Related Announcements

PA-20-272 – Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

RFA-AG-19-005 - Collaborative Network to Advance Deprescribing Research for Older Adults with Multiple Chronic Conditions (R24 Clinical Trial Optional)

Issued by

National Center for Complementary and Integrative Health (NCCIH)

Purpose

This Notice of Special Interest (NOSI) announces the availability of an administrative supplement to support research projects solicited under the U.S. Deprescribing Research Network. Funds provided under this NOSI, therefore, are for the purpose of soliciting and supporting feasibility clinical trials using complementary and integrative health approaches to facilitate the deprescribing of benzodiazepines for individuals who wish to cease use of this medication or for individuals for whom harm of benzodiazepine use may outweigh benefits. It is expected funds from these administrative supplements will primarily support feasibility studies that will generate critical data for the planning and design of subsequent efficacy or effectiveness studies.

Background

Benzodiazepines are a class of psychiatric drugs approved to treat generalized anxiety disorder, insomnia, seizures, social phobia, and panic disorder. While benzodiazepines have been shown to have efficacy in treating these conditions, there are considerable risks associated with benzodiazepine use including abuse, misuse, and addiction, reflected in a recently updated FDA warning label requirement for benzodiazepines to alert the public and health professionals of these serious risks. Despite the risks, benzodiazepine use is on the rise. Between 1996 and 2013, the number of US adults who filled a benzodiazepine prescription rose 67 percent, and a 2018 study using a nationally representative sample showed that benzodiazepines are used by 12.5 percent of the US adult population. Benzodiazepine risks are particularly concerning for older adults, leading the American Geriatrics Society to include benzodiazepines on their Beers list of medications older adults should avoid, citing increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents.

The focus of this administrative supplement is to explore health approaches that would assist in the deprescribing of benzodiazepines. Research is needed in this area because even a short course of treatment lasting days can lead to strong physical dependence, making it difficult to stop taking the medication. Dose reduction or discontinuation can trigger withdrawal symptoms such as anxiety, cognitive difficulty, and suicidal thoughts. Consequently, the deprescribing of benzodiazepines often necessitates a protracted and gradual decrease in dose. No national guidelines exist for benzodiazepine deprescribing – its practice in healthcare is inconsistent and lacks an evidence base. Complementary and integrative interventions, such as cognitive behavioral therapy (CBT), which is a recommended first-line treatment for anxiety, have the potential to augment benzodiazepine treatment such that lower doses may be used and/or may help facilitate a benzodiazepine deprescribing program. Importantly, the data for CBT’s effectiveness in treating anxiety is stronger in older adults, a group that is particularly susceptible to benzodiazepine side effects. In addition to CBT there are promising data for other mind & body interventions including mindfulness meditation, yoga, acceptance and commitment therapy. Likewise, there is strong evidence indicating cannabidiol (CBD) can decrease anxiety, as well as promising data from other natural products such as chamomile, kava, and melatonin. Moreover, interventions such as insomnia-adapted CBT and mindfulness-based stress reduction are effective in improving sleep difficulties related to insomnia, another condition for which benzodiazepines are commonly prescribed.

Research Objectives

The U.S. Deprescribing Research Network (USDeN), which is funded by the National Institute on Aging, has the goal of developing and disseminating evidence about deprescribing in older adults to improve outcomes for these patients. The USDeN has a strong track record of soliciting and supporting pilot deprescribing trials in older adults. Thus, they are ideally suited to coordinate, solicit, support, and provide assistance to a new set of feasibility trials that focus on the deprescribing of benzodiazepines in older adults. NCCIH is particularly interested in supporting feasibility trials of complementary and integrative health approaches that may facilitate the deprescribing of benzodiazepines.

