NOTE: These instructions are consistent with the 2018 Requirements (i.e., the revised Common Rule)
The revised Common Rule (also referred to as the 2018 Requirements)1 at 45 CFR 46.116(h) requires that for each clinical trial conducted or supported by a federal department or agency, one IRB-approved consent form used to enroll subjects must be posted on a publicly available federal website by the awardee or the federal department or agency component conducting the trial. These instructions apply to clinical trials that are conducted or supported by HHS.
At 45 CFR 46.102(b), a clinical trial is defined as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes.
This document provides general instructions on how to comply with 45 CFR 46.116(h). While this document is described as “Instructions,” it includes numerous references to statutory and regulatory requirements, which are generally described as procedures that “must” or “shall” be followed. Where the document describes suggested compliance procedures or nonbinding agency guidance, it generally uses the terms “should” or “recommended” to describe them.
At this time, two federal websites have been identified as places where consent forms can be posted to satisfy 45 CFR 46.116(h): ClinicalTrials.gov2 and a designated docket folder on Regulations.gov (Docket ID: HHS-OPHS-2018-0021).3 The awardee or the federal department or agency conducting the clinical trial may select either website to satisfy the posting requirement.
If ClinicalTrials.gov is selected, a consent form can only be uploaded if the clinical trial is also registered with that website. If the clinical trial is not already registered with ClinicalTrials.gov, then as part of ClinicalTrials.gov registration, information about the trial must be submitted4 and other requirements may be triggered. While the submission of information other than consent forms to ClinicalTrials.gov is not required by the Common Rule, the submission of this additional information is required by the ClinicalTrials.gov final rule, which implements the provisions of section 402(j) of the Public Health Service Act (42 U.S.C. 282(j)).
Posting is required for two categories of clinical trials:
Category 1. Nonexempt clinical trials (as defined by 45 CFR 46.102(b)) conducted or supported by HHS, initially approved by an IRB on or after January 21, 2019.
Category 2. Nonexempt clinical trials (as defined by 45 CFR 46.102(b)) conducted or supported by HHS, initially approved by an IRB before January 21, 2019, that continue on or after January 21, 2019, and for which both of the following are true:
As previously discussed, two federal websites have been identified as satisfying 45 CFR46.116(h): ClinicalTrials.gov and a designated docket folder on Regulations.gov (Docket ID: HHS-OPHS-2018-0021).5 Any clinical trial conducted or supported by HHS must use one of these websites to satisfy 45 CFR 46.116(h). Clinical trial consent forms may be posted to either location.
General information on the format for documents uploaded to ClinicalTrials.gov, including informed consent documents, may be found here:
Specific instructions on how to upload a consent form to the designated docket folder on Regulations.gov may be found on the OHRP website.8
Additional federal websites that will satisfy 45 CFR 46.116(h) may be identified in the future; if so, these instructions will be updated.
The 2018 Requirements state that a consent form must be posted to a designated federal website after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject, as required by the protocol. While a consent form could be posted before a clinical trial closes recruitment, it does not satisfy the requirement at 45 CFR 46.116(h). If a consent form is posted before a clinical trial closes recruitment, it would have to be re-posted after the clinical trial closes recruitment in order for 45 CFR 46.116(h) to be satisfied.
A clinical trial could also close recruitment 61 or more days after the last study visit by any subject, as required by the protocol. This could happen, for example, if a clinical trial ends early because of safety concerns or because of low enrollment. The 2018 Requirements are silent on when a consent form must be posted in order to satisfy 45 CFR 46.116(h) in these circumstances. If a clinical trial closes recruitment 61 or more days after the last study visit by any subject as required by the protocol, OHRP recommends that posting should occur within 60 days of the clinical trial closing to recruitment.
Not all transitioned clinical trials are required to comply with 45 CFR 46.116(h). As described above, clinical trials initially approved before January 21, 2019, that transition to comply with the 2018 requirements generally must comply with 45 CFR 46.116(h) if an institution’s transition determination was documented and dated before the time period specified in 45 CFR 46.116(h)(3) has passed. In other words, studies that have been transitioned to comply with the 2018 Requirements do not have to comply with 45 CFR 46.116(h) if an institution’s transition determination was documented and dated 61 or more days after the last protocol-required study visit by any enrolled subject.
In some circumstances, a clinical trial that an institution transitions to comply with the 2018 Requirements may have used a consent form that complies with the pre-2018 Requirements but not the 2018 Requirements in order to enroll subjects.9 Such consent forms may be posted to satisfy 45 CFR 46.116(h) so long as the form was used to enroll subjects.
OHRP considers the last study visit that occurs only because of the research project (i.e., that would not have happened as part of routine clinical care) to be the “last study visit by any subject, as required by the protocol,” for the purposes of 45 CFR 46.116(h). Further, OHRP’s interpretation is that the last study visit does not have to be an in-person visit. It could be any visit that a subject has with the research team including in-person visits, filling out a survey, or a final telephone conversation, that is required by the protocol.
For example, if a clinical trial requires that subjects fill out surveys after each study-related doctor visit, OHRP would consider the final survey to be the last study visit by any subject as required by the protocol.
In contrast, if an investigator indicates in a protocol that the investigator will collect data by accessing 5 years of follow-up clinical data from procedures that subjects would undergo as part of clinical care, OHRP would not consider these follow-up visits or the investigator’s collection of clinical data from these follow-up visits to be a study visit required by the protocol under 45 CFR 46.116(h). This is because these visits would have occurred irrespective of the research, and no part of the follow-up clinical visits is different than what would occur outside of the research context. In addition, the investigator’s continued collection of the clinical data from the follow-up clinical visits is not considered to be a study visit for purposes of 45 CFR 46.116(h).
