Title 42

SECTION 11.48

11.48 What constitutes clinical trial results information

§ 11.48 What constitutes clinical trial results information?

(a) For each applicable clinical trial, other than a pediatric postmarket surveillance of a device product that is not a clinical trial, for which clinical trial results information must be submitted under § 11.42, the responsible party must provide the following:

(1) Participant flow. Information for completing a table documenting the progress of human subjects through a clinical trial, by arm, including the number who started and completed the clinical trial. This information must include the following elements:

(i) Participant Flow Arm Information. A brief description of each arm used for describing the flow of human subjects through the clinical trial, including a descriptive title used to identify each arm;

(ii) Pre-assignment Information. A description of significant events in the clinical trial that occur after enrollment and prior to assignment of human subjects to an arm, if any; and

(iii) Participant Data. The number of human subjects that started and completed the clinical trial, by arm. If assignment is based on a unit other than participants, also include a description of the unit of assignment and the number of units that started and completed the clinical trial, by arm.

(2) Demographic and baseline characteristics. Information for completing a table of demographic and baseline measures and data collected by arm or comparison group and for the entire population of human subjects who participated in the clinical trial. This information must include the following elements:

(i) Baseline Characteristics Arm/Group Information. A brief description of each arm or comparison group used for describing the demographic and baseline characteristics of the human subjects in the clinical trial, including a descriptive title used to identify each arm or comparison group.

(ii) Baseline Analysis Population Information - (A) Overall Number of Baseline Participants. The total number of human subjects for whom baseline characteristics were measured, by arm or comparison group and overall.

(B) Overall Number of Units Analyzed. If the analysis is based on a unit other than participants, a description of the unit of analysis and the number of units for which baseline measures were measured and analyzed, by arm or comparison group and overall.

(C) Analysis Population Description. If the Overall Number of Baseline Participants (or units) differs from the number of human subjects (or units) assigned to the arm or comparison group and overall, a brief description of the reason(s) for the difference.

(iii) Baseline Measure Information. A description of each baseline or demographic characteristic measured in the clinical trial, including age, sex/gender, race, ethnicity (if collected under the protocol), and any other measure(s) that were assessed at baseline and are used in the analysis of the primary outcome measure(s) in accordance with § 11.48(a)(3). The description of each measure must include the following elements:

(A) Name and description of the measure, including any categories that are used to submit Baseline Measure Data.

(B) Measure Type and Measure of Dispersion: For each baseline measure submitted, an indication of the type of data to be submitted and the associated measure of dispersion.

(iv) Baseline Measure Data. The value(s) for each submitted baseline measure, by arm or comparison group and for the entire population of human subjects for whom baseline characteristics were measured.

(v) Number of baseline participants (and units), by arm or comparison group and overall, if different from the Overall Number of Baseline Participants or Overall Number of Units Analyzed in § 11.48(a)(2)(ii)(A) and (B), respectively.

(3) Outcomes and statistical analyses. Information for completing a table of data for each primary and secondary outcome measure by arm or comparison group, including the result(s) of scientifically appropriate statistical analyses that were performed on the outcome measure data, if any. This information must include the following elements:

(i) Outcome Measure Arm/Group Information. A brief description of each arm or comparison group used for submitting an outcome measure for the clinical trial, including a descriptive title to identify each arm or comparison group.

(ii) Analysis Population Information - (A) Number of Participants Analyzed. The number of human subjects for whom an outcome was measured and analyzed, by arm or comparison group.

(B) Number of Units Analyzed. If the analysis is based on a unit other than participants, a description of the unit of analysis and the number of units for which an outcome was measured and analyzed, by arm or comparison group.

(C) Analysis Population Description. If the Number of Participants Analyzed or Number of Units Analyzed differs from the number of human subjects or units assigned to the arm or comparison group, a brief description of the reason(s) for the difference.

(iii) Outcome Measure Information. A description of each outcome measure, to include the following elements:

(A) Name of the specific outcome measure, including the titles of any categories in which Outcome Measure Data in § 11.48(a)(3)(iv) are aggregated.

