Research Proposal Questions
1. Is my research question ready for a pragmatic trial?
Patients, providers, and researchers all want the best available clinical evidence to inform decisions about which approaches or therapies to provide or recommend. If you are considering a pragmatic or implementation trial design, is there sufficient efficacy information on the intervention to warrant further testing in a large-scale pragmatic or implementation trial across multiple health care systems? Can the intervention be implemented across health care systems?
2. Is my project required to address health disparities?
To determine whether this is a requirement, review the priority language for the Institute or Center that would support your research based on your area of science. Some Institutes and Centers are requiring that applications address health disparities, and others are not. In general, high priority will be given to applications that propose research that would improve health outcomes in Americans across the lifespan and in health disparity populations who experience higher rates of certain diseases and higher morbidity or mortality compared with the general population. The specific population with health disparities may be defined by race, ethnicity, geography, or socioeconomic status. For the purposes of this funding opportunity, the National Institutes of Health–designated U.S. health disparity populations definition includes Blacks/African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minorities. (More information can found at nimhd.nih.gov/about/overview.)
3. Why is there an expanded call for implementation trials? Does my project need to include implementation outcomes?
The NIH Health Care Systems Research Collaboratory will support either pragmatic trials or implementation trials. Applications proposing pragmatic intervention trials are not required to include implementation outcomes, however investigators proposing these studies may improve their ability to deliver the intervention in their trial by utilizing effective implementation strategies or by measuring implementation outcomes. The UG3/UH3 funding opportunity will accept pure implementation trials of effective interventions with the goal of understanding how to get effective interventions into health care delivery with good adoption, implementation, and sustainability. This expanded call is consistent with multiple efforts across NIH to advance dissemination and implementation research (e.g PAR-19-274).
4. To what degree can pilot work be conducted during the UG3 phase, and can any pilot work be done during the first year of the UH3 phase?
In the context of pragmatic trials, “piloting” usually refers to the work investigators do during the planning phase to test their ability to successfully get the intervention into clinical sites, extract needed data from electronic medical records, and assess methods to identify eligible participants and methods for collecting data from participants to augment the electronic health record. Investigators can pilot the intervention and assess its uptake so that when they get to the trial conduct phase, they’re prepared for trial startup. For implementation trials, the planning phase can be used to collect site-specific context data and test the ability to measure implementation outcomes based on electronic health or administrative records. It’s expected that efficacy data for the intervention already exist. The piloting work should be complete prior to the start of the UH3 phase, as the investigators are expected to launch the trial at the beginning of the UH3 phase.
5. Do all software tools needed for implementation need to be developed during the planning phase, or will these be developed after a project is selected for transition to the UH3 (trial conduct) phase?
By the start of the UH3 phase, the study team should have all methods, tools, and software needed to conduct the pragmatic or implementation trial. Tools can be modified as needed during the UH3 phase as appropriate.
6. Is it anticipated that sharing plans will require sharing of preexisting proprietary software that is currently used by partnering health care systems?
Applicants will not be required to share preexisting proprietary software that is currently used by the partnering health care systems. Applicants will be encouraged to share resources and software whenever possible.
7. Is the UG3/UH3 intended to support work of clinicians or interventionists?
Interventions should be delivered as part of routine health care delivery. Thus, funds from the award are typically not used to directly pay for the intervention delivery.
8. Should the pragmatic clinical trials in the UG3/UH3 enroll patients at more than one institution/center?
Trials should be conducted across three or more health care systems that provide care to patient populations and will become part of and work with the NIH Health Care Systems Research Collaboratory. Trials should include a diverse patient population that approximates the U.S. population of patients with the condition being studied. Investigators who propose fewer than three health care systems must provide justification that there is adequate geographic, provider, and racial diversity within the proposed systems so that the trial will be generalizable to other health care systems.
9. What activities should be carried out in the UG3 phase?
During the UG3 or planning phase, activities will generally include, but are not limited to:
- Identify project staff who will participate in the Collaboratory Work Groups (see website for additional Information about the work groups: rethinkingclinicaltrials.org/cores-and-working-groups), which will develop guidelines and practices to be implemented across projects.
- Work with the Collaboratory to implement approved guidelines and practices for electronic data extraction and quality control methods and tools, as well as for electronic data sharing. In the planning phase, this will include developing and validating all electronic data methods and tools within the health care systems needed for the project (e.g., electronic health records, electronic methods for patient identification and outcomes assessment, patient-reported data, biospecimens, images, high-throughput genomic data, family history data, data abstraction and survey instruments) and complete quality control testing at all sites.
