An embedded pragmatic clinical trial (ePCT) is a trial based on implementing an intervention that can be “embedded” within routine care provided within a healthcare system, agency or organization, or other non-healthcare based organizations. The intervention is implemented in a “real-world” environment by practicing clinicians or non-clinical staff, not interventionists. A core component is that the intervention can be maintained for real-world use and sustained beyond the scope of a trial. ePCTs use a variety of systematic research methods to test the effectiveness of the intervention. Randomization for a full scale ePCT generally occurs at the level of an organization, care team or unit rather than at an individual level, though this is not a hard and fast rule. Most ePCTs utilize data available from electronic health records, administrative data, or claims data to assess effectiveness outcomes.

The NIH Health Care Systems Research Collaboratory Living Textbook of Pragmatic Trials is a helpful resource to learn more about ePCTs. Additional resources include the State of the Science for pragmatic trials for non-pharmacological interventions to improve outcomes among people living with dementia and their caregivers; lessons learned from the NIH Health Care Systems Research Collaboratory; and the process of embedding PCTs in health care systems.

Much like a pilot study for a more traditional stage/phase III trial, the goal of a pilot study for an embedded pragmatic clinical trial (ePCT) is to provide important data that can assist with the development of the full-scale ePCT. In a pilot study it is important to think through what are the elements the investigators believe are not yet “fully ready” for a full-scale trial based on the Readiness Assessment for Pragmatic Trials. Issues that may need to be addressed include but are not limited to:

• Modifications to a well-protocoled and tested intervention for delivery in a more pragmatic nature
• Testing whether clinical outcomes can be collected pragmatically
• Testing whether pragmatically collected outcomes are reliable and valid compared to gold standard collection
• Testing randomization schemes
• Testing feasibility and usability of implementation in a real world environment
• Costs of implementing the intervention
• Ability to pragmatically identify subjects

IMPACT Pilot Program RFA is soliciting pilot studies to enable full-scale embedded clinical trials (ePCTs).In the NIA Stage Model, this aligns with a pilot study for a Stage IV effectiveness trial. Pilot studies for Stage III efficacy trials will be administratively triaged.

We strongly encourage investigators to use the Readiness Assessment for Pragmatic Trials (RAPT) model to assess an intervention’s readiness for ePCTs.

Applications must demonstrate a substantially pragmatic design. Applications that are not designed to be pragmatic will be administratively triaged prior to review. Thus, it is important to pay special attention to the specific requirements related to the pragmatic design of the pilot study specified in the Request for Applications (RFA). Scientific review of applications will focus on the degree to which the proposed intervention is ready for an ePCT based on the RAPT Model, and the design of the pilot study represents a pragmatic approach based on the PRECIS-2 framework.

The primary outcome of the pilot study must be the primary clinical outcome anticipated for the full scale ePCT (e.g., antipsychotic use, hospital transfer rates). We recognize the pilot study may have a single arm and will NOT be powered to detect differences in the primary clinical outcome. Rather, the intent is to ascertain feasibility of collecting the primary outcome under the rubric of an ePCT. Additional clinical or scientific outcomes are encouraged and should be specified (e.g., healthcare utilization, medications).

All pilot studies should also include implementation endpoints evaluating the implementation experience (e.g., feasibility, applicability, usability, fidelity).

Ideally, the intervention should have a reasonable evidence-base demonstrating its efficacy as described in the Readiness Assessment for Pragmatic Trials (RAPT) Model paper.

Interventions must be non-pharmacologic in nature and involve people living with dementia or their caregivers. Ideally the intervention (or components thereof) should have a reasonable level of evidence supporting its efficacy as described in the Readiness Assessment for Pragmatic Trials (RAPT) Model paper, and a high potential for implementation in “real world” settings. It may be helpful to consider PCORI Methodology Standards of Complex Interventions.

Yes, you may use two or more sites within the same healthcare organization, but you must provide the rationale for site selection. You should also address how pilot data from sites within a single organization will prepare you for implementation in a future trial involving multiple organizations.

Settings that provide care to people living with dementia and/or their caregivers are permissible within this funding mechanism. Most often this will be a health care setting, but residential (e.g., senior housing) or other settings (e.g., recreational day program) are also acceptable.

The entire process generally takes approximately 6-8 months from the LOI deadline. The time from submission of the full proposal application and notification is typically 3 months.

 Yes. LOIs are required.  Applicants may submit their LOI early, but no later than the LOI deadline.

 No, only one LOI is permitted per cycle from each principal investigator.

LOIs will be reviewed by an interdisciplinary review committee. Generally, applicants will receive a decision on their LOI about 4 weeks after the submission deadline.

