Notice of Correction to Funding Opportunity Description and Application and Submission Information in RFA-HL-19-005 Management of Asthma in Primary Care - Clinical Center (UG3/UH3 - Clinical Trial Required)

Notice Number: NOT-HL-18-646

Key Dates
Release Date: August 23, 2018

Related Announcements

RFA-HL-19-005 , "Management of Asthma in Primary Care- Clinical Center (UG3/UH3 - Clinical Trial Required)"

RFA-HL-19-006, "Management of Asthma in Primary Care - Bioinformatics Group (U24 - Clinical Trial Required)"

Issued by
National Heart, Lung, and Blood Institute (NHLBI)

Purpose

On August 2, 2018, the NHLBI issued Funding Opportunity Announcement RFA-HL-19-005, "Management of Asthma in Primary Care- Clinical Center (UG3/UH3 - Clinical Trial Required). The purpose of this Notice is to clarify that during the UG3 phase of the program, all clinical trials must have started (enrolled at least one subject).

Part 1. Overview Information

Funding Opportunity Purpose

Current language

The purpose of this UG3/UH3 Funding Opportunity Announcement (FOA) is to retrospectively identify and then prospectively compare the best practices being used by primary care providers (PCP) in the United States (US) to manage asthma. The Managing Asthma in Primary Care (MAP) Program will consist of three functional units, including a Primary Care Network (PCN), a Data Management Team (DMT), and a Clinical Consultant Team (CCT). In the UH3 phase of MAP, these units will collaborate to collect data from existing electronic health records (EHRs) using common data elements (CDEs) to capture the characteristics of patients with asthma managed in primary care, their care providers and practice settings, the current management practices (CMPs) or treatment plans used, and the patient outcomes. By the conclusion of the UG3 phase, prospective clinical trials comparing the CMPs that appear most effective in specific patient groups based on the retrospective EHR analysis will be ready to begin. Subsequently in the UH3 phase of the program, the three units will conduct clinical trials to assess those CMPs that were determined to be most effective in specific populations of patients with asthma who are managed in primary care. 

Revised language

The purpose of this UG3/UH3 Funding Opportunity Announcement (FOA) is to retrospectively identify and then prospectively compare the best practices being used by primary care providers (PCP) in the United States (US) to manage asthma. The Managing Asthma in Primary Care (MAP) Program will consist of three functional units, including a Primary Care Network (PCN), a Data Management Team (DMT), and a Clinical Consultant Team (CCT). In the UG3 phase of MAP, these units will collaborate to collect data from existing electronic health records (EHRs) using common data elements (CDEs) to capture the characteristics of patients with asthma managed in primary care, their care providers and practice settings, the current management practices (CMPs) or treatment plans used, and the patient outcomes. By the conclusion of the UG3 phase, prospective clinical trials comparing the CMPs that appear most effective in specific patient groups based on the retrospective EHR analysis will have started (begin enrolling subjects). Subsequently in the UH3 phase of the programthe three units will complete the clinical trials to assess those CMPs that were determined to be most effective in specific populations of patients with asthma who are managed in primary care. 

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

Current Language

The purpose of this UG3/UH3 Funding Opportunity Announcement (FOA) is to retrospectively identify and then prospectively compare the best practices being used by primary care providers (PCP) in the United States (US) to manage asthma. The Managing Asthma in Primary Care (MAP) Program will consist of three functional units, including a Primary Care Network (PCN), a Data Management Team (DMT), and a Clinical Consultant Team (CCT).In the UH3 phase, these units will collaborate to collect data from existing electronic health records (EHRs) using common data elements (CDEs) to capture the characteristics of patients with asthma managed in primary care, their care providers and practice settings, the current management practices (CMPs) or treatment plans used, and the patient outcomes. By the conclusion of the UG3 phase, prospective clinical trials comparing the CMPs that appear most effective in specific patient groups based on the retrospective EHR analysis will be ready to begin. Subsequently in the UH3 phase, the three units will conduct the clinical trials to assess those CMPs that were determined to be most effective in specific populations of patients with asthma who are managed in primary care.

