Central laboratory support is a crucial factor in ensuring consistency and standardization of sample handling and data management in clinical trials. In this blog post, we describe the aspects that effective central laboratory support could offer, as well as factors to take into account when selecting a central laboratory partner.
What is a central laboratory? And what does an effective central laboratory do?
A central laboratory is not just a service that uses a uniform methodology to handle patient specimens, but also offers scientific consulting; solutions for the complex logistics involved, such as for packaging and transport; as well as data management platforms. We will shortly describe each of these aspects below.
Practical harmonized laboratory procedures
Clinical trials typically involve multinational or even global testing sites, which poses the potential problem of sample variability caused by methodological and operational differences, which in turn impacts the error rate and reliability of the overall study. For this reason, a central laboratory service offers a solution, as it uses one harmonized set of standard operating procedures (SOPs), materials, and methods (reagents, laboratory equipment, analysis protocols, reference ranges, etc.). and quality control standards. However, especially in a global study, this does not mean that all testing procedures take place at the same physical location, as this would be logistically very challenging. It is possible to use multiple laboratory locations, but the comparability between different sites often needs to be tested to ensure quality. On a regulatory and technical level, the “ISO 15189:2012 Medical laboratories – Requirements for quality and competence“ accreditation is the international quality standard developed by the International Organization for Standardization. It specifies management requirements (including quality assurances) as well as technical requirements ranging from personnel to laboratory facilities and laboratory information management.
In addition to the actual performance of laboratory services, central laboratories generally have a high level of scientific and analytical expertise. For each clinical trial, there are specific demands, and an effective central laboratory service has experts available to offer tailored consulting on optimal study designs, analytical approaches, and validation procedures. Ideally, a central laboratory service has a network of disease-specific specialists, as well as technical experts that can advise on, for instance, biomarker discovery and use to monitor clinical outcomes. To optimize results and to detect potential problems early, experts should also be available for continuous consultation and maintenance while the trial is conducted. The assistance should be available across time-zones and in different languages, in case operational questions at local investigation sites arise.
Logistics and specimen management
The logistic network of a central laboratory service is perhaps the most essential part. The foremost logistic challenge is maintaining sample stability. In general, this means that a sample needs to be at the central laboratory location within 48 hours after collection at an investigator site, while continuously being kept under the right conditions with a constant temperature (either refrigerated, frozen, or ambient). If this goes wrong, valuable material and clinical data are lost, money is lost on unnecessary word repetition, and patient motivation is jeopardized.
To ensure sample stability and timely delivery, first of all, local personnel require standardized sample collection kits and boxing materials for later shipment. Furthermore, contacts with certified shipment services where couriers are trained on how to handle and prioritize, clinical trial samples should be established. A logistics team should be present to oversee successful sample shipments, which in turn requires a sophisticated package tracking system. Importantly, this logistics team should have contingency plans ready in case shipment services are disrupted or delayed, for instance, due to weather conditions. One can think of alternative shipment partners that can serve as a back-up, or for instance of a regional facility where samples can temporarily be stored under the required harmonized conditions.
Furthermore, experts with up-to-date knowledge of local regulations are of importance, for example, to know how biosamples must be labeled and transported with the appropriate documentation, to ensure instant border passage and timely delivery. In the case of strict export regulations for biosamples, this could also mean that using a local external laboratory might be more advisable than transporting samples across borders. For this reason, experience with operating in markets outside of North America and Europe is advisable when countries in these regions are included in the trial, as experience with regulatory compliance, transportation arrangements, and their appropriate costs, is fundamental for success.
Upon arrival at the central laboratory site, specimens are usually not only processed according to the analysis protocols but are subsequently also stored in a repository under the appropriate conditions (-20°C, -70°C, liquid nitrogen, etc.). This is important in case follow-up or repeat measurements have to be conducted, for instance, because a regulatory agency requires so.
One of the advantages of central laboratory services is that a Laboratory Information Management System (LIMS) is used to ensure data access across investigation sites. With a single integrated global database, one can easily obtain standardized reports of the accumulated clinical data up to that point. Ideally, this provides near real-time access to the data, and enables you to identify trends and potential issues, making proactive decision-making possible.
How to choose a central laboratory support provider?
Now that you know the most important factors that a central laboratory service can contribute to conducting a clinical trial, it is interesting to reflect on this knowledge and to take that into account when selecting a potential collaborator.
First of all, scientific expertise in the relevant disease area is a key factor. This enables a central laboratory service to provide the necessary input for study set-up and maintenance, and also implies expertise for the appropriate techniques and methods (which of course should be checked).
A track-record on facilitating laboratory services for clinical trials in the relevant disease area indicates successful project management skills, but, knowing the abovementioned challenges, one should not hesitate to ask for references about their logistic excellence. Indicators like the received-in-stability (RIS) rate, on-time delivery figures, cost per shipment, and total costs for running previous clinical trials are essential for deciding on a particular partner. Furthermore, experience with operating in the relevant region and regional regulatory expertise is very important. Finally, the costs involved are a crucial factor, and a central laboratory support provider must offer transparency in the estimated costs and the benefits of certain cost categories.