NIDCD Cooperative Agreement for Clinical Trials in Communication Disorders (U01 - Clinical Trial Required) PAR-25-343

NIDCD Cooperative Agreement for Clinical Trials in Communication Disorders (U01 - Clinical Trial Required) PAR-25-343 is sponsored by National Institute on Deafness and Other Communication Disorders (NIDCD). This opportunity supports mission-aligned projects and measurable outcomes.

PAR-25-343: NIDCD Cooperative Agreement for Clinical Trials in Communication Disorders (U01 - Clinical Trial Required) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute on Deafness and Other Communication Disorders ( NIDCD ) Funding Opportunity Title NIDCD Cooperative Agreement for Clinical Trials in Communication Disorders (U01 - Clinical Trial Required) U01 Research Project – Cooperative Agreements Notices of Special Interest associated with this funding opportunity March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility. Assistance Listing Number(s) Funding Opportunity Purpose The NIDCD is committed to identifying effective interventions for the treatment or prevention of communication disorders by supporting well-designed and well-executed clinical trials.

This funding opportunity supports a cooperative agreement between an NIDCD Project Scientist and an Investigator to support a clinical trial that meets ANY of the following criteria: requires FDA oversight, is intended to formally establish efficacy, or has potentially higher risks to participants.

Clinical trial applications exceeding the annual direct costs of $700,000 or more, in certain cases, may also be a criterion for this funding opportunity. These investigator-initiated clinical trials are perceived to benefit from close interaction, oversight, and guidance resulting from a cooperative agreement. Only one clinical trial may be proposed per application submitted to this funding opportunity.

Funding Opportunity Goal(s) To investigate solutions to problems directly relevant to individuals with deafness or disorders of human communication in the areas of hearing, balance, smell, taste, voice, speech, and language.

The National Institute on Deafness and Other Communication Disorders (NIDCD) supports research and research training, including investigation into the etiology, pathology, detection, treatment, and prevention of disorders of hearing and other communication processes, primarily through the support of basic and applied research in anatomy, audiology, biochemistry, bioengineering, epidemiology, genetics, immunology, microbiology, molecular biology, the neurosciences, otolaryngology, psychology, pharmacology, physiology, psychophysics, speech-language pathology, and other scientific disciplines.

The NIDCD supports: (1) Research into the evaluation of techniques and devices used in diagnosis, treatment, rehabilitation, and prevention of disorders of hearing and other communication processes; (2) research into prevention and early detection and diagnosis of hearing loss and speech, voice, and language disorders and research into preventing the effects of such disorders by means of appropriate referral and rehabilitation; (3) research into the detection, treatment, and prevention of disorders of hearing and other communication processes in the elderly population and its rehabilitation to ensure continued effective communication skills; and (4) research to expand knowledge of the effects of environmental agents that influence hearing or other communication processes.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description The purpose of this funding opportunity is to encourage cooperative agreement applications to the National Institute on Deafness and Other Communications Disorders (NIDCD) for investigator initiated clinical trials in communication disorders (hearing, balance, taste, smell, voice, speech and language) with the goal of advancing interventions into standard clinical care through well-designed and well-implemented clinical trials.

The NIH defines a clinical trial as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

This funding opportunity is specifically intended for clinical trials that meet ANY of the following criteria: Requires FDA oversight such as those requiring Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications Have higher risks to participate for example: Involve a non-routine intervention Involve utilization of unlicensed product/device Involve utilization of a licensed product/device for an unapproved indication Pivotal clinical trials such as NIH defined Phase III Clinical Trial: An NIH-defined Phase III clinical trial is a broadly based prospective Phase III clinical investigation, usually involving several hundred or more human subjects, for the purpose of evaluating an experimental intervention in comparison with a standard or controlled intervention or comparing two or more existing treatments.

Often the aim of such investigation is to provide evidence leading to a scientific basis for consideration of a change in health policy or standard of care. The definition includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials are also included.

Clinical trial applications exceeding the annual direct costs of $700,000 or more, in certain cases, may also be a criterion for this funding opportunity. Only one clinical trial may be proposed per application. Each NIDCD U01 Clinical Trial award will support a single clinical trial.