Structure

To complete the objectives of the MAP program, three distinct units will collaborate to collect retrospective data and design clinical trials in the UG3 phase, then conduct prospective clinical trials in the UG3 phase. 

Phases of Award

The UG3 phase will support the development of asthma CDEs to be collected from the EHRs, a prioritized list of asthma outcomes to be measured, any requisite regulatory approvals [such as Institutional Review Board(IRB)/Data and Safety Monitoring Board (DSMB) approval] prior to the initiation of both the retrospective and prospective clinical trials, retrospective data collection from the EHRs using CDEs, transfer of data to the BIG, and then design of the prospective clinical trials based on the results of the retrospective analysis. Applicants are strongly encouraged to address a comprehensive project management plan that includes consideration of the feasibility of completion of on-time and on-budget performance milestones. All necessary activities needed to allow the prospective clinical trials to be successfully launched with adequate resources at the onset of the UH3 award should completed during the UG3 phase. Enrollment into the prospective clinical trials is expected to begin at the onset of the UH3 award. Subject to NIH funding availability and scientific priorities, UH3 awards will be made after administrative review with particular attention to the extent to which the milestones established for the UG3 phase have been met. If the UH3 is funded, an additional administrative review will be scheduled within the first two years of the UH3 to assess progress toward UH3 milestones, including enrollment milestones and data collection (completeness).

Section IV. Application and Submission Information

PHS 398 Research Plan

Specific Aims

Use the Specific Aims of the UG3 phase to describe how the investigators will achieve the objective of designing prospective clinical trials that include the entire spectrum of asthma patients managed by PCPs in the US, based on the evidence obtained the analysis of retrospective EHR data.

Research Strategy

UG3 Phase Milestones

  • Define a comprehensive set of asthma CDEs: The CDEs must encompass all of the potentially relevant factors that may affect (directly or indirectly) the asthma outcomes of patients managed in primary care as well as measure the outcomes. Relevant patient characteristics (including classification of their asthma), provider characteristics, clinical practice settings, CMPs (any intervention intended to affect a patient's asthma, including but not limited to pharmacological treatment, education, monitoring, and environmental assessments or modifications), and clinically relevant asthma outcomes must be captured by the CDEs. The data set provided to the BIG for analysis in the retrospective study will be strictly limited to the CDEs (though the same CDE may be collected at multiple different time points for the same individual). Subsequently, the CDEs will also be used for data collection in the prospective clinical trials. Describe in sufficient detail the approach that the CCT members will use to develop the asthma CDEs, including how they will ensure the CDEs will capture innovative interventions that PCPs may be using in practice.
  • Prioritize the asthma outcome measures: Propose an approach, utilizing the expert opinions of CCT, for prioritizing the most clinically meaningful asthma outcomes that will be captured by the CDEs in the retrospective study and prospective clinical trials. The results of the trials based on these measures should provide evidence to impact the care of patients with asthma managed by a PCP. The approach to prioritization of the asthma outcomes must provide the BIG with sufficient information to select the most effective CMPs in the retrospective study (i.e., the outcomes to be measured may integrate multiple endpoints, but the approach to prioritizing or ranking CMPs must be clearly defined). Use the same outcomes in the prospective clinical trials. Propose different priorities (or goals for care) for specific patient populations. Describe the process for incorporating the perspectives of the PCN members in completing this milestone.
  • Propose an approach for CMP development: The CMPs (which may be groups of interventions) will be defined by the BIG's analysis of the EHR data (without regard to the clinical appropriateness); however the CCT must propose an approach to facilitate the grouping individual interventions. When consulted by the BIG, the CCT will use this approach to achieve the (BIG's) desired number of CMPs. Explain and justify the rationale for how the CCT will group similar (though not identical) interventions. Describe the process for incorporating the perspectives of the PCN members in  completing this milestone.
  • Complete retrospective data collection: Describe the DMT's approach to converting EHR data into CDEs and assessing the integrity of the process. Provide a comprehensive plan (including but not limited to any resources or facilities that will be used as well as data security) for the approach to EHR data collection, from the individual PCN EHRs through the delivery of a complete dataset of asthma CDEs to the BIG. Describe where and how data will be transferred and stored. 
  • Write the protocols for the prospective clinical trials: Describe the CCT's process for developing new protocols for specific patient populations that will allow the relevant CMPs to be compared on the basis of the retrospective study results produced by the BIG. Summarize how the proposed PCN will provide a representative patient population for the entire US population of patients who receive asthma care from a PCP, describe the position of the potential trials along the pragmatic-explanatory continuum using the PRECIS indicators described in https://www.bmj.com/content/350/bmj.h2147 and https://www.precis-2.org, and the PCN's experience in conducting such a trial (including trials based on CDEs collected from EHR data).
  • Obtain approvals of the protocols: Describe the approach to the protection of all human research subjects that will be involved in the retrospective study and prospective clinical trials, including the plan for obtaining consent, IRB approvals, and data safety monitoring oversight and approval. 

