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): A COA is any assessment that may be influenced by human choices, judgement, or motivation and may support either direct or indirect evidence of treatment benefit. Unlike biomarkers that rely completely on an automated process or algorithm, COAs depend on the implementation, interpretation, and reporting from a patient, a clinician, or an observer. The four types of COAs are patient-reported outcome (PRO) measures, clinician-reported outcome (ClinRO) measures, observer-reported outcome (ObsRO) measures, and performance outcome (PerfO) measures.
- Patient-reported outcome (PRO) measures: A PRO is a measurement based on a report that comes from the patient (i.e., study subject) about the status of a patient's health condition without amendment or interpretation of the patient's report by a clinician or anyone else. A PRO can be measured by self-report or by interview, provided that the interviewer records only the patient's response. Symptoms or other unobservable concepts known only to the patient (e.g., pain severity or nausea) can only be measured by PRO measures. PROs can also assess the patient perspective on functioning or activities that may also be observable by others.
- Observer reported outcome (ObsRO) measures: An ObsRO measure does not include medical judgment or interpretation. Generally, ObsROs are reported by a parent, caregiver, or someone who observes the patient in daily life. For patients who cannot respond for themselves (e.g., infants or cognitively impaired), we encourage observer reports that include only those events or behaviors that can be observed. As an example, observers cannot validly report an infant’s pain intensity (a symptom) but can report infant behavior thought to be caused by pain (e.g., crying). For example, in the assessment of a child’s functioning in the classroom, the teacher is the most appropriate observer. Examples of ObsROs include a parent report of a child’s vomiting episodes or a report of wincing thought to be the result of pain in patients who are unable to report for themselves.
- Clinician-reported outcome (ClinRO) measures: A ClinRO is based on a report that comes from a trained health-care professional after observation of a patient’s health condition. A ClinRO measure involves a clinical judgment or interpretation of the observable signs, behaviors, or other physical manifestations thought to be related to a disease or condition. ClinRO measures cannot directly assess symptoms that are known only to the patient (e.g., pain intensity).
- Performance outcome (PerfO) measures: A PerfO is a measurement based on a task(s) performed by a patient according to instructions that is administered by a health care professional. Performance outcomes require patient cooperation and motivation. These include measures of gait speed (e.g., timed 25 foot walk test), memory recall, or other cognitive testing (e.g., digit symbol substitution test).
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.