Notice of Intent to Publish a Funding Opportunity Announcement for Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) (UG3/UH3, Clinical Trials Optional)

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Notice Number: NOT-AT-19-004

Key Dates

Release Date:November 02, 2018
Estimated Publication Date of Funding Opportunity Announcement: December 08, 2018
First Estimated Application Due Date: February 08, 2019
Earliest Estimated Award Date: September 01, 2019
Earliest Estimated Start Date: September 20, 2019

Related Announcements
NOT-AT-19-005

Issued by
National Center for Complementary and Integrative Health (NCCIH)

National Cancer Institute (NCI)

National Institute on Aging (NIA)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Dental and Craniofacial Research (NIDCR)

Purpose

The National Center for Complementary and Integrative Health (NCCIH), along with partnering Institutes/Centers/Offices intends to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) to solicit applications for research to conduct efficient, large-scale pragmatic or implementation trials to improve pain management and reduce the unnecessary use of opioid medications.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.

The FOA is expected to be published in Fall 2018 with an expected application due date in Winter 2019.

This FOA will utilize the UG3/UH3 activity code. Details of the planned FOA are provided below.

This study is part of the of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative will bolster research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at: https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.

Research Initiative Details

This Notice encourages investigators with expertise and insights into this area of evidence-based pain management to begin to consider applying for this new FOA. In addition, collaborative investigations combining expertise in pain management, pragmatic clinical trials, implementation trials, and methods to improve adherence to evidence-based medical guidelines will be encouraged and these investigators should also begin considering applying for this application.

This initiative will encourage UG3/UH3 phased cooperative research applications to conduct efficient, large-scale pragmatic or implementation trials to improve pain management and reduce the unnecessary use of opioid medications. Awards will initially support a one-year milestone-driven planning phase (UG3), with possible transition to an implementation phase (UH3) of up to four years. UG3 projects that have met the scientific milestone and feasibility requirements may transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application.

The overall goal of this initiative is to support the "real world" assessment of health care strategies and clinical practices and procedures in health care system that may lead to improved pain management along with a reduction in unnecessary opioid prescribing. This initiative will requires that the intervention under study be embedded into health care delivery systems, real world settings. Studies can propose to integrate interventions that have demonstrated efficacy into health care systems; or implement health care system changes to improve adherence to evidence-based guidelines. Trials must be conducted across three or more health care systems (HCS) and will become part of and work with the NIH HCS Research Collaboratory supported through the NIH Common Fund. (See https://commonfund.nih.gov/hcscollaboratory).

More than 25 million Americans suffer from chronic pain, a highly debilitating medical condition that is complex and difficult to manage. In recent decades, there has been an over reliance on the prescription of opioids for chronic pain, contributing to a significant and alarming epidemic of opioid overdose deaths and addiction. Extant data suggest that nonopioid pain management interventions show some efficacy for the treatment of acute and chronic pain. The Centers for Disease Control (CDC) guideline for prescribing opioids for chronic pain, for example, states that "nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain." The Clinical Practice Guideline from the American College of Physicians also recommends noninvasive, nonopioid treatments for acute, subacute, and chronic low back pain. Pragmatic trials and implementation, therefore, are needed because policies, clinical practice guidelines, and tools and interventions have not been readily adopted and implemented by health care systems. Research is needed to study strategies to most effectively, equitably, and efficiently implement evidence-based interventions and pain management guidelines.

For the purpose of this Notice of Intent to Publish , we define "embedded pragmatic clinical trial" and "implementation research", as follows:

Embedded pragmatic clinical trials are conducted within the health care delivery setting and are primarily designed to determine the effects of an intervention under the usual conditions in which it will be applied , which is in contrast with explanatory trials that are primarily designed to determine the effects of an intervention under ideal circumstances (http://www.bmj.com/content/350/bmj.h2147). "There are three key attributes of pragmatic clinical trials (PCTs): (1) an intent to inform decision-makers (patients, clinicians, administrators, and policy-makers), as opposed to elucidating a biological or social mechanism; (2) an intent to enroll a population relevant to the decision in practice and representative of the patients or populations and clinical settings for whom the decision is relevant; and (3) either an intent to (a) streamline procedures and data collection so that the trial can focus on adequate power for informing the clinical and policy decisions targeted by the trial or (b) measure a broad range of outcomes (http://rethinkingclinicaltrials.org/chapters/pragmatic-clinical-trial/what-is-a-pragmatic-clinical-trial-2/)."

