Biospecimen laboratories are busy. They likely support numerous trials for a multitude of sponsors simultaneously. As we detailed in this recent blog, scheduling issues for batch runs can be challenging, and turnaround times can be lengthy without visibility into the status of your samples.
During our roundtable last week on Working Effectively with Biospecimen Labs, Slope's Chief Clinical Officer, Hope Meely, facilitated a discussion on key challenges that ranged from queries, lab-to-lab transfers and sample reconciliation, to site training and amendments. The session garnered participation from sponsors, sites, labs, and CROs.
For this week’s blog, we were lucky enough to catch up with one of the roundtable participants — Amy Blyskal, Senior Project Manager, ICON — to do a deeper dive into working with labs and the overall challenges with sample management.
At the roundtable you mentioned currently having challenges with your PK samples in your Phase 1 dose escalation study. Can you elaborate?
PK (pharmacokinetic) sampling is a heavy burden for sites and patients, especially with our first three patients of the dose escalation level. We have intense PK, requiring sampling at pre-dose, half hour, 2, 4, 6, 8, 12, and 24 hours. These samples are so important to understand the peak of the medication, its half-life, and it is critical to have really solid, reliable data on enough patients to dose escalate. To get that data, we need to ensure that PK samples are collected and shipped from the sites to the third-party labs as quickly as possible.
Honestly, the process is broken. To start, sites are filling out paper requisition forms. They then send one part of the requisition, along with the sample, to the central and/or third-party lab. At the same time, the site lab should be scanning the requisition and sending it to the central lab, in order for verification and reconciliation to be completed by a third-party lab.
In this scenario, there is also a lack of visibility regarding patient visits and sample handling at the site. One major reason for this is the site is behind on data entry into the EDC, and the central lab is not receiving the sample requisition forms from the site lab. This disconnect results in confusion and doubt regarding whether the visit occurred and if the sample was taken. The central lab notifies us of missing requisitions, prompting us to contact the third-party lab to confirm sample receipt. Simultaneously, queries to sites encounter a disconnect as data-entry personnel respond with incomplete information. As the sponsor, we must address these queries, further slowing down the reconciliation process. The delay is exacerbated because the data transfer agreement (DTA) between the CRO and the lab was never finalized prior or near to FPI. This leads to data management teams falling behind in handling the reconciliation tasks.
Talk to me a little bit about how the CRO fits into the process.
Many times CROs are intended to be the site-facing portion of sample management. However with PK samples we really need quick answers, so we, as the Sponsor, will reach out to the sites directly to follow up on queries. The downside is that now the sites start to bypass the CRO on other items, which puts more strain on our staff. There are so many different parties involved to cobble together the sample journey.
That sounds chaotic. How much time would you say you and your team spend on sample management issues?
Our pharmacology and clinical teams are doing a ton of work behind the scenes, trying to catch up. Right now we are calling sites daily about our PK samples regarding errors in the requisition, accession numbers that don’t line up, improperly labeled tubes, etc.
I would say my clinical trial associate (CTA) spends about 10 hours a week on lab sample issues and resolving queries.
Given the amount of time being spent on sampling issues, what other tasks are not getting done?
They should be working on the eTMF, filing, reviewing trip reports for trends, etc. These are the tasks that are falling by the wayside, and we just can’t keep up without needing more resources. As a small company, this can be costly.
Switching gears for a moment, one of the other topics of discussion was amendments. What challenges do you see at both the labs and the sites when protocol changes arise that impact sampling?
Amendments inevitably shift timelines. We provide the best draft of the protocol to the labs, who then commit to start planning based on that draft. The labs give us timelines after reviewing the updated lab manual, etc. There are so many documents being thrown about during an amendment — and if anything in the schedule of assessments changes from the initial draft, that further delays the process. Updating the EDC is also a blocker.
Then there is ensuring the sites follow the new protocol, and aren’t using old kits, or old sampling instructions. What we do today is conduct thorough training similar to initiation training at study start-up, emphasizing changes in the schedule of assessments. Challenges arise when CRAs cannot physically monitor kit usage due to the site not being amendable to on-site visits, so monitoring visits continue to be remote. We have to rely on communication between study monitors, coordinators, and lab personnel to ensure compliance with the new process. Additionally, monitoring IRB approvals for protocol-related changes and ensuring proper sample collection is handled manually, leading to potential delays and back-and-forth communication with sites during the analysis phase.
A lot of the issues you mentioned are stemming from manual processes and disconnected systems. What if you could automate the process and have real-time visibility to your samples?
That would be a dream if we could eliminate the manual processes and back and forth processes to track down samples. The sites could perform online accessioning right in the computer and I would know what PK samples were taken, when they were shipped or not, and we really could keep track of them.
I can only imagine the time we could get back, and how we could spend more time where it is needed. We’d definitely be less stressed, and our timelines wouldn’t suffer at every turn.
Thank you for your time today! We greatly appreciate you sharing your experiences with us today.
Don’t miss the opportunity to join one of our other upcoming roundtables.