Managing Data Challenges in Clinical Studies with a Data Safety Monitoring Board

A Data Safety Monitoring Board (DSMB) plays a critical role in ensuring the safety, credibility, and integrity of ongoing clinical trials. Comprising independent professionals with relevant expertise, the DSMB regularly reviews data accumulated from one or more ongoing clinical trial. The DSMB continuously advises the sponsor on the safety of trial subjects and those yet to be recruited to the trial as well as the validity and scientific merit of the trial. This article explores the essential functions of a DSMB and the crucial role data management plays in supporting its activities.

The DSMB serves as a vigilant monitor throughout the trial, conducting planned follow-up evaluations to assess trial effectiveness, participant safety, study conduct, and external data relevant to the trial. It also offers recommendations to the sponsor regarding the continuation, modification, suspension, or termination of a trial, maintaining written records of outcomes while preserving data confidentiality.

Various scenarios warrant the involvement of a data safety monitoring board (DSMB) in a clinical study, such as when there are unusually high safety concerns, to enhance the safety of trial participants, a vulnerable subject population (children, pregnant women, elderly, terminally ill, subjects with diminished mental capacity, or imprisoned), or invasive treatments. Regardless of the circumstances, providing complete and accurate data that is as up to date as possible to the Data Safety Monitoring Board (DSMB) is paramount, as it is the foundation for their recommendations with respect to trial safety and efficacy. The outcomes of all DSMB meetings involve ensuring that members obtain sufficient information in order to:

• Sufficiently review a study.
• Profit from the discussions with the sponsor and investigator representative.
• Identify issues and develop approaches for addressing them.
• Reach a consensus concerning trial recommendations.

The responsibility for delivering high-quality data in order to respond to the DSMB’s requirements lies with the Data Manager, who collaborates with the biostatisticians in the preparation of the tables and statistical analyses that the Data Safety Monitoring Board (DSMB) will receive and use to make their recommendations. During the Clinical Report Form (CRF) specification development, the Data Manager plans in advance, determining the necessary data, level of cleaning requirements, and timelines.

To ensure the clinical data is captured in a timely manner, the Data Manager will discuss and agree on a monitoring plan. For Electronic Data Capture (EDC) studies, targets for data entry into CRFs are defined, while paper studies involve specifying monitoring visits and CRF shipment details. They will implement tracking reports/metrics to monitor what is in-house vs what is still outstanding and share updates with the study team to avoid backlogs.

A crucial part of the Data Manager’s role is to tailor the cleaning strategy, addressing considerations like subject enrolment cut-off dates, last data point entry, and coding of medical terms. It is important to define if there are any external data required for the DSMB. External data are usually on a critical path in terms of vendor management and data transmission. In this case, the Data Manager will:

1. Define data transfer specifications and method of transfer, as well as timelines of data transfers with provider.
2. Define timelines for reconciliation to allow time for query issue and resolution.
3. Keep the study “blinded”, for instance in the case of PK or Biomarkers, data could reveal what the subject is taking – such as active drug or placebo by viewing the data concentrations. In such cases, the Data Manager will perform a data reconciliation on sample nominal time with concentrations.

Collaboration between the Data Manager and the study team is crucial. Regular meetings ensure the sharing of clinical study status, such as if there is a need to run listings and tables in advance to check for potential issues or abnormal trends in the clinical data entered into the database. This proactive approach enables the following:

• The Data Manager can generate queries, to address issues or get a justification/clarification prior to generating outputs for the DSMB.
• Collection of protocol deviations and evaluation of possible impact on clinical data.
• Define data checks within the clinical data management system, such as time window, inclusion/exclusion criteria, plausibility, ranges etc.
• Retrieve deviations collected through monitoring visits – liaise with CRAs.

To successfully complete a clinical study which includes a DSMB, three key points related to data management are essential:

• Clear definition of roles and DSMB data management responsibilities.
• Effective communication within the study team and with external partners.
• Meticulous planning, ensuring that all aspects of data collection, cleaning, and transfer are well-coordinated.

Ensure the accuracy and efficacy of your clinical trial data

Quanticate’s Clinical Data Management Team are dedicated to ensuring high quality clinical data and have a wealth of experience in data capture, processing and collection tools. Our team offer flexible and tailored solutions to ensure the successful completion of clinical studies which include a DSMB. If you would like more information on how we can assist your clinical trial submit an RFI.