Janet Woodcock, M.D., director, Center for Drug Evaluation and Research (CDER) recently remarked that the system of drug regulation needs to evolve so that new science, including advances in clinical trail design and acceptable endpoints, will rapidly translate into new regulatory methods.
To help further this evolution, CDER created the Drug Development Tools (DDTs) Qualification Program. The program is a mechanism for formal review by CDER to qualify drug development tools, and provide a framework for interactions with the Center to better identify data needed to support qualification of these tools.
Qualification is a conclusion that within the stated context of use, the DDT can be relied upon to have a specific interpretation and application in drug development and regulatory review.
Currently there are three types of DDTs that can be qualified under this program: biomarkers, clinical outcomes assessments, and animal models for use under the Animal Rule.
The DDT qualification process creates a path for collaboration among industry, academia, government, and individual investigators; as a result, resources and data can be pooled in a non-competitive setting. This shared approach has a cascading effect which may result in faster DDT development, and enhanced public health benefits. Participation in the DDT qualification program is voluntary.
Biomarker Qualification Program
Biomarkers are measurable characteristics that reflect physiological, pharmacological, or disease processes in animals or humans. One example is a pharmacodynamic, or activity biomarker. An activitybiomarker shows that a biological response has occurred in a patient after the patient has received some type of treatment; examples include blood pressure, cholesterol levels, and intraocular pressure.
Biomarkers being considered for qualification are conceptually independent of the specific test performing the measurement. A biomarker cannot become qualified without a reliable means of measurement; and FDA clearance of a testing device for marketing does not imply that the biomarker it measures has been demonstrated to have a qualified use in drug development and evaluation.
Clinical Outcome Assessment Qualification Program
Clinical outcome assessments (COAs) directly or indirectly measure how patients feel or function, and can be used to determine whether a drug demonstrates a treatment benefit. A treatment benefit can also be defined as a reduction in the risk of an adverse reaction compared to other treatments used in the same context. COA qualification is based on a review of the evidence to support the conclusion that the COA is a well-defined and reliable assessment of a targeted concept, in a specified context of use, in adequate and well-controlled investigations.
Outcomes can be reported by:
- patients – usually through self-reports from subjects involved in studies
- clinicians -- trained health professionals that observe and interpret data and subjects
- observers -- who are not clinically trained but are in a position to report on a patient’s condition or on how a patient functions or behaves; these are usually parents, teachers or care-givers
Animal Model Qualification Program
Under the Animal Rule for drugs and for biologics (links below), FDA can grant marketing approval when the results of well-controlled animal studies establish that the product is reasonably likely to be beneficial in humans. This rule applies only when efficacy studies in humans cannot be ethically conducted and field studies are not feasible. For animal models, the context of use statement may be extensive. It should detail how the model is to be used in drug development, and specify details necessary to replicate the model.