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 December 17th, 2021. Please utilize the updated application form and instructions*
*Updated ROA published on December 17th, 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. Potential applicants can also view the informational slides from the webinar.  Potential applicants are strongly encouraged to talk to EPPIC-Net staff before applying.

Additional information and answers to common questions can be found in the Frequently Asked Questions document. 

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. As part of the NIH HEAL InitiativeSM , 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, Phase 2 clinical trial development and conduct for pain therapeutic development 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) to provide 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) to provide 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.

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

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-22-002  (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.


Through review, highly-assessed applications are 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 use ROA #OTA-20-002 (PDF, 300KB) to submit the dossier application.

Stage 2 applications are reviewed on a rolling basis

Upcoming close dates for dossier application receipt:

November 23, 2021

More to be announced

Through review, highly-assessed applications are selected to proceed to Stage 3.

The asset holder/applicant works with the EPPIC-Net CCC, in consultation with the EPPIC-Net DCC and appropriately-matched Specialized Clinical Centers to develop the clinical protocol. The CCC will become the applicant of record and submit the clinical protocol for final review. Protocols selected through review are presented to the NINDS Council and HEAL Leadership, who approve protocols for funding and study implementation within EPPIC-Net.

Asset holders must review and indicatie their understanding of the terms and conditions for use of EPPIC-Net outlined in the "EPPIC-Net Asset Owner Acknowledgement" prior to movement to protocol development. A written agreement between the CCC and the asset holder, defining the relationship, will also be put in place.

The CCC uses 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.

Independent/objective review at each stage is followed by administrative review by NINDS for fit with the EPPIC-Net and NIH HEAL InitiativeSM  mission.


  • 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 development and  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.
  • Intellectual property and products studied within EPPIC-Net remain the property of the asset owner
  • Data Ownership: The data generated through partcipation in EPPIC-Net are owned by the EPPIC-Net Clinical Research Site or entity that generated it.
  • Data Sharng: The Other Transactions award recipient (the CCC for EPPIC-Net clinical trials) and ther collaborators must and will comply with all NIH and HEAL Initiative Data Sharing polices established during the project period. These policies are outlined on the NIH websites:
  • To learn more about the EPPIC-Net Program and how to prepare the preliminary application, please view our March 2021 informational webinar. Potential applicants can also view the informational slides from the webinar (PDF, 2.5 MB).
  • Potential Applicants are strongly encouraged to talk to EPPIC-Net staff prior to application.