During my 18 years at a major pharmaceutical company I initiated and managed the introduction of many new technologies into both pre-clinical and clinical project teams. One of my greatest challenges was translating new biomarker discoveries into assays that could be used successfully to support clinical trials.
Discovery of new clinical biomarkers is occurring at a furious pace, which is encouraging to both drug developers and patients hoping to shorten clinical study and approval timelines. However, qualification of these new biomarkers has just begun and, while the FDA has recently outlined a proscriptive qualification process, it is unclear what biomarkers will ultimately receive regulatory approval (or how long it will take).
So, you may find yourself in the situation where you are aware of a new biomarker that could be a significant improvement over existing assays used to support clinical trials but the data to support that contention is not yet available. Under these circumstances, what is the best way to proceed?
I recommend you answer the following six questions before adding a new biomarker to your clinical trial protocol:
- How will the new biomarkers be used? Using novel biomarkers for a late stage project is hard to justify, both from the standpoint of use in decision-making and high likely cost for a large trial. By comparison, including a new biomarker in an early stage project with a small number of subjects that will only be used to guide internal company decisions would be expected to be both low risk and relatively low cost.
- What commercial assays are available for the selected biomarker(s) and how extensive is the assay validation? If no commercially available assay is available, add at least a year to your project timeline so the assay can be developed and validated.
- What human biological samples will be available and what matrix should be measured (urine, serum, plasma)? Many biomarker programs rise and fall on the availability and quality of samples.
- What steps have been taken towards biomarker qualification and what is needed? If the desired biomarker is truly novel and ultimately expected to be used in support of regulatory filings, plan for a long timeline.
- What is known about the biological variability of the chosen biomarker in the general population and/or the trial population? A biomarker that is highly variable in the trial population could require very large sample sizes to obtain meaningful results.
- What will be the cost of the new biomarker assay? Current assays for safety monitoring, for example, can sometimes cost a dollar or less. By comparison, a new assay can be a hundred-fold higher so it would be wise to be prepared to defend the budget.
These are just a few of the important questions to answer before introducing a new biomarker into a clinical trial protocol. In my next post, I’ll describe some important practical steps for getting a new biomarker program off the ground.
Stephen T. Furlong, Ph.D., Former Discovery Medicine Director and Safety Science Lead at AstraZeneca, Current Principal at Better Biomarkers and YourEncore Expert
