New technologies are driving the integration of the next-generation of biomarkers into clinical trials. Quest Diagnostics provides differentiated biomarker assays, accelerating clinical research programmes through its assay development and laboratory management services.
Biopharma companies are seeking laboratories able to deliver the flexibility needed to develop specialised biomarkers, validations and comprehensive testing services. All-encompassing laboratory test menus are being forced to expand in areas such as immunoassay development, anatomic pathology, flow cytometry, circulating tumour cell analyses and molecular genetic assays. Furthermore, scientific expertise in cytokine multiplexing, HIV testing and immuno-histochemistry may enhance the likelihood that some biomarkers will be developed into novel companion diagnostics, allowing for individualised patients therapies known as 'personalised medicine'.
Quest Diagnostics highlights three examples where biomarker expertise and flexible laboratory management played a critical role in advancing the development of a new diagnostic for a clinical trial.
A leading pharmaceutical company needed to identify biomarkers that would correlate with response to a novel therapy with the ultimate aim of finding those that could be used to prospectively separate responders from non-responders. Quest Diagnostics' dedicated biomarker laboratory developed and validated 14 novel immunohistochemistry assays, two in situ hybrid-isation assays and two serum markers that were used retrospectively during several phase 2 studies. Archived tumour blocks and fresh serum were obtained from the study subjects, tested in batch analysis, and correlated with response data.
From the original list of 18 biomarkers, two were identified that positively correlated with clinical benefit and two others that negatively correlated with clinical benefit. This shortlist was incorporated into subsequent clinical trials to further establish their roles as predictors of response and to finalise plans for a companion diagnostic assay in the new therapy's registration.
A novel therapy comprising an antibody conjugated to a toxin required that an assay be developed in order to increase the safety profile of the initial clinical trials. The sponsor sought an assay that would identify subjects who would be unlikely to benefit from the therapy because they are negative for the antibody target. The company provided the antibody to the Quest Diagnostics biomarker laboratory, which developed and validated an immuno-histochemistry assay.
The test was to be used to screen subjects for enrolment into the trial, so Quest Diagnostics offered a 48-hour turnaround time from receipt of sample to result. In many cases, this entailed selecting the appropriate tissue block from several that were sent for the subject, sectioning and staining for the novel biomarker. High-quality staining and analysis techniques were required to meet the strict turnaround time requirement of the study.
A mid-sized biotechnology company devised a novel immunohistochemical (IHC) assay for use in a developmen¬tal therapy programme, using proprietary reagents. Due to the desire to have the assay performed in a CAP/CLIA-cer¬tified laboratory, the company approached Quest Diagnostics for support in running the assay in its clini¬cal trials programmes. As this was a last-minute decision on the part of the sponsor, time was of-the-essence to carry out this technical transfer.
After reviewing the assay protocol on paper, the biomarker laboratory team visited the sponsor's laboratory to personally observe hands-on running of the assay. Shortly thereafter, reagents were provided to Quest Diagnostics and inter-laboratory concordance studies were carried out.
These studies showed excellent concordance between the two laboratories, so the Quest Diagnostics team went on to perform analytical validation and gear up for performing the assay in compliance with CAP and CLIA regulations. The sponsor was able to use the data from the study in support of an FDA filing for its therapy. Moreover, it was able to make this submission without having to delay its timelines.
Advances in science and technology are driving new assay development, thus fuelling the trend for more biomarkers in clinical trial protocols.
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