[UPDATED 15-Nov] The Data Safety Monitoring Board (DSMB) for the CLEAR III clinical trial met today in both a closed session (to review unblinded data on the first 100 patients without the management team being present) and an open session where they asked questions of the project management and biostatistics teams from the BIOS Coordinating Center at Johns Hopkins. The official letter and a copy of the minutes have now been released and are attached below.
The DSMB stated "no safety or performance issues were identified" and that "the trial should proceed as planned". The DSMB went on to compliment the investigators and the study team "for being ahead of schedule on recruitment and for providing a clear and thorough data report."
As an independent committee appointed by NIH/NINDS, the Data Safety and Monitoring Board, by mandate, reviews unblinded data to assess safety and efficacy and the potential for stopping the study early. As part of this routine mandate to ensure study integrity, the DSMB asked for an analysis of test article shipment data.
As we all know, when drug is shipped to sites, it comes in a container filled with dry ice and includes a temperature monitoring device. That device is then returned to the Trial Pharmacist for confirmation that there were no temperature excursions during transit.
Shipments are sometimes inadvertently delayed. In such cases, per protocol, that shipment will be destroyed and replaced with a new batch of drug. The process is working well and there are no safety concerns, but to be prudent, the DSMB is taking the additional effort to confirm that there is nothing in the actual study data to remotely suggest any drug potency issues that could confound trial analysis. The BIOS Coordinating Center will be compiling and submitting that data shortly.
Meanwhile, the DSMB's only critique was that some sites have become a little lax in reporting their screen failure data. The committee members stressed that this seemly-mundane task is actually quite important for assessing the generalizability of the study results.
They also encouraged investigators to ensure that patients are being proactively screened in real-time for this study, not after the fact by surveillance of medical records. Of course, this is of importance to ensure continued steady and prompt enrollment (so that potential patients are identified before the eligibility time window expires), but this too has added importance -- that may not be as self-evident -- for ensuring the ability to generalize the study results to the broader patient population once the trial is concluded. The Coordinating Center will therefore be presenting screening data and stressing this important issue to the sites in an upcoming webinar.
As a last matter, the board scheduled a follow-up teleconference, with a limited data review, for June 2012 at which point a formal meeting date will be established to review full data on the first 250 subjects, to include the Day-180 outcomes data.
In conclusion, the trial management team wants to express appreciation to the investigators, coordinators, monitors, site managers and other investigational site, BIOS coordinating center and Emissary International staff that worked so hard to complete data entry, verify source documents, resolve queries, and finalize the data for this meeting. We also want to formally recognize the contributions of Alicia Wentz and John Muschelli from the data management team that put in so many long hours to analyze the data and produce the study report.
Thank you everyone for making this important clinical trial a success!
Logged-in users can see some photos from the meeting here.
Attached below is the official letter from the DSMB, a copy of the minutes, and a copy of the IND Safety Report. This latter document and the official letter should be submitted to the clinical site Institutional Review Boards (IRB) or Ethics Committees (EC) per local requirements. It will be submitted by the Johns Hopkins Coordinating Committee to the U.S. FDA, NIH, and the international regulatory agencies.
|DSMB Oct-2011 Meeting Report||142.98 KB|
|CLEAR-III DSMB Meeting Minutes Oct-2011||226.34 KB|
|CLEAR-III Annual Report to Sites & Regulatory Agencies||402.96 KB|