. Applications that include more than one clinical trial or other non-clinical trial studies will not be supported by this NOFO. Drug, biologic, or device interventions require applicants to provide documentation from the FDA (see Section 4.

5 of PHS Human Subjects and Clinical Trials Information).

Clinical trials that do not involve FDA oversight, are not intended to formally establish efficacy (may inform subsequent studies but not aimed or sufficiently powered to directly change health policy or standard of care) and where the risks are no more than the potential risks encountered in routine medical care or procedures are encouraged to apply to the Parent R01 Clinical Trial Required NOFO.

Investigators are strongly encouraged to contact Dr. Trinh Ly, prior to submission, to ensure this is the correct NOFO for their proposed research. Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. 2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO. Required: Only accepting applications that propose clinical trial(s).

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are not limited but need to reflect the actual needs of the proposed project.

The scope of the proposed project should determine the project period. The maximum project period is 5 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession 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 Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. Funds to perform the human subjects research component of the clinical trial will be provided to the award recipient and used by the award recipient on a capitation basis ( https://grants.

nih. gov/grants/guide/notice-files/NOT-OD-18-222. html ) in accordance with budgets approved by NIDCD.

Describe the amount and rationale in the Budget Justification section. All instructions in the How to Apply-Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions: If you answered “Yes” to the question “Are Human Subjects Involved?

” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the How to Apply- Application Guide must be followed.

Section 2 - Study Population Characteristics Include the following additional information: 2. 4 Inclusion of Women and Minorities Applications in response to this funding opportunity must include a plan to conduct analyses to evaluate differences which may impact the intervention outcome(s) among sex subgroups within the “Inclusion of Women and Minorities” attachment, as applicable.

When there are no prior studies strongly supporting significant differences among the sex subgroups, an exploratory subgroup analysis may be appropriate. 2. 5 Recruitment and Retention Plan Applications in response to this funding opportunity must propose innovative and proactive recruitment strategies for involving appropriate populations as applicable and justified by the scientific goals.

In addition to stating the demographic breakdown of the geographic area in which the science will be conducted and describing the planned distribution of subjects by sex, race, and ethnicity, a recruitment plan focused specifically on engaging appropriate populations must be included.

The recruitment plan should include: an outline of operational measures that will be implemented to ensure robust clinical trial participation a description of outreach, enrollment and retention strategies to reduce identified barriers and sustain the engagement of relevant participants.

a detailed plan to increase community engagement that: describes community partners and how they will be collaboratively engaged in the research project (e.g., activities, frequency and duration of involvement) justifies how the planned partners and their level of involvement are relevant and will enhance the research project Basic elements of the study timeline must also include a Milestones Plan.

Applications must include a series of milestones for completion of the clinical trial and provide contingency plans should there be delays in attaining them. The milestones will undergo peer review and will be incorporated into the terms of award. Applicants are required to provide detailed project performance and timeline objectives.

This plan must include a timeline for the following general milestones, as applicable; Completion of regulatory approvals Enrollment of the first subject; Enrollment of 25%, 50%, 75% and 100% of the projected recruitment time period for all study subjects, including women, minorities and children (as appropriate); Scheduled interim analyses Completion of data collection time period; Completion of primary endpoint and secondary endpoint data analyses time period; Posting of primary outcome results in registry Completion of final study report; and Detailed protocol-specific performance milestones and timeline; These milestones will be negotiated at the time of the award, if appropriate.

Section 3 - Protection and Monitoring Plans 3. 1 Protection of Human Subjects Include the following additional information: 3. 1.

1. b Study Procedures, Materials and Potential Risks For risks identified from all sources and where feasible note the expected frequency, severity, and duration of the risk(s). 3.

1. 3 Potential Benefits of the Proposed Research to Research Participants and Others State the problem or question (e.g., describe the population, disease, current standard of care, if one exists, and limitations of knowledge or available therapy) and the reason for conducting the clinical trial.

