August 4, 2023
- June 21, 2023 - Cooperative Agreement to Support an Evidence-Based Clinical Practice Guideline for the Management of Laparoscopic Abdominal Surgeries (U01) Clinical Trials Not Allowed. See NOFO RFA-FD-23-035.
FOOD AND DRUG ADMINISTRATION (FDA)
This Notice is to notify applicants that updates have been made in Part 2. Sections I, III, and IV for the RFA-FD-23-035 "Cooperative Agreement to Support an Evidence-Based Clinical Practice Guideline for the Management of Laparoscopic Abdominal Surgeries (U01) Clinical Trials Not Allowed"
Part 2. Full Text Announcement
Section I. Notice of Funding Opportunity Description
Background
FDA is working to confront the staggering human toll of the drug overdose crisis. Ensuring the availability of evidence-based, indication-specific prescribing information has always been part of FDA’s approach to ensuring the safe use of the products it regulates, including opioid analgesic products. However, the nation is facing a crisis: Millions of Americans are misusing and abusing opioids,[1] and in 2021 there were 16,706 reported deaths involving prescription opioids.[2] FDA’s goal is to reduce the opportunities for opioid misuse and abuse while ensuring that its actions are tailored to patient needs and promote adequate treatment of pain.
Recognizing the critical role that health care providers play in addressing this public health priority, and consistent with the goals of Section 3002 of the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (SUPPORT Act),[3] FDA is re-examining the evidence on the use of opioids in the treatment of acute pain with a goal of improving opioid prescribing. Acute pain usually occurs suddenly and has a known cause like an injury, surgery, or infection. Examples of acute pain could be pain that occurs following a tooth extraction, broken arm, or surgical procedure.[4] By decreasing unnecessary and/or inappropriate exposure to opioid analgesics through refinement of prescribing practices for acute pain, health care providers may reduce the rate of new opioid use disorders (OUDs) as well as opioid-involved overdose, accidental poisoning, and death. To do this, health care providers need the most current and comprehensive guidance on the safe management of acute pain.
Some people who develop an OUD are first exposed to opioid analgesics through a lawful prescription from a health care provider. While the number of opioid prescriptions dispensed and the number of opioid morphine milligram equivalents they contain have been on a steady decline for the last few years, concerns remain about opioid analgesic prescriptions for larger quantities than appropriate for the medical need being addressed. Patients commonly report having unused opioid tablets, pills, or capsules following surgical procedures.[5] Unused pills may be diverted to illicit markets or misused or abused by friends or family members — 45% of people who report misuse or abuse of prescription pain relievers obtained the most recently misused drugs from a friend or relative.[6] In addition, patients who are prescribed more medication than necessary themselves have increased opportunities for misuse and abuse — 43% of people who report misuse or abuse of prescription pain relievers obtained their most recently misused drugs through their own prescription.[7]
The variation in opioid prescribing (including over-prescribing) for surgical and medical conditions suggests that guidelines for acute pain management for these conditions would be beneficial for health care providers, their patients, and public health. One approach to setting such standards would be to establish evidence-based clinical practice guidelines (CPGs) for opioids for acute pain management.
NASEM Consensus Study Report
To address the need for a more consistent approach to the development of CPGs, in August 2018, FDA awarded a contract to the National Academies of Sciences, Engineering, and Medicine (NASEM) to help advance the development of evidence-based guidelines for appropriate opioid analgesic prescribing for acute pain resulting from specific conditions or procedures where such guidelines do not exist. The primary scope of NASEM’s work was to (1) gain an understanding of what evidence is needed to ensure that all current and future clinical practice guidelines for treating acute pain with opioid analgesics are evidenced-based to inform prescribing, (2) determine what research is needed to generate that evidence in a practical and feasible manner, and (3) recommend 10 clinical therapeutic areas (surgical procedures or medical conditions) for which either no prescribing guidelines for treating acute pain exist or for which evidence to support existing clinical practice guidelines for opioid analgesic prescribing is lacking.
