Pt. 11 purchase of any covered outpatient drug. (2) A covered entity that is a free- standing cancer hospital cannot use a GPO to purchase orphan drugs when they are transferred, prescribed, sold, or otherwise used for an indication other than the rare condition or dis- ease for which that orphan drug was designated under section 526 of the FFDCA. (3) A covered entity that is a free- standing cancer hospital may use a GPO for purchasing orphan drugs when orphan drugs are transferred, pre- scribed, sold, or otherwise used for the rare disease or condition for which it was designated under section 526 of the FFDCA. (4) If a covered entity that is a free- standing cancer hospital chooses to use a GPO for purchasing an orphan drug used for a rare disease or condition for which it is designated, it is required to maintain auditable records that dem- onstrate full compliance with the or- phan drug purchasing requirements and limitations. A free-standing cancer hospital covered entity that cannot or does not wish to maintain auditable records sufficient to demonstrate com- pliance, must notify HRSA and pur- chase all orphan drugs outside of the 340B Program, regardless of indication for which the drug is used, and is not permitted to use a GPO to purchase those drugs. Once a free-standing can- cer hospital is enrolled in 340B, it may change its decision to purchase all or- phan drugs outside of the 340B Program on a quarterly basis by notifying HRSA. This documentation will be made public. This information will also be verified during the annual recertifi- cation process. (e) Identification of orphan drugs. Des- ignations under section 526 of the FFDCA are the responsibility of and administered by the FDA. Only covered outpatient drugs that match the list- ing and sponsor of the orphan designa- tion are considered orphan drugs for purposes of this section. HRSA will publish on its public Web site FDA’s section 526 list of drugs that will gov- ern the next quarter’s purchases. (f) Failure to comply. Failure to com- ply with this section shall be consid- 42 CFR Ch. I (10–1–16 Edition) ered a violation of sections 340B(a)(5) and 340B(e) of the PHSA, as applicable. PART 11—CLINICAL TRIALS REG- ISTRATION AND RESULTS INFOR- MATION SUBMISSION (Eff. 1-18- 17) Subpart A—General Provisions Sec. 11.2 What is the purpose of this part? 11.4 To whom does this part apply? 11.6 What are the requirements for the sub- mission of truthful information? 11.8 In what format must clinical trial in- formation be submitted? 11.10 What definitions apply to this part? Subpart B—Registration 11.20 Who must submit clinical trial reg- istration information? 11.22 Which applicable clinical trials must be registered? 11.24 When must clinical trial registration information be submitted? 11.28 What constitutes clinical trial reg- istration information? 11.35 By when will the NIH Director post clinical trial registration information submitted under § 11.28? Subpart C—Results Information Submission 11.40 Who must submit clinical trial results information? 11.42 For which applicable clinical trials must clinical trial results information be submitted? 11.44 When must clinical trial results infor- mation be submitted for applicable clin- ical trials subject to § 11.42? 11.48 What constitutes clinical trial results information? 11.52 By when will the NIH Director post submitted clinical trial results informa- tion? 11.54 What are the procedures for requesting a waiver of the requirements for clinical trial results information submission? Subpart D—Additional Submission of Clinical Trial Information 11.60 What requirements apply to the vol- untary submission of clinical trial infor- mation for clinical trials of FDA-regu- lated drug products (including biological products) and device products? 11.62 What requirements apply to applicable clinical trials for which submission of clinical trial information has been deter- mined by the Director to be necessary to protect the public health? 130 Public Health Service, HHS § 11.4 11.64 When must clinical trial information submitted to ClinicalTrials.gov be updated or corrected? Subpart E—Potential Legal Consequences of Non-Compliance 11.66 What are potential legal consequences of not complying with the requirements of this part? AUTHORITY: 42 U.S.C. 282(i); 42 U.S.C. 282(j); 5 U.S.C. 301; 42 U.S.C. 286(a); 42 U.S.C. 241(a); 42 U.S.C. 216(b). SOURCE: 81 FR 65138, Sept. 21, 2016, unless otherwise noted. EFFECTIVE DATE NOTE: At 81 FR 65138, Sept. 21, 2016, Part 11 was added, effective Jan. 18, 2017. Subpart A—General Provisions § 11.2 What is the purpose of this part? This part implements section 402(j) of the Public Health Service Act (42 U.S.C. 282(j)) by providing require- ments and procedures for the submis- sion of clinical trial information for certain applicable clinical trials and other clinical trials to the Director of the National Institutes of Health (NIH) to be made publicly available via ClinicalTrials.gov, the Internet-acces- sible clinical trial registry and results data bank established by the National Library of Medicine (NLM) at https:// clinicaltrials.gov. § 11.4 To whom does this part apply? (a) This part applies to the respon- sible party for an applicable clinical trial that is required to be registered under § 11.22, a clinical trial for which clinical trial registration information or clinical trial results information is submitted voluntarily in accordance with § 11.60, or an applicable clinical trial that is required by the Director to have clinical trial information sub- mitted to protect the public health under § 11.62. (b) The responsible party must com- municate the identity and contact in- formation of the responsible party to the Director by submitting the Respon- sible Party, by Official Title and Re- sponsible Party Contact Information data elements under § 11.28(a)(2)(iii)(B) and (a)(2)(iv)(F) as part of the clinical trial information submitted at the time of registration. Changes must be communicated to the Director by up- dating information in accordance with § 11.64(a). (c) Determination of responsible party. For purposes of this part, each applica- ble clinical trial or other clinical trial must have one responsible party. With respect to a clinical trial, the sponsor of the clinical trial will be considered the responsible party unless and until a principal investigator has been des- ignated the responsible party, in ac- cordance with paragraph (c)(2) of this section. With respect to a pediatric postmarket surveillance of a device product that is not a clinical trial, the responsible party is the entity that the U.S. Food and Drug Adminstration (FDA), under section 522 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 3601), orders to conduct the pedi- atric postmarket surveillance of a de- vice product. (1) Determination of sponsor. For pur- poses of this part, each applicable clin- ical trial or other clinical trial must have one sponsor. (i) When an applicable clinical trial or other clinical trial is conducted under an investigational new drug ap- plication (IND) or investigational de- vice exemption (IDE), the IND or IDE holder will be considered the sponsor. (ii) When an applicable clinical trial or other clinical trial is not conducted under an IND or IDE, the single person or entity who initiates the trial, by preparing and/or planning the trial, and who has authority and control over the trial, will be considered the spon- sor. (2) Designation of a principal investi- gator as the responsible party. (i) The sponsor may designate a prin- cipal investigator as the responsible party if such principal investigator meets all of the following require- ments: (A) Is responsible for conducting the trial; (B) Has access to and control over the data from the trial; (C) Has the right to publish the re- sults of the trial; and (D) Has the ability to meet all of the requirements for submitting and up- dating clinical trial information as specified in this part. 131 § 11.6 (ii) With regard to an applicable clin- ical trial or other clinical trial, a des- ignation by the sponsor under para- graph (c)(2)(i) of this section shall con- sist of the sponsor obtaining from the principal investigator an acknowledg- ment of the principal investigator’s re- sponsibilities under this part as respon- sible party, and the principal investi- gator acknowledging the designation as responsible party to the Director in the format specified at https:// prsinfo.clinicaltrials.gov. (3) Withdra al of the designation of a principal investigator as the responsible party. In the event that a principal investi- gator who has been designated the re- sponsible party no longer meets or is no longer able to meet all the require- ments for being so designated under paragraph (c)(2)(i) of this section, the sponsor must withdraw the designation in the format specified at https:// prsinfo.clinicaltrials.gov, at which time the sponsor will be considered the re- sponsible party unless and until the sponsor makes a new designation in ac- cordance with paragraph (c)(2) of this section. § 11.6 What are the requirements for the submission of truthful informa- tion? The clinical trial information sub- mitted by a responsible party under this part shall not be false or mis- leading in any particular. A responsible party who submits false and/or mis- leading information is subject to civil monetary penalties and/or other civil or criminal remedies available under U.S. law. § 11.8 In what format must clinical trial information be submitted? Information submitted under this part must be submitted electronically to ClinicalTrials.gov, in the format specified at https:// prsinfo.clinicaltrials.gov. § 11.10 What definitions apply to this part? (a) The following definitions apply to terms used in this part: Adverse event means any untoward or unfavorable medical occurrence in a human subject, including any abnor- 42 CFR Ch. I (10–1–16 Edition) mal sign (for example, abnormal phys- ical exam or laboratory finding), symp- tom, or disease, temporally associated with the subject’s participation in the research, whether or not considered re- lated to the subject’s participation in the research. See also the definition of ‘‘serious adverse event.’’ Applicable clinical trial means an ap- plicable device clinical trial or an ap- plicable drug clinical trial. Expanded access use under section 561 of the Fed- eral Food, Drug, and Cosmetic Act (21 U.S.C. 360bbb) is not an applicable clin- ical trial. Applicable device clinical trial means: (1) A prospective clinical study of health outcomes comparing an inter- vention with a device product subject to section 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360(k), 21 U.S.C. 360e, 21 U.S.C. 360j(m)) against a control in human subjects (other than a small clinical trial to determine the feasi- bility of a device product, or a clinical trial to test prototype device products where the primary outcome measure relates to feasibility and not to health outcomes); (2) A pediatric postmarket surveil- lance of a device product as required under section 522 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 3601); or (3) A clinical trial of a combination product with a device primary mode of action under 21 CFR part 3, provided that it meets all other criteria of the definition under this part. Applicable drug clinical trial means a controlled clinical investigation, other than a phase 1 clinical investigation, of a drug product subject to section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) or a biological prod- uct subject to section 351 of the Public Health Service Act (42 U.S.C. 262), where ‘‘clinical investigation’’ has the meaning given in 21 CFR 312.3 and ‘‘phase 1’’ has the meaning given in 21 CFR 312.21. A clinical trial of a com- bination product with a drug primary mode of action under 21 CFR part 3 is also an applicable drug clinical trial, provided that it meets all other cri- teria of the definition under this part. 132 Public Health Service, HHS § 11.10 Approved drug means a drug product that is approved for any use under sec- tion 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) or a bio- logical product licensed for any use under section 351 of the Public Health Service Act (42 U.S.C. 262). Approved or cleared device means a de- vice product that is cleared for any use under section 510(k) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C 360(k)) or approved for any use under sections 515 or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C 360e, 360j(m)). Arm means a pre-specified group or subgroup of human subject(s) in a clin- ical trial assigned to receive specific intervention(s) (or no intervention) ac- cording to a protocol. Clinical study means research accord- ing to a protocol involving one or more human subjects to evaluate biomedical or health-related outcomes, including interventional studies and observa- tional studies. Clinical trial means a clinical inves- tigation or a clinical study in which human subject(s) are prospectively as- signed, according to a protocol, to one or more interventions (or no interven- tion) to evaluate the effect(s) of the intervention(s) on biomedical or health-related outcomes. Clinical trial information means the data elements, including clinical trial registration information and clinical trial results information, that the re- sponsible party is required to submit to ClinicalTrials.gov, as specified in sec- tion 402(j) of the Public Health Service Act (42 U.S.C. 282(j)) and this part. Clinical trial registration information means the data elements that the re- sponsible party is required to submit to ClinicalTrials.gov, as specified in sec- tion 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) or § 11.28, as applicable. Clinical trial results information means the data elements that the responsible party is required to submit to ClinicalTrials.gov, as specified in sec- tions 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and (I)) or § 11.48, as applica- ble. If a responsible party submits clin- ical trial results information volun- tarily for a clinical trial, clinical trial results information also means § 11.60(b)(2)(i)(B) or § 11.60(c)(2)(i)(B), as applicable. Comparison group means a grouping of human subjects in a clinical trial that is or may be used in analyzing the re- sults data collected during the clinical trial. Completion date means, for a clinical trial, including an applicable clinical trial, the date that the final subject was examined or received an interven- tion for the purposes of final collection of data for the primary outcome, whether the clinical trial concluded ac- cording to the pre-specified protocol or was terminated. In the case of clinical trials with more than one primary out- come measure with different comple- tion dates, this term refers to the date on which data collection is completed for all of the primary outcomes. For a pediatric postmarket surveillance of a device product that is not a clinical trial, completion date means the date on which the final report of the pedi- atric postmarket surveillance of the device product is submitted to FDA. For purposes of this part, completion date is referred to as ‘‘primary comple- tion date.’’ Control or controlled means, with re- spect to a clinical trial, that data col- lected on human subjects in the clin- ical trial will be compared to concur- rently collected data or to non-concur- rently collected data (e.g., historical controls, including a human subject’s own baseline data), as reflected in the pre-specified primary or secondary out- come measures. For purposes of this part, all clinical trials with one or more arms and pre-specified outcome measure(s) are controlled. Device means a device as defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321(h)). Director means the NIH Director or any official of NIH to whom the NIH Director delegates authorities granted in section 402(j) of the Public Health Service Act (42 U.S.C. 282(j)). Drug means a drug as defined in sec- tion 201(g) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321(g)) or a biological product as defined in section 351 of the Public Health Service Act (42 U.S.C. 262). 