Provide a discussion of studies that led to the proposed clinical trial and information or data from preliminary studies which address the need for, safety and the feasibility of the trial as well as evidence of the potential efficacy for each proposed intervention including, A summary of findings from nonclinical in vitro or in vivo studies that have potential clinical significance and justify the safe administration of the intervention into humans A summary of relevant clinical research and any history of human use or exposure to the study intervention, including use in other countries, and clinical pharmacology studies Pertinent results for preliminary studies which justify the specific intervention dose selection, and administration method and schedule.

For a Phase III/pivotal clinical trial application, provide a summary of studies that led to the proposed clinical trial and data from Phase I and II clinical trials including trails including summaries of evidence for the potential safety and efficacy for each proposed intervention, dose selected and administration schedule.

Discussion of important literature and data that are relevant to the trial and that provide background for the trial Applicable clinical, epidemiological, or public health background or context of the clinical trial Importance of the clinical trial and any relevant treatment issues or controversies 3.

3 Data and Safety Monitoring Plan The Data and Safety Monitoring Plan (DSMP) must address the following areas: Where the monitoring will occur; How site(s)/center(s), and participating facilities (labs, pharmacies) will be monitored.

Also address the appropriate oversight over the conduct of the trial, including at a minimum the appropriate clinical monitoring independent of the study team, safety monitoring, regulatory submissions and compliance and quality management.

Provide a data management plan addressing the following areas: (1) database system to be employed, (2) compliance with federal regulations, (3) security and emergency back-up, and (4) quality assurance and quality control of data from clinical sites and laboratories, as appropriate. Applications that lack the DSMP are incomplete and will not be reviewed. 3.

5. Overall Structure of the Study Team An overview of the organizational structure including an organizational chart and details of the operations of the Study Chair, Clinical Coordinating Center, Data Coordinating Center, and Clinical Centers if applicable. The Clinical or Operational Coordinating Center and the Data Coordinating Center may be the same organization in some circumstances.

The study team should include: A Clinical Operational Coordinating Center that provides overall project management and coordination for the clinical trial to ensure completion of pre-implementation requirements and enrollment meet timeline goals; data quality and integrity; conformance to implementing the Manual of Procedures (MOP); quality assurance and control; safety monitoring and reporting Statistical support through the complete life cycle of the clinical trial including protocol development & study design, statistical analysis, and preparation of data/progress/safety monitoring reports & publications.

It is expected that a statistician will be included as key personnel Clinical Centers that are responsible for implementing the protocol, recruiting patients, providing the intervention/prevention required, conducting patient follow up, and submitting clinical trial data Data management support (including a Data Coordinating Center for multi-site clinical trials) design and implementation of data forms, data entry accuracy and timeliness, data management, data quality assurance and control, and data storage/repository.

It is expected that a data manager will be included as key personnel. Central resource centers such as a central laboratory, pharmacy or radiographic center, if appropriate. Section 4 - Protocol Synopsis 4.

1.

a Detailed Description: In addition to providing a narrative description of the protocol and statistical methods as instructed for the PHS Human Subjects and Clinical Trials Information form, this section must also include: A clear definition of the protocol hypothesis Justification and support for selection of primary endpoint(s) as the most appropriate to inform future studies and to advance the intervention into clinical practice including clinical relevance, acceptance by regulatory authorities (e.g., FDA) and clinical community (e.g., compared with gold standard), validity, and reliability of the measurement.

For surveys and questionnaires, note for what populations the instrument was previously validated and specifically if the instrument was previously validated for the target study population Include the following additional information within the narrative study description: Identify each study group(s)/arm(s) including dose/duration of intervention for each, total number of participants and number of participants in each group/arm If applicable, describe the rationale for the type and selection of control (e.g., placebo, active drug, dose-response, historical).

Discuss known or potential problems associated with the control group chosen in light of the specific disease and intervention(s) being studied Provide a justification for the route of administration, planned maximum dosage, and dosing regimen, including starting dose, of the study intervention(s) and control product(s) A description of the type/design of trial to be conducted (e.g., randomized, placebo-controlled, double-blinded, parallel design, open-label, dose escalation, dose-ranging, adaptive, cluster randomized, group sequential, multi-regional, superiority or non-inferiority design) A description of methods to be used to minimize bias Provide the plan for blinding and randomization (if applicable) Provide the plan for interim analysis If applicable, include halting or stopping rules If applicable, include an interim futility analysis with stopping rules to stop the trial if it is determined the trial is unable to achieve it's objective (e.g., statistical significance unlikely to be achieved) If stratification(s) is included, identify the stratification planned (e.g., sex, race/ethnicity, age, dose) Provide the following information for drug, biologic and device interventions Name (brand name and generic if applicable) For devices, device support duration, expiration and battery life if applicable 4.