(B) Description of the metric used to characterize the specific outcome measure.

(D) Outcome Measure Type. The type of outcome measure, whether primary, secondary, other pre-specified, or post-hoc.

(E) Measure Type and Measure of Dispersion or Precision. For each outcome measure for which data are collected, the type of data submitted and the measure of dispersion or precision.

(F) Unit of Measure. For each outcome measure for which data are collected, the unit of measure.

(iv) Outcome Measure Data. The measurement value(s) for each outcome measure for which data are collected, by arm or comparison group and by category (if specified).

(v) Statistical Analyses. Result(s) of scientifically appropriate tests of the statistical significance of the primary and secondary outcome measures, if any.

(A) A statistical analysis is required to be submitted if it is:

(1) Pre-specified in the protocol and/or statistical analysis plan and was performed on the outcome measure data,

(2) Made public by the sponsor or responsible party prior to the date on which clinical trial results information is submitted for the primary outcome measures(s) studied in the clinical trial to which the statistical analysis applies, or

(3) Conducted on a primary outcome measure in response to a request made by FDA prior to the date on which clinical trial results information is submitted for the primary outcome measure(s) studied in the clinical trial to which the statistical analysis applies.

(B) Information for each statistical analysis specified in paragraph (a)(3)(v)(A) of this section must include the following elements:

(1) Statistical Analysis Overview: Identification of the arms or comparison groups compared in the statistical analysis; the type of statistical test conducted; and, for a non-inferiority or equivalence test, a description of the analysis that includes, at minimum, the power calculation and non-inferiority or equivalence margin.

(2) One of the following, as applicable:

(i) Statistical Test of Hypothesis: The p-value and the procedure used for the statistical analysis; or

(ii) Method of Estimation: The estimation parameter, estimated value, and confidence interval (if calculated).

(4) Adverse event information. (i) Information to describe the methods for collecting adverse events during an applicable clinical trial:

(A) Time Frame. The specific period of time over which adverse event information was collected and for which information is submitted in paragraph (a)(4)(iii) of this section.

(B) Adverse Event Reporting Description. If the adverse event information collected in the clinical trial is collected based on a different definition of adverse event and/or serious adverse event than defined in this part, a brief description of how those definitions differ.

(C) Collection Approach. The type of approach taken to collect adverse event information, whether systematic or non-systematic.

(ii) Information for completing three tables summarizing anticipated and unanticipated adverse events collected during an applicable clinical trial:

(A) Table of all serious adverse events grouped by organ system, with the number and frequency of each event by arm or comparison group;

(B) Table of all adverse events, other than serious adverse events, that exceed a frequency of 5 percent within any arm of the clinical trial, grouped by organ system, with the number and frequency of each event by arm or comparison group; and

(iii) Information for each table specified in paragraph (a)(4)(ii) of this section must include the following elements, unless otherwise specified:

(A) Adverse Event Arm/Group Information. A brief description of each arm or comparison group used for submitting adverse event information from the clinical trial, including a descriptive title used to identify each arm or comparison group.

(B) Total Number Affected. The overall number of human subjects affected, by arm or comparison group, by:

(1) Serious adverse event(s);

(2) Adverse event(s) other than serious adverse events that exceed a frequency of 5 percent within any arm of the clinical trial; and

(3) Deaths due to any cause.

(C) Total Number at Risk. The overall number of human subjects included in the assessment, by arm or comparison group, for:

(1) Serious adverse events;

(2) Adverse event(s) other than serious adverse events that exceed a frequency of 5 percent within any arm of the clinical trial; or

(3) Deaths due to any cause.

(D) Adverse Event Information. For the two tables described in paragraphs (a)(4)(ii)(A) and (B) of this section, a description of each type of serious adverse event and other adverse event that is not a serious adverse event and exceeds a frequency of 5 percent within any arm of the clinical trial, consisting of the following attributes:

(1) Descriptive term for the adverse event; and

(2) Organ system associated with the adverse event.