As part of this work, NASEM scanned the landscape of existing opioid analgesic prescribing guidelines, examined how they were developed, identified any gaps in evidence for those guidelines, and outlined the research needed to generate the evidence to fill the gaps. Additionally, NASEM held a series of meetings and public workshops to engage a broad range of stakeholders, including the Centers for Disease Control and Prevention (CDC), which contributed expert knowledge on existing guidelines and on emerging evidence, or specific policy issues, related to the development and availability of opioid analgesic prescribing guidelines based on their specialties. In December 2019, NASEM published its findings in the report, Framing Opioid Prescribing Guidelines for Acute Pain: Developing the Evidence.[8]
According to the consensus study report, NASEM identified laparoscopic abdominal surgeries (e.g., appendectomy, bariatric surgery, cholecystectomy, colectomy, hysterectomy, and prostatectomy) as a priority area for evidence-based guideline development because of the prevalence of laparoscopic abdominal surgeries, the prevalence of opioid prescribing, and the evidence of over-prescribing.
The NASEM report further recommended that organizations developing evidence-based CPGs on opioid prescribing for acute pain establish a process for disseminating, implementing, and monitoring the uptake and impacts of the CPG on opioid prescribing practices.
Research Objective
FDA seeks to stimulate development of evidence-based CPGs for acute pain conditions where such guidelines don’t exist. The Agency proposes a multi-year, multi-phase project to fund an evidence-based CPG for the management of postoperative pain after diagnostic and procedural laparoscopic abdominal surgeries. This process draws on previous guideline development efforts on the treatment of dental pain (surgical and non-surgical), treatment of postoperative pain in obstetric patients who have undergone surgeries, and safe tapering of benzodiazepines.
This funding opportunity announcement invites researchers to submit applications for the development, implementation, dissemination, and evaluation of an evidence-based CPG for the management of postoperative pain after diagnostic and procedural laparoscopic abdominal surgeries that advances safe prescribing of opioid analgesics. FDA believes a successful project might best be approached in a phased manner. In the description below FDA provides an example of an approach that could address development, implementation, and evaluation of such a potential project. This is not the only approach that could be pursued, but it provides one model for consideration by applicants.
Project Example
The project is divided into three phases:
- Phase 1: Development of the Evidence-Based Clinical Practice Guideline for the Management of Postoperative Pain After Diagnostic and Procedural Laparoscopic Abdominal Surgeries
- Phase 2: Implementation and Dissemination of the CPG
- Phase 3: Evaluation/Assessment of the CPG
Upon completion of Phase 1, the applicant works with FDA to initiate the dissemination and implementation plan (Phase 2). The effectiveness of CPGs in improving the quality of health care depends on the degree to which health care providers are aware of the guidelines and alter practice behavior to incorporate the guidelines.
After adoption of the guideline, the applicant plans to conduct an evaluation of the guideline (Phase 3) to assess the impact on prescribing practices and outcomes and ensure the guideline is applied in the manner for which it was intended.
Applicant Approach
Phase 1: Development of the Evidence-Based Clinical Practice Guideline for the Management of Postoperative Pain After Diagnostic and Procedural Laparoscopic Abdominal Surgeries
Activities may include, but are not limited to:
- Establishing a guideline development team with the expertise and experience to achieve the goals of this FOA. Such a team would ideally have existing strong relationships with experts in the field including but not limited to primary care practitioners, medical specialists, surgical specialists, allied care practitioners, and other health care providers, as well as methodologists, epidemiologists, and statisticians. The team should include the perspectives of patients/patient advocates, health care systems, electronic health record developers, and payers. Diverse expertise, experience, and geographic locations are desirable.
- Considering the recommendations outlined in the NASEM report, including the analytic framework and evidence evaluation framework.[9]
- Establishing the scope of the guideline and setting. Ideally, the guideline will cover the management of postoperative pain after diagnostic and procedural laparoscopic abdominal surgeries. Ideally, the CPG would state the patient populations to which the CPG is applicable (e.g., adults versus children) and those subpopulations for whom the CPG recommendations may need to be modified, such as patients with comorbidities, prior opioid exposure, or opioid use disorder. Ideally, the guideline would define the contextual aspects of prescribing, such as setting, prescriber type, and prior treatments.
