“Enrolled” is defined in 42 CFR 11.10(a) as a human subject’s, or their legally authorized representative’s, agreement to participate in a clinical trial following completion of the informed consent process, as required in 21 CFR Part 50 and/or 45 CFR Part 46, as applicable. The regulation explains that, for the purposes of this part, potential subjects who are screened for the purpose of determining eligibility for a trial, but do not participate in the trial, are not considered enrolled, unless otherwise specified by the protocol.
The Enrollment data element is defined in 42 CFR 11.10(b)(18) as 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. That regulation further explains that once the trial has reached the primary completion date, the responsible party must update the Enrollment data element to reflect the actual number of human subjects enrolled in the clinical trial.
The Final Rule preamble (81 FR 65022) provides additional clarification of the “enroll or enrolled” definition in 42 CFR 11.10(a) by addressing two scenarios involving signing of the informed consent document. The first scenario involves the use of a separate informed consent document for screening. In this situation, there are two distinct informed consent documents: one for trial screening (for eligibility) and if eligible, one for trial participation. Under this first scenario, the signing of the second separate informed consent document for trial participation would mean the subject is enrolled in the clinical trial.
In the second scenario, there is only one informed consent document for both trial screening and trial participation. In this scenario, the Final Rule preamble explains that a participant would not be considered enrolled until he or she met all the eligibility criteria assessed during screening, unless the participant is considered enrolled as outlined specifically in the protocol. (81 FR 65022) The Final Rule preamble further explains that when there is only one informed consent document for both trial screening and trial participation, registration information must be submitted as described in 42 CFR 11.24 no later than 21 calendar days after the first participant signs the informed consent form and begins trial participation, in accordance with the protocol.
Based on this clarification, when there is only one informed consent document for both trial screening and trial participation, whether a human subject “participates” in a study, and is therefore considered “enrolled” under the definition in 42 CFR 11.10(a), is determined by the protocol. This determination may vary across clinical trial protocols. For example, assignment to a study arm may be considered the beginning of trial participation based on a particular study protocol. In this example, if the study was halted prematurely before any subjects were assigned to a study arm (i.e., the Overall Recruitment Status is “Withdrawn”), none of the subjects would be considered enrolled, even though they had already signed the informed consent document. Also, if a human subject signs the informed consent document but then withdraws his or her informed consent before participation begins, the subject would not be considered “enrolled” in the clinical trial under the definition.
We also note that the definition of “enrolled” is important for determining the Study Start Date. Study Start Date is defined in 42 CFR 11.10(b)(16) as the estimated 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.