133 § 11.10 Enroll or enrolled means a human sub- ject’s, or their legally authorized rep- resentative’s, agreement to participate in a clinical trial following completion of the informed consent process, as re- quired in 21 CFR part 50 and/or 45 CFR part 46, as applicable. For the purposes of this part, potential subjects who are screened for the purpose of determining eligibility for a trial, but do not par- ticipate in the trial, are not considered enrolled, unless otherwise specified by the protocol. Human subjects protection revie board means an institutional review board (IRB) as defined in 21 CFR 50.3 or 45 CFR 46.102, as applicable, that is re- sponsible for assuring the protection of the rights, safety, and well-being of human subjects involved in a clinical trial and is adequately constituted to provide assurance of that protection. An IRB may also be known as an ‘‘independent ethics committee.’’ Interventional means, with respect to a clinical study or a clinical investiga- tion, that participants are assigned prospectively to an intervention or interventions according to a protocol to evaluate the effect of the interven- tion(s) on biomedical or other health- related outcomes. Investigational Device Exemption (IDE) has the meaning given in 21 CFR part 812. Investigational Ne Drug Application (IND) has the meaning given in 21 CFR 312.3. NCT number means the unique identi- fication code assigned to each record in ClinicalTrials.gov, including a record for an applicable clinical trial, a clinical trial, or an expanded access program. Ongoing means, with respect to a clinical trial of a drug product (includ- ing a biological product) or a device product and to a date, that one or more human subjects is enrolled in the clin- ical trial, and the date is before the primary completion date of the clinical trial. With respect to a pediatric postmarket surveillance of a device product, ongoing means a date between the date on which FDA approves the plan for conducting the surveillance and the date on which the final report is submitted to FDA. Outcome measure means a pre-speci- fied measurement that will be used to 42 CFR Ch. I (10–1–16 Edition) determine the effect of an experi- mental variable on the human sub- ject(s) in a clinical trial. See also the definitions of ‘‘primary outcome meas- ure’’ and ‘‘secondary outcome meas- ure.’’ Pediatric postmarket surveillance of a device product means the active, sys- tematic, scientifically valid collection, analysis, and interpretation of data or other information conducted under sec- tion 522 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360l) about a marketed device product that is ex- pected to have significant use in pa- tients who are 21 years of age or young- er at the time of diagnosis or treat- ment. A pediatric postmarket surveil- lance of a device product may be, but is not always, a clinical trial. Primary completion date means, for purposes of this part, ‘‘completion date.’’ See the definition of ‘‘comple- tion date.’’ Primary outcome measure means the outcome measure(s) of greatest impor- tance specified in the protocol, usually the one(s) used in the power calcula- tion. Most clinical trials have one pri- mary outcome measure, but a clinical trial may have more than one. For pur- poses of this part, ‘‘primary outcome’’ has the same meaning as primary out- come measure. Principal investigator means the indi- vidual who is responsible for the over- all scientific and technical direction of the study. Protocol means the written descrip- tion of the clinical trial, including ob- jective(s), design, and methods. It may also include relevant scientific back- ground and statistical considerations. Responsible party means, with respect to a clinical trial, the sponsor of the clinical trial, as defined in 21 CFR 50.3; or the principal investigator of such clinical trial if so designated by a spon- sor, grantee, contractor, or awardee, so long as the principal investigator is re- sponsible for conducting the trial, has access to and control over the data from the clinical trial, has the right to publish the results of the trial, and has the ability to meet all of the require- ments under this part for the submis- sion of clinical trial information. For a pediatric postmarket surveillance of a device product that is not a clinical 134 Public Health Service, HHS § 11.10 trial, the responsible party is the enti- ty who FDA orders to conduct the pedi- atric postmarket surveillance of the device product. Secondary outcome measure means an outcome measure that is of lesser im- portance than a primary outcome measure, but is part of a pre-specified analysis plan for evaluating the effects of the intervention or interventions under investigation in a clinical trial and is not specified as an exploratory or other measure. A clinical trial may have more than one secondary outcome measure. For purposes of this part, ‘‘secondary outcome’’ has the same meaning as secondary outcome meas- ure. Secretary means the Secretary of Health and Human Services or any other official(s) to whom the Secretary delegates the authority contained in section 402(j) of the Public Health Service Act (42 U.S.C. 282(j)). Serious adverse event means an ad- verse event that results in any of the following outcomes: Death, a life- threatening adverse event as defined in 21 CFR 312.32, inpatient hospitalization or prolongation of existing hospitaliza- tion, a persistent or significant inca- pacity or substantial disruption of the ability to conduct normal life func- tions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threat- ening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the human subject and may require medical or surgical inter- vention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hos- pitalization, or the development of a substance use disorder. Sponsor means either a ‘‘sponsor’’ or ‘‘sponsor-investigator,’’ as each is de- fined in 21 CFR 50.3. Study completion date means, for a clinical trial, the date the final subject was examined or received an interven- tion for purposes of final collection of data for the primary and secondary outcome measures and adverse events (e.g., last subject’s last visit), whether the clinical trial concluded according to the pre-specified protocol or was ter- minated. U.S. FDA-regulated device product means, for purposes of this part, a de- vice product subject to section 510(k), 515, 520(m), or 522 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360(k), 21 U.S.C. 360e, 21 U.S.C. 360j(m), 21 U.S.C. 360l). U.S. FDA-regulated drug product means, for purposes of this part, a drug product subject to section 505 of the Federal Food, Drug, and Cosmetic Act or a biological product subject to sec- tion 351 of the Public Health Service Act (21 U.S.C. 355, 42 U.S.C. 262) . (b) The following definitions apply to data elements of clinical trial informa- tion referenced in this part, unless oth- erwise specified: (1) Brief Title means a short title of the clinical trial written in language intended for the lay public, including any acronym or abbreviation used pub- licly to identify the clinical trial. (2) Official Title means the title of the clinical trial, corresponding to the title of the protocol. (3) Brief Summary means a short de- scription of the clinical trial, including a brief statement of the clinical trial’s hypothesis, written in language in- tended for the lay public. (4) Primary Purpose means the main objective of the intervention(s) being evaluated by the clinical trial. (5) Study Design means a description of the manner in which the clinical trial will be conducted, including the following information: (i) Interventional Study Model. The strategy for assigning interventions to human subjects. (ii) Number of Arms. The number of arms in the clinical trial. For a trial with multiple periods or phases that have different numbers of arms, it means the maximum number of arms during all periods or phases. (iii) Arm Information. A description of each arm of the clinical trial that indi- cates its role in the clinical trial, pro- vides an informative title, and, if nec- essary, additional descriptive informa- tion (including which interventions are 135 § 11.10 administered in each arm) to differen- tiate each arm from other arms in the clinical trial. (iv) Allocation. The method by which human subjects are assigned to arms in a clinical trial. (v) Masking. The party or parties, if any, involved in the clinical trial who are prevented from having knowledge of the interventions assigned to indi- vidual human subjects. (6) Study Phase means, for a clinical trial of a drug product (including a bio- logical product), the numerical phase of such clinical trial, consistent with terminology in 21 CFR 312.21, such as phase 2 or phase 3, and in 21 CFR 312.85 for phase 4 studies. (7) Study Type means the nature of the investigation or investigational use for which clinical trial information is being submitted, e.g., interventional, observational. (8) Pediatric Postmarket Surveillance of a Device Product means a clinical trial or study that includes a U.S. FDA-reg- ulated device product as an interven- tion and is a pediatric postmarket sur- veillance of a device product ordered under section 522 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 369l). (9) Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study means the name(s) of the dis- ease(s) or condition(s) studied in the clinical trial, or the focus of the clin- ical trial. Use, if available, appropriate descriptors from NLM’s Medical Sub- ject Headings (MeSH)-controlled vocab- ulary thesaurus or terms from another vocabulary, such as the Systematized Nomenclature of Medicine—Clinical Terms (SNOMED CT), that has been mapped to MeSH within the Unified Medical Language System (UMLS) Metathesaurus. (10) Intervention Name(s) means a brief descriptive name used to refer to the intervention(s) studied in each arm of the clinical trial. A non-proprietary name of the intervention must be used, if available. If a non-proprietary name is not available, a brief descriptive name or identifier must be used. (11) Other Intervention Name(s) means other current and former name(s) or alias(es), if any, different from the Intervention Name(s), that the sponsor has used publicly to identify the inter- 42 CFR Ch. I (10–1–16 Edition) vention(s), including, but not limited to, past or present names such as brand name(s), or serial numbers. (12) Intervention Description means de- tails that can be made public about the intervention, other than the Interven- tion Name(s) and Other Intervention Name(s), sufficient to distinguish the intervention from other, similar inter- ventions studied in the same or an- other clinical trial. For example, inter- ventions involving drugs may include dosage form, dosage, frequency, and du- ration. (13) Intervention Type means, for each intervention studied in the clinical trial, the general type of intervention, e.g., drug, biological/vaccine, or, de- vice. (14) Device Product Not Approved or Cleared by U.S. FDA means that at least one device product studied in the clinical trial has not been previously approved or cleared by FDA for one or more uses. (15) Product Manufactured in and Ex- ported from the U.S. means that any drug product (including a biological product) or device product studied in the clinical trial is manufactured in the United States or one of its terri- tories and exported for study in a clin- ical trial in another country. (16) Study Start Date means the esti- mated date on which the clinical trial will be open for recruitment of human subjects, or the actual date on which the first human subject was enrolled. (17) Primary Completion Date means the estimated or actual primary com- pletion date. If an estimated primary completion date is used, the respon- sible party must update the Primary Completion Date data element once the clinical trial has reached the pri- mary completion date to reflect the ac- tual primary completion date. (18) Enrollment means the estimated total number of human subjects to be enrolled (target number) or the actual total number of human subjects that are enrolled in the clinical trial. Once the trial has reached the primary com- pletion date, the responsible party must update the Enrollment data ele- ment to reflect the actual number of human subjects enrolled in the clinical trial. 136 Public Health Service, HHS § 11.10 (19) Primary Outcome Measure Informa- tion means a description of each pri- mary outcome measure, to include the following information: (i) Name of the specific primary out- come measure; (ii) Description of the metric used to characterize the specific primary out- come measure; and (iii) Time point(s) at which the meas- urement is assessed for the specific metric used. (20) Secondary Outcome Measure Infor- mation means a description of each sec- ondary outcome measure, to include the following information: (i) Name of the specific secondary outcome measure; (ii) Description of the metric used to characterize the specific secondary outcome measure; and (iii) Time point(s) at which the meas- urement is assessed for the specific metric used. (21) Eligibility Criteria means a limited list of criteria for selection of human subjects to participate in the clinical trial, provided in terms of inclusion and exclusion criteria and suitable for assisting potential human subjects in identifying clinical trials of interest. (22) Sex/Gender means the sex and, if applicable, gender of the human sub- jects who may participate in the clin- ical trial. (23) Age Limits means the minimum and maximum age of human subjects who may participate in the clinical trial, provided in relevant units of time. (24) Accepts Healthy Volunteers means that human subjects who do not have a disease or condition, or related condi- tions or symptoms, under study in the clinical trial are permitted to partici- pate in the clinical trial. (25) Overall Recruitment Status means the recruitment status for the clinical trial as a whole, based on the status of the individual sites. If at least one fa- cility in a multi-site clinical trial has an individual site status of ‘‘recruit- ing,’’ then the overall recruitment sta- tus for the trial must be ‘‘recruiting.’’ (26) Why Study Stopped means, for a clinical trial that is suspended or ter- minated or withdrawn prior to its planned completion as anticipated by the protocol, a brief explanation of the reason(s) why the clinical trial was stopped. (27) Individual Site Status means the recruitment status of each partici- pating facility in a clinical trial. (28) Availability of Expanded Access means, for an applicable drug clinical trial of a drug product (including a bio- logical product) that is not an ap- proved drug product (including a bio- logical product), and for which the re- sponsible party is both the manufac- turer of the drug product (including a biological product) and the sponsor of the applicable clinical trial: (i) An indication of whether there is expanded access to the investigational drug product (including a biological product) under section 561 of the Fed- eral Food, Drug, and Cosmetic Act (21 U.S.C. 360bbb) for those individuals who do not qualify for enrollment in the applicable clinical trial, under one or more of the following types of ex- panded access programs: for individual patients, including for emergency use, as specified in 21 CFR 312.310; for inter- mediate-size patient populations, as specified in 21 CFR 312.315; or under a treatment IND or treatment protocol, as specified in 21 CFR 312.320; and (ii) If expanded access is available under section 561 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360bbb), the NCT number of the ex- panded access record. (29) Name of the Sponsor means the name of the entity or individual who is the sponsor of the clinical trial, as de- fined in this part. (30) Responsible Party, by Official Title means an: (i) Indication of whether the respon- sible party is the sponsor of the clin- ical trial, as that term is defined in 21 CFR 50.3; the sponsor-investigator, as that term is defined in 21 CFR 50.3; or a principal investigator designated pursuant to this part; and (ii) Either: (A) The official name of the entity, if the responsible party is an entity; or (B) The official title and primary or- ganizational affiliation of the indi- vidual, if the responsible party is an in- dividual. (31) Facility Information means, for each participating facility in a clinical trial, the following information: 137 § 11.10 (i) Facility Name, meaning the full name of the organization where the clinical trial is being conducted; (ii) Facility Location, including city, state, country and zip code for U.S. lo- cations (including territories of the United States) and city and country for locations in other countries; and (iii) Either: (A) For each facility participating in a clinical trial, Facility Contact, in- cluding the name or title, telephone number, and email address of a person to whom questions concerning the trial and enrollment at that site can be ad- dressed; or (B) Central Contact Person, including the name or title, toll-free telephone number, and email address of a person to whom questions concerning enroll- ment at any location of the trial can be addressed. (32) Unique Protocol Identification Number means any unique identifier as- signed to the protocol by the sponsor. (33) Secondary ID means: (i) Any identifier(s) other than the organization’s unique protocol identi- fier or NCT number that is assigned to the clinical trial, including any unique clinical trial identifiers assigned by other publicly available clinical trial registries. If the clinical trial is funded in whole or in part by a U.S. Federal Government agency, the complete grant or contract number must be sub- mitted as a Secondary ID. (ii) A description of the type of Sec- ondary ID. (34) U.S. Food and Drug Administration IND or IDE Number means an indication of whether there is an IND or IDE for the clinical trial and, if so, each of the following elements: (i) Name or abbreviation of the FDA center with whom the IND or IDE is filed; (ii) IND or IDE number assigned by the FDA center; and (iii) For an IND, the IND serial num- ber, as defined in 21 CFR 312.23(e), if any, assigned to the clinical trial. (35) Human Subjects Protection Revie Board Status means information to in- dicate whether a clinical trial has been reviewed and approved by a human sub- jects protection review board or wheth- er such review is not required per ap- plicable law (e.g., 21 CFR part 56, 45 42 CFR Ch. I (10–1–16 Edition) CFR part 46, or other applicable regula- tion). Human Subjects Protection Re- view Board Status must be listed as ‘‘approved’’ if at least one human sub- jects protection review board has ap- proved the clinical trial. (36) Record Verification Date means the date on which the responsible party last verified the clinical trial informa- tion in the entire ClinicalTrials.gov record for the clinical trial, even if no additional or updated information was submitted at that time. (37) Responsible Party Contact Informa- tion means administrative information to identify and allow communication with the responsible party by tele- phone, email, and regular mail or de- livery service. Responsible Party Con- tact Information includes the name, of- ficial title, organizational affiliation, physical address, mailing address, phone number, and email address of the individual who is the responsible party or of a designated employee of the or- ganization that is the responsible party. (38) Studies a U.S. FDA-regulated De- vice Product means that a clinical trial studies a device product subject to sec- tion 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360(k), 21 U.S.C. 360e, 21 U.S.C. 360j(m)). (39) Studies a U.S. FDA-regulated Drug Product means a clinical trial studies a drug product (including a biological product) subject to section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) or section 351 of the Pub- lic Health Service Act (42 U.S.C. 262). (40) Post Prior to U.S. FDA Approval or Clearance means, for an applicable de- vice clinical trial of a device product that has not been previously approved or cleared, the responsible party indi- cates to the Director that it is author- izing the Director, in accordance with § 11.35(b)(2)(ii), to publicly post its clin- ical trial registration information, which would otherwise be subject to delayed posting, as specified in § 11.35(b)(2)(i), prior to the date of FDA approval or clearance of its device product. (41) Study Completion Date means the estimated or actual study completion date. Once the clinical trial has reached the study completion date, the 138 Public Health Service, HHS § 11.24 responsible party must update the Study Completion Date data element to reflect the actual study completion date in accordance with § 11.64(a)(1)(ii)(J) . Subpart B—Registration § 11.20 Who must submit clinical trial registration information? The responsible party for an applica- ble clinical trial specified in § 11.22 must submit clinical trial registration information for that clinical trial. § 11.22 Which applicable clinical trials must be registered? (a) General specification. (1) Any appli- cable clinical trial that is initiated after September 27, 2007, must be reg- istered. (2) Any applicable clinical trial that is initiated on or before September 27, 2007, and is ongoing on December 26, 2007, must be registered. (3) Determining the date of initiation for an applicable clinical trial. An appli- cable clinical trial, other than a pedi- atric postmarket surveillance of a de- vice product that is not a clinical trial, is considered to be initiated on the date on which the first human subject is enrolled. A pediatric postmarket sur- veillance of a device product that is not a clinical trial is considered to be initiated on the date on which FDA ap- proves the plan for conducting the sur- veillance. (b) Determination of applicable clinical trial for a clinical trial or study initiated on or after January 18, 2017. A clinical trial or study that, at any point in time, meets the conditions listed in paragraph (b)(1) or (2) of this section will be considered to meet the defini- tion of an applicable clinical trial. (1) Applicable device clinical trial. A clinical trial or study that meets the conditions listed in either paragraph (b)(1)(i) or (ii) of this section is an ap- plicable device clinical trial: (i) The study is a pediatric postmarket surveillance of a device product as required by FDA under sec- tion 522 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 3601). (ii) The study is a clinical trial with one or more arms that meets all of the following criteria: (A) Study Type is interventional; (B) Primary Purpose of the clinical trial is other than a feasibility study; (C) The clinical trial Studies a U.S. FDA-regulated Device Product; and (D) One or more of the following ap- plies: (1) At least one Facility Location is within the United States or one of its territories, (2) A device product under investiga- tion is a Product Manufactured in and Exported from the U.S. or one of its territories for study in another coun- try, or (3) The clinical trial has a U.S. Food and Drug Administration IDE Number. (2) Applicable drug clinical trial. A clinical trial with one or more arms that meets the following conditions is an applicable drug clinical trial: (i) Study Type is interventional; (ii) Study Phase is other than phase 1; (iii) The clinical trial Studies a U.S. FDA-regulated Drug Product; and (iv) One or more of the following ap- plies: (A) At least one Facility Location for the clinical trial is within the United States or one of its territories, (B) A drug product (including a bio- logical product) under investigation is a Product Manufactured in and Ex- ported from the U.S. or one of its terri- tories for study in another country, or (C) The clinical trial has a U.S. Food and Drug Administration IND Number. § 11.24 When must clinical trial reg- istration information be submitted? (a) General. Except as provided in paragraph (b) of this section, the re- sponsible party for an applicable clin- ical trial for which submission of clin- ical trial registration information is required must submit the clinical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) or § 11.28(a), as applica- ble, not later than December 26, 2007, or 21 calendar days after the first human subject is enrolled, whichever date is later. (b) Exceptions:. (1) The responsible party for an applicable clinical trial that is a clinical trial and for which 139 § 11.28 the submission of clinical trial reg- istration information is required and that is not for a serious or life-threat- ening disease or condition must submit clinical trial registration information as specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) or § 11.28(a), as applicable, not later than September 27, 2008, or 21 calendar days after the first human subject is enrolled, which- ever date is later. (2) The responsible party for an appli- cable device clinical trial that is a pe- diatric postmarket surveillance of a device product and is not a clinical trial must submit clinical trial reg- istration information, as specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) or § 11.28(b), not later than December 26, 2007, or 21 calendar days after FDA approves the postmarket surveillance plan, which- ever date is later. § 11.28 What constitutes clinical trial registration information? (a) For each applicable clinical trial that must be registered with ClinicalTrials.gov, other than a pedi- atric postmarket surveillance of a de- vice product that is not a clinical trial, the responsible party must submit the following information: (1) For such applicable clinical trials that were initiated before January 18, 2017, the responsible party must submit the information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)). (2) For such applicable clinical trials that are initiated on or after January 18, 2017, the responsible party must submit the data elements listed below: (i) Descriptive information: (A) Brief Title; (B) Official Title; (C) Brief Summary; (D) Primary Purpose; (E) Study Design; (F) Study Phase, for an applicable drug clinical trial; (G) Study Type; (H) Pediatric Postmarket Surveil- lance of a Device Product, for an appli- cable device clinical trial that is a Pe- diatric Postmarket Surveillance of a Device Product; 42 CFR Ch. I (10–1–16 Edition) (I) Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study; (J) Intervention Name(s), for each intervention studied; (K) Other Intervention Name(s), for each intervention studied; (L) Intervention Description, for each intervention studied; (M) Intervention Type, for each intervention studied; (N) Studies a U.S. FDA-regulated De- vice Product; (O) Studies a U.S. FDA-regulated Drug Product; (P) Device Product Not Approved or Cleared by U.S. FDA, if any studied intervention is a device product; (Q) Post Prior to U.S. FDA Approval or Clearance, for an applicable device clinical trial that studies at least one device product not previously approved or cleared by the U.S. FDA; (R) Product Manufactured in and Ex- ported from the U.S., if the entry for U.S. Food and Drug Administration IND or IDE Number in § 11.28(a)(2)(iv)(C) indicates that there is no IND or IDE for the clinical trial, and the entry(ies) for Facility Informa- tion in § 11.28(a)(2)(iii)(C) include no fa- cility locations in the United States or its territories; (S) Study Start Date; (T) Primary Completion Date; (U) Study Completion Date; (V) Enrollment; (W) Primary Outcome Measure Infor- mation, for each primary outcome measure; and (X) Secondary Outcome Measure In- formation, for each secondary outcome measure. (ii) Recruitment information: (A) Eligibility Criteria; (B) Sex/Gender; (C) Age Limits; (D) Accepts Healthy Volunteers; (E) Overall Recruitment Status; (F) Why Study Stopped; (G) Individual Site Status; and (H) Availability of Expanded Access. If expanded access is available for an investigational drug product (including a biological product), an expanded ac- cess record must be submitted in ac- cordance with § 11.28(c), unless an ex- panded access record was submitted 140 Public Health Service, HHS § 11.28 previously in accordance with that pro- vision. (iii) Location and contact informa- tion: (A) Name of the Sponsor; (B) Responsible Party, by Official Title; and (C) Facility Information. (iv) Administrative data: (A) Unique Protocol Identification Number; (B) Secondary ID; (C) U.S. Food and Drug Administra- tion IND or IDE Number; (D) Human Subjects Protection Re- view Board Status; (E) Record Verification Date; and (F) Responsible Party Contact Infor- mation. (b) Pediatric postmarket surveillance of a device product that is not a clin- ical trial. For each pediatric postmarket surveillance of a device product that is not a clinical trial, the responsible party must submit the fol- lowing information: (1) For such applicable device clinical trials that were initiated before Janu- ary 18, 2017, the responsible party must submit the information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)). (2) For such applicable device clinical trials that are initiated on or after January 18, 2017, the responsible party must submit the data elements listed below: (i) Descriptive information: (A) Brief Title. A short title of the pe- diatric postmarket surveillance of a device product in language intended for the lay public. If an acronym or abbre- viation is used to publicly identify the surveillance, it must be provided. (B) Official Title. The title of the pedi- atric postmarket surveillance of a de- vice product, corresponding to the title of the protocol or the FDA-approved plan for conducting the surveillance (C) Brief Summary. A short descrip- tion of the pediatric postmarket sur- veillance of a device product, including a brief statement of the hypothesis or objective, written in language intended for the lay public, and a general de- scription of the surveillance design, in- cluding relevant population informa- tion (D) Study Type. The type of study being registered. In the case of a pedi- atric postmarket surveillance of a de- vice product that is not a clinical trial, a study type of ‘‘observational’’ is re- quired. (E) Pediatric Postmarket Surveillance of a Device Product. For a study that in- cludes an FDA-regulated device prod- uct as an intervention and is a pedi- atric postmarket surveillance of a de- vice product (F) Primary Disease or Condition Being Studied, or the Focus of the Study. The name(s) of the disease(s) or condi- tion(s) being studied in the pediatric postmarket surveillance of a device product, or the focus of the surveil- lance study. Use, if available, appro- priate descriptors fromNLM’s MeSH- controlled vocabulary thesaurus or terms from another vocabulary, such as the SNOMED CT, that has been mapped to MeSH within the UMLS Metathesaurus. (G) Intervention Name(s). A brief de- scriptive name used to refer to each intervention studied in the pediatric postmarket surveillance of a device product. A non-proprietary name of the intervention must be used, if available. If a non-proprietary name is not avail- able, a brief descriptive name or identi- fier must be used. (H) Other Intervention Name(s). Any other current and former name(s) or alias(es), different from the Interven- tion Name(s), that the sponsor has used publicly to identify the intervention(s), including, but not limited to, past or present names such as brand name(s), or serial numbers (I) Intervention Description. Details that can be made public about each intervention, other than the Interven- tion Name(s) and Other Intervention Name(s), sufficient to distinguish the intervention from other, similar inter- ventions studied in the same or an- other clinical trial or pediatric postmarket surveillance of a device product that is not a clinical trial (J) Intervention Type. For each inter- vention studied in the pediatric postmarket surveillance of a device product, the general type of interven- tion (K) Study Start Date. The date on which FDA approves the pediatric 141 § 11.28 postmarket surveillance plan, as speci- fied in 21 CFR 822.19(a). (L) Primary Completion Date. The esti- mated or actual date on which the final report of the pediatric postmarket sur- veillance of a device product is ex- pected to be submitted to FDA. Once the final report has been submitted, this is the actual date on which the final report is submitted to