by Adam Aulbach, DVM, DACVP
Biomarkers are a useful tool in clinical trials, especially in identifying a drug’s impact on organs or tissues before any injury is clinically evident. It’s still early in their use in preclinical development; however, they are proving helpful in identifying major safety issues and showing promise for future use.
Presently, biomarkers are used with clinical and pathology endpoints to identify the effects of a preclinical drug candidate far earlier than do traditional tests alone. But sometimes those biomarkers can lead to conflicting data. The assays may be so sensitive that they show evidence of toxicity—often a submicroscopic effect—that doesn’t appear in conventional study endpoints. How to explain those results, and whether they are relevant, presents a challenge best addressed by consulting with a pathologist before designing a study. Understanding the timing of pathologic processes is critical to interpreting results.
Today, choosing the right biomarker for a preclinical study means finding one that is detectable, measurable, and validated. The latter may prove difficult since the characteristics of a validated preclinical biomarker are still being debated. The Predictive Safety Test Consortium, (PSTC) was established to qualify new biomarkers for preclinical use. A few are approved by the FDA, but minimum threshold criteria have yet to be determined. Preclinical laboratories are still awaiting standardized guidance on validation practices.
Another contemporary challenge is a lack of regulatory oversight for preclinical biomarker kits. Different kits using the same biomarker may use radically different methods; others may not work across different species. Those inconsistencies mean contract research organizations (CROs) need to do their homework, find a manufacturer with kits that work best for them, and stick with that provider.
Despite these difficulties, biomarkers offer great potential for the future. But what will that future look like?
First, it will be more standardized. The industry needs greater guidance from regulatory agencies on the minimum requirements for biomarker validation. This action will standardize the validation process across the industry.
Second, collaboration between pathologists and analytical groups will lead to new biomarkers that are more useful in preclinical studies. Standardized for validation and data submission, along with shared biomarker data, will accelerate development of new tools and processes.
Finally, the future will demand greater reliability in biomarker kits. With proper reagent manufacturing standards in place and more regulatory oversight, preclinical CROs will gain more confidence in the biomarkers available for use. The key to success will be three-pronged: solid regulatory standards, manufacturer accountability, and new automated technologies from industry and academia.
As emerging developments in biomarkers address present needs, researchers will be better equipped to apply these tools effectively, making faster, better, more efficient decisions on the treatments of tomorrow.
Adam Aulbach, DVM, DACVP, is Director of Clinical Pathology and Principal Clinical Pathologist at MPI Research. Find out how MPI Research is applying biomarkers to advance the science of preclinical development by contacting us at email@example.com.