In this blog, Alla Muchnik, Senior Clinical Data Manager at Cytel, discusses how specialist CROs can add value and streamline processes by providing oversight of data management services delivered by another CRO. This model helps to fulfill essential regulatory obligations for biopharma companies who may lack their own internal oversight resources.
The Good Clinical Data Management Practices document produced by the SCDM includes a specific section on Vendor Selection and Management, - such is its importance for ensuring quality in clinical trials. It states: “Vendors provide services that are critical to the successful outcome of a clinical study, yet sponsors retain the ultimate responsibility for activities that are outsourced. If a sponsor is willing to give control of some study activities to a vendor, the sponsor should take measures to ensure the vendor is delivering products or services of acceptable and repeatable quality.” Specifically, concerning data management processes, multiple vendors and interactions are involved including contract research organizations (CROs), EDC vendors, clinical laboratories, and ePRO vendors. The International Conference on Harmonization (ICH) E6 R2 also states “Ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor.” Therefore, the sponsor must manage vendors in a fashion that ensures quality, integrity, and reliability. Not only is this ICH statement essential for the sponsor to adhere to, but it must also be at the forefront of vendors’ working practices when considering the quality of documentation and deliverables. Documented processes should be followed to ensure that quality data is received from vendors, as well as to evaluate vendor services consistently.
Bridging the Oversight Gap
Despite this obligation for the sponsor to retain full responsibility for their outsourced services, an ‘oversight gap' can occur particularly within lean, virtually structured organizations. Sponsors may outsource their data management services to a full-service CRO for their trial, but don’t have a data management resource in-house available to oversee the data management deliverables and ensure adherence to proper processes. In such situations, an increasingly popular solution is to contract a specialist CRO such as Cytel, to oversee data management deliverables of the primary or full-service CRO on their behalf. This provider can represent and act on behalf of the sponsor to provide a second pair of eyes on the primary CRO's deliverables and consulting on best practices and process improvements. There are very measurable benefits of this model:
The sponsor benefits from budget savings by retaining a virtual structure for the specific tasks associated with data management oversight. The ‘oversight' data manager provides an additional dimension of expertise and ongoing quality control over the main CRO's deliverables. This role results in invaluable and proactive feedback to the sponsor that assures compliance with SOPs, GCP and industry regulations. It can also be highly beneficial for the primary CRO to streamline communication directly - data manager to data manager and avoid misunderstandings and bottlenecks. Typical activities that form part of this type of oversight arrangement include a review of critical documents for study/ EDC design, CRFs, Metadata, Data Management Plan; data transfer plan; randomization specifications, and many others.
Partnership to Deliver Value Let’s examine further the kind of improvements and benefits that these partnerships can deliver to the different pieces of the data management value chain.
• CRF design: by reviewing the CRF produced by the primary CRO we can collaboratively create the most efficient design. By starting on the right foot, with the optimal design, we are then able to support data validation further downstream by, for example, following CDISC standardization, layout best practices, and addressing any missing data collection questions that were required by the protocol. • Review of Metadata and UAT to provide detailed feedback on issues, and suggestions on how to resolve them. • Review and optimize edit checks to ensure real-time data validation- improving the data quality outcome and streamlining the data verification process. • Review and enhance the Data Management Plan and optimize data transfer flow. • Quality control of SAE Reconciliation ensuring there are no unreported SAEs. • Best Practice Guidance: For example, identifying ways to efficiently lock the data on a rolling basis based on the subject's study completion date, so that by the time the last patient completes their last visit (LPV), 70% of the data is "soft-locked." Such approaches help to smooth the timeline to database lock.
Enhanced Communication An oversight data manager can help to streamline communication and improve efficiency by interacting directly with the primary CRO's data manager and addressing the issues that affect the database readiness and proactively suggesting resolutions. The oversight data manager can also support the deliverables by providing a checklist and templates to capture the essential tasks and assure quality.
The oversight data manager will also provide essential evaluation and assurance that the CRO is following the data management plan for specific milestones. A critical aspect of meeting oversight obligations is to review the full-service CRO’s SOPs for particular data management areas, and tasks to proactively identify insufficiencies or issues and of course address them.
Success in data management oversight depends on a deep understanding of the entire end-to-end data management process. The CCDM certification can be a useful guide as to whether the proposed data manager within the oversight vendor has the relevant skillsets. Beyond this, domain knowledge in the particular therapeutic area of the project, experience as a database designer, knowledge of the specific EDC platform in use, and understanding of the relevant GCP and regulatory documentation are also important.
Finally, as with many aspects of clinical trials, it is critical to engage with an experienced provider and to hire a data manager who has the confidence and excellent communication skills to navigate multiple stakeholder relationships. Flexibility and responsiveness are vital attributes to ensure that timelines are met, and issues addressed quickly.
The timing of such engagements also needs to be carefully considered. It is beneficial to bring on the data management oversight partner as early as possible in the trial planning, at least by the finalization of the study protocol. In this way, the oversight data manager can proactively identify any inconsistencies in the ‘Schedule of Measurements’ section of the protocol and address them early enough to avoid the need for protocol amendments down the line. Furthermore, by participating in the early stages of project start-up activities, the oversight data manager can be on hand to evaluate the proposed data management timelines and provide recommendations for the most efficient way to meet them, as well as evaluate and optimize the processes to lead into a timely database lock.
Cytel’s expert data management team has extensive experience providing data management oversight of other CRO activities. Click the button below to learn more about our team and services.
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About the Author
Alla Muchnik is a Senior Clinical Data Manager at Cytel. She has over 25 years of clinical research experience including extensive data management experience in a wide variety of therapeutic areas. Alla has versatile experience in designing and programming the databases for Phase 2- 4 clinical trials as well as registries using the leading clinical trial software packages. She is experienced in managing the end to end data management process from start-up through to the study close out and the database lock activities. Alla received her BA from the Vinnitsa State University in Ukraine and is fluent in Russian and Ukrainian languages.