- Considering the appropriate use and dosing of opioids for the indication as well as the optimal opioid prescribing strategies based on a review of existing evidence. Ideally, the CPG would explicitly state the role of opioid alternatives, such as acetaminophen, and the role of opioids in the context of non-opioid pharmacologic and non-pharmacologic alternatives.
- Describing the role of patient education and shared decision-making in the guideline. Ideally, the CPG would integrate patient education on pain management to help align patients’ expectations about pain control with opioid prescribing practices, and the applicant would identify shared decision-making as a key component of patient-centered health care. Shared decision-making is defined as a process in which clinicians and patients work together to make decisions and select tests, treatment, and care plans based on clinical evidence that balances risks and expected outcomes with patient preferences and values.[10]
- Considering how to decrease opioid prescribing without compromising patient pain management.
- Considering evidence from published literature or other sources on patient-reported amount of opioids used after surgical procedures (including observational studies), where such articles or evidence are available, that may inform recommendations for initial prescribing amounts.
- Providing a plan to address considerations for potential sociodemographic disparities, health equity issues, and special populations (e.g., geriatric and pediatric patients) in pain management.
- Providing a plan to provide guidelines where evidence doesn’t exist or may be outdated.
FDA understands that there are several evidence gaps in the realm of prescribing opioids. Discussing the general challenge of gaps in evidence, the NASEM report states the following:
Several strategies are used by CPG developers to address these challenges. To facilitate greater individualization of therapy, CPGs can explicitly consider patient, setting, clinician, and other factors that affect response to therapy, to the extent possible. When evidence is lacking with which to guide individualization of therapy for certain subgroups (e.g., patients with history of opioid use disorder), CPGs can acknowledge the evidence gaps and indicate situations in which deviation from recommendations may be warranted.[11]
Phase 2: Implementation and Dissemination of the CPG
Activities may include, but are not limited to:
- Proposing an implementation and dissemination plan for adoption of the guideline by specialty societies, health care providers, health systems, and payers. Applicant may identify innovative strategies to promote guideline uptake (e.g., health care provider education, chair-side educational tools, clinical decision support tools) and approaches that leverage existing health information technology or electronic health record systems.
- Proposing an implementation and dissemination plan (including a notification to FDA) of any related publications or events.
- High-level evaluation plan
- Impact of the CPG on prescribing practices
- Presence of unintended negative consequences for patients and/or providers
- Suggestions for broader adoption and improved implementation of the CPG
- Prescriber feedback
- Suggestions for updating the CPG based on opioid dosing, monitoring, and assessment
- CPG revision plan to accommodate newly available evidence and analysis findings
- Lessons learned
Identifying outcomes of interest, which may include but are not limited to:
- Adoption metrics of CPG by:
- Prescriber specialty
- Healthcare setting (e.g., urban/rural, academic center, hospital, urgent care/emergency department, inpatient/outpatient, primary care/specialist, telehealth)
- Patient populations (e.g., pediatric/adolescent/adult/geriatric, different demographics, different body mass index groups, underserved areas)
- Barriers impacting implementation (e.g., workflow/system limitations, insurance coverage, lack of flexibility)
- Impact of CPG on prescriber preferences
- Feedback on pain management with use of CPG (patient and prescriber)
- Phase 1: Development of the Evidence-Based Clinical Practice Guideline for the Management of Postoperative Pain After Diagnostic and Procedural Laparoscopic Abdominal Surgeries
- Phase 2: Implementation and Dissemination of the CPG
- Phase 3: Evaluation/Assessment of the CPG
References
[1] Substance Abuse and Mental Health Services Administration. (2022). Key substance use and mental health indicators in the United States: Results from the 2021 National Survey on Drug Use and Health (HHS Publication No. PEP22-07-01-005, NSDUH Series H-57). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/report/2021-nsduh-annual-national-report. Accessed May 2023.
[2] National Institute on Drug Abuse. (2023). Drug overdose death rates. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates. Accessed May 2023.
[3] Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (SUPPORT Act). https://www.congress.gov/bill/115th-congress/house-bill/6/text. Accessed May 2023.