(E) Adverse Event Data. For the two tables described in paragraphs (a)(4)(ii)(A) and (B) of this section and for each adverse event listed in accordance with paragraph (a)(4)(iii)(D) of this section:

(1) Number of human subjects affected by such adverse event.

(2) Number of human subjects at risk for such adverse event.

(5) Protocol and statistical analysis plan. A copy of the protocol and the statistical analysis plan (if not included in the protocol), including all amendments that have been approved by a human subjects protection review board (if applicable) before the time of submission under this subsection and that apply to all clinical trial Facility Locations. The responsible party must include the Official Title (as defined in § 11.10(b)(2)), NCT number (as defined in § 11.10(a)) (if available), and date of the protocol and the statistical analysis plan on the cover page of each document. The responsible party may redact names, addresses, and other personally identifiable information, as well as any trade secret and/or confidential commercial information (as those terms are defined in the Freedom of Information Act (5 U.S.C. 552) and the Trade Secrets Act (18 U.S.C. 1905)) contained in the protocol or statistical analysis plan prior to submission, unless such information is otherwise required to be submitted under this part. The protocol and statistical analysis plan must be submitted in a common electronic document format specified at https://prsinfo.clinicaltrials.gov.

(6) Administrative information - (i) Results Point of Contact. Point of contact for scientific information about the clinical trial results information, including the following:

(A) Name or official title of the point of contact

(B) Name of the affiliated organization, and

(ii) Certain Agreements. An indication of whether the principal investigator is an employee of the sponsor and, if not, whether there exists any agreement (other than an agreement solely to comply with applicable provisions of law protecting the privacy of human subjects participating in the clinical trial) between the sponsor or its agent and the principal investigator that restricts in any manner the ability of the principal investigator, after the primary completion date of the clinical trial, to discuss the results of the clinical trial at a scientific meeting or any other public or private forum or to publish in a scientific or academic journal information concerning the results of the clinical trial

(7) Additional clinical trial results information for applicable device clinical trials of unapproved or uncleared device products. (i) For an applicable device clinical trial of an unapproved or uncleared device product and for which clinical trial registration information has not been posted publicly on Clinical Trials.gov by the Director in accordance with § 11.35(b)(2)(i), the responsible party must provide the following data elements, as the data elements are defined in § 11.10(b): Brief Title; Official Title; Brief Summary; Primary Purpose; Study Design; Study Type; Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study; Intervention Name(s); Other Intervention Name(s); Intervention Description; Intervention Type; Device Product Not Approved or Cleared by U.S. FDA, if any studied intervention is a device product; Study Start Date; Primary Completion Date; Study Completion Date, Enrollment; Primary Outcome Measure Information; Secondary Outcome Measure Information; Eligibility Criteria; Sex/Gender; Age Limits; Accepts Healthy Volunteers; Overall Recruitment Status; Why Study Stopped; Name of the Sponsor; Responsible Party, by Official Title; Facility Name and Facility Location, for each participating facility in a clinical trial; Unique Protocol Identification Number; Secondary ID; Human Subjects Protection Review Board Status; and Record Verification Date.

(ii) The responsible party shall submit all the results information specified in paragraph (a)(7)(i) and must submit an affirmation that any information previously submitted to ClinicalTrials.gov for the data elements listed in paragraph (a)(7)(i) of this section have been updated in accordance with § 11.64(a) and are to be included as clinical trial results information.

(b) Pediatric postmarket surveillance of a device product that is not a clinical trial. For each pediatric postmarket surveillance of a device product that is not a clinical trial, the responsible party must submit a copy of any final report that is submitted to FDA as specified in 21 CFR 822.38. The responsible party may redact names, addresses, and other personally identifiable information or commercial confidential information contained in the final report prior to submission to NIH, unless such information is otherwise required to be submitted under this part. The final report must be in a common electronic document format specified at https://prsinfo.clinicaltrials.gov.