Note that with respect to multisite studies, OHRP considers that the last study visit by any subject, as required by the protocol, refers to the last study visit that occurs at any of the sites involved in the research activity, not to the last study visit that occurs at a particular site.
Under the 2018 Requirements, “the awardee(s)” or a federal agency component(s) conducting a trial, is (are) responsible for compliance with this posting requirement. For the purposes of 45 CFR 46.116(h), OHRP interprets the term “awardee” to refer to the institution (or one of the institutions) engaged in the HHS-conducted or -supported research. However, the posting responsibility may be assigned to an investigator or IRB staff person, among others. For example, an awardee may assign the posting responsibility to the principal investigator on a protocol or to a contractor. For the purpose of satisfying 45 CFR 46.116(h), OHRP considers the entity responsible for posting to be either the awardee or the HHS component conducting the trial. In cooperative research studies, the entity(ies) responsible for posting is (are) also the awardee(s) or the HHS component(s) conducting the trial.
If multiple awardees or multiple federal agency components are conducting the clinical trial, any one of these entities can post a clinical trial informed consent form to satisfy 45 CFR 46.116(h). In such scenarios, OHRP recommends that awardees or federal agency components reach agreement on which awardee or federal agency component will post a clinical trial informed consent form. As described previously, only one clinical trial informed consent form needs to be posted in order to satisfy 45 CFR 46.116(h).
If ClinicalTrials.gov is used to satisfy the Common Rule’s posting requirement: The awardee or HHS component conducting the trial, as specified in the 2018 Requirements at 45 CFR 46.116(h)(1), is legally responsible for posting clinical trial consent forms. However, the responsible party, as defined by the ClinicalTrials.gov final rule (see 42 CFR 11.10(a)), is legally responsible for meeting the requirements of 42 CFR part 11 and can upload information for a registered clinical trial to ClinicalTrials.gov. In order to submit a consent form to ClinicalTrials.gov, a responsible party must register the trial with ClinicalTrials.gov, which may trigger other requirements under the ClinicalTrials.gov final rule at 42 CFR part 11.
Under 45 CFR 46.116(h)(2), if a federal department or agency conducting or supporting a clinical trial determines that certain information should not be made public on a federal website, the federal department or agency may permit or require redactions to the information posted. Redacted forms may be posted only if the federal department or agency conducting or supporting a trial has permitted or required the redactions.
Yes. Uploading and submitting a clinical trial consent form to either ClinicalTrials.gov or Regulations.gov will be considered to satisfy the posting requirement at 45 CFR § 46.116(h).
The requirement for posting at 45 CFR § 46.116(h) states that only one IRB-approved consent form used in subject enrollment must be posted for each clinical trial. More than one IRB-approved consent form used in subject enrollment may be posted, but only one is required.
No. While it is permissible for an updated consent form to be posted, the 2018 Requirements do not require this.
45 CFR § 46.116(h) does not specify a language for a posted consent form. OHRP recommends that if an English language consent form is available, that version of the form should be posted. Note that the ClinicalTrials.gov Protocol Registration and Results System (PRS) User’s Guide10 states that all clinical trial information must be submitted in English. Clinical trial informed consent forms written in a language other than English may be submitted to the Regulations.gov docket folder.
Yes. Do not post any documents that have been signed by research subjects or that contain names of individual research subjects. No personally identifiable information (PII) or other patient information should be on the form.
45 CFR 46.116(h) requires that one IRB-approved consent form be posted for each clinical trial. Thus, for cooperative research where different versions of a consent form might be used at different sites, only one consent form must be posted. More than one IRB-approved informed consent form may be posted, but only one is required under the 2018 Requirements.
The earliest that a consent form may be posted in order to satisfy 45 CFR 46.116(h) is when all sites have closed recruitment.
In this scenario, part of the clinical trial is being conducted by an HHS component. For this reason, 45 CFR 46.116(h) applies to the clinical trial as conducted at the HHS research institutions. Only one clinical trial consent form needs to be posted in order for the posting requirement to be satisfied for all HHS sites. The earliest that a consent form may be posted to satisfy 45 CFR 46.116(h) is when all HHS sites have closed to recruitment.
As previously described, under the 2018 Requirements it is up to the awardee or HHS component conducting the clinical trial to decide whether to post a clinical trial consent form to the designated docket folder on Regulations.gov or to ClinicalTrials.gov. (Note that additional posting locations might be identified in the future.)
One factor to consider in deciding where to post a form is whether the individual responsible for posting is the same as the responsible party who is required under the ClinicalTrials.gov final rule to update a clinical trial record. For example, if the cooperative research activity is industry-sponsored but involves an HHS research site or sites, the individual responsible for the ClinicalTrials.gov entry in accordance with the ClinicalTrials.gov final rule might not be associated with the HHS site(s). In that circumstance, the HHS research site(s) can use Regulations.gov to satisfy 45 CFR 46.116(h). Alternatively, the HHS research site(s) could work with the responsible party responsible for maintaining the ClinicalTrials.gov record to upload a consent form in accordance with 45 CFR 46.116(h) and the ClinicalTrials.gov final rule.
No, if documentation of informed consent is waived in accordance with 45 CFR 46.117(c)(1), the posting requirement does not apply.
Yes. If a short form written consent procedure is used, then one copy of the short form and the study summary that was presented orally to subjects during subject enrollment (as required by 45 CFR 46.117(b)(2)) must be posted.
No. A clinical trial that is subject to the 2018 Requirements only because the institution has checked the box on its FWA is not required to comply with the consent form posting requirement at 45 CFR 46.116(h).