Yes, you may include key references to support the pilot project description.  Please limit references to no more than 1 page in addition to the 2-page pilot project description.

No, you do not need to include a detailed budget with the LOI application.

Exact timelines will vary. Generally, the timeline from the LOI deadline to project start date is approximately 6-8 months. This timeline assumes there are no delays in receiving approvals from the National Institute on Aging, the IRB that oversees all IMPACT Collaboratory-funded research, and Data Safety and Monitoring Board.

The National Institute on Aging (NIA) IMPACT Collaboratory is led by Principal Investigators from Brown University and Hebrew SeniorLife. The grants administration team of the Administrative Core is housed at Brown. Therefore, Brown University will execute the subcontracts for Pilot Grants.

Any organization (including for-profit organizations) that has a Unique Entity Identifier (UEI) and processes for following federal guidelines/regulations for using research funds meet eligibility criteria for this grant.  The UEI Number has replaced the DUNS Number as the primary means of entity identification for federal awards government-wide.

You may apply provided your visa immigration status is acceptable and you are employed by a U.S. institution. Individuals who are noncitizens of the U.S. or do not have a Permanent Resident Card should contact the IMPACTcollaboratory@hsl.harvard.edu prior to submitting a Letter of Intent.

No. Applications may have only one principal investigator.

Investigators may apply if the applicant holds an earned doctorate and is not a trainee, such as a post-doctoral fellow. Applicants must be of sufficient stature to be considered a principal investigator within their organization.

No. Research cannot be performed in study sites outside of the U.S.
Non-domestic (non-U.S.) entities (foreign institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. organizations are not eligible to apply.

Dementia affects all Americans and disproportionately impacts African Americans. At the same time, disparities in dementia care are well-documented. Ensuring the research supported by the IMPACT Collaboratory includes people from diverse backgrounds and culturally-tailored interventions to promote health equity is core to its mission.

For more guidance, please see our Best Practices for Integrating Health Equity into ePCTs.

No. The pilot project must consider issues related to health equity throughout the Research Plan. Rationale should be provided about how aspects of the study design (for example, selection of health care system location, target study population demographics, and/or tailoring of the intervention to different cultures) are and are not, relevant to people from diverse backgrounds. It may not be possible to address all issues within the scope of a pilot study, however at minimum, investigators should describe how the pilot project experience will inform the design of a future large-scale ePCT in terms of its relevance to people from diverse backgrounds who are living with dementia and/or their caregivers.  These requirements are in addition to the required NIH Planned Inclusion Enrollment Table(s) and statement about minority representation.

Applicants must specify quarterly milestones as part of the full proposal application. Quarterly milestones are required to ensure that pilot ePCTs are progressing in a timely fashion given the 1-year grant period. Quarterly milestones must be specific and measurable since they will be used to assess feasibility by the reviewers and Pilot Core Executive Committee as part of the application review process.

This pilot funding mechanism follows NIH guidelines in regard to allowable costs and activities.

No. Each pilot application may budget up to $175,000 in direct costs. Indirect costs may be budgeted at your institution's negotiated facilities and administrative rate.

No. You do not need to include costs for the IRB in your budget. These costs will be supported by the IMPACT Collaboratory.

Yes. You will need to include costs for the PI's travel and accommodation to one in-person IMPACT Collaboratory Meeting in Bethesda, MD during the pilot year.

You will be asked to attend and present at a future IMPACT Scientific Meeting in Bethesda, MD, but travel and accommodations for this will be supported by the IMPACT Collaboratory. You do not need to include this in your budget, as it will occur after your pilot project has ended.

Yes you may have up to 2 subawards. Each subaward must have a separate budget and budget justification, at least one Key Personnel, and a Unique Entity Identifier (UEI). The UEI Number has replaced the DUNS Number as the primary means of entity identification for Federal awards government-wide.

Whenever appropriate, purchase of services and consulting agreements are encouraged.  Service and consulting agreements do not count towards the number of subawards. Federal regulations providing guidance for making an accurate determination are available at 2 CFR 200.331. Purchase of services and consulting agreements should be listed within the PI’s main budget. Subaward indirect costs will be excluded from the direct cost limit of $175,000.

The table below may help to determine whether to use a Subaward or a Consultant/Contractor. Whenever feasible, purchase of services and/or consultant agreements are strongly preferred.

Applicants who are invited for a full proposal will be immediately connected to the IMPACT Collaboratory Investigator Navigation Team. The Navigator will play an active role in linking applicants to appropriate Cores and Teams for support in developing a high-quality full proposal. Applicants will be asked to complete a needs assessment to help target their needs to the appropriate Cores and Teams.