Agency Information Collection Activities; Proposals, Submissions, and Approvals: Diversity Action Plans for Clinical Studies

Agency Information Collection Activities; Proposed Collection; Comment Request; Diversity Action Plans for Clinical Studies

Dates

Either electronic or written comments on the collection of information must be submitted by September 20, 2024.

Electronic Submissions

Submit electronic comments in the following way:

• Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov.

• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see "Written/Paper Submissions" and "Instructions").

Written/Paper Submissions

Submit written/paper submissions as follows:

• Mail/Hand Delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in "Instructions."

Instructions: All submissions received must include the Docket No. FDA-2024-N-1298 for "Diversity Action Plans To Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies." Received comments, those filed in a timely manner (see ADDRESSES ), will be placed in the docket and, except for those submitted as "Confidential Submissions," publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.

• Confidential Submissions-To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states "THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION." The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as "confidential." Any information marked as "confidential" will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the "Search" box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.

Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002; or Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002; or Office of the Center Director, Guidance and Policy Development, Center for Devices and Radiological Health, 10903 New Hampshire Ave., Bldg. 66, Rm. 5431, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.

Supplementary Information

Under the PRA (44 U.S.C. 3501-3521), Federal Agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. "Collection of information" is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 60-day notice in the Federal Register concerning each proposed collection of information before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing this notice of the proposed collections of information as set forth in the draft guidance for industry "Diversity Action Plans To Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies."

With respect to the following collection of information, FDA invites comments on these topics: (1) whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology.

Diversity Action Plans (DAPs) for Clinical Studies

OMB Control No. 0910-NEW

This information collection supports the implementation of sections 3601 and 3602 of the Food and Drug Omnibus Reform Act of 2022 (FDORA) included as part of the Consolidated Appropriations Act, 2023 (Pub. L. 117-328). In the Federal Register of June 28, 2024 (89 FR 54010), FDA announced the availability of a draft guidance for industry entitled "Diversity Action Plans To Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies," as required under FDORA. The guidance is available from our website at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-action-plans-improve-enrollment-participants-underrepresented-populations-clinical-studies. Statutory requirements in sections 505(z) and 520(g) of the FD & C Act (21 U.S.C. 355(z) and 360j(g)) are discussed in the draft guidance document, including the content of a DAP (guidance Section V), applicable timelines (guidance Section VI), procedures for submitting a DAP and receiving feedback (guidance Section VII), and requesting a DAP waiver (guidance Section VIII).

A DAP must include the sponsor's goals for enrollment in the clinical study disaggregated by race, ethnicity, sex, and age group of clinically relevant study populations, the sponsor's rationale for those goals, including sufficient information and analysis to explain how the goals were determined, and an explanation of how the sponsor intends to meet such goals. The appropriate submission for a medical product type (investigational new drug application (IND) for drugs and biological products, and investigational device exemptions (IDE), premarket notification (510(k)), premarket approval application (PMA), and de novo classification request (De Novo) for devices) should include a cover letter identifying the submission as a DAP and whether the DAP submission is for an initial or a revised plan.

DAP Waiver Requests should be submitted with a cover letter identifying the submission as a Diversity Action Plan-Waiver request. The waiver request should also identify the submission number, applicable clinical study name or identification number, and a justification for the waiver request, including relevant data and information. DAP submission and waiver requests should be submitted electronically.

DAP submissions and waiver requests are processed through FDA's Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), and Center for Devices and Radiological Health (CDRH) according to product type.

We estimate the burden of this collection of information as follows:

We are expanding the scope of our currently approved collection inventory to acknowledge the establishment of DAP requirements under FDORA and to account for burden that may be attendant to the submission of a DAP or for requesting a waiver. As explained in the draft guidance document Section VII (Procedures for Submitting the Diversity Action Plan and Receiving Feedback), the submission process will vary depending on the medical product type.

As reflected in table 1, we estimate a one-time burden of 728 hours and 728 responses, cumulatively, with regard to reviewing the guidance and to any necessary adjustment respondents may need to make in complying with applicable requirements.

As reflected in table 2, we assume recurring activities to include the preparation, submission, and retention of information consistent with statutory requirements and discussed in the draft guidance and, therefore, estimate an annual recordkeeping burden of 738 responses and 43,688 hours, including the submission of DAPs and waiver requests to FDA. We discuss these revisions and adjustments with regard to drugs and devices, respectively.

A. Section 505(z)(1) of the FD & C Act (21 U.S.C. 355(z)(1))-Drugs and Biological Products

Regulations establishing procedures and requirements governing clinical investigations for investigational new drugs and biological products are found in part 312 (21 CFR part 312). Specifically, regulations in part 312, subpart D, establish responsibilities for sponsors and investigators of new drugs, including requirements applicable to the investigational plans. Relatedly, regulations in 21 CFR 312.2(e) and 312.145 provide for the issuance of Agency guidance to assist respondents who must comply with part 312 and other requirements applicable to the clinical investigation of new drugs and biological products. The intent of the current draft guidance is to increase enrollment of participants who are members of historically underrepresented populations in clinical studies to help improve the strength and generalizability of the evidence for the intended use population. We have developed and issued other guidance documents also intended to enhance the representativeness of clinical trial populations and to improve enrollment of participants from underrepresented populations in clinical trials. ⁽¹⁾

As outlined in Section VII of the guidance, DAPs for drug and biological products must be submitted to the IND under which the applicable clinical study is to be conducted and, for applicable submissions, must be submitted in eCTD format through FDA's Electronic Submissions Gateways (ESG and ESG-NextGen). Based on our experience with current IND submissions, we estimate receipt of 240 DAPs annually, for FDA's drug and biological product programs. We assume an average of 100 hours are necessary to prepare and submit a DAP.

