Pre-Application Information Webinar for PAR-21-183, "Developing Digital Therapeutics for Substance Use Disorders

United States

The National Institute on Drug Abuse (NIDA) hosted an informational webinar to provide information and respond to questions from prospective applicants who may be interested in submitting grant applications in response to the funding opportunity (NOFO) PAR-21-183 - Developing Digital Therapeutics for Substance Use Disorders (UG3/UH3 Clinical Trial optional) - Webinar Notice - https://grants.nih.gov/grants/guide/notice-files/NOT-DA-21-052.html

Presentations

Developing Digital Therapeutics for Substance Use Disorders -  Pre-Application Webinar

Participating Agencies

• FUNDING- National Institute on Drug Abuse (NIDA)
• ADVISORY- Food and Drug Administration (FDA)

Funding Opportunity Purpose

This funding opportunity seeks to support 

1. Research to develop and test DTx for stand-alone treatments or integrated with FDA-approved SUD treatments; 
2. Specific DTx indications: prevention of SUD initiation, medication adherence, treatment retention, treatment of withdrawal, abstinence, or reduction of relapse

Digital therapeutics are clinical-grade mobile, web, or other software-based platforms designed to deliver treatments for medical conditions or diseases

These therapeutic interventions do not include wellness apps or telehealth which provides remote access to a clinician

PAR-21-183 is a U-Mechanism Cooperative Agreement

• Cooperative agreements are similar to R-mechanism awards
• In addition to a Program Officer, a NIDA Science Officer is assigned
• Science Officers actively work with the grantee to support the research. For example, this may include providing input on study design, interacting with FDA, evaluation of results and meeting of milestones and go/no-go criteria

UG3/UH3 – What is a Phased Award? 

• The UG3/UH3 Cooperative Agreement involves 2 phases 
  • The UG3 phase, for up to 2 years, is designed to support a project with specific milestones and go/no-go criteria to be met by the end of the period 
  • The UH3 phase is to provide funding for up to 3 additional years following successful completion of the UG3 
• UG3 projects that meet their milestones and go/no-go criteria will be administratively considered by NIDA and prioritized for transition to the UH3 phase 
• Investigators submitting to this funding opportunity must address both UG3 and UH3 phases

UG3 Transition: Milestones and Go/No-Go Criteria

• Transition from the UG3 to UH3 phase is based on
  • Meeting milestones and go/no-go criteria
  • Programmatic priority
  • Available funds
• The milestones and go/no-go criteria must 
  • Include quantifiable measures
  • Be designed on what is needed to reach the next stage of development

Example Activities in the UG3 Phase

• Development of a finalized version of the DTx and validation in the study population;
• Evidence that the intervention effects efficacy related endpoints
  • For example: craving, dependence, days of abstinence, etc;
• Evidence the intervention effects behavioral endpoints as they relate to SUD
  • For example: measures of working memory, impulsivity, risk-taking propensity, distress tolerance, self-regulation, stress reactivity, etc;
• Evidence an adequate dose range/treatment duration for the DTx intervention(s) can be applied with acceptable safety, tolerability, adherence, etc;
• Evidence when integrated with an FDA-approved treatment, there is enhanced adherence, retention, efficacy or effects on other measures relevant to the approved treatment;
• Completion of a proof-of-concept, feasibility clinical trial;
• Q-submission to obtain FDA feedback on the regulatory pathway;
• Completion of IDE-enabling studies;
• Filing an IDE;
• Approval of an IDE or confirmation that an IDE is not required

UH3 Phase

• Funding for the UH3 phase is contingent on successfully meeting the milestones in the UG3 phase.
• The UH3 phase supports the next step in the development of the intervention and progression towards FDA authorization. 
• Applicants are expected to describe the entry and exit points of the proposed research in the development continuum. 
• The application should provide quantifiable milestones to determine success of the UH3.

