Notice of Change to Research Objectives Section I. Funding Opportunity Description for RFA-FD-19-006 "Development of Standard Core Clinical Outcomes Assessments (COAs) and Endpoints (UG3/UH3 Clinical Trial Optional)"

Notice Number: NOT-FD-19-007

Key Dates
Release Date: March 5, 2019

Related Announcements
RFA-FD-19-006

Issued by
U.S. Food and Drug Administration (FDA)
Center for Drug Evaluation and Research (CDER)
Office of the Center Director (OCD)

Purpose

This notice is to update the second set of bullets under the Research Objectives in Section I. Funding Opportunity Description for RFA-FD-19-006 "Development of Standard Core Clinical Outcomes Assessments (COAs) and Endpoints (UG3/UH3 Clinical Trial Optional)."

Now reads:

Research Objectives

Under the UG3/UH3 phases, applicants will conduct a well-managed, transparent, and methodologically-sound process following a core set development strategy and protocol. FDA is interested in the identification of modifiable disease and treatment impacts that matter most to people living with a disease or condition. To minimize ambiguity and uncertainty for both regulatory decision makers and drug developers, FDA is not only interested in the high-level concepts related to those impacts but also in the set of specific instruments, tools, and endpoints for a given disease or condition.

The core set development work pursued under the cooperative agreement should be informed by FDA guidance documents (e.g., patient-focused drug development methodological guidances), the COA compendium, drug development tools qualification guidelines, a review of the literature (including a gap analysis to evaluate the use of existing tools), and current knowledge of the disease area.

To ensure the development of coordinated and quality core set(s) in or across disease states, existing publicly available COAs and available outcome sets can be leveraged to pursue development of a core set. A core set could include publicly available COAs that have already been evaluated against standards outlined in the FDA Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims and related documents and undergone sufficient psychometric testing to provide evidence that demonstrates they are fit-for-purpose for regulatory use. For disease areas such as rare diseases, where there may not be existing COAs, de novo instrument development or testing available COAs in new populations may be necessary. Given this understanding, proposed activities in both phases will depend on the specific condition of interest and research strategy proposed by the applicant (e.g., proposed outcomes of interest, type of COA, expressed aim).

Since the UG3/UH3 cooperative agreement is a phased approach, FDA understands that, depending on the proposal, the information generated early in the UG3 phase may be at an early proof-of concept stage. However, it is expected that all work products, including de novo or modified COAs and additional COA supportive evidence generated through both the UG3 and UH3 phases of this FOA are currently or will be publicly available by the end of the grant period, at no cost or nominal cost. In addition, it will be important to ensure that identified concepts, COAs, and endpoints reflect what is most important and relevant in stakeholder decision making. To facilitate this, stakeholders including patients, care partners, FDA reviewers, drug developers, as well as other government and academic researchers, health care providers, health technology assessors and health payers, will ideally be engaged at key milestones via public meetings. The scope of this cooperative agreement will cover all aspects of planning (e.g., protocol development, literature review, gap analysis), implementation (e.g., execution of plan, active stakeholder engagement, development of work products) and other tasks necessary to support the objectives specified.

For this cooperative agreement, development of a standard core set(s) of instruments, tools and their related endpoints may either focus on a specified disease area or a disease impact that may span multiple disease areas. FDA encourages using the following criteria to identify a disease area or disease impact for the development of standard core set(s) under this FOA:

  • Disease areas that are chronic, symptomatic, or affect functioning and activities of daily living

  • Disease areas that represent a broad range in terms of size of the affected population, including common conditions experienced by large numbers of patients and rare diseases that affect much smaller patient populations

  • Disease impacts that are relevant to patients' experience across a range of disease areas

FDA is interested in supporting the development of standard core sets for disease areas or disease impacts that are representative of the disease conditions encountered in regulatory decision making, relevant to other regulators, health technology assessors and payers, and expected to support efficient regulatory review and decision-making. Moreover, FDA is interested in the development of standard core sets of COA and related endpoints, not only for use in adults but also those for use in pediatric trials. To that end, and based on the criteria outlined above, FDA has identified the following areas of interest for the purpose of this FOA:

  • COAs and endpoints for use in trials in gastrointestinal diseases/conditions, specifically for use across gastrointestinal diseases/conditions with overlapping signs and symptoms. These include, but are not limited to, abdominal pain, nausea, vomiting, bloating, postprandial fullness, and bowel symptoms (e.g., constipation, diarrhea) COAs and endpoints to assess physical/functional status including, but not limited to, standardized assessment of activities of daily living dependent on gross and fine motor function (including upper and lower limb function) across a range of diseases and populations; COAs and endpoints should incorporate any use of assistive devices

  • COAs and endpoints for use in migraine trials, including functional impact or disability from migraine

  • COAs and endpoints for use in trials of opioid sparing drugs intended to treat acute pain

  • COAs and endpoints for use in schizophrenia trials, including but not limited to, shortened versions of current instruments, as appropriate

FDA is also interested in applications for disease areas or disease impacts that are not represented on this list. When proposing an alternative disease area or disease impact for consideration, applicants should describe how they applied the above criteria to identify the alternative disease area or disease impact for standard core set development.

For awards made under this FOA the projects will be funded as phased awards. Contingent on continued availability of funds, this would include one to two years in the planning phase (UG3) and three to four years in the implementation phase (UH3). Funds will be awarded to applicants pursuing development of a single core set for a disease area and/or multiple core sets. Applicants must clearly specify in the application whether they will be pursuing development of a single or multiple core set(s) for a disease area. Outlined below are activities that should generally be included in each phase.

