Table 5 Sharing of interim information indicated in encountered Data Safety Monitoring Board (DSMB) charters
Have you ever been involved in a trial where it was explicitly stated in the Data Safety Monitoring Board (DSMB) charter what interim information/data/results should be shared and with whom that information should be shared during the trial’s interim? | |||
Total responses to question: 207 | |||
Response | Count; % [95% CI] | ||
No | 103; 49.8% [42.8% to 56.7%] | ||
Yes | 104; 50.2% [43.3% to 57.2%] | ||
For those that answered “yes” and according to any DSMB charter(s) they encountered, which of the following pieces of interim information should be shared during the interim of a trial, with whom and under what circumstance the sharing would happen. | |||
Interim Information | Count; % [95% CI] B | With whom should that information be shared? | Under what circumstance this information should be shared according to the charter? Summary of responses |
Interim Combined Event Rate | 55; 26.6% [20.7% to 33.1%] | Various parties indicated: • Sponsor • Investigator • Funder • Steering Committee • Regulator • Other relevant parties | Various responses were given. Singular parties: • With the investigator: if the overall rate was much lower than hypothesized and if there was a need to adjust the sample size • With the Steering Committee: always shared at each meeting without restrictions. To help with potential sample size re-estimation and re-assess power without unmasking group event rates. When the overall rate is much lower than anticipated • With the sponsor: shared during open session report. To help with potential sample size re-estimation. Help sponsor anticipate the length of the trial. Sharing was up to the DSMB’s discretion • With the regulatory agency: If there was a safety issue A combination of parties: • With select members of the sponsor, steering committee or investigator(s): pre-specified in the charter. When benchmarks are not met or when there is determined need for a sample size re-estimation. Need to share if there was a recommendation from the DSMB to stop the trial because of futility or efficacy. Such information is only used for internal decision-making and is not for publication or further dissemination • With the sponsor, funder or investigator(s): once accrual was complete and the primary outcome was known for at least a certain set percentage of those enrolled. It was also indicated that this information was shared at every planned interim look • With relevant parties: for safety and ethical issues |
Interim Control Event Rate | 16; 7.7% [4.5% to 12.2%] | Various parties indicated: • Sponsor • Investigator • Funder • Steering Committee • Regulator • Other relevant parties | Various responses were given. Singular parties: • With the Steering Committee: pre-specified in the charter. If the event rate was different from what was pre-specified in the protocol • With the sponsor: when there is a futility analysis and if the interim control event rate differed majorly from the design assumptions • With the regulatory agency: if there was a safety issue A combination of parties: • Select members of sponsor/funder, Steering Committee or investigator(s): o Pre-specified in the charter. sharing this information was not data driven o It would be shared once accrual was complete and the primary outcome was known for at least a certain set percentage of those enrolled. It was also indicated in another instance that interim control event rate was shared at every planned interim look • With relevant parties: For safety and ethical issues |
Adaptive Conditional Power | 19; 9.2% [5.6% to 13.9%] | Various parties indicated: • Sponsor • Investigator • Funder • Steering Committee • Other relevant parties | Various responses were given. Singular parties: • With the sponsor: would be shared at interim at the time of formal futility analysis • With the Steering Committee: would be shared at interim at the time of formal futility analysis and when a boundary was crossed. Also shared when there was a need for a management decision to be made A combination of parties: • Select members of sponsor/funder, Steering Committee or investigator(s): if the adaptive conditional power falls below a pre-fixed level or when there was data supporting stopping the trial. Pre-specified in the charter. Such information is only used for internal decision-making and is not for publication or further dissemination. In one instance it was also shared at the annual meeting report • With relevant parties: for safety and ethical issues |
Unconditional Conditional Power | 18; 8.7% [5.3% to 13.4%] | Various parties indicated: • Sponsor • Investigator • Funder • Steering Committee • Regulator • Other relevant parties | Various responses were given. Singular parties: • With the sponsor: would be shared at interim at the time of formal futility analysis and for a needed sample size recalculation • With the Steering Committee: would be shared at interim when there was a clear benefit or harm to whatever was being investigated and to re-assess power without unmasking interim results A combination of parties: • With select members of sponsor/funder, Steering Committee or investigator(s): pre-specified in the charter. When there was data supporting stopping the trial • With relevant parties: for safety and ethical issues There was an argument that such information is implicitly available, even if it is not directly provided |
Other information | |||
Information about trial conduct | 21; 10.1% [6.4 to 15.1%] | Various parties indicated: • Sponsor • Investigator • Funder • Steering Committee • Regulator | A combination of parties: • With the sponsor/funder, Steering Committee, investigator(s) or regulator if needed: This is not confidential information and should be shared during DSMB open sessions according to the charter with any relevant party at the open session and those responsible for the conduct of the trial to ensure the integrity of the trial’s conduct and correct problems as soon as possible |
Safety issue or concern | 16; 7.7% [4.5% to 12.2%] | Various parties indicated: • Sponsor • Investigator • Funder • Steering Committee • Regulator | A combination of parties: • With the sponsor/funder, Steering Committee, investigator(s) or regulator if needed: This is not confidential information and should be shared during DSMB open sessions according to the charter with any relevant party at the open session and those responsible for the conduct of the trial. It is important to share this information to help those responsible for the trial’s conduct to ensure participant safety |
DSMB trial recommendations such as stopping or continuing the trial and possible sample size adjustment. | 15; 7.2% [4.1% to 11.7%] | Various parties indicated: • Sponsor • Steering Committee | A combination of parties: • With the Steering Committee or sponsor: Pre-specified in the charter. Typical information shared in this circumstance would not include unmasked group information. However, it was indicated that if there cases where unmasked information would be shared if the decision to stop the trial has been made (e.g., for futility, efficacy or if some other pre-specified boundary has been reached) |
Overall patient baseline characteristics | 3; 1.4% [0.3% to 4.2%] | Various parties indicated: • Sponsor • Investigator • Funder • Steering Committee • Regulator | A combination of parties: • Sponsor/funder, Steering Committee, investigator(s) or regulator if needed: this is not confidential information would be shared during DSMB open sessions according to the charter with any relevant party at the open session and those responsible for the conduct of the trial |
Unmasked treatment arm information | 1; 0.5% [0.01% to 2.7%] | Various parties indicated: • Sponsor • Investigator • Public | A combination of parties: • With the sponsor, investigator(s) or public: it was also mentioned that primary outcome data by treatment group was once shared with the sponsor, investigator or public if the primary outcome is known for at least set percentage of trial patients and the target sample size was enrolled |