FDA. (ii) Location and contact informa- tion: (A) Name of the Sponsor. (B) Responsible Party, by Official Title: (1) If the responsible party is an enti- ty, the official name of the entity; or (2) If the responsible party is an indi- vidual, the official title and primary organizational affiliation of the indi- vidual. (C) Contact Information. The name or official title, toll-free telephone num- ber, and email address of a person to whom questions concerning the pedi- atric postmarket surveillance of a de- vice product can be addressed. (iii) Administrative data: (A) Unique Protocol Identification Number. The unique identifier assigned to the pediatric postmarket surveil- lance of a device product by the spon- sor, if any. (B) Secondary ID: (1) Identifier(s) other than the organization’s unique protocol identifier or NCT number that is assigned to the pediatric postmarket surveillance of a device product, if any, including any unique identifiers as- signed by other publicly available clin- ical study registries. If the pediatric postmarket surveillance of a device product is funded in whole or in part by a U.S. Federal Government agency, the complete grant or contract number must be submitted as a Secondary ID. (2) For each secondary ID listed, a de- scription of the type of secondary ID. (C) Human Subjects Protection Revie Board Status. Information to indicate whether a pediatric postmarket sur- veillance of a device product has been reviewed and approved by a human sub- jects protection review board or wheth- er such review is not required per ap- plicable law (e.g., 21 CFR part 56, 45 CFR part 46, or other applicable regula- tion). Human Subjects Protection Re- view Board Status must be listed as 42 CFR Ch. I (10–1–16 Edition) ‘‘approved’’ if at least one human sub- jects protection review board has ap- proved the pediatric postmarket sur- veillance. (D) Record Verification Date. The date on which the responsible party last verified the clinical trial information in the entire ClinicalTrials.gov record for the pediatric postmarket surveil- lance of a device product, even if no ad- ditional or updated information was submitted at that time (E) Responsible Party Contact Informa- tion. Administrative information suffi- cient to identify and allow communica- tion with the responsible party by tele- phone, email, and regular mail or de- livery service. Responsible Party Con- tact Information includes the name, of- ficial title, organizational affiliation, physical address, mailing address, phone number, and email address of the individual who is the responsible party or of a designated employee of the or- ganization that is the responsible party. (c) Expanded access record. If ex- panded access is available, as specified in 21 CFR 312.315 (for an intermediate- size patient population) or 21 CFR 312.320 (under a treatment IND or treatment protocol), for an investiga- tional drug product (including a bio- logical product) studied in an applica- ble drug clinical trial, and the data ele- ments set forth in paragraphs (c)(1) through (4) of this section have not been submitted in an expanded access record for that investigational product, the responsible party, if both the man- ufacturer of the investigational prod- uct and the sponsor of the applicable clinical trial, must submit the clinical trial information specified in para- graphs (c)(1) through (4) of this section to ClinicalTrials.gov in the form of an expanded access record. If expanded ac- cess is available only as specified in 21 CFR 312.310 (for individual patients, in- cluding for emergency use) for an in- vestigational drug product (including a biological product) studied in an appli- cable drug clinical trial, and the data elements set forth in paragraphs (c)(1)(i), (iii), (iv), (vi), (ix), (x), (c)(2)(iv), (c)(3), (c)(4)(i), (iii),(iv), and (v) of this section have not been sub- mitted in an expanded access record for 142 Public Health Service, HHS § 11.28 that investigational product, the re- sponsible party, if both the manufac- turer of the investigational product and the sponsor of the applicable clin- ical trial, must submit the clinical trial information specified in those paragraphs to ClinicalTrials.gov in the form of an expanded access record. (1) Descriptive information: (i) Brief Title. A short title identi- fying the expanded access, written in language intended for the lay public. If an acronym or abbreviation is used publicly to identify the expanded ac- cess, it must be provided. (ii) Official Title. The title, if any, of the expanded access program cor- responding to the title that has been submitted to FDA for that program (iii) Brief Summary. A short descrip- tion of the availability of expanded ac- cess, including the procedure for re- questing the investigational drug prod- uct (including a biological product). (iv) Study Type. The nature of the in- vestigation or investigational use for which clinical trial information is being submitted, i.e., ‘‘expanded ac- cess’’. (v) Primary Disease or Condition. The name(s) of the disease(s) or condi- tion(s) for which expanded access to the investigational drug product (in- cluding a biological product) is avail- able. Use, if available, appropriate descriptors from NLM’s MeSH-con- trolled vocabulary thesaurus, or terms from another vocabulary, such as the SNOMED CT, that has been mapped to MeSH within the UMLS Metathesaurus. (vi) Intervention Name(s). A brief de- scriptive name used to refer to the in- vestigational drug product (including a biological product) that is available through expanded access. A non-propri- etary name of the intervention must be used, if available. If a non-proprietary name is not available, a brief descrip- tive name or identifier must be used. (vii) Other Intervention Name(s). Any other current and former name(s) or alias(es), different from the Interven- tion Name(s), that the sponsor has used publicly to identify the intervention, including, but not limited to, past or present names such as brand name(s), or serial numbers. (viii) Intervention Description. Details that can be made public about each intervention, other than the Interven- tion Name(s) or Other Intervention Name(s), sufficient to distinguish the intervention from other, similar inter- ventions that are available through ex- panded access or in clinical trials. (ix) Intervention Type. For each inves- tigational drug product (including a bi- ological product) for which expanded access is available, the general type of intervention, e.g., drug. (x) Expanded Access Type. The type(s) of expanded access for which the inves- tigational drug product (including a bi- ological product) is available, as speci- fied in § 11.10(b)(28). (2) Recruitment information: (i) Eligibility Criteria. A limited list of criteria for determining who is eligible to receive the investigational drug product (including a biological prod- uct) through expanded access, provided in terms of inclusion and exclusion cri- teria and suitable for assisting poten- tial patients in identifying investiga- tional drug products (including biologi- cal products) of interest for which ex- panded access is available. (ii) Sex/Gender. The sex and gender (if applicable) of the patients for whom expanded access is available. (iii) Age Limits. The minimum and maximum age of patients for whom ex- panded access is available, provided in relevant units of time. (iv) Expanded Access Status. The sta- tus of availability of the investiga- tional drug product (including a bio- logical product) through expanded ac- cess. (3) Contact information: (i) Name of the Sponsor. (ii) Responsible Party, by Official Title. The official name of the entity. (iii) Contact Information. The name or official title, toll-free telephone num- ber, and email address of a person to whom questions concerning expanded access can be addressed. (4) Administrative data: (i) Unique Protocol Identification Num- ber. Any unique identifier assigned by the sponsor to refer to the availability of its investigational drug product (in- cluding a biological product) for ex- panded access use or to identify the ex- panded access record. 143 § 11.35 (ii) Secondary ID: (A) Any identi- fier(s) other than the Unique Protocol Identification Number or the NCT number that is assigned to the ex- panded access record, including any unique identifiers assigned by other publicly available clinical trial or ex- panded access registries. (B) For each Secondary ID listed, a description of the type of Secondary ID. (iii) U.S. Food and Drug Administra- tion IND Number. An indication of whether there is an IND and, if so, each of the following elements: (A) Name or abbreviation of the FDA center with whom the IND is filed (i.e., CDER or CBER), if applicable; (B) IND number (assigned by the FDA center) under which the investiga- tional drug product (including a bio- logical product) is being made avail- able for expanded access, if applicable; and (C) IND serial number. as defined in 21 CFR 312.23(e), if any, assigned to the expanded access. (iv) Record Verification Date. The date on which the responsible party last verified the information in the ex- panded access record, even if no addi- tional or updated information was sub- mitted at that time. (v) Responsible Party Contact Informa- tion. Administrative information suffi- cient to identify and allow communica- tion with the responsible party enter- ing the clinical trial information into the expanded access record by tele- phone, email, and regular mail or de- livery service. Responsible Party Con- tact Information includes the name, of- ficial title, organizational affiliation, physical address, mailing address, phone number, and email address of the individual who is the responsible party or of a designated employee of the or- ganization that is the responsible party. § 11.35 By when will the NIH Director post clinical trial registration infor- mation submitted under § 11.28? (a) Applicable drug clinical trial. The Director will post publicly on ClinicalTrials.gov the clinical trial reg- istration information, except for cer- tain administrative data, for an appli- cable drug clinical trial not later than 42 CFR Ch. I (10–1–16 Edition) 30 calendar days after the responsible party has submitted such information, as specified in § 11.24. (b) Applicable device clinical trial. (1) For an applicable device clinical trial of a device product that was previously approved or cleared, the Director will post publicly on ClinicalTrials.gov the clinical trial registration information, except for certain administrative data, as soon as practicable, but not later than 30 calendar days after clinical trial results information is required to be posted, as specified in § 11.52. (2) For an applicable device clinical trial of a device product that has not been previously approved or cleared: (i) The Director will post publicly on ClinicalTrials.gov the clinical trial reg- istration information, except for cer- tain administrative data, not earlier than the date of FDA approval or clear- ance of the device product and not later than 30 calendar days after the date of such approval or clearance, ex- cept as otherwise provided in para- graph (b)(2)(ii) of this section. (ii) If, prior to the date of approval or clearance of the device product, the re- sponsible party for an applicable clin- ical trial that is initiated on or after January 18, 2017, indicates to the Direc- tor, by submitting the Post Prior to U.S. FDA Approval or Clearance data element under § 11.28(a)(2)(i)(Q), that it is authorizing the Director to publicly post its clinical trial registration in- formation, which would otherwise be subject to delayed posting as specified in paragraph (b)(2)(i) of this section, prior to the date of FDA approval or clearance of its device product, the Di- rector will publicly post the registra- tion information, except for certain ad- ministrative data, as soon as prac- ticable. Subpart C—Results Information Submission § 11.40 Who must submit clinical trial results information? The responsible party for an applica- ble clinical trial specified in § 11.42 must submit clinical trial results infor- mation for that clinical trial. 144 Public Health Service, HHS § 11.44 § 11.42 For which applicable clinical trials must clinical trial results in- formation be submitted? (a) Applicable clinical trials for hich the studied product is approved, licensed, or cleared by FDA. Unless a waiver of the requirement to submit clinical trial results information is granted in accordance with § 11.54, clinical trial results information must be submitted for any applicable clinical trial for which the studied product is approved, licensed, or cleared by FDA for which submission of clinical trial registration information is required in accordance with the following: (1) If the primary completion date is before January 18, 2017, the responsible party must submit the clinical trial re- sults information specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)); or (2) If the primary completion date is on or after January 18, 2017, the respon- sible party must submit the clinical trial results information specified in § 11.48. (b) Applicable clinical trials for hich the studied product is not approved, li- censed, or cleared by FDA. Unless a waiver of the requirement to submit clinical trial results information is granted in accordance with § 11.54, clin- ical trial results information specified in § 11.48 must be submitted for any ap- plicable clinical trial with a primary completion date on or after January 18, 2017 for which clinical trial registra- tion information is required to be sub- mitted and for which the studied prod- uct is not approved, licensed, or cleared by FDA. § 11.44 When must clinical trial results information be submitted for appli- cable clinical trials subject to § 11.42? (a) Standard submission deadline. In general, for applicable clinical trials subject to § 11.42, clinical trial results information specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)) or in § 11.48, as applicable, must be sub- mitted no later than 1 year after the primary completion date of the appli- cable clinical trial. (b) Delayed submission of results infor- mation ith certification if seeking ap- proval, licensure, or clearance of a ne use—(1) General requirements. If, prior to the results information submission deadline specified under paragraph (a) of this section, the responsible party submits a certification that an applica- ble clinical trial involves an FDA-regu- lated drug product (including a biologi- cal product) or device product that pre- viously has been approved, licensed, or cleared, for which the manufacturer is the sponsor of the applicable clinical trial and for which an application or premarket notification seeking ap- proval, licensure, or clearance of the use being studied (which is not in- cluded in the labeling of the approved, licensed, or cleared drug product (in- cluding a biological product) or device product) has been filed or will be filed within 1 year with FDA, the deadline for submitting clinical trial results in- formation, as specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)) or § 11.48, as applicable, will be 30 calendar days after the earliest of the following events: (i) FDA approves, licenses, or clears the drug product (including a biologi- cal product) or device product for the use studied in the applicable clinical trial; (ii) FDA issues a letter that ends the regulatory review cycle for the applica- tion or submission but does not ap- prove, license, or clear the drug prod- uct (including a biological product) or device product for the use studied in the applicable clinical trial; or (iii) The application or premarket notification seeking approval, licen- sure, or clearance of the new use is withdrawn without resubmission for not less than 210 calendar days. (2) T o-year limitation. Notwith- standing the deadlines specified in paragraph (b)(1) of this section, the re- sponsible party must submit clinical trial results information specified in paragraph (b)(1) of this section not later than the date that is 2 years after the date that the certification was sub- mitted, except to the extent that para- graph (d) of this section applies. 