Axio Research is the world leader in successfully planning and managing DMCs
// Data Monitoring Committees
Axio’s biostatistical group offers deep expertise in supporting data monitoring committees (DMCs). Based on your requirements, Axio can select committee members, prepare your charter, and merge treatment assignments with clinical data. Our comprehensive services for DMCs also include creating and presenting open and closed reports, completing meeting minutes, and providing institutional review board (IRB) notification documents.
We deliver accurate, polished reports within tight timelines and will act as liaison between you and your DMC.
Among our areas of experience are: cardiovascular disorders and devices, dermatology, endocrinology, gastroenterology, hematology, hepatology, immunology, infectious diseases, inflammatory diseases, mental health disorders, nephrology, neurology, obesity, oncology, ophthalmology, pain, psychiatry, pulmonary disorders, rheumatology, substance abuse disorders, tropical diseases, urology, and vaccines.
Axio’s PhD and master’s-level biostatisticians have supported more than 150 DMCs. A cross-section of our recent DMC experience is described below.
|Small molecule||Prostate Cancer|
|Biologic||Chronic Heart Failure|
|Small molecule||Myeloid Leukemia|
Preparing Data Monitoring Committee Charters
We can help you to meet your study’s DMC Charter requirements efficiently and accurately. FDA and ICH Guidelines (Guidance for Clinical Trial Sponsors, and E9: Statistical Principles for Clinical Trials) recommend adoption of a charter for DMCs to: outline roles and responsibilities; specify the interim analyses to be performed; and clarify reporting relationships. Axio can cost-effectively prepare your DMC charter from a template. The contents typically include:
- DMC Membership
- Blinding/unblinding of DMC reports and DMC meeting participants
- Reporting relationships
- Statistical considerations and monitoring guidelines
- An overview of the study design
- How the false positive error rate is allocated
- Group sequential monitoring guidelines
- An outline of open and closed DMC report contents
Drafting Interim Analysis Plans
Our professionals are well versed in crafting well-defined Interim analysis plans. As part of your DMC charter or as a separate document, Axio will draft an interim analysis plan detailing the calculations to be performed and displays to be included for each interim examination of the trial data. Stopping boundaries are included, but are adjusted as needed for each interim look at the actual data.
We have extensive experience with tricky endpoints such as time to disease progression, time to failure of local control, relapse, and composite cardiovascular endpoints.
Drafting, Programming, and Testing Tables, Listings, and Figures
Let us manage your DMC reporting needs. Axio can draft mock shells for the tables, listings, and figures to be included in the open and closed DMC reports. These drafts will provide sufficient detail for your DMC members to envision the resulting report elements. We revise mock report elements based on sponsor and DMC recommendations, and prepare a final version after the initial DMC planning meeting.
Based upon the approved mock tables, listings, and figures, Axio develops and tests programs using SAS and S-Plus to produce the report elements required for the DMC reports. The SAS datasets contain the required variables, transformed and recoded appropriately, for the tables/figures/analyses in an appropriate format.
We favor aggressive timeline management for DMC reports. We will work with your study team to make sure transfers of test data arrive. Our associates will prepare a draft open report and dummy-coded closed report for your review, obtain real-time serious adverse event (SAE) data, and maintain ongoing communications with your other CROs.
Producing and Distributing DMC Reports
Axio’s capable team will produce the tables, listings, and figures that comprise both the open and closed DMC reports—tailored to your specifications. If requested, a narrative can accompany the DMC report, explaining:
- A summary of the study protocol and monitoring plans
- Any specific questions or concerns that the sponsor wishes the DMC to address
- A brief narrative description of each of the tables with sufficient detail to enable the DMC to understand them
Our extensive experience in designing and producing DMC reports has helped us develop an innovative and productive approach. We suggest including only the most important tables: Report elements that are distracting or irrelevant should be omitted. Helping the DMC members make efficient use of their time encourages their careful review.
In some cases, certain data need to be redacted prior to inclusion in the draft open report provided to your blinded team. We can prepare tables without dose, specific lab data, or other data that would unblind. We can even prepare different types of draft open reports if different levels of blinding exist within your company. As an example, in some cases, we have maintained two different independent statisticians for the same DMC: one blinded to interact with the DMC, the other unblinded to supervise programming efforts. We are flexible and willing to perform outside the box.
We maintain a file transfer protocol (FTP) site and a Web portal that allows calendar posting and reviews of notes. We can post DMC reports or not, according to sponsor preference. Email communications are easy for many members, but may present privacy problems when sent through university exchange servers.
Presenting Open and Closed DMC Reports
Our biostatisticians will make themselves available to your DMC. The Axio biostatistician working with your trial can attend your DMC meetings to present the materials, field questions about the data or analyses, and take minutes. If requested and appropriate, Axio can provide additional analyses to the DMC membership to aid them in their oversight role.