Revised language

The purpose of this UG3/UH3 Funding Opportunity Announcement (FOA) is to retrospectively identify and then prospectively compare the best practices being used by primary care providers (PCP) in the United States (US) to manage asthma. The Managing Asthma in Primary Care (MAP) Program will consist of three functional units, including a Primary Care Network (PCN), a Data Management Team (DMT), and a Clinical Consultant Team (CCT). In the UG3 phase, these units will collaborate to collect data from existing electronic health records (EHRs) using common data elements (CDEs) to capture the characteristics of patients with asthma managed in primary care, their care providers and practice settings, the current management practices (CMPs) or treatment plans used, and the patient outcomes. By the conclusion of the UG3 phase, prospective clinical trials comparing the CMPs that appear most effective in specific patient groups based on the retrospective EHR analysis will have begun collecting data on enrolled subjects. Subsequently in the UH3 phase, the three units will complete the conduct of the clinical trials to assess those CMPs that were determined to be most effective in specific populations of patients with asthma who are managed in primary care.

Structure

To complete the objectives of the MAP program, three distinct units will collaborate to collect retrospective data and design clinical trials in the UG3 phase, then conduct prospective clinical trials in the UG3 phase. 

Phases of Award

The UG3 phase will support the development of asthma CDEs to be collected from the EHRs, a prioritized list of asthma outcomes to be measured, any requisite regulatory approvals [such as Institutional Review Board(IRB)/Data and Safety Monitoring Board (DSMB) approval] prior to the initiation of both the retrospective and prospective clinical trials, retrospective data collection from the EHRs using CDEs, transfer of data to the BIG, and then design of the prospective clinical trials based on the results of the retrospective analysis. Applicants are strongly encouraged to address a comprehensive project management plan that includes consideration of the feasibility of completion of on-time and on-budget performance milestones. All necessary activities needed to allow the prospective clinical trials to be successfully launched during the UG3 phase must be completed. Enrollment into the prospective clinical trials must begin prior to the onset of the UH3 award. Subject to NIH funding availability and scientific priorities, UH3 awards will be made after administrative review with particular attention to the extent to which the milestones established for the UG3 phase have been met. If the UH3 is funded, an additional administrative review will be scheduled within the first two years of the UH3 to assess progress toward UH3 milestones, including enrollment milestones and data collection (completeness). 

Section IV. Application and Submission Information

PHS 398 Research Plan

Specific Aims

Use the Specific Aims of the UG3 phase to describe how the investigators will achieve the objective of designing and initiating prospective clinical trials that include the entire spectrum of asthma patients managed by PCPs in the US, based on the evidence obtained the analysis of retrospective EHR data.

