New federal guidance for advancing clinical research
Drug development tools (DDTs) are methods, materials or measures that help to accelerate drug development and can be applied to a broad range of products and therapeutic areas. As part of the FDA's Critical Path Initiative (CPI), the Center for Drug Evaluation and Research (CDER) has undertaken multiple initiatives to support the development of new DDTs. Among these is the creation of a formal qualification process which details the kinds of data that should be submitted by a sponsor to support qualification of a DDT. The guidance provides both a framework for interactions between CDER and the entity proposing the DDT and a mechanism for CDER's formal review of the data. The DDT qualification process is intended to expedite development of publicly available DDTs that can be widely employed in clinical studies.
Among the most widely used DDTs are Biomarkers, which are defined in the guidance as ‘a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathologic processes, or biological responses to a therapeutic intervention'. There are different types of biomarkers that provide clinicians with important information for determining eligibility, safety, and efficacy in clinical trials. Biomarkers are used to assay many different types of biological parameters including radiographic or other imaging-based measurements. For example, biomarkers can be measured before treatment to aid in patient selection for a study and quantitative changes in biomarkers may be used to monitor drug efficacy or identify potential safety risks.
Biomarkers are also utilized as an enrichment strategy to select patients likely to present clinical phenotypes or disease progression or to identify subpopulations of patients likely to respond to treatment intervention. Highlighting the importance of enrichment strategies for clinical trials, the FDA issued a draft guidance in 2012 on the topic of enrichment strategies for clinical trials. Enrichment strategies using imaging biomarkers are often implemented in clinical studies providing sponsors and clinicians with important patient information.
Imaging Biomarker Qualification
Qualification of a DDT ensures that the tool can be relied on to have a specific interpretation and application in drug development and regulatory review within an explicit context of use (COU). The guidance highlights six parameters which should be discussed in the COU statement for imaging biomarker qualification:
- What is the identity of the biomarker (e.g. specific exam, imaging modality)
- What is the biomarker measuring? (e.g. lesion number, tumor diameter, hippocampal volume)
- Characteristics of study subjects (e.g. age, disease)
- Purpose of use in drug development (e.g. diagnostic, enrichment, stratification)
- Application of the biomarker (e.g., dose finding studies, proof of concept studies),
- Interpretation and decision/action based on biomarker (e.g., Biomarker levels above X are used to determine outcome Y)
Qualification of a DTT has long reaching benefits not only for DTT developers, but also for the FDA, patients and the scientific community as a whole. Some of the key benefits include expanding use in clinical trials across multiple clinical disorders, drugs, or drug classes, a decreased burden on regulatory agencies for detailed review, and encouraging a collaborative setting for the advancement of additional DTTs.