Clinical trial monitoring plans are essential to ensuring the completeness and accuracy of reported study data based on currently approved study documents and regulatory requirements. By tracking critical processes, sponsors should ideally have direct oversight of real-time research site activity and compliance trends.
Unfortunately, as we highlighted in "4 Questions to Ask When Developing a Monitoring Strategy for a Complex Clinical Trial", clinical trial complexity has muddled the effectiveness of traditional monitoring approaches. Exciting innovations in clinical research come at the expense of more study design components (e.g. cohorts, substudies, adaptive designs, etc.), study stakeholders, and lab testing, all which demand more complicated lab kitting designs and biosampling schemes.
The following blog considers the importance of factoring clinical inventory management, sample management, and sample tracking into your monitoring strategy, ensuring that you are able to manage your complex clinical trial processes with precision, efficiency, and compliance.
As we discussed in this blog for research sites, common attributes of complex clinical trials directly impact various site workflows. Early-phase studies, for instance, tend to require intensive, complicated biospecimen collections. Late-phase studies, on the other hand, tend to have higher enrollment rates. The challenges with each phase of clinical research may be different, but their challenges impact research site compliance nonetheless.
This is especially true because in today’s clinical trials, different patients who are participating in the same study may have unique biospecimen collections and data points. Frequent protocol amendments and study modifications that impact lab manual procedures also have downstream effects on research site workflows, including the addition or removal of a kit from a study, the addition or removal of a specimen collection from a specific lab kit, or even changes in shipping frequency for one sample.
Not only does study complexity jeopardize research site compliance with approved study documents (such as the protocol and lab manual), but it also makes it more difficult for sponsors to monitor study activity in real-time. If sponsors aren’t able to ensure that their research sites have the correct lab kits on hand prior to upcoming patient visits, then how can sponsors guarantee a seamless experience for the patients who are participating in their trials? How can they minimize the risks of protocol deviations and downstream sample handling issues?
And if sponsors can’t enforce guardrails that would help sites collect and manage all the required samples for every patient visit and their associated metadata (such as collection dates, times, and administrative questions), then how can sponsors prevent missed collections, mishandled samples, and queries?
If sponsors have to resort to manually tracing the physical journey of one biospecimen across disconnected stakeholders, systems, and paper-based audit trails, then how are they supposed to perform real-time sample tracking that could identify a sample handling issue before it’s too late, provide an answer to a query, or offer insight into aggregated biospecimen compliance trends?
Per ICH GCP guidelines for clinical trials, one of the main purposes of monitoring is to ensure that “reported trial data are accurate, complete, and verifiable from source documents.” With that in mind, it’s critical to understand the ways in which clinical inventory and patient samples directly affect the overall data integrity of a clinical trial, and why it is therefore critical to have a monitoring plan in place for these two variables.
Although it may seem obvious, research sites are not able to collect patient samples unless they have sufficient clinical inventory for a patient visit. Without the sufficient lab kits and ancillary supplies that research sites need to conduct a patient visit, study coordinators may resort to pulling a lab kit for a different visit or trial, manually piecing together their own lab kit using supplies that they already have on hand, or otherwise rescheduling a patient visit. These scenarios can result in protocol deviations, missed collections, sample mishandling issues, and queries.
Even if research sites have a good handle on managing their clinical inventory, site staff run the risk of committing critical sample management errors. Relying heavily on static lab manuals and templated versions of the lab manual, nurses, phlebotomists, and study coordinators may accidentally overlook important sample collection, processing, storage, and shipment instructions. As a result, patient samples are at an increased risk of not being viable for testing. In fact, testing may not be possible at all if a critical biospecimen was not collected in the first place.
The impacts on trial data quality can be significant and far-reaching; not only could it impact patient safety, screening, enrollment, and retention, but it can also delay critical study milestones — including dose escalation decisions, data analyses, and database locks.
Centralized monitoring strategies enable sponsors to remotely evaluate study data in a timely manner. By supplementing on-site monitoring with additional centralized monitoring processes that enable sponsors and CRAs to quickly identify missing or inconsistent data, protocol deviations, data trends, performance metrics, and more, sponsors can quickly adapt and address issues with lab kits and patient samples before it’s too late, identify opportunities for site retraining, and make better-informed decisions about their trials.
A robust clinical trial monitoring plan should also include a risk-based approach that enables sponsors to quickly identify and mitigate critical issues with data integrity. Centralized monitoring should be part of a risk-based approach, but mitigating the downstream effects of clinical trial planning and design on research site compliance should also include a strategy to prevent compliance issues from occurring to begin with.
For this reason, sponsors should explore novel approaches to monitoring that empower research sites to proactively improve their management of their lab kits and biospecimens. Paper-based processes and spreadsheets are no longer sufficient for managing the clinical supplies and patient samples needed to conduct complex clinical trials.
By factoring lab kit management, sample management, and sample tracking into their monitoring strategies, sponsors can safeguard the patient experience on a clinical trial, bolster the data integrity, and accelerate study timelines.
To learn more, check out our white paper on de-risking your clinical trial data by turning your static lab manuals into software-guided workflows.