Comprehensive standalone DMC services

A data monitoring committee (DMC) is an independent group of experts who conduct regular reviews of the research protocols, clinical trial data and statistical analyses. Based on the result of these reviews, the group provides advice and recommendations on patient safety (including early trial terminations), validity and scientific merit of continuing the trial, as well as identifies patient safety risks.

A DMC is utilised in a clinical trial when recommended by the Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA). It is considered good practice to implement a DMC when there is more than minimal risk to patient safety; the trial is for an at-risk population (elderly, paediatric, emergency situations or vulnerable populations), very large populations or for specific oncology indications. A DMC adds increased safety oversight for studies where it would be unethical to continue the trial because the investigational product is either very effective or not effective. In addition, a DMC is strongly recommended for adaptive design studies.

Comprehensive DMC management includes an independent reporting statistician (IRS), DMC statistical programmer and DMC project manager (PM):

• IRS: The IRS has experience and a full understanding of DMCs, as well as the expectations of the DMC members in reviewing the clinical trial data. Their role is to prepare the DMC analysis plan with data from the sponsor, ICON, or a third party vendor. They are independent from the study in both open-label and blinded trials. The IRS provides a confidential point of contact for the DMC requests on data clarifications and ad hoc data analyses. The IRS also acts as a liaison between external data management vendors and the internal team with a full understanding of the communication limitations of an unblinded role.
• DMC statistical programmer: The IRS partners with a DMC-dedicated unblinded statistical programmer who efficiently programs all appropriate outputs, focuses on the timely production of outputs from raw data sources and is dedicated exclusively to DMC projects.
• DMC PM: To ensure the whole process runs smoothly, a DMC PM is essential. This role creates the DMC membership, including identification, vetting and contracting of members. The DMC PM drafts the DMC charter, which outlines the expectations of the DMC. Along with the administrative duties, such as ensuring there is a secure workspace for the data, meeting coordination and minutes, the DMC PM must coordinate the data flow from the raw data to the final outputs provided to the DMC. Lastly, the DMC PM is both the point of contact for the DMC and the liaison between the DMC and the sponsor to ensure transparent communication.

ICON was chosen to provide a comprehensive DMC solution for a phase 2 non-alcoholic steatohepatitis (NASH) trial run by a small biopharma company based in the United States. A DMC-specific statistical analysis plan (SAP) and tables, figures and listings (TFLs) were requested for both a main study and an extension study, with a primary endpoint of overall improvement.

Because the DMC unit and the data management group were not within the same company, the first challenge was coordinating the flow of the data. The second challenge occurred after the start of the study when enrollment was unexpectedly faster than anticipated. This rapid enrolment meant reassessing all of the timelines to ensure a timely data cut, and ultimately, data delivery to the DMC with adequate time for their review.

To meet the unique needs of the study, a NASH expert statistician was assigned as the IRS. A collaborative relationship was quickly established with the third-party vendor by the DMC PM. A DMC charter was developed to ensure clarification of roles and responsibilities of all parties with input and approval from the sponsor, DMC members and the data management group prior to the DMC organisational meeting. The DMC PM established the NASH-specific safety committee with members who served on previous ICON NASH DMCs with experience in both the therapeutic area and serving on DMCs. With regard to the main study and extension study, the IRS assisted the sponsor in visualising the presentation of results after the rerandomisation. It was essential that adequate resources were dedicated to ensuring the data was ready for the first DMC meeting considering the shortened timeframe. The IRS worked with DMC members to ensure the extension study TFLs were presented in a way that would be easy for them to interpret.

By utilising experienced DMC management team members, all the DMC meeting outputs were delivered on time, despite having multiple vendors. The DMC members were able to thoroughly review all safety data due to the high-quality outputs provided, as described by the DMC chairperson. Ultimately, patient safety was protected, and the sponsor’s investment was safeguarded.

The DMC recommended continuing the trial at all DMC meetings to date.