Need additional data items during the closed session? Our biostatisticians are able to provide this upon request. We are calm under pressure and maintain the flexibility to adapt to changing situations. Our team will moderate all communications between you and the DMC and ensure that the procedures in the DMC charter are followed and that documents are completed, signed, and archived properly.
We are keenly aware of the importance of maintaining a good “poker face” in DMC meetings—to maintain confidentiality and study integrity. Newer statisticians at Axio are trained to enable them to interact closely with a study team without giving verbal or nonverbal cues about treatment arm results.
Verifying Treatment Codes
Upon receipt of treatment codes, kit numbers, etc. we can perform a reconciliation to check whether all patients’ kits match the treatment randomization code. Often, site errors can be caught early. We also scan study results to determine whether efficacy and safety findings appear to be consistent with the treatment groups.
Producing Safety Updates for DMCs
Safety updates are tailored to your trial and DMC. We can set up real-time SAE reporting or monthly or quarterly reporting for DMC members or DMC chairs. Our team can summarize narratives from Council for International Organizations of Medical Sciences (CIOMS) or other reporting systems, provide cumulative counts by treatment arm, and customize reports in a multitude of other ways. We can help you design this process to streamline your annual safety reports as a subset of the DMC report.
To assist several of our clients with their internal decision making, we have created a second version of the DMC report that includes only the clean data—or only subjects with a specified minimum quantity of follow-up data.
Working with Non-Axio-Generated DMC Reports
Some of our clients have requested that we use their programming code to produce report elements. We verify against dummy treatment codes with the sponsor, then merge in the true treatment assignments for the DMC report. We have even accommodated a last-minute request to substitute for another independent statistician who became ill.
Identifying DMC Members and Establishing Agreements
Axio can identify clinicians, biostatisticians, and bioethicists to serve on the DMC. We can establish all necessary agreements with DMC members, including confidentiality, conflict of interest, and consulting agreements. Our team can also provide training to the DMC members regarding their roles and responsibilities during the study.
Responding to Real-Time Data Challenges
DMC reports differ in several key ways from final statistical reports. Axio’s experience with mid-study and registry data gives us the flexibility to work successfully with unclean or incomplete data. Our biostatisticians are accustomed to real-time data and are trained to find and respond to anomalies, outliers, data errors, and alterations to data structures.
When data arrive from disparate sources, they must be merged to create a coherent and internally consistent report. For example, we can track when clinical laboratory data are expected, flag patients with missing data, standardize units, and incorporate these improvements into the DMC report. We are accustomed to handling these problems on a large scale and have developed systems and processes to efficiently handle the issues that inevitably arise.
The Axio statistician checks the data for adverse events (AEs), lab values, or other data points of potential interest and then scans for obvious outliers or data errors. Our systems auto-check log files, auto-generate tables of contents, and auto-check data structures from different data transfers.
Our specialists have developed several macros for creating summary report elements from free-text fields, using character string searches within SAS. We can work with your clinical team to perform qualitative coding to allow DMC members to quickly grasp results without wading through long listings.
Coordinating DMC Meeting Arrangements
Another area where our experienced team can capably manage all details without a hitch is in managing your DMC meetings. Axio coordinates and hosts in-person and teleconference DMC meetings. We can make all travel, hotel, and catering arrangements for these gatherings. Our attention to detail is legendary: We frequently facilitate meetings that include individuals on different continents, checking flight times and providing international teleconference numbers. We can also coordinate and attend social DMC events, such as pre-meeting dinners. We make ourselves available for DMC teleconferences at any hour of the day or night.
It is our practice to send out meeting notices well in advance, to follow up with reminders, and to have a staff member ready to contact and assist DMC members who have not dialed in to a teleconference when expected. We prepare and distribute an agenda—and ensure that all agenda items are covered during the meeting.
Axio can also coordinate all correspondence with the DMC members, including curricula vitae, disclosure declarations, contracts, agendas, meeting binders, invoices, and honoraria. After all in-person meetings, we ensure that no confidential information is left in the meeting room.
Working with Your Study Team and Your DMC
In our experience, Axio’s involvement with DMC study teams pays off. We like to be involved. Many companies are new to DMC procedures. We invite you to consider a visit to your company by one or more of our DMC statisticians. They can show your team how to support your DMC—and what is of interest to DMC members. We can help you understand what goes on behind closed doors and recommend how everyone can interact with one another to make the DMC experience as effective as possible.
Similarly, we’ve found it a valuable practice to schedule a debriefing meeting at the conclusion of each study, with the goal of sharing what worked well and what did not. That way, everyone involved can apply that knowledge to the next study.