145 § 11.44 (3) Additional requirements. If a re- sponsible party who is both the manu- facturer of the drug product (including a biological product) or device product studied in an applicable clinical trial and the sponsor of the applicable clin- ical trial submits a certification in ac- cordance with paragraph (b)(1) of this section, that responsible party must submit such a certification for each ap- plicable clinical trial that meets the following criteria: (i) The applicable clinical trial is re- quired to be submitted in an applica- tion or premarket notification seeking approval, licensure, or clearance of a new use; and (ii) The applicable clinical trial stud- ies the same drug product (including a biological product) or device product for the same use as studied in the ap- plicable clinical trial for which the ini- tial certification was submitted. (c) Delayed submission of results ith certification if seeking initial approval, li- censure, or clearance.—(1) General re- quirements. If, prior to the submission deadline specified under paragraph (a) of this section, a responsible party sub- mits a certification that an applicable clinical trial studies an FDA-regulated drug product (including a biological product) or device product that was not approved, licensed, or cleared by FDA for any use before the primary comple- tion date of the trial, and that the sponsor intends to continue with prod- uct development and is either seeking, or may at a future date seek, FDA ap- proval, licensure, or clearance of the drug product (including a biological product) or device product under study, the deadline for submitting clinical trial results information, as specified in § 11.48, will be 30 calendar days after the earlier of the date on which: (i) FDA approves, licenses, or clears the drug product (including a biologi- cal product) or device product for any use that is studied in the applicable clinical trial; or (ii) The marketing application or premarket notification is withdrawn without resubmission for not less than 210 calendar days. (2) T o-year limitation. Notwith- standing the deadlines established in paragraph (c)(1) of this section, the re- sponsible party must submit clinical 42 CFR Ch. I (10–1–16 Edition) trial results information specified in paragraph (c)(1) of this section not later than 2 years after the date on which the certification was submitted, except to the extent that paragraph (d) of this section applies. (d) Submitting partial results informa- tion. (1) If clinical trial results infor- mation specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)) or § 11.48, as applica- ble, has not been collected for a sec- ondary outcome measure(s) or addi- tional adverse event information by the primary completion date, the re- sponsible party must submit the re- maining required clinical trial results information for secondary outcome measure(s) or additional adverse event information for that clinical trial by the following deadlines: (i) For secondary outcome meas- ure(s), by the later of: (A) One year after the date on which the final subject is examined or re- ceives an intervention for the purposes of final collection of data for that sec- ondary outcome measure, whether the clinical trial was concluded according to the pre-specified protocol or was ter- minated; or (B) If a certification to delay results information submission has been sub- mitted under paragraph (b) or (c) of this section, the date on which results information for the primary outcome measures is due pursuant to paragraph (b) or (c) of this section. (ii) For additional adverse event in- formation, by the later of: (A) One year after the date of data collection for additional adverse event information, whether the clinical trial was concluded according to the pre- specified protocol or was terminated; or (B) If a certification to delay results information submission has been sub- mitted under paragraph (b) or (c) of this section, the date on which results information for the primary outcome measures is due pursuant to paragraph (b) or (c) of this section. (2) Except, if clinical trial results in- formation was submitted for the pri- mary outcome measure(s) prior to the effective date of these regulations but data collection for all of the secondary 146 Public Health Service, HHS § 11.44 outcome measure(s) or additional ad- verse event information is not com- pleted until on or after January 18, 2017, clinical trial results information for all primary and secondary outcome measures and adverse event informa- tion for the clinical trial must be sub- mitted as specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)). (3) For each submission of partial re- sults information for a clinical trial, as specified in paragraph (d)(1) of this sec- tion: (i) If any amendments were made to the protocol and/or statistical analysis plan as described in § 11.48(a)(5) since the previous submission of partial re- sults information, the responsible party must submit a copy of the re- vised protocol and/or statistical anal- ysis plan; and (ii) If information about certain agreements as described in § 11.48(a)(6)(ii) has changed since the previous submission of partial results information, the responsible party must submit information to reflect the new status of certain agreements be- tween the principal investigator and the sponsor. (e) Extensions for good cause. (1) A re- sponsible party may request an exten- sion of the deadline for submitting clinical trial results information sub- ject to paragraphs (e)(1)(i) and (ii) of this section or section 402(j)(3)(E)(vi) of the Public Health Service Act (42 U.S.C. 282(j)(3)(E)(vi)), as applicable, and may request more than one exten- sion for the same applicable clinical trial. (i) The responsible party must sub- mit a request for an extension to ClinicalTrials.gov prior to the date on which clinical trial results information would otherwise be due in accordance with paragraph (a), (b), (c), (d), (e), or (f) of this section. (ii) A request for an extension must contain the following: (A) Description of the reason(s) why clinical trial results information can- not be provided according to the dead- line, with sufficient detail to allow for the evaluation of the request; and (B) Estimate of the date on which the clinical trial results information will be submitted. (2) Decision and submission deadline. The Director will provide a response electronically to the responsible party indicating whether the requested ex- tension demonstrates good cause and has been granted. (i) If the extension request is grant- ed, the responsible party must submit clinical trial results information not later than the date of the deadline specified in the electronic response. (ii) If the extension request is denied, the responsible party must either ap- peal in accordance with paragraph (e)(3) of this section or submit clinical trial results information specified in § 11.48 by the later of the submission deadline specified in paragraph (a), (b), (c), (d), (e), or (f) of this section, as ap- plicable, or 30 calendar days after the date on which the electronic notice of the denial is sent to the responsible party. (3) Appealing a denied extension re- quest. (i) A responsible party who seeks to appeal a denied extension request or the deadline specified in a granted ex- tension must submit an appeal to the Director in the format specified at https://prsinfo.clinicaltrials.gov/ not later than 30 calendar days after the date on which the electronic notification of the granting or denial of the request is sent to the responsible party. (ii) An appeal must contain an expla- nation of the reason(s) why the initial decision to deny the extension request or to grant the extension request with a shorter deadline than requested should be overturned or revised, with sufficient detail to allow for the eval- uation of the appeal. (iii) The Director will provide an electronic notification to the respon- sible party indicating whether the re- quested extension has been granted upon appeal. (iv) If the Director grants the exten- sion request upon appeal, the respon- sible party must submit clinical trial results information not later than the deadline specified in the electronic no- tification specified in paragraph (e)(3)(iii) of this section. 147 § 11.48 (v) If the Director denies the appeal of a denied extension request, the re- sponsible party must submit clinical trial results information by the later of the deadline specified in paragraph (a), (b), (c), (d), (e), or (f) of this section, or 30 calendar days after the electronic notification of the denial of the appeal, specified in paragraph (e)(3)(iii) of this section, is sent to the responsible party. (vi) If the Director denies an appeal of a denied deadline specified in a granted extension request, the respon- sible party must submit clinical trial results information by the later of the deadline specified in the notification granting the extension request, speci- fied in paragraph (e)(2)(i) of this sec- tion, or 30 calendar days after the elec- tronic notification denying the appeal, specified in paragraph (e)(3)(iii) of this section, is sent to the responsible party. (f) 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 as defined in this part, the responsible party must sub- mit clinical trial results information as specified in § 11.48(b) or section 402(j)(C)(3) of the Public Health Service Act (42 U.S.C. 282(j)(C)(3)), as applica- ble, not later than 30 calendar days after the date on which the final report of the approved pediatric postmarket surveillance of a device product, as specified in 21 CFR 822.38, is submitted to FDA. § 11.48 What constitutes clinical trial results information? (a) For each applicable clinical trial, other than a pediatric postmarket sur- veillance of a device product that is not a clinical trial, for which clinical trial results information must be sub- mitted under § 11.42, the responsible party must provide the following: (1) Participant flo . 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 Flo Arm Information. A brief description of each arm used for 42 CFR Ch. I (10–1–16 Edition) describing the flow of human subjects through the clinical trial, including a descriptive title used to identify each arm; (ii) Pre-assignment Information. A de- scription of significant events in the clinical trial that occur after enroll- ment and prior to assignment of human subjects to an arm, if any; and (iii) Participant Data. The number of human subjects that started and com- pleted the clinical trial, by arm. If as- signment is based on a unit other than participants, also include a description of the unit of assignment and the num- ber of units that started and completed the clinical trial, by arm. (2) Demographic and baseline charac- teristics. 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 par- ticipated in the clinical trial. This in- formation must include the following elements: (i) Baseline Characteristics Arm/Group Information. A brief description of each arm or comparison group used for de- scribing the demographic and baseline characteristics of the human subjects in the clinical trial, including a de- scriptive title used to identify each arm or comparison group. (ii) Baseline Analysis Population Infor- mation—(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 com- parison group and overall. (C) Analysis Population Description. If the Overall Number of Baseline Par- ticipants (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 demo- graphic characteristic measured in the clinical trial, including age, sex/gender, race, ethnicity (if collected under the 148 Public Health Service, HHS § 11.48 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 Dis- persion: For each baseline measure sub- mitted, an indication of the type of data to be submitted and the associ- ated measure of dispersion. (C) Unit of Measure. For each baseline measure for which data are collected, the unit of measure. (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 characteris- tics were measured. (v) Number of baseline participants (and units), by arm or comparison group and overall, if different from the Overall Number of Baseline Partici- pants or Overall Number of Units Ana- lyzed in § 11.48(a)(2)(ii)(A) and (B), re- spectively. (3) Outcomes and statistical analyses. Information for completing a table of data for each primary and secondary outcome measure by arm or compari- son group, including the result(s) of scientifically appropriate statistical analyses that were performed on the outcome measure data, if any. This in- formation must include the following elements: (i) Outcome Measure Arm/Group Infor- mation. A brief description of each arm or comparison group used for submit- ting an outcome measure for the clin- ical 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 compari- son 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. (C) Time point(s) at which the meas- urement was assessed for the specific metric. (D) Outcome Measure Type. The type of outcome measure, whether primary, secondary, other pre-specified, or post- hoc. (E) Measure Type and Measure of Dis- persion 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 out- come measure for which data are col- lected, the unit of measure. (iv) Outcome Measure Data. The meas- urement 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 re- sponsible 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 ap- plies, or (3) Conducted on a primary outcome measure in response to a request made 149 § 11.48 by FDA prior to the date on which clin- ical trial results information is sub- mitted for the primary outcome meas- ure(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 Overvie : Iden- tification 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-inferi- ority or equivalence margin. (2) One of the following, as applica- ble: (i) Statistical Test of Hypothesis: The p- value and the procedure used for the statistical analysis; or (ii) Method of Estimation: The esti- mation parameter, estimated value, and confidence interval (if calculated). (4) Adverse event information. (i) Infor- mation to describe the methods for col- lecting adverse events during an appli- cable clinical trial: (A) Time Frame. The specific period of time over which adverse event infor- mation was collected and for which in- formation is submitted in paragraph (a)(4)(iii) of this section. (B) Adverse Event Reporting Descrip- tion. If the adverse event information collected in the clinical trial is col- lected 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 ex- ceed a frequency of 5 percent within any arm of the clinical trial, grouped 42 CFR Ch. I (10–1–16 Edition) by organ system, with the number and frequency of each event by arm or com- parison group; and (C) Table of all-cause mortality, with the number and frequency of deaths due to any cause by arm or comparison group. (iii) Information for each table speci- fied in paragraph (a)(4)(ii) of this sec- tion must include the following ele- ments, unless otherwise specified: (A) Adverse Event Arm/Group Informa- tion. 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 com- parison 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 seri- ous adverse events that exceed a fre- quency 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 seri- ous adverse events that exceed a fre- quency 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 ad- verse 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 accord- ance with paragraph (a)(4)(iii)(D) of this section: (1) Number of human subjects af- fected by such adverse event. 