As noted in Section VIII of the guidance, the appropriateness of a DAP waiver is case-specific and depends on factors relevant to a specific development program. Sponsors should submit their DAP waiver requests electronically to the applicable IND for consideration by FDA. We estimate receipt of 5 waiver requests annually for CDER and CBER combined and estimate that each waiver request would require 16 hours to prepare and submit.

Related information collection activities are currently approved under OMB control number 0910-0014. We intend to revise the scope of the information collection to account for DAP submissions and waiver requests and to adjust our estimated burden for the activities in the relevant information collection after evaluating DAP submissions received.

B. Section 520(g)(9) of the FD & C Act (21 U.S.C. 360j(g))-Devices

Regulations that govern the clinical investigation of medical devices are found in part 812 (21 CFR part 812) (investigational device exemptions (IDE)), where regulations in subpart B set forth content elements, and 21 CFR 812.20 specifically requires the submission of an investigational plan. Consistent with Section VII of the draft guidance, a DAP submission should be accompanied by a cover letter and submitted as part of the IDE application for clinical studies of significant risk devices, or for device studies that require development of a Diversity Action Plan but do not require an IDE (see Section III of the guidance), the DAP must be submitted as part of a 510(k), PMA, or De Novo. Currently, CDRH maintains dedicated IT systems intended to facilitate the uniform submission of information by respondents (CDRH Customer Collaboration Portal, https://www.fda.gov/medical-devices/industry-medical-devices/send-and-track-medical-device-premarket-submissions-online-cdrh-portal ). Although electronic submission is not mandatory for all device submissions, most forms are completed and submitted electronically.

In estimating the burden per response for a DAP submitted to CDRH, we considered the differences in requirements for the specific development programs ( i.e., IDE, IND, PMA, De Novo, and 510(k)) and the content and number of clinical studies that may be included in a submission. The burden to submit a DAP for a device may vary to the extent that submitters have already considered the enrollment of participants from underrepresented populations, as recommended in existing guidance documents related to improving clinical studies. ⁽²⁾ We assume a range of 16 to 40 hours is necessary to prepare and submit a DAP to CDRH. Based on our experience with current submissions, we estimate 488 DAP submissions annually.

Similarly, requests for waivers from any requirement in part 812 are provided for in § 812.10, and requests for waivers from applicable requirements under § 812.28(a)(1) and (b) are provided for in § 812.28(c). As discussed in Section VIII of the draft guidance, requests to waive the requirement to submit a DAP should be submitted electronically as a stand-alone submission for consideration by FDA. Further, the appropriateness of a waiver is case-specific and depends on factors relevant to a specific development program. We assume a range of 8 to 16 hours is necessary to prepare and submit a DAP waiver, and we assume 5 DAP waiver requests annually.

Under section 520(g)(9)(A)(ii) of the FD & C Act, the sponsor of a device for which submission of an application for an IDE is not required must develop a diversity action plan for any clinical study with respect to the device, except for a device being studied as described in § 812.2(c). Such diversity action plan must be submitted in any 510(k), De Novo, or PMA for such device. Regulations that govern 510(k), De Novo, and PMA are found in 21 CFR parts 807 subpart E, 860 subpart D, and 814 subparts A through E, respectively. Related information collection activities are currently approved under OMB control numbers 0910-0078 (IDE), 0910-0231 (PMA), 0910-0844 (De Novo), and 0910-0120 (510(k)), respectively. We intend to revise the scope of the information collections to account for DAP submissions and waiver requests. We will adjust our estimated burden in these information collections after evaluating the DAP submissions we receive.

The draft guidance also refers to previously approved FDA collections of information. The collections of information in 21 CFR part 314 relating to new drug marketing applications have been approved under OMB control number 0910-0001. The collections of information in 21 CFR part 601 relating to biological product development and marketing applications have been approved under OMB control number 0910-0338. The collections of information pertaining to submission of a biologics license application under section 351(k) of the Public Health Service Act (42 U.S.C. 262(k)) have been approved under OMB control number 0910-0718. The collections of information in 21 CFR part 50 for protection of human subjects have been approved under OMB control number 0910-0130. The collections of information pertaining to the Q-Submission program for medical devices have been approved under OMB control number 0910-0756.

⁽¹⁾  "Enhancing the Diversity of Clinical Trial Populations-Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry," available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enhancing-diversity-clinical-trial-populations-eligibility-criteria-enrollment-practices-and-trial.

⁽²⁾  See e.g., "Evaluation and Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device Clinical Studies," https://www.fda.gov/regulatory-information/search-fda-guidance-documents/evaluation-and-reporting-age-race-and-ethnicity-specific-data-medical-device-clinical-studies, and "Evaluation of Sex-Specific Data in Medical Device Clinical Studies," https://www.fda.gov/regulatory-information/search-fda-guidance-documents/evaluation-sex-specific-data-medical-device-clinical-studies-guidance-industry-and-food-and-drug.