- Assess adequacy and finalize clinically relevant outcome measures with other Collaboratory investigators. Awarded applicants will work with other Collaboratory investigators and NIH to identify common outcome measures (quality of life, pain, fatigue, physical functioning, and other measures) and will work with the Collaboratory Coordinating Center (CCC) and NIH to develop metrics for resource utilization for planning and implementing Collaboratory pragmatic trials. If an award is made, NIH and CCC staff will work with the program directors/principal investigators to facilitate coordination among projects, if appropriate.
- Refine estimates of requirements with guidance from NIH and the CCC for sample size, numbers of sites, site-to-site heterogeneity, and the implementation timetable based on data derived from the partnering health care systems.
- Develop detailed plans for site implementation, including site staff, method of identification, randomization (as applicable), and participant recruitment and acquisition and administration/implementation of the intervention if applicable.
- Address all ethical issues and issues related to human subject safety oversight for the project, including development of informed consent documents or opt-out consent if applicable, and finalize the site of Institutional Review Board (IRB) review. Applicants must propose a single IRB or centralized IRB approach for trial oversight to facilitate both appropriate and timely study conduct.
- Address all potential regulatory elements of the proposed trial (if applicable).
- Develop a detailed budget for conduct and completion of the project, including preparation of a final planning phase report and end-of-study data sharing requirements.
- Finalize detailed plans for data coordination and quality control for the UH3 phase. The CCC will not provide these functions for individual projects. Data coordinating activities for individual projects must be separately budgeted as part of the UH3 budget.
10. Given that there are two stages, the UG3 and UH3, how should the aims and research strategy sections of the application be structured?
Page 1 of the application must include specific aims for each of the two stages. Typically, investigators divide the remaining pages into two discrete descriptions, first the UG3 and then the UH3. In the request for applications (RFA), there is a list of things that must take place in each phase. You can use this as a guide. Information already described for the UG3 need not be repeated in the UH3 section; you can just refer to it. If your project meets the definition of a clinical trial, you also can provide additional details, such as inclusion/exclusion criteria and details of the protocol, in the Study Record.
11. Do applications need to include a complementary intervention?
Applications do not need to include complementary health approaches. Applications must fit the mission of one of the participating Institutes or Centers and the goals of the RFA.
12. How much evidence is needed for an intervention to justify a primary focus on implementation rather than intervention effectiveness?
The amount of evidence to justify implementation will often depend on the volume of evidence suggesting a health benefit and the relevance of that evidence to the context and population for which it is intended to be used. Where there are still key questions about the link between the intervention and targeted health outcomes, investigators can consider the use of a hybrid effectiveness-implementation design, where questions of both effectiveness and implementation can be addressed.
13. For implementation trials, should my project include a relevant conceptual framework?
While the RFA does not require the use of a dissemination and implementation theory, model, or framework, investigators may find that the use of an existing model (e.g. https://dissemination-implementation.org) can ease in articulating causal relationships around the implementation process, determine relevant implementation strategies to test, or identify implementation outcomes to measure.
14. Must the three health care systems all be participating members of the NIH Collaboratory or members of the Health Care Systems Research Network?
No. Organizations that have not previously participated in Collaboratory projects are welcome. The Collaboratory has worked with organizations that provide health care but might not be considered typical health care systems, such as dialysis providers and corporations that provide health care.
However, all participating health care systems must be large-scale health care delivery organizations with electronic records, and investigators must have ready access to the electronic records needed to assess study outcomes. The definition of a health care system in the RFA was intentionally broad so that investigators can propose ideas that might not have been anticipated. If you are unsure whether an organization you want to work with is acceptable, please contact a program officer.
Note that for this RFA, it is important for results to be generalizable and applicable to a broad patient population. Typically, sites from multiple regions around the country would be included in a study. However, no foreign sites can be included, although foreign consultants are acceptable.
15. Is it necessary to budget for a statistician or will one be provided by the CCC?
You will definitely need a Ph.D.-level statistician for both the design stage of your trial and the development of the analytic plan. The CCC is a resource center, not a data coordinating center for your trial. It will not collect, store, or analyze your data. Your application needs to include full information about the ways in which you will obtain and analyze your data, which is why you will need to budget for a biostatistician.