Should read:

Research Objectives

Under the UG3/UH3 phases, applicants will conduct a well-managed, transparent, and methodologically-sound process following a core set development strategy and protocol. FDA is interested in the identification of modifiable disease and treatment impacts that matter most to people living with a disease or condition. To minimize ambiguity and uncertainty for both regulatory decision makers and drug developers, FDA is not only interested in the high-level concepts related to those impacts but also in the set of specific instruments, tools, and endpoints for a given disease or condition.

The core set development work pursued under the cooperative agreement should be informed by FDA guidance documents (e.g., patient-focused drug development methodological guidances), the COA compendium, drug development tools qualification guidelines, a review of the literature (including a gap analysis to evaluate the use of existing tools), and current knowledge of the disease area.

To ensure the development of coordinated and quality core set(s) in or across disease states, existing publicly available COAs and available outcome sets can be leveraged to pursue development of a core set. A core set could include publicly available COAs that have already been evaluated against standards outlined in the FDA Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims and related documents and undergone sufficient psychometric testing to provide evidence that demonstrates they are fit-for-purpose for regulatory use. For disease areas such as rare diseases, where there may not be existing COAs, de novo instrument development or testing available COAs in new populations may be necessary. Given this understanding, proposed activities in both phases will depend on the specific condition of interest and research strategy proposed by the applicant (e.g., proposed outcomes of interest, type of COA, expressed aim).

Since the UG3/UH3 cooperative agreement is a phased approach, FDA understands that, depending on the proposal, the information generated early in the UG3 phase may be at an early proof-of concept stage. However, it is expected that all work products, including de novo or modified COAs and additional COA supportive evidence generated through both the UG3 and UH3 phases of this FOA are currently or will be publicly available by the end of the grant period, at no cost or nominal cost. In addition, it will be important to ensure that identified concepts, COAs, and endpoints reflect what is most important and relevant in stakeholder decision making. To facilitate this, stakeholders including patients, care partners, FDA reviewers, drug developers, as well as other government and academic researchers, health care providers, health technology assessors and health payers, will ideally be engaged at key milestones via public meetings. The scope of this cooperative agreement will cover all aspects of planning (e.g., protocol development, literature review, gap analysis), implementation (e.g., execution of plan, active stakeholder engagement, development of work products) and other tasks necessary to support the objectives specified.

For this cooperative agreement, development of a standard core set(s) of instruments, tools and their related endpoints may either focus on a specified disease area or a disease impact that may span multiple disease areas. FDA encourages using the following criteria to identify a disease area or disease impact for the development of standard core set(s) under this FOA:

  • Disease areas that are chronic, symptomatic, or affect functioning and activities of daily living

  • Disease areas that represent a broad range in terms of size of the affected population, including common conditions experienced by large numbers of patients and rare diseases that affect much smaller patient populations

  • Disease impacts that are relevant to patients' experience across a range of disease areas

FDA is interested in supporting the development of standard core sets for disease areas or disease impacts that are representative of the disease conditions encountered in regulatory decision making, relevant to other regulators, health technology assessors and payers, and expected to support efficient regulatory review and decision-making. Moreover, FDA is interested in the development of standard core sets of COA and related endpoints, not only for use in adults but also those for use in pediatric trials. To that end, and based on the criteria outlined above, FDA has identified the following areas of interest for the purpose of this FOA:

  • COAs and endpoints for use in trials in gastrointestinal diseases/conditions, specifically for use across gastrointestinal diseases/conditions with overlapping signs and symptoms. These include, but are not limited to, abdominal pain, nausea, vomiting, bloating, postprandial fullness, and bowel symptoms (e.g., constipation, diarrhea)

  • COAs and endpoints to assess physical/functional status including, but not limited to, standardized assessment of activities of daily living dependent on gross and fine motor function (including upper and lower limb function) across a range of diseases and populations; COAs and endpoints should incorporate any use of assistive devices

  • COAs and endpoints for use in migraine trials, including functional impact or disability from migraine

  • COAs and endpoints for use in trials of opioid sparing drugs intended to treat acute pain

  • COAs and endpoints for use in schizophrenia trials, including but not limited to, shortened versions of current instruments, as appropriate

FDA is also interested in applications for disease areas or disease impacts that are not represented on this list. When proposing an alternative disease area or disease impact for consideration, applicants should describe how they applied the above criteria to identify the alternative disease area or disease impact for standard core set development.

For awards made under this FOA the projects will be funded as phased awards. Contingent on continued availability of funds, this would include one to two years in the planning phase (UG3) and three to four years in the implementation phase (UH3). Funds will be awarded to applicants pursuing development of a single core set for a disease area and/or multiple core sets. Applicants must clearly specify in the application whether they will be pursuing development of a single or multiple core set(s) for a disease area. Outlined below are activities that should generally be included in each phase.

Inquiries

Please direct all inquiries to:

Financial/Grants Management Contact(s)

Shashi Malhotra
Office of Acquisitions & Grants Services (OAGS)
Food and Drug Administration
Email: Shashi.Malhotra@fda.hhs.gov

Scientific/Research Contact(s)

Pujita Vaidya
Center for Drug Evaluation and Research (CDER)
Email: CDER_StandardCoreCOAs@fda.hhs.gov