Early Phase Pain Investigation Clinical Network (EPPIC-Net)

Early Phase Pain Investigation Clinical Network (EPPIC-Net)

Download the Preliminary Application Packet  (PDF, 3MB) *Updated application packet posted on February 25th, 2021. Please utilize the updated application form and instructions*

*Updated ROA published on February 25th, 2021. Please utilize this number when submitting preliminary applications*

Please Note: Preliminary applications are accepted at any time and reviewed on a rolling basis.

Detailed information regarding the EPPIC-Net application and review process is available below.

To learn more about the EPPIC-Net Program and how to apply and prepare and application, please view our March 2021 informational webinar. Here are informational slides from the webinar.

The NIH HEAL Initiative

The Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, is an aggressive, trans-NIH effort to speed scientific solutions to stem the national opioid public health crisis. Launched in April 2018, the initiative is focused on improving prevention and treatment strategies for opioid misuse and addiction, and enhancing pain management. For more information, visit: NIH HEAL Initiative.

A major goal of the HEAL Initiative is to spur the development of effective, non-addictive treatments to reduce the burden of illness due to pain and to reduce risk of addiction. Over the past 2 years, NIH has gathered input from experts from the U.S. Food and Drug Administration (FDA), academia, and the private sector to identify key gaps and opportunities for the development of new treatments for pain. Through these consultations, NIH identified the need for a sophisticated clinical trial network to design and execute innovative early phase trials of promising non-addictive pain therapies in well-characterized patient cohorts with pain conditions of high unmet need. The Early-Phase Pain Investigation Clinical Network (EPPIC-Net), led by the NINDS, seeks to fill this need by establishing a clinical trials network for highly meritorious assets for the treatment of pain.

Through EPPIC Net, NIH aims to: 

  • Provide academic and industry investigators with expert infrastructure and support for early-phase clinical testing of pain therapeutics across populations and the lifespan
  • Reduce reliance on opioids by accelerating early-phase clinical trials of non-addictive pain therapeutics, including drugs and devices

Studies in EPPIC-Net will:

  • Test new, non-addictive pain therapeutics in early-stage trials of drugs, biologics, and devices, focused on Phase 2 clinical trials
  • Provide proof-of-concept testing and validation of potential biomarkers for utility in assessing target engagement or pain outcomes
  • Develop and test innovative clinical trial paradigms to engineer adaptive, ever-improving early-phase testing of new pain therapies
  • Establish multiple well-characterized cohorts of different pain conditions for clinical trials

For assets submitted to EPPIC-Net, NIH will prioritize applications for:

  • Drugs or biologics with an existing IND or devices with an existing IDE
  • Drugs, biologics or devices with potential to treat pain conditions of high unmet need
  • Drugs, biologics or devices that have high potential to move to industry-funded phase 3 efficacy trials and into clinical use

The EPPIC-Net infrastructure

The EPPIC-Net Infrastructure, established through a competitive grant process, includes:

The Clinical Coordinating Center (CCC) provides protocol development, overall trial management, site and investigator training, and interface with IRB. The EPPIC-Net CCC is at the Massachusetts General Hospital.

The Data Coordinating Center (DCC) provides data management and analysis expertise and tools, quality assurance, and centralized data and biorepositories. The EPPIC-Net DCC is at the NYU Langone Health Center.

Clinical Research Sites (Hubs) provide clinical researchers with pain expertise, focused patient populations, and wide outreach into pain communities, and conduct the research procedures. EPPIC-Net has 12 research hubs.

View the EPPIC-Net Coordinating and Specialized Centers contact list

EPPIC-Net Application Process

The application and review process for EPPIC-Net has 3 stages.

1. Register in eRA Commons using ASSIST. The ROA number to be used in eRA Commons is #OTA-21-005  (PDF, 180KB)

2. Review the information in the Preliminary Application Packet :

3. Complete the brief EPPIC-Net Preliminary Application (PDF, 3MB).

4. Submit the preliminary application packet to EPPIC-Net via eRA Commons.


Following independent review, top-ranking applications will be selected to proceed to Stage 2.

Stage 2 invited applicants work with an NIH contractor to prepare a dossier with detailed information on the asset, including drug pharmacology or device specifications.

Stage 2 applicants will use ROA #OTA-20-002 (PDF, 300KB) to submit the dossier application.

Stage 2 applications will be reviewed on a rolling basis

Upcoming close dates for dossier application receipt:

Review Round 13: March 15, 2021

Review Round 14: May 1, 2021

Following further independent review, top-ranking applications will be selected to proceed to Stage 3.

The asset holder works with the EPPIC-Net CCC, in consultation with the EPPIC-Net DCC and appropriately-matched Clinical Research Sites to develop the clinical protocol. The CCC will become the applicant of record and submit the clinical protocol for a final independent review. Top-ranking protocols will be presented to the NINDS Council and HEAL Leadership, who will approve protocols for funding and study implementation within EPPIC-Net.

Stage 3 applicants will use ROA #OTA-20-008 (PDF, 458KB) to submit the clinical trial protocol application.


NIH promotes a process whereby applications submitted to the NIH are evaluated in a manner that is fair, equitable, timely, and free of bias. Independent, expert review  for EPPIC-Net applications is carried out by a Scientific Review Panel composed of federal and non-federal scientists with expertise in relevant scientific disciplines and current research areas.  The same Panel reviews EPPIC-Net applications at each stage (preliminary application, dossier application, protocol/OTA application), although a different subset of members may be present at each meeting.

Panel rosters are provided for information purposes only. Applicant investigators and institutional officials must not communicate directly with Panel members about an application before or after the review. Failure to observe this policy will create a serious breach of integrity in the review process, and may lead to sanctions, including withdrawal of the application.

View the EPPIC-Net OTA Review Committee Roster.


  • Stage 1 application is open to all; Stages 2 and 3 are by invitation only.
  • No funding is associated with application stages 1 and 2.
  • Successful asset applicants receive access to EPPIC-Net resources for conduct of the clinical trial for their asset. Asset applicants do not receive funding. Funding for selected clinical protocols is provided to the EPPIC-Net infrastructure components for conduct of the trial.
  • To learn more about the EPPIC-Net Program and how to apply and prepare and application, please view our March 2021 informational webinar. Here are informational slides from the webinar.
  • Intellectual property and products studied within EPPIC-Net remain the property of the asset owner