150 Public Health Service, HHS § 11.48 (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 in- cluded 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 docu- ment. The responsible party may re- dact names, addresses, and other per- sonally identifiable information, as well as any trade secret and/or con- fidential 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, un- less such information is otherwise re- quired 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) Re- sults Point of Contact. Point of contact for scientific information about the clinical trial results information, in- cluding the following: (A) Name or official title of the point of contact (B) Name of the affiliated organiza- tion, and (C) Telephone number and email ad- dress of the point of contact. (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 re- stricts in any manner the ability of the principal investigator, after the pri- mary completion date of the clinical trial, to discuss the results of the clin- ical trial at a scientific meeting or any other public or private forum or to publish in a scientific or academic journal information concerning the re- sults of the clinical trial (7) Additional clinical trial results infor- mation for applicable device clinical trials of unapproved or uncleared device prod- ucts. (i) For an applicable device clin- ical 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 accord- ance with § 11.35(b)(2)(i), the responsible party must provide the following data elements, as the data elements are de- fined in § 11.10(b): Brief Title; Official Title; Brief Summary; Primary Pur- pose; Study Design; Study Type; Pri- mary Disease or Condition Being Stud- ied in the Trial, or the Focus of the Study; Intervention Name(s); Other Intervention Name(s); Intervention De- scription; 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 Com- pletion Date, Enrollment; Primary Outcome Measure Information; Sec- ondary 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 clin- ical trial; Unique Protocol Identifica- tion Number; Secondary ID; Human Subjects Protection Review Board Sta- tus; and Record Verification Date. (ii) The responsible party shall sub- mit all the results information speci- fied in paragraph (a)(7)(i) and must sub- mit an affirmation that any informa- tion previously submitted to ClinicalTrials.gov for the data elements listed in paragraph (a)(7)(i) of this sec- tion 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 151 § 11.52 specified in 21 CFR 822.38. The respon- sible party may redact names, address- es, and other personally identifiable in- formation or commercial confidential information contained in the final re- port 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 elec- tronic document format specified at https://prsinfo.clinicaltrials.gov. § 11.52 By when will the NIH Director post submitted clinical trial results information? Except for clinical trial results infor- mation submitted under section 402(j)(4)(A) of the PHS Act and § 11.60, the Director will post publicly clinical trial results information on ClinicalTrials.gov not later than 30 cal- endar days after the date of submis- sion. § 11.54 What are the procedures for re- questing and obtaining a waiver of the requirements for clinical trial results information submission? (a) Waiver request. (1) A responsible party for an applicable clinical trial with a primary completion date on or after January 18, 2017 may request a waiver from any applicable require- ment(s) of this subpart C by submitting a waiver request in the format speci- fied at https://prsinfo.clinicaltrials.gov/ to the Secretary or delegate prior to the deadline specified in § 11.44(a) for sub- mitting clinical trial results informa- tion. (2) The waiver request must contain: (i) The NCT number, Brief Title, and Name of the Sponsor of the applicable clinical trial for which the waiver is re- quested; (ii) The specific requirement(s) of this subpart C for which the waiver is requested; and (iii) A description of the extraor- dinary circumstances that the respon- sible party believes justify the waiver and an explanation of why granting the request would be consistent with the protection of public health or in the in- terest of national security. (3) The responsible party will not be required to comply with the specified requirements of this subpart for which a waiver is granted. 42 CFR Ch. I (10–1–16 Edition) (4) The responsible party must com- ply with any requirements of this sub- part for which a waiver is not granted or must submit an appeal as set forth in paragraph (b) of this section. The deadline for submitting any required clinical trial results information will be the later of the original submission deadline or 30 calendar days after the notification of the denial is sent to the responsible party. (b) Appealing a denied aiver request. (1) A responsible party for an applica- ble clinical trial with a primary com- pletion date on or after January 18, 2017 may appeal a denied waiver re- quest by submitting an appeal to the Secretary or delegate in the format specified at https:// prsinfo.clinicaltrials.gov/ not later than 30 calendar days after the date on which the electronic notification of the denial in paragraph (a)(4) of this sec- tion denying the request is sent to the responsible party. (2) The responsible party is not re- quired to comply with any require- ments of this subpart for which a waiv- er is granted upon appeal. (3) The responsible party must sub- mit clinical trial results information to comply with any requirements of this subpart that are not waived upon appeal by the later of the original sub- mission deadline or 30 calendar days after the notice of the denial upon ap- peal is sent to the responsible party. (c) If a waiver is granted under para- graph (a) or (b) of this section: (1) The Director will include a nota- tion in the clinical trial record that specified elements of the requirements of this part have been waived. (2) The Secretary will notify, in writ- ing, the appropriate committees of Congress and provide an explanation for why the waiver was granted, not later than 30 calendar days after any waiver is granted. (d) A responsible party for an appli- cable clinical trial with a primary completion date before January 18, 2017 may request a waiver from any applica- ble requirement(s) for clinical trial re- sults information submission by sub- mitting a waiver request, as specified in section 402(j)(3)(H) of the Public Health Service Act (42 U.S.C. 282(j)(3)(H)). 152 Public Health Service, HHS § 11.60 Subpart D—Additional Submission of Clinical Trial Information § 11.60 What requirements apply to the voluntary submission of clinical trial information for clinical trials of FDA-regulated drug products (in- cluding biological products) and de- vice products? (a) If a responsible party voluntarily submits clinical trial information for a clinical trial described in paragraph (a)(1) of this section, the responsible party must meet the conditions speci- fied in paragraph (a)(2) of this section. (1) The requirements of paragraph (a) of this section apply to a clinical trial that was initiated before January 18, 2017 and has a primary completion date before January 18, 2017, and that is ei- ther: (i) A clinical trial of an FDA-regu- lated drug product (including a biologi- cal product) or device product that is not an applicable clinical trial, or (ii) An applicable clinical trial that is not otherwise required to submit clinical trial registration information. (2) If the responsible party for a clin- ical trial described in paragraph (a)(1) of this section voluntarily submits clinical trial registration information and/or clinical trial results informa- tion, the responsible party must com- ply with the following requirements: (i) The responsible party must sub- mit the information in paragraphs (b)(2)(i)(A), (B), or (C) of this section for the clinical trial being submitted voluntarily. (A) If the responsible party volun- tarily registers a clinical trial, the re- sponsible party must submit clinical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)). (B) If the responsible party volun- tarily submits clinical trial results in- formation for a clinical trial for which the clinical trial registration informa- tion specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) has not been sub- mitted, the responsible party must sub- mit the clinical trial results informa- tion specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)). (C) If the responsible party both vol- untarily submits clinical trial registra- tion information and voluntarily sub- mits clinical trial results information, the responsible party must submit both clinical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) and clinical trial results information specified in sec- tions 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)). (ii) If, on or after September 27, 2007, a manufacturer submits an application or premarket notification to FDA for approval, licensure, or clearance of a drug product (including a biological product) or device product under sec- tions 505, 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C 355, 360(k), 360e, 360j(m)) or section 351 of the Public Health Service Act (42 U.S.C. 262) for the use studied in the clinical trial submitted under para- graph (a)(1) of this section, the respon- sible party specified in paragraph (a)(1) of this section must also submit the in- formation specified in paragraph (a)(2)(iii) of this section by the deadline specified in paragraph (a)(2)(iv)(B) of this section for any applicable clinical trial that has not been submitted to ClinicalTrials.gov and that meets the following criteria: (A) The applicable clinical trial is re- quired to be submitted to FDA under sections 505, 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355, 360(k), 360e, 360j(m)) or section 351 of the Public Health Service Act (42 U.S.C. 262) in an application or premarket notification for approval, li- censure, or clearance to market the drug product (including a biological product) or device product for the use studied in the clinical trial specified in paragraph (a)(1) of this section; and (B) The manufacturer of the drug product (including a biological prod- uct) or device product studied in the applicable clinical trial is also the re- sponsible party for the clinical trial specified in paragraph (a)(1) of this sec- tion. 153 § 11.60 (iii) Information to be submitted for clinical trials described in paragraph (a)(2)(ii) of this section: (A) If the clinical trial information voluntarily submitted for a clinical trial described in paragraph (a)(1) of this section consists only of the clin- ical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)), the information to be submitted in accordance with paragraph (a)(2)(ii) of this section must consist, at minimum, of the clinical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)). (B) If the clinical trial information voluntarily submitted for a clinical trial described by paragraph (a)(1) of this section consists of the clinical trial results information specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)), the information to be sub- mitted in accordance with paragraph (a)(2)(ii) of this section must consist of the clinical trial results information specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)). (C) If the clinical trial information voluntarily submitted for a clinical trial described by paragraph (a)(1) of this section consists of both the clin- ical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) and the clinical trial results information specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)), the information to be sub- mitted in accordance with paragraph (a)(2)(ii) of this section must consist of both the clinical trial registration in- formation specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) and the clinical trial results informa- tion specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)). (iv) Submission deadlines: 42 CFR Ch. I (10–1–16 Edition) (A) Secondary outcome measure(s) and adverse event information for vol- untarily submitted clinical trials, under paragraph (a) of this section: (1) If data collection for secondary outcome measure(s) for a voluntarily submitted clinical trial under para- graph (a) of this section is not com- pleted by the primary completion date of the voluntarily submitted clinical trial, clinical trial results information for the secondary outcome measure(s) required in section 402(j)(3)(C) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C)) must be submitted by the later of the date that the clinical trial results information is voluntarily sub- mitted for the primary outcome meas- ure(s) or 1 year after the date on which the final subject was examined or re- ceived an intervention for the purposes of final collection of data for the sec- ondary outcome(s), whether the clin- ical trial was concluded according to the pre-specified protocol or was termi- nated. (2) If data collection for adverse event information continues after the primary completion date of the volun- tarily submitted clinical trial, any ad- verse event information collected after the primary completion date and sub- ject to the submission requirements in section 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(I)) must be submitted by the later of the date that the clinical trial results informa- tion is voluntarily submitted for the primary outcome measure(s) or 1 year after the date of final collection of data for adverse event information, whether the clinical trial was con- cluded according to the pre-specified protocol or was terminated. (B) The clinical trial information specified in paragraph (a)(2)(iii) of this section must be submitted not later than the later of the date on which the application or premarket notification to FDA for approval, licensure, or clearance to market a drug product (in- cluding a biological product) or device product under section 351 of the Public Health Service Act (42 U.S.C. 262) or section 505, 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355, 360(k), 360e, 360j(m)) for the use studied in the clinical trial specified under paragraph (a)(1) of this 154 Public Health Service, HHS § 11.60 section is submitted to FDA or the date on which the clinical trial infor- mation specified in paragraph (a)(2)(i) of this section for the clinical trial specified under paragraph (a)(1) of this section is submitted to ClinicalTrials.gov. (b) If a responsible party voluntarily submits clinical trial information for a clinical trial described in paragraph (b)(1) of this section, the responsible party must meet the conditions speci- fied in paragraph (b)(2) of this section. (1) The requirements of paragraph (b) of this section apply to a clinical trial that was initiated before January 18, 2017 and has a primary completion date on or after January 18, 2017, and that is either: (i) A clinical trial of an FDA-regu- lated drug product (including a biologi- cal product) or device product that is not an applicable clinical trial; or (ii) An applicable clinical trial that is not otherwise required to submit clinical trial registration information. (2) If the responsible party for a clin- ical trial described in paragraph (b)(1) of this section voluntarily submits clinical trial registration information and/or clinical trial results informa- tion, the responsible party must com- ply with the following requirements: (i) The responsible party must sub- mit the information in paragraph (b)(2)(i)(A), (B), or (C) of this section for the clinical trial being submitted voluntarily. (A) If the responsible party volun- tarily registers a clinical trial, the re- sponsible party must submit clinical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)). (B) If the responsible party volun- tarily submits clinical trial results in- formation for a clinical trial for which the clinical trial registration informa- tion specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) has not been sub- mitted, the responsible party must sub- mit the data elements specified in § 11.48, as well as the data elements listed below, as those data elements are defined in § 11.10(b) and apply to the clinical trial and the intervention(s) studied: Brief Title; Official Title; Brief Summary; Primary Purpose; Study De- sign; Study Phase, for a clinical trial of a drug product (including a biological product); Study Type; Pediatric Postmarket Surveillance of a Device Product; Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study; Intervention Name(s), for each intervention studied; Other Intervention Name(s), for each intervention studied; Intervention De- scription, for each intervention stud- ied; Intervention Type, for each inter- vention studied; Device Product Not Approved or Cleared by U.S. FDA, if