Setting up a Central Lab for a Clinical Trial

Large lab ABC sends you its $1M proposal for a Phase III study. However you know that the actual sample analysis is performed by three referral labs-A, B, and C. Upon reaching out to them directly, you learn that the sum total of their individual proposals for the same test panels turns out to be 30 percent lower as compared to the previous scenario. The ultimate decision “ABC vs A+B+C” is a no-brainer, right?

Wrong.

Let’s assume that the scenario with three separate labs was selected for the study. This means that your sites will receive three separate sets of lab kits, manuals, and requisition forms-from all three providers. Worse, there will likely be three separate courier companies involved in sample shipment. Any experienced site should be able to handle this set up; however it can be expected that the study budget will grow due to investigator grant increase to offset the increased complexity. For less experienced sites, potential errors and re-sampling should also be factored in. In either scenario, courier cost will automatically increase and these are hundreds, or even thousands, of samples for any moderately sized study.

There will also be additional cost involved on CRO’s end. Having three separate labs (versus 1) would mean three times as many electronic transfers and reconciliation campaigns. Plus, there’s vendor management cost involved, which will also grow proportionately.

What happens if a lab undergoes a merger or acquisition? This typically means updates to FDA 1572 form for all sites, update on CAP/CLIA certificates and lab director CVs (with associated potential gaps in the TMF), release of one more set of lab supplies/courier instructions to the sites-all which mean extra cost. Going with three separate labs triplicates the chance of these events happening in the study.

Same applies to another very likely scenario-when a protocol amendment comes up, it is quite often associated with changes to lab procedures or visit schedule adjustments (or both). This entails three separate change orders with the labs-each one having its unique complexities and study teams to work with. Likewise, here we are speaking about three new potential bulk shipments to the sites to update their kit stock.

Chances are, this is an international study, and the smaller labs might not well have the required experience with various local customs and regulations. When the project team learns about lab kits held by any various customs agency one week prior to SIVs, the small lab in Michigan (or Singapore) originally shipping these kits may well throw their hands up in the air and concede that their experience with ROW specifics may have been limited and they don’t have a clear plan B. The associated issues may be benign enough (e.g. kits may just need to be returned to the shipper for CE marking), or they may take some time to be resolved (e.g. communication about importer of records with the local customs) or they may take months (e.g. application for import/export licenses and work with the local authorities). If you’re lucky enough, the CRO will provide its helping hand for a fee, but if the labs were selected and contracted by the study sponsor, the actual mileage and experience may vary and you may have to find someone local to rectify customs issues quickly.  

Before and throughout the study, due diligence and oversight for all vendors involved will need to be performed. During study closeout, there will be document transfer from the vendors for the TMF. With increased number of study labs this will inevitably add to time, effort, and budget expenditures.

Finally, very unfortunate scenarios do happen and you are likely to have a case or two when a subject’s sample is sent accidentally to lab B in lab C tubes… via courier company contracted by lab A. This opens up a few additional questions about sample viability, associated safety and ethical considerations, or even privacy issues (e.g. when the case in question is about a genetic sample), and any scenario will mean long hours invested to investigate and resolve the case, as well as prevent it from happening in the future.

There are less tangible considerations in the mix, such as patient and site satisfaction with sample-related procedures. This aspect will have an impact on subject recruitment rates, patient compliance, and protocol adherence so any complex set-up will prove to be detrimental to the overall study success. More complicated laboratory procedures are also oftentimes associated with longer review times by the local ECs, as well as potential discrepancies between study protocol, IM/SIV presentations, and laboratory manuals.

Still think about saving 30 percent in lab fees during study start up?

In many cases, going with just one central lab will be a straightforward, clean, and efficient decision. In the long run, it can also save you money, even if this might not be so evident during the bidding stage. Having a secondary lab might make sense if there is the need for a very special test panel, something that the big lab may not necessarily be able to arrange for; however, the likelihood of this scenario is quite small. In vast majority of cases, it might be better, even if somewhat counter-intuitive, to keep all eggs in one basket and have just one single central laboratory in the clinical trial. Chances are, a larger lab is more experienced in clinical trials, too and it is impossible to quantify this benefit.

Victor Muts, MD, PhD
Associate Project Director, CNS
Syneos Health