Internal DSMC Completion

Q: Who/what does a DSMC consist of?

• A DSMC consists of no fewer than 3 members; including 2 clinical investigators and a biostatistician who are not involved with the study.
  
  

Q: Who can be selected as a DSMC member?

• Only individuals who are not working on the trial may be selected. Members should disclose any conflicts of interest with the study. Individuals should not be selected if any conflicts are identified.
  
  

Q: Who is in charge of appointing committee members?

• The PI is responsible for appointing committee members. It’s a good idea to involve clinicians with different backgrounds and expertise. We recommend that at least one appointed member have previous DSMC experience.
  
  

Q: How does a DSMC get started?

• Generally, it’s a good idea to set up an initial meeting. At this meeting, your team could determine: the scheduling of meetings; the format of the meeting or agenda; timing of the delivery of the report to the DSMC members prior to the meeting; definition of a "quorum" of DSMC members; handling of meeting minutes; and other aspects of the process.
  
  

Q: How often should the committee meet?

• Per Siteman’s Data Safety Monitoring Plan, a DSMC must meet at least twice a year. Some studies may require more frequent monitoring.
  
  

Q: Are committee members paid for review?

• Committee members may receive some type of payment as indicated by the study budget. DSMB members do not have to be paid. WUSTL affiliates often help monitor studies as part of their service to the institution.
  
  

Q: What are the responsibilities of the DSMC members?

1. Members should familiarize themselves with the research protocol(s) and plans for data and safety monitoring.

2. Review interim analyses of outcome data and cumulative toxicity data summaries to determine whether the trial should continue as originally designed, should be changed, or should be terminated

3. Review reports of related studies to determine whether the monitored study needs to be changed or terminated.

4. Review major proposed modifications to the study prior to their implementation (e.g., termination, dropping an arm based on toxicity results or other reported trial outcomes, increasing target sample size)

5. Following each DSMC meeting, provide PI with written a report outlining any recommendations or concerns.
   
   

Q: What is the structure of the DSMC meeting?

1. Start with an open session in which members of the clinical trial team may be present, at the request of the DSMC, to review the conduct of the trial and to answer questions from members of the DSMC. The focus in the open session may be on accrual, protocol compliance, and general toxicity issues.

2. Following this session, a closed session involving the DSMC members, and the study’s statistician should be held to discuss any un-blinded data if applicable, or to discuss issues regarding study conduct. In order to meet the responsibilities for monitoring the safety of participants and the integrity of the data, DSMCs must be able to access unmasked data whenever masked data are presented. It is generally recommended that all data be presented to the DSMB in an un-masked manner; however, if the awardee leading the trial(s) desires to keep some data masked, then this is acceptable provided that any DSMB member’s request for unmasking of trial data is honored.

3. A final session gives the DSMC members an opportunity to discuss the general conduct of the trial, all outcome results, and take votes as necessary.
   
   

Q: How long should each meeting be and what should be reviewed?

1. The length of the meeting and what is reviewed will vary greatly on the specific trial.

2. The DSMC may wish to review the following:

   1. Review data (including blinded data) over the course of the trial relating to efficacy.

   2. Review recruitment, randomization, compliance, retention, protocol adherence, trials operating procedures, forms completion, intervention effects, gender and minority inclusion, and subject safety.

   3. Identify problems relating to safety over the course of the study.

   4. Identify needs for additional data relevant to safety issues and request these data from the study team.

   5. Propose appropriate analyses and periodically review developing data on safety and endpoints.

   6. At each meeting, consider the rationale for continuation of the study, with respect to recruitment, progress of randomization, retention, protocol adherence and compliance, data management, safety issues, outcome data, if relevant, and make a recommendation for or against continuation of the trial.

   7. Provide advice on issues regarding data discrepancies found by the data auditing system or other sources.

Q: What recommendations can DSMC members make?

1. A DSMC can make recommendations to continue, modify, or stop the research based on an assessment of risks and benefits. A DSMC has the authority to request additional analyses and may schedule additional follow up meetings. A DSMC can make recommendations to the protocol, procedures or treatment. In short, there are numerous recommendations a DSMC could make.

2. The majority of the time, a DSMC will agree to continue a study without modification. In an instance where a recommendation is made, the DSMC should provide clear rationale in writing to the study team.
   
   

Q: Can the review occur over email?

• No. DSMC meetings are usually held in person, but conference calls may be acceptable in certain circumstances.
  
  

Q: Is there a pre-existing set charter for Siteman?

• Yes, there is charter language that should be included in protocols that required a DSMC:

  • In compliance with the Washington University Institutional Data and Safety Monitoring Plan, the Data and Safety Monitoring Committee (DSMC) will meet to review toxicity data at least every 6 months following the activation of the first secondary site.
    
    

  • The report will be prepared by the statistician with assistance from the study team and will be submitted to the Quality Assurance and Safety Monitoring Committee (QASMC). This report will include:

    • HRPO protocol number, protocol title, Principal Investigator name, data coordinator name, regulatory coordinator name, and statistician
      

    • Date of initial HRPO approval, date of most recent consent HRPO approval/revision, date of HRPO expiration, date of most recent QA audit, study status, and phase of study
      

    • History of study including summary of substantive amendments; summary of accrual suspensions including start/stop dates and reason; and summary of protocol exceptions, error, or breach of confidentiality including start/stop dates and reason
      

    • Study-wide target accrual and study-wide actual accrual including numbers from participating sites
      

    • Protocol activation date at each participating site
      

    • Average rate of accrual observed in year 1, year 2, and subsequent years at each participating site
      

    • Expected accrual end date and accrual by site
      

    • Objectives of protocol with supporting data and list the number of participants who have met each objective

    • Measures of efficacy

    • Early stopping rules with supporting data and list the number of participants who have met the early stopping rules

    • Summary of toxicities at all participating sites

    • Abstract submissions/publications

    • Summary of any recent literature that may affect the safety or ethics of the study
      
      

  • The study principal investigator and Research Patient Coordinator will monitor for serious toxicities on an ongoing basis. Once the principal investigator or Research Patient Coordinator becomes aware of an adverse event, the AE will be reported to the HRPO and QASMC according to institutional guidelines.

  • A DSMC will consist of no fewer than 3 members including 2 clinical investigators and a biostatistician. Like investigators, DSMC members are subject to the Washington University School of Medicine policies regarding standards of conduct. Individuals invited to serve on the DSMC will disclose any potential conflicts of interest to the trial principal investigator and/or appropriate university officials, in accordance with institution policies. Potential conflicts that develop during a trial or a member’s tenure on a DSMC must also be disclosed.

  • Refer to the Washington University Quality Assurance and Data Safety Monitoring Committee Policies and Procedures for full details on the responsibilities of the DSMC at http://www.siteman.wustl.edu/uploadedFiles/Research_Programs/Clinical_Research_Resources/Protocol_Review_and_Monitoring_Committee/QASMCQualityAssurcance.pdf
    

Q: What documentation of the meeting is required, if any?

• We recommend that the DSMC keep minutes of all meetings (see Guidance for Industry, ICH E6, Good Clinical Practice: Consolidated Guidance, Section 5.5 at 5.5.2.

• We recommend that the DSMC divide meeting minutes into two parts, according to whether they include discussion of un-blinded data. The second part of the minutes discussing un-blinded data would not be circulated.

• We also recommend that after each meeting, the DSMC issue a written report to the PI based on the meeting minutes. This report does not have to be extremely detailed, but should include sufficient information to explain the rationale for any recommended changes. If no changes are recommended, the report may be as simple as "The DSMC recommends that the study continue as designed."