Animal Models: For DDT considerations, an animal model is one in which a disease process/pathological condition can be investigated, and in which the disease/condition in multiple important aspects corresponds to the human disease/condition of interest. The animal model(s) should meet the four criteria outlined in the Animal Rule such that the effectiveness of the product in animals can be a reliable indicator of its effectiveness in humans.
Biomarkers: A biological marker or biomarker is defined as a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or biological responses to a therapeutic intervention. A biomarker can be a physiologic, pathologic, or anatomic characteristic or measurement that is thought to relate to some aspect of normal or abnormal biologic function or process. Biomarkers measured in patients prior to treatment may be used to select patients for inclusion in a clinical trial. Changes in biomarkers following treatment may predict or identify safety problems related to a drug candidate or reveal a pharmacological activity expected to predict an eventual benefit from treatment.
Clinical outcome assessments (COA): Clinical outcome assessments (COAs) either directly or indirectly measure how patients feel or function and can be used to determine whether or not a drug has been demonstrated to provide a treatment benefit. Treatment benefit can also be defined in terms of a safety benefit compared to other treatments in the same context of use. 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(s) in a specified context of use in adequate and well-controlled investigations.
A COA is composed of a measure that produces a score plus clearly defined methods and instructions for administration or responding, a standard format for data collection, and well-documented methods for scoring, analysis, and interpretation of results in the targeted patient population. COAs can measure treatment benefit directly or indirectly. For COAs that measure treatment benefit indirectly, qualification also includes a review of the evidence that the concept assessed is an adequate replacement for how patients feel or function in daily life. One of the distinguishing characteristics of COAs is who is doing the reporting of the outcome, i.e., the patient, a clinician, or another observer. A patient-reported outcome (PRO) is a measurement based on a report that comes directly from the patient (i.e., study subject) about the status of a patient’s health condition without amendment or interpretation of the patient’s response by a clinician or anyone else. A clinician-reported outcome (ClinRO) assessment is based on clinical observation and interpretation by a trained clinician. An observer-reported outcome (ObsRO) is assessed by observers without the need for clinical expertise.
- Patient-reported outcome (PRO) assessment: A measurement based on a report that comes directly from the patient (i.e., study subject) about the status of particular aspects of or events related to a patient’s health condition. PROs are recorded without amendment or interpretation of the patient’s response by a clinician or other observer. A PRO measurement can be recorded by the patient directly, or recorded by an interviewer provided that the interviewer records exactly the patient’s response.
- Observer reported outcome (ObsRO) assessment: An assessment that is determined by an observer who does not have a background of professional training that is relevant to the measurement being made, i.e., a non-clinician observer such as a teacher or caregiver. This type of assessment is often used when the patient is unable to self-report (e.g., infants, young children). An ObsRO assessment should only be used in the reporting of observable concepts (e.g., signs or behaviors); ObsROs cannot be validly used to directly assess symptoms (e.g., pain) or other unobservable concepts.
- Clinician-reported outcome (ClinRO) assessment: An assessment that is determined by an observer with some recognized professional training that is relevant to the measurement being made.
Context of use: The context of use is a complete and precise statement which describes the appropriate use of the DDT, and how the qualified DDT is applied in drug development and regulatory review. The context of use statement would describe all important criteria regarding the circumstances under which the DDT is qualified.
DDT-specific guidance: Document signed by the CDER Director at the conclusion of the qualification process indicating that a DDT is qualified for a specific context of use. This document includes information relevant for use of the qualified DDT in its specific context of use, along with its assessment and conclusion of the supporting data for qualification. This document is posted on the DDT Qualification Web Site to ensure public availability of the DDT and the corresponding notice will be posted in the Federal Register. In accord with Good Guidance Practices, the initial posting of the qualification will be as a draft appendix to the DDT qualification process guidance, with an identified period for public comment. Subsequent to that, the comments will be considered and the appendix reposted as a final guidance appendix with any revisions that are appropriate. Once qualified, DDTs will be publicly available for use in any drug development program for the qualified context of use.
Drug Development Tool (DDT): A measurement or method (and associated materials) that aids drug development. DDTs include, but are not limited to, biomarkers, clinical outcome assessments, and animal models. DDTs suitable for the CDER DDT Qualification process are a subset of all types of DDTs, and should be intended for potential use, over time, in multiple drug development programs. DDTs used as clinical outcome assessments may sometimes be called an instrument. The term “instrument,” or “tool,” refers to the means to capture data plus all the information and documentation that support its use within the intended context of use.
Publicly Available: The DDT is available to any user for inclusion in any drug development program in its qualified form and context of use at the time of its qualification. FDA will promote public knowledge of the qualified DDTs by listing them on the FDA web site. Qualification does not waive ownership rights/intellectual property rights.
When submitters enter the qualification process, they agree that the qualified DDT will be made publicly available for use in drug development programs in the specified context of use. To this effect, the notice of the DDT-specific guidance will be published in the Federal Register and the DDT guidance along with summary reviews of the information submitted to support the qualification decision will be posted on this website. When a DDT is a proprietary instrument available for use only with the agreement of the owner of the DDT instrument (e.g., specific questionnaires), CDER will direct the public on how to obtain the qualified DDT from the DDT submitter.
Qualification: Qualification is a conclusion that within the stated context of use, the results of DDT measurements can be relied upon to have a specific interpretation and application in drug development and regulatory decision-making as long as:
- There are no serious study flaws (unverifiable data, improper performance of the assays, etc.);
- There are no attempts to apply the DDT outside the qualified context of use; and
- There are no new and conflicting scientific facts not known at the time the qualification was determined.
Qualification Programs: CDER programs developed to include the DDT Qualification Process and the regulatory infrastructure and documentation needed to support this Process.
Qualification Process: Process for consultation and advice and review of potential DDTs as outlined in the guidance.
Qualification Review Team (QRT): The QRT is comprised of a multidisciplinary group of FDA staff. Each team is recruited based upon the specific DDT and the context of use proposed by the submitter.
Sponsor: A person or entity that submits an application for an IND to conduct clinical trials of an investigational product.
Submitter: Submitter is a person, group, organization or consortium that takes responsibility for and initiates a DDT qualification proposal.
Submission for DDT qualification: Any correspondence and documents provided to CDER as part of the qualification process. Submissions are classified under the following categories:
- Pre-submission request
- Letter of Intent
- Briefing Package
- Supporting Document(s) for Consultation and Advice Stage
- Qualification Package
Within these categories, submitters should provide any documents relevant to DDT development and qualification appropriate for the purpose of the submission in that stage of the DDT Qualification process. Submitters are strongly encouraged to consider the use of relevant data standards (e.g., CDISC) in data submission.
Treatment Benefit: The effect of treatment on how a patient survives, feels, or functions. Treatment benefit can be demonstrated by either an effectiveness or safety advantage. For example, the treatment effect may be measured as an improvement or delay in the development of symptoms or as a reduction or delay in treatment-related toxicity.