Working with the FDA

• Investigators are strongly encouraged to contact the FDA Center for Devices and Radiological Health (CDRH) via the Pre-Submission process to discuss the proposed development pathway and clinical validation data requirements
• See FDA presentation (below)

Administrative Review by NIH Staff 

Submissions evaluated by NIH staff for:

• Completeness
  • Presence of both UG3 and UH3 phase
  • Presence of required application sections
  • Biosketch requirement (NOT-OD-21-073)
  • Clinical trial information (for clinical trial applications)
  • Adherence to NIH application policies (Appendix, Human Subjects, etc.)
• Funding opportunity requirements
  • Presence of milestone and timeline sections
  • Adherence to the prescribed direct budget cost for the UG3 phase (500k/yr.)
  • Duration of the UG3 phase (2 years. max)

Incomplete applications or applications not adhering to the funding opportunity requirements may be returned without review

Peer Review Panel

• Peer review of applications conducted at NIDA
• Special Emphasis Panel created by the SRO based on the areas of science described in the application
• Conflicts of interest are managed for all panel members
• At least three reviewers assigned to evaluate each application
• Panel will receive guidance from NIH staff on how to evaluate the application
• Panel members have at least 30 days to evaluate the application
• Meeting roster is publicly available 30 days before the meeting

Application Review Criteria – Section V of Funding Opportunity (NOFO)

Core Review Criteria

• Significance
• Investigators
• Innovation
• Approach
• Environment

Additional Review Criteria

• Study Timeline (for CT application)
• Protection of Human Subjects
• Inclusion of Women, Minorities, and Individuals Across the Lifespan
• Resubmission

Overall Impact

• Likelihood for the project to exert a sustained, powerful influence on the research field(s) involved

Additional Review Considerations

• Resource Sharing Plan
• Budget
• Foreign Organizations

Review Criterion Details

Significance

• Addresses an important problem or a critical barrier to progress in the field
• Rigor of prior research that serves as the key support for the proposed project
• Contribution to scientific knowledge, technical capability, and/or clinical practice

Investigators

• Experience, Expertise, Accomplishments, and Leadership plan
• Funding opportunity specific: Methodological and statistical expertise to evaluate digital intervention design, user engagement, and functional outcomes

Innovation

• Novelty of proposed project – concept, methodologies, intervention, invention, new application

Environment

• Institutional support, physical resources, collaborative arrangements
• Funding opportunity specific: Support for timely subject recruitment and completion of both phases

Approach

• Establishes feasibility, strategies for a robust and unbiased approach Addresses potential problems, alternative strategies, risk management, and benchmarks for success  Considers biological variables and protection of human subjects
• Funding opportunity specific:
  • Regulatory pathway & requirements for product approval 
  • Appropriateness and adequacy of milestones and go/no-go criteria
  • Quality of the proposed product design and preliminary data
  • Quality of measures proposed for user engagement/adherence, efficacy or behavioral endpoints 
  • Sufficiency of data to evaluate efficacy for reduced substance use or abstinence

Peer Review Outcome

• As part of the scientific peer review, all applications will receive a written critique (summary statement)
• Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score
• Summary statement will be available within 4-6 weeks after the peer review meeting

Award and Eligibility Information

• Award Information:
  • The funding opportunity will support New Applications
  • The funding opportunity is Clinical Trial Optional – accepting applications that either propose or do not propose clinical trials (as specified in the funding opportunity)
  • Application budgets are limited to $500,000 direct costs per year in UG3 phase
  • Unlimited budget in UH3 phase but must reflect actual needs of the proposal
  • The project period is limited to 2 years for the UG3 and 3 years for UH3 phases
• Eligibility:
  • Refer to the funding opportunity for specific information on eligible applicants, eligible individuals, required registrations, and other eligibility information

Key Dates for 2021 Submissions

• Letter of Intent Due Date:  July 2, 2021; November 6, 2021
• Application Due Date:   August 4, 2021; December 6, 2021
• AIDS Application Due Date:  Not applicable to this funding opportunity
• Scientific Merit Review:  November 2021; March 2022
• Advisory Council Review:  January 2022 ; May 2022
• Earliest Start Date:  April 2022; July 2022