Research Strategy

UG3 Phase Milestones

  • Define a comprehensive set of asthma CDEs: The CDEs must encompass all of the potentially relevant factors that may affect (directly or indirectly) the asthma outcomes of patients managed in primary care as well as measure the outcomes. Relevant patient characteristics (including classification of their asthma), provider characteristics, clinical practice settings, CMPs (any intervention intended to affect a patient's asthma, including but not limited to pharmacological treatment, education, monitoring, and environmental assessments or modifications), and clinically relevant asthma outcomes must be captured by the CDEs. The data set provided to the BIG for analysis in the retrospective study will be strictly limited to the CDEs (though the same CDE may be collected at multiple different time points for the same individual). Subsequently, the CDEs will also be used for data collection in the prospective clinical trials. Describe in sufficient detail the approach that the CCT members will use to develop the asthma CDEs, including how they will ensure the CDEs will capture innovative interventions that PCPs may be using in practice.
  • Prioritize the asthma outcome measures: Propose an approach, utilizing the expert opinions of CCT, for prioritizing the most clinically meaningful asthma outcomes that will be captured by the CDEs in the retrospective study and prospective clinical trials. The results of the trials based on these measures should provide evidence to impact the care of patients with asthma managed by a PCP. The approach to prioritization of the asthma outcomes must provide the BIG with sufficient information to select the most effective CMPs in the retrospective study (i.e., the outcomes to be measured may integrate multiple endpoints, but the approach to prioritizing or ranking CMPs must be clearly defined). Use the same outcomes in the prospective clinical trials. Propose different priorities (or goals for care) for specific patient populations. Describe the process for incorporating the perspectives of the PCN members in completing this milestone.
  • Propose an approach for CMP development: The CMPs (which may be groups of interventions) will be defined by the BIG's analysis of the EHR data (without regard to the clinical appropriateness); however the CCT must propose an approach to facilitate the grouping individual interventions. When consulted by the BIG, the CCT will use this approach to achieve the (BIG's) desired number of CMPs. Explain and justify the rationale for how the CCT will group similar (though not identical) interventions. Describe the process for incorporating the perspectives of the PCN members in completing this milestone.
  • Complete retrospective data collection: Describe the DMT's approach to converting EHR data into CDEs and assessing the integrity of the process. Provide a comprehensive plan (including but not limited to any resources or facilities that will be used as well as data security) for the approach to EHR data collection, from the individual PCN EHRs through the delivery of a complete dataset of asthma CDEs to the BIG. Describe where and how data will be transferred and stored. 
  • Write the protocols for the prospective clinical trials: Describe the CCT's process for developing new protocols for specific patient populations that will allow the relevant CMPs to be compared on the basis of the retrospective study results produced by the BIG. Summarize how the proposed PCN will provide a representative patient population for the entire US population of patients who receive asthma care from a PCP, describe the position of the potential trials along the pragmatic-explanatory continuum using the PRECIS indicators described in https://www.bmj.com/content/350/bmj.h2147 and https://www.precis-2.org, and the PCN's experience in conducting such a trial (including trials based on CDEs collected from EHR data).
  • Obtain approvals of the protocols: Describe the approach to the protection of all human research subjects that will be involved in the retrospective study and prospective clinical trials, including the plan for obtaining consent, IRB approvals, and data safety monitoring oversight and approval.
  • Initiate the conduct of the clinical trials: Describe the plan for demonstrating all of the clinical trials have been initiated and adequate data collection from all PCP practices participating in the clinical trials has begun. 

All other aspects of the FOA remain unchanged.

Inquiries

Please direct all inquiries to:

Michelle Freemer, MD, MPH
National Heart, Lung, and Blood Institute/ Division of Lung Diseases
Telephone: 301-435-0202
Email:michelle.freemer@nih.gov