any studied intervention is a device product; Product Manufactured in and Exported from the U.S.; Studies a U.S. FDA-regulated Device Product; Studies a U.S. FDA-regulated Drug Product; Study Start Date; Primary Completion Date; Study Completion Date; Enroll- ment; Eligibility Criteria; Sex/Gender; Age Limits; Accepts Healthy Volun- teers; Overall Recruitment Status; Why Study Stopped; Availability of Ex- panded Access, if any studied interven- tion is an investigational drug product (including a biological product); Name of the Sponsor; Responsible Party, by Official Title; Facility Information, for each participating facility; Unique Protocol Identification Number; Sec- ondary ID; U.S. Food and Drug Admin- istration IND or IDE Number; Human Subjects Protection Review Board Sta- tus; Record Verification Date; and Re- sponsible Party Contact Information. (C) If the responsible party both vol- untarily submits clinical trial registra- tion information and voluntarily sub- mits clinical trial results information, the responsible party must submit both the clinical trial registration informa- tion specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) and the clinical trial results information specified in § 11.48. (ii) If, on or after September 27, 2007, a manufacturer submits an application or premarket notification to FDA for approval, licensure, or clearance of a drug product (including a biological product) or device product under sec- tion 505, 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355, 360(k), 360e, 360j(m)) or section 351 of the Public Health Service 155 § 11.60 Act (42 U.S.C. 262) for the use studied in the clinical trial submitted under para- graph (b)(1) of this section, the respon- sible party specified in paragraph (b)(1) of this section must also submit the in- formation specified in paragraph (b)(2)(iii) of this section by the deadline specified in paragraph (b)(2)(iv)(B) of this section for any applicable clinical trial that has not been submitted to ClinicalTrials.gov and that meets the following criteria: (A) The applicable clinical trial is re- quired to be submitted to FDA under section 505, 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355, 360(k), 360e, 360j(m)) or section 351 of the Public Health Service Act (42 U.S.C. 262) in an application or premarket notification for approval, li- censure, or clearance to market the drug product (including a biological product) or device product for the use studied in the clinical trial specified in paragraph (b)(1) of this section; and (B) The manufacturer of the drug product (including a biological prod- uct) or device product studied in the applicable clinical trial is also the re- sponsible party for the clinical trial specified in paragraph (b)(1) of this sec- tion. (iii) Information to be submitted for clinical trials described in paragraph (b)(2)(ii) of this section: (A) If the clinical trial information voluntarily submitted for a clinical trial described in paragraph (b)(1) of this section consists only of the clin- ical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)), the information to be submitted in accordance with paragraph (b)(2)(ii) of this section must consist, at minimum, of the clinical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)). (B) If the clinical trial information voluntarily submitted for a clinical trial described by paragraph (b)(1) of this section consists of the clinical trial results information specified in § 11.60(b)(2)(i)(B), the information to be submitted in accordance with para- graph (b)(2)(ii) of this section must 42 CFR Ch. I (10–1–16 Edition) consist of the clinical trial results in- formation specified in § 11.60(b)(2)(i)(B). (C) If the clinical trial information voluntarily submitted for a clinical trial described by paragraph (b)(1) of this section consists of both the clin- ical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) and the clinical trial results information specified in § 11.48, the information to be submitted in accordance with paragraph (b)(2)(ii) of this section must consist of both the clinical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) and the clinical trial results information specified in § 11.48. (iv) Submission deadlines: (A) Secondary outcome measure(s) and adverse event information for vol- untarily submitted clinical trials, under paragraph (b) of this section: (1) If data collection for secondary outcome measure(s) for a voluntarily submitted clinical trial under para- graph (b) of this section is not com- pleted by the primary completion date of the voluntarily submitted clinical trial, clinical trial results information for the secondary outcome measure(s) required in § 11.48(a)(3) must be sub- mitted by the later of the date that the clinical trial results information is vol- untarily submitted for the primary outcome measure(s) or 1 year after the date on which the final subject was ex- amined or received an intervention for the purposes of final collection of data for the secondary outcome(s), whether the clinical trial was concluded accord- ing to the pre-specified protocol or was terminated. (2) If data collection for adverse event information continues after the primary completion date of the volun- tarily submitted clinical trial, any ad- verse event information collected after the primary completion date and sub- ject to the submission requirements in § 11.48(a)(4) must be submitted by the later of the date that the clinical trial results information is voluntarily sub- mitted for the primary outcome meas- ure(s) or 1 year after the date of final collection of data for adverse event in- formation, whether the clinical trial 156 Public Health Service, HHS § 11.60 was concluded according to the pre- specified protocol or was terminated. (B) The clinical trial information specified in paragraph (b)(2)(iii) of this section must be submitted not later than the later of the date on which the application or premarket notification to FDA for approval, licensure, or clearance to market a drug product (in- cluding a biological product) or device product under section 351 of the Public Health Service Act (42 U.S.C. 262) or section 505, 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355, 360(k), 360e, 360j(m)) for the use studied in the clinical trial specified under paragraph (b)(1) of this section is submitted to FDA or the date on which the clinical trial infor- mation specified in paragraph (b)(2)(i) of this section for the clinical trial specified under paragraph (b)(1) of this section is submitted to ClinicalTrials.gov. (c) If a responsible party voluntarily submits clinical trial information for a clinical trial described in paragraph (c)(1) of this section, the responsible party must meet the conditions speci- fied in paragraph (c)(2) of this section. (1) The requirements of paragraph (c) of this section apply to a clinical trial that was initiated on or after January 18, 2017 and has a primary completion date on or after January 18, 2017, and that is either: (i) A clinical trial of an FDA-regu- lated drug product (including a biologi- cal product) or device product that is not an applicable clinical trial; or (ii) An applicable clinical trial that is not otherwise required to submit clinical trial registration information. (2) If the responsible party for a clin- ical trial described in paragraph (c)(1) of this section voluntarily submits clinical trial registration information and/or clinical trial results informa- tion, the responsible party must com- ply with the following requirements: (i) The responsible party must sub- mit the information in paragraph (c)(2)(i)(A), (B), or (C) of this section for the clinical trial being submitted voluntarily. (A) If the responsible party volun- tarily registers a clinical trial, the re- sponsible party must submit the clin- ical trial registration information specified in § 11.28(a). (B) If the responsible party volun- tarily submits clinical trial results in- formation for a clinical trial for which the clinical trial registration informa- tion specified in § 11.28(a) has not been submitted, the responsible party must submit the data elements specified in paragraph (b)(2)(i)(B) of this section. (C) If the responsible party both vol- untarily submits clinical trial registra- tion information and voluntarily sub- mits clinical trial results information, the responsible party must submit both the clinical trial registration informa- tion specified in § 11.28(a) and the clin- ical trial results information specified in § 11.48. (ii) If, on or after September 27, 2007, a manufacturer submits an application or premarket notification to FDA for approval, licensure, or clearance of a drug product (including a biological product) or device product under sec- tion 505, 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355, 360(k), 360e, 360j(m)) or section 351 of the Public Health Service Act (42 U.S.C. 262) for the use studied in the clinical trial submitted under para- graph (c)(1) of this section, the respon- sible party specified in paragraph (c)(1) of this section must also submit the in- formation specified in paragraph (c)(2)(iii) of this section by the deadline specified in paragraph (c)(2)(iv)(B) of this section for any applicable clinical trial that has not been submitted to ClinicalTrials.gov and that meets the following criteria: (A) The applicable clinical trial is re- quired to be submitted to FDA under section 505, 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355, 360(k), 360e, 360j(m)) or section 351 of the Public Health Service Act (42 U.S.C. 262) in an application or premarket notification for approval, li- censure, or clearance to market the drug product (including a biological product) or device product for the use studied in the clinical trial specified in paragraph (c)(1) of this section; and (B) The manufacturer of the drug product (including a biological prod- uct) or device product studied in the applicable clinical trial is also the re- sponsible party for the clinical trial 157 § 11.60 specified in paragraph (c)(1) of this sec- tion. (iii) Information to be submitted for clinical trials described in paragraph (c)(2)(ii) of this section: (A) If the clinical trial information voluntarily submitted for a clinical trial described in paragraph (c)(1) of this section consists only of the clin- ical trial registration information specified in § 11.28(a), the information to be submitted in accordance with paragraph (c)(2)(ii) of this section must consist, at minimum, of the clinical trial registration information specified in § 11.28(a). (B) If the clinical trial information voluntarily submitted for a clinical trial described by paragraph (c)(1) of this section consists of the clinical trial results information specified in § 11.60(c)(2)(i)(B), the information to be submitted in accordance with para- graph (c)(2)(ii) of this section must consist of the clinical trial results in- formation specified in § 11.60(c)(2)(i)(B). (C) If the clinical trial information voluntarily submitted for a clinical trial described by paragraph (c)(1) of this section consists of both the clin- ical trial registration information specified in § 11.28(a) and the clinical trial results information specified in § 11.48, the information to be submitted in accordance with paragraph (c)(2)(ii) of this section must consist of both the clinical trial registration information specified in § 11.28(a) and the clinical trial results information specified in § 11.48. (iv) Submission deadlines: (A) Secondary outcome measure(s) and adverse event information for vol- untarily-submitted clinical trials, under paragraph (c) of this section: (1) If data collection for secondary outcome measure(s) for a voluntarily submitted clinical trial under para- graph (c) of this section is not com- pleted by the primary completion date of the voluntarily submitted clinical trial, clinical trial results information for the secondary outcome measure(s) required in § 11.48(a)(3) must be sub- mitted by the later of the date that the clinical trial results information is vol- untarily submitted for the primary outcome measure(s) or 1 year after the date on which the final subject was ex- 42 CFR Ch. I (10–1–16 Edition) amined or received an intervention for the purposes of final collection of data for the secondary outcome(s), whether the clinical trial was concluded accord- ing to the pre-specified protocol or was terminated. (2) If data collection for adverse event information continues after the primary completion date of the volun- tarily submitted clinical trial, any ad- verse event information collected after the primary completion date and sub- ject to the submission requirements in § 11.48(a)(4) must be submitted by the later of the date that the clinical trial results information is voluntarily sub- mitted for the primary outcome meas- ure(s) or 1 year after the date of final collection of data for adverse events in- formation, whether the clinical trial was concluded according to the pre- specified protocol or was terminated. (B) The clinical trial information specified in paragraph (c)(2)(iii) of this section must be submitted not later than the later of the date on which the application or premarket notification to FDA for approval, licensure, or clearance to market a drug product (in- cluding a biological product) or device product under section 351 of the Public Health Service Act (42 U.S.C. 262) or section 505, 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355, 360(k), 360e, 360j(m)) for the use studied in the clinical trial specified under paragraph (c)(1) of this section is submitted to FDA or the date on which the clinical trial infor- mation specified in paragraph (c)(2)(i) of this section for the clinical trial specified under paragraph (c)(1) of this section is submitted to ClinicalTrials.gov. (v) All submissions of clinical trial information under paragraph (c) of this section are subject to the applicable update and corrections requirements specified in § 11.64. (d) Statement to accompany applica- ble clinical trials submitted under paragraphs (a), (b), and (c) of this sec- tion. Each applicable clinical trial for which clinical trial information is sub- mitted under paragraphs (a), (b), and (c) of this section and posted on ClinicalTrials.gov will include the state- ment ‘‘This clinical trial information was submitted voluntarily under the 158 Public Health Service, HHS § 11.64 applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was sub- mitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.)’’ § 11.62 What requirements apply to ap- plicable clinical trials for which submission of clinical trial informa- tion has been determined by the Di- rector to be necessary to protect the public health? (a) A responsible party who receives notification that the Director has de- termined that posting of clinical trial information for an applicable clinical trial described in paragraph (b) of this section is necessary to protect the pub- lic health must submit clinical trial in- formation as specified in paragraph (c) of this section. (b) An applicable clinical trial sub- ject to this section must be either: (1) An applicable clinical trial of an approved, licensed, or cleared drug product (including a biological prod- uct) or device product that has a pri- mary completion date on or after Sep- tember 27, 1997; or (2) An applicable clinical trial that is subject to registration under § 11.22(a) and studies a drug product (including a biological product) or device product that is unapproved, unlicensed, or uncleared, regardless of whether ap- proval, licensure, or clearance was, is, or will be sought, and that is not other- wise subject to results information submission in accordance with the reg- ulation. (c) Deadline for submission of clin- ical trial information: (1) General. Except as provided in paragraphs (c)(2) and (c)(3) of this sec- tion, a responsible party for an applica- ble clinical trial that is subject to this section must submit the clinical trial registration information specified in § 11.28(a) and the clinical trial results information specified in § 11.48(a) not later than 30 calendar days after the submission date specified in the notifi- cation described in paragraph (a) of this section. (2) Exception. If a responsible party submits a certification consistent with § 11.44(b) or (c) not later than 30 cal- endar days after the submission date specified in the notification described in paragraph (a) of this section, the re- sponsible party must submit the clin- ical trial results information specified in § 11.48(a) not later than the deadline specified in § 11.44(b) or (c), as applica- ble. (3) If a responsible party submitted clinical trial registration information describing the applicable clinical trial specified in the notification described in paragraph (a) of this section prior to the date on which the notification is sent to the responsible party, the re- sponsible party must update such clin- ical trial information to reflect changes, if any, in the applicable clin- ical trial not later than 30 calendar days after the submission date speci- fied in the notification described in paragraph (a) of this section, irrespec- tive of the deadline for updates speci- fied in § 11.64. § 11.64 When must clinical trial infor- mation submitted to ClinicalTrials.gov be updated or corrected? (a) Updates. (1) Clinical trial registra- tion information: (i) The responsible party for an appli- cable clinical trial for which clinical trial registration information was re- quired to be submitted if the clinical trial was initiated before January 18, 2017, must submit updates in accord- ance with the following: (A) In general, changes to the clinical trial registration information specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) that was required at the time of submission must be updated not less than once every 12 months. (B) Overall Recruitment Status must be updated not later than 30 calendar days after any change in overall re- cruitment status. (C) Primary Completion Date must be updated not later than 30 calendar days after the clinical trial reaches its actual primary completion date. (ii) The responsible party for an ap- plicable clinical trial, or for another 159 § 11.64 clinical trial for which registration in- formation was voluntarily submitted pursuant to § 11.60(c), if the clinical trial was initiated on or after January 18, 2017, must submit updates in ac- cordance with the following: (A) In general, changes to clinical trial registration information specified in § 11.28 must be updated not less than once every 12 months. (B) If the first human subject was not enrolled in the clinical trial at the time of registration, the Study Start Date data element must be updated not later than 30 calendar days after the first human subject is enrolled. (C) Intervention Name(s) must be up- dated to a non-proprietary name not later than 30 calendar days after a non- proprietary name is established for any intervention included in the Interven- tion Name(s) data element. (D) Availability of expanded access: (1) If expanded access to an investiga- tional drug product (including a bio- logical product) becomes available after an applicable clinical trial of that product has been registered, the re- sponsible party, if both the manufac- turer of the investigational drug prod- uct (including a biological product) and the sponsor of the applicable clinical trial, must, not later than 30 calendar days after expanded access becomes available, update the Availability of Expanded Access data element for that applicable clinical trial and, unless an expanded access record has already been created as required by § 11.28(a)(2)(ii)(H), submit the data ele- ments in accordance with § 11.28(c) to create an expanded access record. (2) No later than 30 calendar days after the date on which the responsible party receives an NCT number for an expanded access record created as re- quired by § 11.28(a)(2)(ii)(H), the respon- sible party must update the Avail- ability of Expanded Access data ele- ment by entering the NCT number in the clinical trial record for the applica- ble clinical trial. (E) Expanded access record: (1) Expanded Access Status, under § 11.28(c)(2)(iv), must be updated not later than 30 calendar days after a change in the availability of expanded access to an investigational drug prod- uct (including a biological product) 42 CFR Ch. I (10–1–16 Edition) under section 561 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360bbb). (2) Expanded Access Type, under § 11.28(c)(1)(x), must be updated not later than 30 calendar days after a change in the type(s) of expanded ac- cess available for an investigational drug product (including a biological product) under section 561 of the Fed- eral Food, Drug, and Cosmetic Act (21 U.S.C. 360bbb). (F) Overall Recruitment Status must be updated not later than 30 calendar days after any change in overall re- cruitment status. If, at any time, Over- all Recruitment Status is changed to ‘‘suspended,’’ ‘‘terminated,’’ or ‘‘with- drawn,’’ the responsible party must also submit the Why Study Stopped data element. (G) Individual Site Status must be updated not later than 30 calendar days after a change in status for any indi- vidual site. (H) Human Subjects Protection Re- view Board Status must be updated not later than 30 calendar days after a change in status. (I) Primary Completion Date must be updated not later than 30 calendar days after the clinical trial reaches its ac- tual primary completion date. At the time, the date is changed to ‘‘actual,’’ and the Enrollment data element specifying the actual number of par- ticipants enrolled must be submitted. (J) Study Completion Date must be updated not later than 30 calendar days after the clinical trial reaches its ac- tual study completion date. (K) Responsible Party, by Official Title must be updated not later than 30 calendar days after a change in the re- sponsible party or the official title of the responsible party. (L) Responsible Party Contact Infor- mation must be updated not later than 30 calendar days after a change in the responsible party or the contact infor- mation for the responsible party. (M) Device Product Not Approved or Cleared by U.S. FDA must be updated not later than 15 calendar days after a change in approval or clearance status has occurred. (N) Record Verification Date must be updated any time the responsible party reviews the complete set of submitted 160 Public Health Service, HHS § 11.64 clinical trial information for accuracy and not less than every 12 months, even if no other updated information is sub- mitted at that time. (O) If a protocol is amended in such a manner that changes are commu- nicated to human subjects in the clin- ical trial, updates to any relevant clin- ical trial registration information data elements must be submitted not later than 30 calendar days after the pro- tocol amendment is approved by a human subjects protection review board. (iii) In addition to the update re- quirements established in paragraphs (a)(1)(i) and (a)(1)(ii) of this section, clinical trial registration information must be updated at the time that clin- ical trial results information for that clinical trial is initially submitted. (A) If the clinical trial was initiated before January 18, 2017, a responsible party must submit updates to the clin- ical trial registration information de- scribed in § 11.64(a)(1)(i). (B) If the clinical trial was initiated on or after January 18, 2017, the respon- sible party must submit updates to the clinical trial registration information in accordance with § 11.64(a)(1)(ii). (2) Clinical trial results information. The responsible party for an applicable clinical trial, or for another clinical trial for which results information was voluntarily submitted pursuant to § 11.60(b) or (c), where the clinical trial has a Primary Completion Date on or after January 18, 2017, must submit up- dates in accordance with the following: (i) In general, changes to required clinical trial results information, other than the protocol and statistical anal- ysis plan specified in § 11.48(a)(5) and certain agreements specified in § 11.48(a)(6)(ii),must be updated not less than once every 12 months. (ii) For applicable device clinical trials of unapproved or uncleared de- vice products, the responsible party must update the following data ele- ments, as defined in § 11.10(b), in ac- cordance with the following: (A) Intervention Name(s) must be up- dated to a non-proprietary name not later than 30 calendar days after a non- proprietary name is established for any intervention included in the Interven- tion Name(s) data element. (B) Primary Completion Date must be updated not later than 30 calendar days after the clinical trial reaches its actual primary completion date. At the time the date is changed to ‘‘actual,’’ the Enrollment data element speci- fying the actual number of participants enrolled must be submitted. (C) Study Completion Date must be updated not later than 30 calendar days after the clinical trial reaches its ac- tual study completion date. (D) Overall Recruitment Status must be updated not later than 30 calendar days after any change in overall re- cruitment status. If, at any time, Over- all Recruitment Status is changed to ‘‘suspended,’’ ‘‘terminated,’’ or ‘‘with- drawn,’’ the responsible party must also submit the Why Study Stopped data element. (E) Record Verification Date must be updated any time the responsible party reviews the complete set of submitted clinical trial information for accuracy and not less than every 12 months, even if no other updated information is sub- mitted at that time. (3) A responsible party’s obligation to submit updates as specified in this sec- tion ends on the date on which all re- quired clinical trial results informa- tion has been submitted as specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C)) and 42 U.S.C. 282(j)(3)(I)) or as specified in § 11.48, as applicable, and corrections have been made or addressed in response to any electronic notice received under § 11.64(b)(1). If no clinical trial results information is required to be sub- mitted, a responsible party’s obligation to submit updates to clinical trial reg- istration information ends on the date on which all required clinical trial reg- istration information has been sub- mitted as specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii) or § 11.28, as applicable, and corrections have been made or addressed in re- sponse to any electronic notice re- ceived under § 11.64(b)(1). (4) Public availability of updates. (i) Updates to clinical trial registration information and clinical trial results 161 § 11.66 information will be posted in accord- ance with § 11.35 and § 11.52, respec- tively. (ii) The Director will retain prior clinical trial registration information and clinical trial results information and make it publicly available in ac- cordance with § 11.35 and § 11.52, respec- tively, through ClinicalTrials.gov so that updates do not result in the re- moval of any information from the original submission or any preceding update. (b) Corrections—(1) Quality control. After clinical trial registration infor- mation has been submitted as specified in section 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) or § 11.28, as applicable, or clinical trial results information has been submitted as specified in sections 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)) or § 11.48, as applicable, including the up- dates specified in paragraph (a) of this section, the Director may provide elec- tronic notification to the responsible party of apparent errors, deficiencies, and/or inconsistencies in the submitted information identified during proce- dures for quality control review estab- lished by the Director, as specified at https://prsinfo.clinicaltrials.gov. The re- sponsible party must correct or address all apparent errors, deficiencies, and/or inconsistencies identified in the notifi- cation not later than 15 calendar days for clinical trial registration informa- tion, or 25 calendar days for clinical trial results information, after the date of the electronic notification sent to the responsible party. (2) Other corrections. (i) A responsible party who becomes aware of errors, other than those specified in paragraph (b)(1) of this section, in any clinical trial information submitted under this part shall have not more than 15 cal- endar days for clinical trial registra- tion information, or 25 calendar days for clinical trial results information, to correct or address such errors. (ii) A responsible party’s obligation to correct or address errors as specified in paragraph (b)(2) of this section ends on the date on which all required clin- ical trial results information has been submitted as specified in sections 42 CFR Ch. I (10–1–16 Edition) 402(j)(3)(C) and 402(j)(3)(I) of the Public Health Service Act (42 U.S.C. 282(j)(3)(C) and 42 U.S.C. 282(j)(3)(I)) or § 11.48, as applicable, and corrections have been made or addressed in re- sponse to any electronic notice re- ceived under § 11.64(b)(1). If no clinical trial results information is required to be submitted, a responsible party’s ob- ligation to correct or address errors ends on the date on which all required clinical trial registration information has been submitted as specified in sec- tion 402(j)(2)(A)(ii) of the Public Health Service Act (42 U.S.C. 282(j)(2)(A)(ii)) or § 11.28, as applicable, and corrections have been made or addressed in re- sponse to any electronic notice re- ceived under § 11.64(b)(1). (3) Compliance with the quality con- trol review process, including the re- quirements of this section, does not constitute a legal defense to enforce- ment pursuant to section 301(jj) of the Federal Food, Drug and Cosmetic Act (21 U.S.C. 331(jj)), section 303(f)(3) of the Federal Food, Drug and Cosmetic Act (21 U.S.C. 333(f)(3)), or any other Fed- eral law. Subpart E—Potential Legal Con- sequences of Non-Compli- ance § 11.66 What are potential legal con- sequences of not complying with the requirements of this part? (a) Civil or criminal judicial actions. Failure to comply with the require- ments of this part, issued under section 402(j) of the Public Health Service Act (42 U.S.C. 282(j)), is a prohibited act under one or more provisions of section 301(jj) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 331(jj)): (1) Failure to submit the certifi- cation required by section 402(j)(5)(B) of the Public Health Service (42 U.S.C. 282(j)(5)(B)) that all applicable require- ments of section 402(j) have been met, or knowingly submitting a false cer- tification under section 402(j)(5)(B), is a prohibited act under section 301(jj)(1) of the Federal Food, Drug, and Cos- metic Act. (2) Failure to submit clinical trial in- formation required under section 402(j) of the Public Health Service Act is a prohibited act under section 301(jj)(2) 162 Public Health Service, HHS § 11.66 of the Federal Food, Drug, and Cos- metic Act. (3) Submission of clinical trial infor- mation under section 402(j) that is false or misleading in any particular is a prohibited act under section 301(jj)(3) of the Federal Food, Drug, and Cos- metic Act. (b) Civil monetary penalty actions. Any person who violates section 301(jj) of the Federal Food, Drug, and Cosmetic Act is subject to civil monetary pen- alties under section 303(f)(3) of the Fed- eral Food, Drug, and Cosmetic Act (21 U.S.C. 333(f)(3)). (c) Grant funding actions. Under sec- tion 402(j)(5)(A) of the Public Health Service Act (42 U.S.C. 282(j)(5)(A)), if an applicable clinical trial is funded in whole or part by the Department of Health and Human Services, any re- quired grant or progress report forms must include a certification that the responsible party has made all required registration and results submissions. If it is not verified that the required reg- istration and results clinical trial in- formation for each applicable clinical trial for which a grantee is the respon- sible party has been submitted, any re- maining funding for a grant or funding for a future grant to such grantee will not be released. If the head of an HHS agency verifies that a grantee has not submitted such required clinical trial information, the agency head will pro- vide notice to the grantee of the non- compliance and allow the grantee 30 days to correct the non-compliance and submit the required clinical trial infor- mation. 163