Hi. I’m Dr. Shashi Amur with the FDA’s Center for Drug Evaluation and Research, also known as CDER.
In this module, I’ll explain the concept of context of use with reference to biomarker qualification.
Through CDER’s Biomarker Qualification Program, the information supporting qualified biomarkers is made broadly available for use by multiple stakeholders—including drug companies, academic researchers, and consortia—to aid in developing new medical treatments. Once qualified, a biomarker can be utilized across drug development programs for that specific context of use without the need for each program to re-review the requisite supporting information.
The context of use is central to biomarker qualification, since the context of use drives the level of evidence needed, which in turn drives the qualification process.
In the simplest terms, the context of use specifies how the drug development tool—in this case, a biomarker—is to be used and its purpose in supporting the development of drugs or biologics.
The context of use statement also describes important criteria regarding the circumstances under which the biomarker is qualified.
An appropriately constructed context of use consists of two main parts: the Use Statement and the Conditions for Qualified Use.
The Use Statement should be concise and include the name and identity of the biomarker and its purpose in drug development.
The Conditions for Qualified Use is a comprehensive description of conditions for the biomarker to be used in the qualified setting.
The BEST glossary defines seven categories of biomarkers, shown in the slide. It is important to remember that each biomarker category can have multiple contexts of use. For example, a prognostic biomarker can be used to stratify patients or for enrichment in clinical trials.
Things to consider when developing a context of use include the identity of the biomarker, the aspect of the biomarker that is measured and the form in which it is used for biological interpretation, the species and characteristics of the animal or subjects studied, the purpose of use in drug development, the drug development circumstances for applying the biomarker, and the interpretation and decision or action based on the biomarker. Not all of these are relevant for every biomarker, but they should be evaluated for relevance to the biomarker being developed.
Let’s take a closer look at a real-world example of a context of use for a clinical biomarker: total kidney volume. This biomarker is qualified as a prognostic enrichment biomarker in clinical studies for treatment of autosomal dominant polycystic kidney disease. Here, in the top section, is the
Use Statement, as published in the FDA’s biomarker guidance. It consists of a short paragraph identifying the imaging biomarker, which is total kidney volume, and explaining how it can be used in combination with baseline eGFR and patient age to select patients for inclusion in interventional clinical trials.
In the bottom section, the conditions for qualified use are listed. The actual guidance document and the accompanying supporting documents, including the executive summary as well as reviews, provide greater detail about each of these conditions listed here.
Accumulating the data necessary to support a biomarker for qualification can take considerable time and resources. Often, submitters of biomarker data do not have all of the information needed to support an extensive context of use. One approach is to qualify a biomarker for a “limited” context of use to facilitate the integration of the biomarker in drug development and the further accumulation of supportive data on its use. A limited context of use qualification provides a more concise indication for the use of the biomarker. As the biomarker is used for the limited context of use, additional evidence accumulates that can help in qualifying the biomarker for the “expanded” context of use.
I hope this brief introduction to the context of use will stimulate more thinking about how to apply biomarkers to enhance drug development.
CDER provides other tools and information to aid in developing biomarkers and incorporating them in clinical trials.
Examples of these tools are shown here.
Please visit CDER’s website to learn more about biomarkers and to access additional information about biomarker qualification.