Before FDA grants the initial meeting under the RDEA Pilot Program, the Agency and the sponsor must agree on the information that FDA may disclose publicly. In a disclosure agreement with sponsors, FDA intends to include, as applicable, the following categories of information. This program is a pilot program, and the disclosure elements may be updated as the program evolves. 

  1. Disease/condition of interest
  2. For all novel endpoints: Rationale for the proposed endpoint:
    1. Description of the proposed novel endpoint, measurement, and context of use
    2. Population in which the endpoint is being studied
    3. The specific biomarker(s), clinical outcome assessment(s) (COA(s)), and/or digital health technology (DHT) used to develop or measure the novel endpoint
    4. Rationale for the assessment type (DHT, COA, and/or biomarker)
    5. Rationale for the concept of interest and/or outcome the endpoint is intended to measure
    6. Summary of the data that supports the validity of the endpoint and assessment(s), and that the assessment tool(s) is fit-for-purpose
    7. Interpretation of meaningfulness of treatment benefit in the context of the product’s benefits and risks (if applicable)
  3. For all novel endpoints:  Design and analyses for clinical studies developing and/or studying the endpoint for regulatory decision-making:
    1. Study design(s) (non-interventional or interventional)
    2. Study objectives
    3. Sample size
    4. Study schema
    5. Treatment allocation (randomization, control, blinding)
    6. Estimand(s) of interest:
      1. Treatment (if applicable)
      2. Target study population (general description of study population; patient selection including disease definition and diagnostic criteria and tool)
      3. Variable (the proposed novel endpoint definition)
      4. Intercurrent events (types of intercurrent events and how to address)
      5. Population-level summary for the variable
    7. Timing & frequency of data collection
    8. Approach to evaluating analytical validity of test, tool, or instrument
    9. Approach to assessing and controlling for bias
    10. Approach to handling variability in data collection or of missing or misclassified data
    11. Statistical test(s) used to detect change measured by the endpoints and/or statistical tests used to establish the relationship between the endpoint and outcome of interest
    12. Qualitative or mixed methods approaches used to detect change measured by the endpoints and/or used to establish the relationship between the endpoint and outcome of interest
    13. Real-world data sources
      1. Category (e.g., electronic health records, medical claims, registries) and brief description of data sources
      2. Data reliability, including data accrual and assurance processes
      3. Relevance of data to the research question being addressed
      4. Timing and completeness of key data elements
      5. Validation efforts related to key data elements
      6. Linkage to other data sources and additional data collection
  4. For all novel endpoints: Sponsor’s plan to engage with patients to solicit input in developing the novel endpoint
  5. For endpoints that include a COA:
    1. qualitative and quantitative evidence to support the development of the scoring of the COA, specifically the following eight evidence components
      1. Suitability of the COA type for the context of use (e.g., patient-reported, observer-reported, clinician-reported, performance-based)
      2. COA captures all important aspects of the concept of interest
      3. Respondents understand instructions, items/tasks as intended
      4. Scores of the COA measure the concept of interest with limited to no influence from interfering factors
      5. COA scoring method is appropriate for the concept of interest
      6. COA score(s) correspond to the health experience related to the concept of interest
      7. COA score and COA-based endpoint are sufficiently sensitive to detect consequential changes within patients over time
      8. Interpretation of meaningfulness of treatment benefit in the context of the product’s benefits and risks
  6. For endpoints that include a biomarker
    1. Identity of the biomarker and type (e.g., molecular, histologic, radiographic, physiologic)
    2. Intended regulatory use (e.g., traditional vs. accelerated approval)
    3. Patient populations and outcomes used to support clinical validity
    4. Biologic/mechanistic rationale
    5. Outcome biomarker is intended to predict and clinical performance characteristics
    6. Important subgroups and limitations of interpretation
    7. Analytical method validation approach
    8. Assay type and analytical performance characteristics
    9. Rationale for centralized vs. local testing
  7. For endpoints that involve use of a DHT
    1. Description of the design and operation of the DHT
    2. For DHT verification, validation, and usability studies 
      1. Physical parameters measured by the DHT
      2. Evidence that the parameters measured by the DHT are measured accurately and precisely
      3. What aspect of the data collected will be used to support the endpoint
      4. Evidence that the DHT appropriately assesses the clinical event or characteristic in the intended population of interest
      5. Description that the DHT captures a concept that is clinically meaningful to patients
      6. Description of how to create and interpret scores that measure the concept of interest with limited to no influence from interfering factors
      7. Evidence that the score from the DHT and DHT-based endpoint are sufficiently sensitive to detect consequential changes within patients over time
      8. Description of how the endpoint using measures from a DHT relates to existing endpoints, if applicable, or how the DHT provides a new means of measuring an endpoint
      9. Approach to testing the ability of future trial participants to use the DHT as directed in the protocol and results of usability testing
  8. For multiple endpoints (including multi-component endpoints)
    1. Individual components (e.g., of composite and muti-component endpoints), including information for each component as applicable (refer to bullets 5 through 7)
    2. Suitability of the multiple endpoints for the context of use, including clinical importance of the components
    3. Aspects of the concept of interest captured by the overall endpoint and each component
    4. Measurement strategy and the anticipated role of the endpoint (e.g., primary, secondary) in clinical trial testing hierarchies
    5. Limitations of interpretation
    6. Validation approach
  9. Any modifications or amendments to any of the above that occur during interactions about the proposed rare disease novel endpoint between submitter and FDA