2020-14998. Cancer Clinical Trial Eligibility Criteria: Minimum Age Considerations for Inclusion of Pediatric Patients; Guidance for Industry and Institutional Review Boards; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice of availability.

SUMMARY:

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry and institutional review boards (IRBs) entitled “Cancer Clinical Trial Eligibility Criteria: Minimum Age Considerations for Inclusion of Pediatric Patients.” This guidance is one in a series of guidances that provide recommendations regarding eligibility criteria for clinical trials of drugs or biological products regulated by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) for the treatment of cancer. Specifically, this guidance includes recommendations on the inclusion of pediatric patients (i.e., children and adolescents) in clinical trials for cancer treatments. This guidance finalizes the draft guidance entitled “Cancer Clinical Trial Eligibility Criteria: Minimum Age for Pediatric Patients” that published on March 13, 2019.

DATES:

The announcement of the guidance is published in the Federal Register on July 13, 2020.

ADDRESSES:

You may submit either electronic or written comments on Agency guidances at any time as follows:

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-2019-D-0358 for “Cancer Clinical Trial Eligibility Criteria: Minimum Age Considerations for Inclusion of Pediatric Patients.” Received comments 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.

You may submit comments on any guidance at any time (see 21 CFR 10.115(g)(5)).

Submit written requests for single copies of this 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 to the 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. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT:

Julia Beaver, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2100, Silver Spring, MD 20993-0002, 240-402-0489; or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry and IRBs entitled “Cancer Clinical Trial Eligibility Criteria: Minimum Age Considerations for Inclusion of Pediatric Patients.” This guidance provides recommendations on the inclusion of pediatric patients in clinical trials of drugs or biological products regulated by CDER and CBER for the treatment of cancer.

A clinical trial's eligibility criteria (for inclusion and exclusion) are essential components of the trial, defining the characteristics of the study population. Because there is variability in investigational drugs and trial objectives, eligibility criteria should be developed, taking into consideration the mechanism of action of the drug, the targeted disease or patient population, the anticipated safety of the investigational drug, the availability of adequate safety data, and the ability to recruit trial participants from the patient population to meet the objectives of the clinical trial. However, some eligibility criteria have become commonly accepted over time or used as a template across trials without clear scientific or clinical rationale. Unnecessarily restrictive eligibility criteria may slow patient accrual, limit patients' access to clinical trials, and lead to trial results that do not fully represent treatment effects in the patient population that will ultimately use the drug. Broadening cancer trial eligibility criteria can maximize the generalizability of trial results and the ability to understand the therapy's benefit-risk profile across the patient population likely to use the drug in clinical practice and should be considered to avoid jeopardizing patient safety. Early evaluation and development of potentially effective drugs, particularly targeted drugs, in pediatric patients may provide information on safe and effective use, therefore reducing risks associated with off label use, and accelerate the development of effective, innovative therapies for pediatric patients.

The guidance includes recommendations regarding minimum age eligibility criteria and addresses specific situations in which the inclusion of children (for the purposes of this guidance, ages 2 years to younger than 12 years) and adolescents (for the purposes of this guidance, ages 12 years to 17 years) is appropriate in cancer trials (i.e., based on disease biology and clinical course, molecular target of the investigational drug, and/or its molecular mechanism). In addition, the guidance includes ethical and regulatory considerations for including pediatric patients in such trials.

In the Federal Register of March 13, 2019 (84 FR 9130), FDA announced the availability of the draft guidance entitled “Cancer Clinical Trial Eligibility Criteria: Minimum Age for Pediatric Patients.” FDA received comments and considered those comments as the guidance was finalized. The final guidance recommends specific issues to discuss with FDA and provides additional recommendations for providing care in pediatric oncology trials. In addition, the final guidance includes additional information for clarification, for example regarding types of evidence that could support inclusion of children and dosing considerations in early phase trials.

This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the current thinking of FDA on “Cancer Clinical Trial Eligibility Criteria: Minimum Age Considerations for Inclusion of Pediatric Patients.” It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

This guidance refers to previously approved FDA collections of information. These collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). The collections of information in 21 CFR part 312 have been approved under OMB control number 0910-0014; the collections of information in 21 CFR 201.56 and 201.57 have been approved under OMB control number 0910-0572.

III. Electronic Access

Persons with access to the internet may obtain the guidance at either https://www.fda.gov/​drugs/​guidance-compliance-regulatory-information/​guidances-drugs,, https://www.fda.gov/​vaccines-blood-biologics/​guidance-compliance-regulatory-information-biologics/​biologics-guidances,, or https://www.regulations.gov.

Dated: July 7, 2020.

Lowell J. Schiller,

Principal Associate Commissioner for Policy.