3.

Statistical Design and Power In addition to the information requested in the PHS Human Subjects and Clinical Trials Information Instructions, provide detail on: Justification on the selection of the primary outcome and corresponding primary endpoint (measurement and window of observation), including Acceptance by regulatory authorities (e.g., FDA) and clinical community Effect size that is clinically meaningful The sample size determination including information needed to validate your calculations and judge the feasibility of enrolling and following the necessary number of participants.

In particular, specify all of the following: Outcome measure used for Calculations Test statistic Null and alternative Hypotheses Type I error rate (alpha) Power level (e.g., 80% power) Assumed event rate for dichotomous outcome (or mean and variance of continuous outcome) for each study arm, justified and referenced by historical data as much as possible.

Also, provide information to support the clinical relevance of the selected effect size Statistical method used to calculate the sample size, with a reference for it and for any software utilized Anticipated impact of dropout rates, withdrawal, cross-over to other study arms, missing data, etc. on study power Method for adjusting calculations for planned interim analyses, if any Discuss whether the sample size provides sufficient power for addressing secondary endpoints or exploratory analyses 4.

5 Will the study use an FDA-regulated intervention? In addition to the information requested in the PHS Human Subjects and Clinical Trials Information Instructions, if the intervention is a drug, biologic, or device, applicants must provide documentation from the FDA providing information on one of the following scenarios: Format: Attach this information as a PDF file. The filename "FDA Documentation.

pdf" should be used. See NIH’s Format Attachments page. Applications that lack this document are incomplete and will not be reviewed.

The protocol has been submitted under an open IND and the IND is not under full or partial hold. Under this scenario, applicants must provide documentation such as a "may proceed" email or letter from the FDA. The protocol has been submitted as an original IDE or as a new study under an open IDE, and FDA has fully approved the IDE or IDE supplement.

Under this scenario, applicants must provide documentation of an IDE or IDE supplement full approval letter from the FDA. The IDE or IDE supplement is required to be specific for the clinical trial protocol proposed (e.g., design, sample size, population, device model, etc.) and correspond with the FDA approval. Collation of multiple IDE supplement approvals for different components of the protocol is not adequate.

The protocol has been submitted under an IND and is on full or partial hold. Under this scenario applicants must provide full documentation from the FDA on the reasons for hold and the FDA recommendations. Applicants should discuss how they intend to address the hold issues and when they believe they will have FDA approval to proceed with trial implementation.

The protocol has been submitted as an original IDE or as a new study under an open IDE, and FDA has conditionally approved the IDE or IDE supplement. Under this scenario applicants must provide full documentation from the FDA on the conditions of approval. Applicants should discuss how they intend to address these conditions and when they believe they will have FDA approval to proceed with trial implementation.

The protocol is exempt from an IND. Under this scenario applicants must provide a copy of the exemption letter from the FDA. The protocol is either exempt from the IDE regulations or does not require IDE approval because it is determined to be nonsignificant risk.

Under this scenario applicants must provide either an IDE exemption letter or a copy of the risk determination letter from the FDA or IRB. NIDCD may request specifically for risk determination documentation from the FDA. Note: Do not include the IND/IDE application, manufacturer’s product specifications, study protocol, or protocol amendments in this attachment Section 5 - Other Clinical Trial-related Attachments 5.

1 Other Clinical Trial-related Attachments For this clinical trial Funding Opportunity, the following document must be submitted as an "Other Clinical Trial-related Attachment". Applications that lack these documents are incomplete and will not be reviewed. Trial Management Plan : ONLY for multi-site clinical trials.

A description of how the proposed trial will be managed must be provided as an attachment using the filename "Trial Management Plan. pdf" and may not exceed 5 pages. Describe the strategy that will be used throughout the project to ensure that management activities of the clinical trial are met including directly supporting the needs