Feasibility trials should provide data that are critical for the planning and design of a subsequent clinical efficacy or effectiveness trial evaluating complementary and integrative approaches to facilitate benzodiazepine deprescribing. The data collected should be used to fill gaps in scientific knowledge necessary to develop a competitive full-scale clinical trial, including, but not limited to the following: examining feasibility and acceptability of interventions; adapting an intervention to a specific population; refining the intervention to determine the most appropriate frequency or duration; determining feasibility of recruitment, retention and data collection procedures; refining and assessing the feasibility of protocolized multimodal interventions; or examining acceptability and adherence of control conditions. This NOSI will not support randomized clinical trials that test or determine efficacy or effectiveness.

The following are examples of feasibility trials of interest:

• Assessment of acceptability and adherence to dose, frequency and/or duration of the intervention(s) in a benzodiazepine deprescribing program (e.g., tapering).
• Intervention refinement tailored to meet the unique needs of benzodiazepine deprescribing approaches.
• Iterative study refinement to address challenges with intervention fidelity, participant adherence, selection of appropriate outcomes, ability to capture outcome measures within designated time frames, and/or participant retention.
• Assessment of acceptability or feasibility of randomization or other aspects of trial design involving the use of benzodiazepine deprescribing with complementary and integrative interventions.

Goals of the work to be supported by the administrative supplement:

• Conduct outreach to the scientific community about the availability of feasibility trial funding
• Solicit, review, and prioritize feasibility trials that explore the use of complementary or integrative approaches to facilitate the deprescribing of benzodiazepines in older adults, when indicated
• Support 4-5 feasibility trials with budgets up to $200,000 total costs (includes Direct and Indirect costs)
• Integrate feasibility trial investigators into the USDeN cores and working groups

Application and Submission Information

Applications for this initiative must be submitted using the following opportunity or its subsequent reissued equivalent.

• PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

All instructions in the SF424 (R&R) Application Guide and PA-20-272 must be followed, with the following additions:

Eligible Individuals (Program Director/Principal Investigator)

Awardee/Applicant(s) must hold an active grant funded under RFA-AG-19-005. The project period for the parent award must be active, and cannot be in a no cost extension, for the 1 year of this administrative supplement project.

Budget

One U.S. Deprescribing Research Network Administrative Supplement will be awarded as a single year award with a maximum total cost of $900,000 to support multiple awards.

The administrative supplement request is permitted for 1 year of support only. The earliest anticipated start date is September 30, 2022.

Submitting Applications

• For administrative supplements to grants and cooperative agreements, requests must be submitted in accordance with the parent program announcement PA-20-272.
• Applicants should begin the supplement application abstract by stating “This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-AT-22-012.”
• Supplement requests should be submitted electronically.
• Administrative supplement applications to PA-20-272 must use the application form package with the Competition ID that contains “FORMS-F-ADMINSUPP”. In addition, the process for Streamlined Submissions using the eRA Commons cannot be used for this initiative.
• In order to facilitate efficient processing of the request applicants are strongly encouraged to notify Dr. Marcel Salive (marcel.salive@nih.gov) and Dr. Peter Murray (peter.murray@nih.gov) that a request has been submitted in response to this NOSI.
• Page Limits: Applications are limited to 12 pages.
• Due Date: All requests, regardless of the parent award funding mechanism, must be received by 5:00 PM local time on March 31, 2022, for possible funding in FY 2022.

Evaluation Process:

NIA and NCCIH will conduct administrative reviews of applications and will support the most meritorious applications submitted for consideration that can best support soliciting, reviewing, and supporting a set of feasibility clinical trials of complementary and integrative health approaches to support the deprescribing of benzodiazepines.

NOTE: For funding consideration, applicants must include “NOT-AT-22-012” (without quotation marks) in the Agency Routing Identifier field (box 4b) of the SF424 R&R form. Applications without this information in box 4b will not be considered for this initiative.

• Applications nonresponsive to terms of this NOSI willnot be considered for the NOSI initiative.
• Requests are limited to one year of support.
• Potential applicants are strongly encouraged to contact the NCCIH Program Officer to discuss responsiveness before submitting:

Inquiries

Please direct all inquiries to:

Peter Murray, Ph.D.

National Center for Complementary and Integrative Health (NCCIH)

(301) 496-4054

peter.murray@nih.gov