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

Details

Monday, June 7, 2021 2:00pm to 3:30pm

Virtual

Contact

Will M. Aklin, Ph.D.

Division of Therapeutics and Medical Consequences

aklinwm@mail.nih.gov

Meeting Summary

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

Research to develop and test DTx for stand-alone treatments or integrated with FDA-approved SUD treatments;
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

Sample Early Interaction progression shows pre-submission moving on to IDE or Marketing Submission

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:

Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
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;
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
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