Implementation research seeks to understand the behavior of practitioners and support staff, organizations, consumers and family members, and policymakers in context as key influences on the adoption, implementation and sustainability of evidence-based health interventions and guidelines (e.g., Community Guide to Preventive Services, U.S. Preventive Services Task Force, and clinical and professional societies' recommendations and guidelines). Implementation research studies should not assume that effective interventions can be integrated into any service setting and for consumer groups and populations without attention to local context, nor that a unidirectional flow of information (e.g., publishing a recommendation, trial, or guideline) is sufficient to achieve practice change.

Research Objectives

The proposed pragmatic trials or implementation research studies must meet the following criteria:

• The project must test an intervention, or coordinate several interventions (which can be treatments, preventive actions, or organizational changes) that are robust, apply broadly to pain patient populations and are suitable for use in multiple health systems, with the broad goal of determining whether the intervention(s) improves pain outcomes, and adds value to the utilization of the nation’s health care resources.
• The intervention(s) must be reasonably simple and not require a complex structure for implementation or monitoring. System level interventions may be particularly suitable.
• As in routine practice, the project must allow for interventions to be implemented with maximal flexibility and by all appropriate practitioners.
• The project must leverage opportunities made available through the health care systems and use outcomes that can be captured with passive follow-up by electronic health records, with minimal need for adjudication. Augmentation of the electronic health record is allowable for patient reported data and outcomes, although this should be streamlined and collected only at necessary time points.
• The project outcome measure(s) must be clinically meaningful and important to stakeholders including patients, providers, health care systems, and policy makers. Outcome measures must provide useful information to medical decision makers, whether patients, care providers, health care systems or payers.
• The project design must incorporate rigorous controls, prospectively identified, preferably by randomization.
• Proposed analytic plans for projects that proposed cluster-randomized trials must address adequacy of sample size and study power, and employ analytic strategies relevant for such pragmatic trial designs.
• The project must enroll patients based on broad eligibility criteria to maximize generalizability.

During the UG3 or planning phase activities will generally include, but are not limited to:

• 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 (pain severity, pain interference, and pain functioning, as well as others).
• Refine estimates, with guidance from NIH and the CCC, for sample size, numbers of sites, site to site heterogeneity, and implementation timetable.
• 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.
• 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.

Project Implementation Phase (UH3): The objective of the two-to-four-year UH3 implementation phase is to conduct the Trial in accordance with activities planned in the UG3 phase. Each project is expected to implement all aspects of the proposed pragmatic or implementation trial.

Utilization of milestones is a key characteristic of this initiative. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. Projects should include well-defined milestones for the planning phase (UG3) and annual milestones for the implementation phase (UH3).

Research Areas of Interest

Applicants should propose a pragmatic or implementation trial to address one or more critical research questions important for improved pain management within health care systems. For example:

• Studies to test the effect of system level innovations to improve implementation of established guidelines for nonopioid approaches to pain management and comorbid conditions;
• Assessment of the effectiveness of integrating evidence-based pain management strategies into health care delivery to reduce the transition from acute to chronic pain;
• Studies of implementation strategies to support the adoption and integration of effective pain management treatments, clinical procedures or guidelines into existing care systems;
• Studies to identify effective implementation strategies for integrating multiple evidence-based practices within community or clinical settings to meet the needs of pain patients and diverse systems of care;
• Studies testing the effectiveness and impact on utilization of health care services of implementation strategies to reduce health disparities and improve quality of pain management among rural, minority, low literacy and numeracy, and other underserved populations

Clinical Trials Not Supported by this initiative

The following types of clinical trials are not intended to be supported by this FOA and applications proposing such activities will be deemed non-responsive and returned without review:

• Phase I trials whether single or multi-site
• Single site trials
• Studies to understand the mechanism of the intervention
• Studies to assess initial feasibility of an intervention
• Drug or device safety trials

Funding Information

Estimated Total Funding $4,500,000 in FY2019
Expected Number of Awards 7
Estimated Award Ceiling $500,000 in direct costs
Primary CFDA Numbers 93.213, 93.393, 93.866, 93.865, 93.121

Anticipated Eligible Organizations

Inquiries

Please direct all inquiries to:

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