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. Disclosure negotiations are not an opportunity to eliminate categories of relevant information but to clarify whether for the specific development program, information may need to be described in a particular way to protect the integrity of the study. 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:

3. Description of the proposed novel endpoint, measurement, and context of use

4. Population in which the endpoint is being studied

5. The specific biomarker(s), clinical outcome assessment(s) (COA(s)), and/or digital health technology (DHT) used to develop or measure the novel endpoint

6. Rationale for the assessment type (DHT, COA, and/or biomarker)

7. Rationale for the concept of interest and/or outcome the endpoint is intended to measure

8. Summary of the data that supports the validity of the endpoint and assessment(s), and that the assessment tool(s) is fit-for-purpose

9. Interpretation of meaningfulness of treatment benefit in the context of the product’s benefits and risks (if applicable)

10. For all novel endpoints: Design and analyses for clinical studies developing and/or studying the endpoint for regulatory decision-making:

11. Study design(s) (non-interventional or interventional)

12. Study objectives

13. Sample size

14. Study schema

15. Treatment allocation (randomization, control, blinding)

16. Estimand(s) of interest:

17. Treatment (if applicable)

18. Target study population (general description of study population; patient selection including disease definition and diagnostic criteria and tool)

19. Variable (the proposed novel endpoint definition)

20. Intercurrent events (types of intercurrent events and how to address)

21. Population-level summary for the variable

22. Timing & frequency of data collection

23. Approach to evaluating analytical validity of test, tool, or instrument

24. Approach to assessing and controlling for bias

25. Approach to handling variability in data collection or of missing or misclassified data

26. 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

27. 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

28. Real-world data sources

29. Category (e.g., electronic health records, medical claims, registries) and brief description of data sources

30. Data reliability, including data accrual and assurance processes

31. Relevance of data to the research question being addressed

32. Timing and completeness of key data elements

33. Validation efforts related to key data elements

34. Linkage to other data sources and additional data collection

35. For all novel endpoints: Sponsor’s plan to engage with patients to solicit input in developing the novel endpoint

36. For endpoints that include a COA:

37. qualitative and quantitative evidence to support the development of the scoring of the COA, specifically the following eight evidence components

38. Suitability of the COA type for the context of use (e.g., patient-reported, observer-reported, clinician-reported, performance-based)

39. COA captures all important aspects of the concept of interest

40. Respondents understand instructions, items/tasks as intended

41. Scores of the COA measure the concept of interest with limited to no influence from interfering factors

42. COA scoring method is appropriate for the concept of interest

43. COA score(s) correspond to the health experience related to the concept of interest

44. COA score and COA-based endpoint are sufficiently sensitive to detect consequential changes within patients over time

45. Interpretation of meaningfulness of treatment benefit in the context of the product’s benefits and risks

46. For endpoints that include a biomarker:

47. Identity of the biomarker and type (e.g., molecular, histologic, radiographic, physiologic)

48. Intended regulatory use (e.g., traditional vs. accelerated approval)

49. Patient populations and outcomes used to support clinical validity

50. Biologic/mechanistic rationale

51. Outcome biomarker is intended to predict and clinical performance characteristics

52. Important subgroups and limitations of interpretation

53. Analytical method validation approach

54. Assay type and analytical performance characteristics

55. Rationale for centralized vs. local testing

56. For endpoints that involve use of a DHT:

57. Description of the design and operation of the DHT

58. For DHT verification, validation, and usability studies

59. Physical parameters measured by the DHT

60. Evidence that the parameters measured by the DHT are measured accurately and precisely

61. What aspect of the data collected will be used to support the endpoint

62. Evidence that the DHT appropriately assesses the clinical event or characteristic in the intended population of interest

63. Description that the DHT captures a concept that is clinically meaningful to patients

64. Description of how to create and interpret scores that measure the concept of interest with limited to no influence from interfering factors

65. Evidence that the score from the DHT and DHT-based endpoint are sufficiently sensitive to detect consequential changes within patients over time

66. 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

67. Approach to testing the ability of future trial participants to use the DHT as directed in the protocol and results of usability testing

68. For multiple endpoints (including multi-component endpoints):

69. Individual components (e.g., of composite and muti-component endpoints), including information for each component as applicable (refer to bullets 5 through 7)

70. Suitability of the multiple endpoints for the context of use, including clinical importance of the components

71. Aspects of the concept of interest captured by the overall endpoint and each component

72. Measurement strategy and the anticipated role of the endpoint (e.g., primary, secondary) in clinical trial testing hierarchies

73. Limitations of interpretation

74. Validation approach

75. Any modifications or amendments to any of the above that occur during interactions about the proposed rare disease novel endpoint between submitter and FDA

Excluded from Disclosure:

The Agency does not intend to share specifics regarding the sponsor’s name, treatment of interest (i.e., product name or molecular structure), a complete description of study eligibility criteria, or patient-level data.