[4] Centers for Disease Control and Prevention (2020). Opioids for acute pain: What you need to know. https://www.cdc.gov/drugoverdose/pdf/patients/Opioids-for-Acute-Pain-a.pdf. Accessed May 2023.
[5] Bicket MC et al. (2017). Prescription opioid analgesics commonly unused after surgery: A systematic review. JAMA Surg. 2017;152(11):1066-1071.
[6] Substance Abuse and Mental Health Services Administration. (2022). Key substance use and mental health indicators in the United States: Results from the 2021 National Survey on Drug Use and Health (HHS Publication No. PEP22-07-01-005, NSDUH Series H-57). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/report/2021-nsduh-annual-national-report. Accessed May 2023.
[7] Ibid.
[8] National Academies of Sciences, Engineering, and Medicine (2020). Framing opioid prescribing guidelines for acute pain: Developing the evidence. https://www.nap.edu/catalog/25555/framing-opioid-prescribing-guidelines-for-acute-pain-developing-the-evidence. Accessed May 2023.
[9] Ibid.
[10] HealthIT.gov: National Learning Consortium (2013). Shared decision making. https://www.healthit.gov/sites/default/files/nlc_shared_decision_making_fact_sheet.pdf. Accessed May 2023.
[11] National Academies of Sciences, Engineering, and Medicine (2020). Framing opioid prescribing guidelines for acute pain: Developing the evidence. https://www.nap.edu/catalog/25555/framing-opioid-prescribing-guidelines-for-acute-pain-developing-the-evidence. Accessed May 2023.
See Section VIII. Other Information for award authorities and regulations.
Section III. Elgibility Information
- Elgible Applicants
Eligible Organizations
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for FDA support as Public or Private Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Governments
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
- U.S. Territory or Possession
Other
- Independent School Districts
- Public Housing Authorities/Indian Housing Authorities
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Faith-based or Community-based Organizations
- Regional Organizations
Foreign Institutions
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.
Foreign components, as defined in the HHS Grants Policy Statement, are not allowed.
Section IV. Application and Submission Information
Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:
For this specific FOA, the Research Strategy section is limited to 12 pages.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy: All applicants must specifically address the ability to achieve the following objectives in the cooperative agreement in the Research Strategy:
- Demonstrate the ability to develop, disseminate, implement, and evaluate an evidence-based Clinical Practice Guideline (CPG) for the management of postoperative pain after diagnostic and procedural laparoscopic abdominal surgeries.
- Demonstrate the ability to systematically collect, review, and summarize evidence, as well as strategically address gaps in evidence during guideline development.
- Work in collaboration with FDA to support and advance safe prescribing of opioid analgesics for patients following diagnostic and procedural laparoscopic abdominal surgeries.
- Demonstrate technical expertise in clinical practice guideline development and clinical expertise in the fields involved with postoperative pain after diagnostic and procedural laparoscopic abdominal surgeries is treated (e.g., primary care, medical specialties, surgical specialties, and allied care).
- Demonstrate the ability to establish collaborations with and include the perspectives of health care providers who treat postoperative pain after diagnostic and procedural laparoscopic abdominal surgeries; patients/patient advocates; health care systems; electronic health record developers; payers; and other relevant stakeholders throughout the course of the project.
- Demonstrate the ability to establish an adequate administrative and scientific infrastructure to implement all phases of this project under this collaborative effort.
- Identify and/or hire sufficient qualified personnel to conduct the necessary research and project-manage all related activities, including review of project milestones for degree of completion, preparation/reporting of project findings, periodic and final reports, all for approval by FDA, and for subsequent distribution in the public domain.
- In conjunction with FDA, develop plans for the conduct of identified project activities.
- Identify and/or build, and effectively leverage, databases and other facilities and/or resources for the conduct of identified project activities.
- Upon completion of the project, propose related studies/projects, if needed, to build on the findings of the project and continue to leverage established resources and personnel.
- In collaboration with FDA, develop needed training, workshops, and/or educational materials.
Kimberly Pendleton
Office of Acquisitions & Grants Services (OAGS)
Food and Drug Administration
Telephone: 240-402-7610
Email: Kimberly.Pendleton@fda.hhs.gov
and Human Services (HHS)