Key Contacts

• Program Officials
  • Will M. Aklin, NIDA – aklinwm@mail.nih.gov
  • Kevin Walton, NIDA – kevin.walton@nih.gov 
• Review
  • Dharmendar Rathore, NIDA - dharmendar.rathore@nih.gov
• Grants Management
  • Pamela Fleming, NIDA – pfleming@mail.nih.gov

Interacting with FDA and considerations for Digital Therapeutics - Developing Digital Therapeutics for Substance Use Disorders

Outline

• FDA guidance documents
• Early interaction with FDA
• Investigational device exemptions and study risk determinations
• Points to consider for digital therapeutic device intended for SUD
• FDA/CDRH/OHT5 overview and organization

FDA Guidance Documents

• General Wellness Guidance Document
• Policy for Device Software Functions and Mobile Medical Applications
• Significant Risk/Non-Significant Risk Guidance Document
• FDA and Industry Procedures for Section 513(g) Requests for Information under the Federal Food, Drug, and Cosmetic Act
• “Software as a Medical Device (SAMD): Clinical Evaluation”
• Benefit Risk Guidance for IDE Submissions
• Benefit-Risk Guidance for Medical Device Premarket Approval and De Novo Classifications
• Benefit-Risk Guidance for 510(k) Submissions
• IDE Submission Information
• Design Considerations for Pivotal Clinical Investigations Guidance

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Q-Submissions

WHAT: an opportunity to obtain FDA feedback prior to IDE or marketing submission
WHAT YOU GET: Written feedback and an optional meeting
WHAT IT IS NOT: Pre-submissions are NOT intended for “pre-review” of data
The purpose of any discussion during the meeting is to clarify our feedback, not to respond in real-time to new information or proposals.

Guidance Document

• “Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff”

When is an IDE Needed?

• When a device is a significant risk device.
• 21 CFR 812.3(m) defines “Significant Risk” as and investigational device that:

1. Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
2. Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
3. Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or
4. Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

Study Risk Determinations

WHAT IT IS: an opportunity to obtain FDA feedback on whether your proposed study is a significant risk or non-significant risk study

WHAT YOU GET: Written letter outlining FDA’s determination of your proposed study as significant risk or non-significant risk

Guidance Document

• “Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors: Significant Risk and Nonsignificant Risk Medical Device Studies”

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www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm

Office of Health Technology 5 (OHT 5: Neurological and Physical Medicine Devices)
Office Director	Christopher Loftus, M.D. (Acting)	301-796-4377
Deputy Office Director	John Marler, M.D.	301-796-4221
Deputy Office Director	CAPT Nina Mezu-Nwaba	301-796-5494
Chief Medical Officer	Christopher Loftus, M.D.	301-796-4377
Associate Director	Vacant
Associate Director for Operations	Tonja Galberth	301-796-5959
Associate Director for Professional Development	Vacant
Safety Signal Manager	Sonja Sokic	240-402-3679

Division of Health Technology 5 A (Neurosurgical, Neurointerventional and Neurodiagnostic)
Division Director	Xiaolin Zheng, Ph.D.	301-796-2823
Assistant Director for Neurosurgical Devices	Adam Pierce	240-402-6128
Assistant Director for Neurointerventional Devices	Naira Muradyan	240-402-4098
Assistant Director for Neurodiagnostic Devices	Jay Gupta	301-796-2795

Division of Health Technology 5 B (Neuromodulation and Rehabilitation Devices)
Division Director	Vivek Pinto, Ph.D.	301-796-6610
Assistant Director for Neurostimulation-Neurology Devices	Patrick Antkowiak, Ph.D. (Acting)
Assistant Director for Neuromodulation-Psychiatry Devices	Pamela Scott	301-796-5433
Assistant Director for Acute Injury Devices	Heather Dean, Ph.D.	240-402-9874
Assistant Director for Neurodegenerative Devices	Amber Ballard, Ph.D.	240-402-9983

Point of Contact for General Submission Questions

DICE - Division of Industry and Consumer Education

EMAIL : DICE@fda.hhs.gov

Phone: 1(800) 638-2041 or (301) 796-7100
Press 1 to speak to the Consumer Team
Press 2 to speak to the Industry Team