Endpoint analysis:
  • Provide information regarding data collection and summary statistics for the primary and secondary endpoints as applicable.
  • For trials with several arms/cohorts: Provide per arm information for endpoints. State whether each arm is open or closed. If arms are closed prior to completion of enrollment as outlined in statistical section, provide rationale for doing so.
• Summary Statement by the Principal Investigator  (See submission template for more information)
• Summary of all amendments that have been submitted since the most recent Continuing Review, including those that are pending IRB approval, and those that are planned for submission in the very near future.

The completed report should be reviewed by the PI and then emailed to Susan McMullen by the due date.

Receipt of Approval from SMC:

• Approval from the SMC will be sent to the PI and research contact.  The approval outcome letter should be uploaded into iRIS.
• A copy should be saved in the regulatory files.

Uploading Outcome letter / Approval into iRIS:

• Once logged into iRIS, go under the DSMB/SMC Outcome letter submission tab.
• Open a new form and complete the appropriate information.
• Make note of the date of the review and whether any outcome action is required.
• Upload the outcome letter in iRIS.
• Submit and apply signoff in iRIS.

Step 2: Preparation of Report for Safety Monitoring Committee

Guidelines for Preparing NCI CCR Safety Monitoring Committee (SMC) Reports

General:  The NCI SMC requests that all communications with the Committee come through the study Principal Investigator (PI).

Format of SMC Reports

• Accrual to date by year (see sample table below) per treatment arm (reporting per dose level for phase I studies is not required) and site: 

  	Arm or Site # 1	Arm or Site # 2	Arm or Site # 3	Arm or Site # 4
  Year 1 (dates)
  Year 2 (dates)
  Year 3 (dates)
  Total

• A report of all grade 3 or greater expected or unexpected adverse events that have an attribution of “possibly,” “probably”, or “definitely” related to the research.   The report will list the highest grade of each toxicity per patient.  For all grade 5 events reported, an autopsy report should be included with the submission if there is one available.

Please note:  The Harris IT team will create a customized report for each protocol once it is placed on the agenda. Susan McMullen will enter a request for the report with the IT team. It will be the responsibility of the teams to insure that their AE data is current in C3D through the date of the notification of the impending SMC review (data entry to be completed no later than 3 weeks prior to the submission due date), to review the reports for accuracy, and to include the reports with their SMC submissions.

•  For each protocol, the information must be broken down by:
  • Study Site
  • Patient Subgroup (if applicable)
  • Arm (if applicable)
  • In transplant studies, by donors and recipients.  
• The report must include:
  • CTCAE Term
  • Grade
  • Attribution to Research
  • Attribution to the IND(s), if appropriate
• and provide tallies for:
  • Number of events since last SMC Reporting
  • Longest event duration since last SMC Reporting
  • Number of events since Study Start
  • Longest event duration since Study Start
  • Number of unique patients

• For multi-institutional trials: Please comment on frequency of monitoring and completeness of data submission by participating sites.

• Please identify any commercial sponsorships, payments, royalties, or CRADAs (include #) associated with the protocol.  

• Endpoint analysis:
  • Provide information regarding data collection and summary statistics for the primary and secondary endpoints as applicable.
  • For trials with several arms/cohorts: Provide per arm information for endpoints. State whether each arm is open or closed. If arms are closed prior to completion of enrollment as outlined in statistical section, provide rationale for doing so.

• Summary Statement by the Principal Investigator: This should include but not be limited to major clinical events by treatment arm or study site. In addition, a description of any other complications or any unanticipated problems regarding study conduct should be included. If applicable, provide the safety monitoring data for any gene therapy study. For transplant studies, please include information about engraftment and the incidence and grading of acute and chronic GVHD.             

• Please list and summarize all amendments that have been submitted since the most recent Continuing review, including those that are pending IRB approval, and those that are planned for submission in the very near future. Amendments that contain only administrative changes should be listed as such.  No summary is required.