Testing drives drug development. From laboratory tests on patient specimens comes almost all of the clinical data needed for a new drug application. How and where those specimens are collected, transported, stored, and analyzed impacts the quality and usefulness of the data they produce. In the past, most tests were processed by local, academic, and specialized testing laboratories and coordinated by each investigator. However, centralized testing is becoming an accelerated trend – one that uses advanced technology and global operations to concentrate oncology clinical trial tests in a single, central laboratory.
The core value of a central lab is consistency. When local laboratories perform testing, their results will be different and results vary over the course of the trial. Central laboratory testing, on the other hand, offers ‘combinable data.’ The end product is that a result from a central laboratory is similar regardless of the global location where it originated from and the lab location where it is tested. At all of Covance’s central laboratories — in Indianapolis, Geneva, Singapore, Shanghai, and Tokyo — we generate data from the same analytical method platform, SOPs, equipment, reagents, and standards, eliminating variables that affect tests results.
Driving Consistency with Standardized Collection Kits
Sample collection kits embody the basic principle and goal of the central laboratory: consistency. The idea is to remove as many variables from the testing environment as possible, and one way of doing that is to produce a standardized kit.
The central lab standardized specimen collection kit contains every useful article needed to obtain specimens and ship them back to the central lab. Thus, the standardized collection kit removes variables from the specimen collection process. The kits are unique to each visit and there are also special kits for retests, end-of-trial activities, and anatomic pathology specimens.
Specimen Collection Solutions
Standardization promotes another basic—and productive—central laboratory solution to specimen collection: ease of use for the investigator and staff who do the actual collection of the samples. Covance has optimized and simplified our collection procedures so that investigator and site staff are confident in handling specimens so trials can begin enrolling with minimum delay; redraws and missed data points are minimized; and the maximum required data is delivered by making the sampling process easy for the sites.
One of the critical success points in performing an oncology study is that the correct piece of tissue be identified and used for the scientific specimen. For this reason, Covance created a document that encourages the investigator to contact and engage with the source laboratory and its pathologist to help select the tissue block that contains the best target.
This document, developed in early 2011, has now been used in numerous studies and is being requested for studies that are currently in setup. It is “personalized” to each study and includes directions for identifying specimens that either lack the target tissue or contain it. In oncology trials that use anatomic pathology specimens, this document is probably the most effective tool available to increase the study yield.
Distance could be the nemesis of central anatomical testing, were it not for the extraordinary yet reliable coordination of transport, communication, and now our ability to perform “target enrichment” through digital imaging. Compared to a blood sample, which rep¬resents a tiny percentage of the body, a biopsy of a freckle or mole may contain 100% of the target lesion, which is irreplaceable in oncology trials.
The economics of anatomic pathology specimens is quite different from clinical pathology specimens. While it is possible to go back and collect urine, blood, plasma, and serum, you rarely go back and recollect biopsy samples. Therefore, they are particularly vulnerable if mishandled at any step in the clinical trial conduct.
Through high resolution digital imaging and a network of web-based systems, samples – regardless of origin – can be evaluated by pathologists located anywhere on the globe with internet access. Studies based in China also benefit from expanded, new anatomic pathology and histology (APH) capabilities in our Shanghai location. Covance also opened Histology labs with Aperio capabilities in Singapore.
Currently, Covance uses digital imaging in two ways: processing of specimens for genetic or genomic testing and provision of images to the sponsor. Images can also be stored in a variety of electronic formats and given to our sponsors to use as they see fit for the evaluation of their study. While we do not make diag¬nostic interpretations on tissue samples at Covance, if our sponsor wishes, we can employ expert pathologists who can look at the images and make a diagnosis.
Expanded APH Capabilities Improves Turnaround Times
In November 2013, Covance entered into an exclusive alliance with NeoGenomics, Inc., a leading provider of oncology-focused testing services, to provide our sponsors with seamless global specialty testing services critical to oncology trials.
Together with NeoGenomics, we now offer fully integrated anatomic pathology services – from sample preparation, staining and imaging to pathology interpretation by leading pathologists – in an end-to-end manner. Providing these integrated services through our Covance laboratory co-located within NeoGenomics’ Florida facility will improve turnaround time crucial to oncology clinical trials.
We intend to expand these joint capabilities globally at Covance’s central laboratory locations in China (Shanghai), Switzerland and Singapore.
Central Labs and Biomarker Excellence
Covance has a specialized biomarker unit that focuses on translational assets that inform clinical and discovery programs. One way this unit complements Covance’s central lab capabilities is by absorbing, studying and working with transfer technology from a biopharmaceutical client. For example, our sponsor may have an assay that they want to explore in the context of a clinical trial, but it hasn’t yet been clinically validated. Covance’s biomarker scientists can perform additional clinical work to prepare the assay up to that point, then transfer it to the central lab where our Genetics Department and anatomic pathology and histology services can prepare the specimens for use in that assay.
For personalized medicine, the clinical focus is a target lesion and a statistically related dimension. What Covance does best is support testing for safety assessments along with esoteric assays needed for endpoints. We can also provide in-house biomarker analysis expertise. Combining all of this information into a single database streamlines reconciliation and eases review for our sponsors.
Oncology Data: Shifting from Local
In recent years, we have seen a shift from local laboratories to centralized analysis in the support of oncology studies. Nonetheless, industry resistance to the central model persists. One traditional argument for the use of local laboratories is patient safety and dosing — but the central lab’s quick turnaround of data actually enhances safety, speeds dosing adjustments, and facilitates other needed changes to the trial.
In oncology studies, the drugs themselves are toxins. Therefore, if you are looking at local laboratory data for patient safety and dosing, the variability in data from one locale to the next means that patients may be receiving different doses in different locations. This increases the complexity of data interpretation for the statisticians.
Whether or not companies deploy more global trials, the shift to central labs will continue, as we produce scientifically objective and combinable results.
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