In 2007, the Food and Drug Administration (FDA) issued regulations under the Food and Drug Administration Amendments Act of 2007 requiring that all “applicable clinical device trials” and “applicable clinical drug trials” (both defined below) initiated after September 27, 2007, must be registered on not later than 21 days after the first patient is enrolled. On January 4, 2011, FDA issued a final rule modifying the informed consent requirements (76 Fed. Reg. 256 (Jan. 4, 2011)). On February 9, 2012, FDA issued the Guidance, “Questions and Answers on Informed Consent Elements, 21 CFR § 50.25(c).” This Guidance is intended to help sponsors, investigators and Institutional Review Boards (IRBs) better understand the new informed consent requirement set forth in 21 CFR 50.25(c).

The January 2011 Final Rule amended FDA’s informed consent regulations to require that informed consent documents and processes for applicable drug (including biological products) and device clinical trials include a specific statement (below) that clinical trial information will be entered into the clinical trial registry databank maintained by the National Institutes of Health/National Library of Medicine (NIH/NLM). It is applicable to all clinical trials initiated on or after March 7, 2012.

The Guidance explains that the following statement must be reproduced word-for-word in informed consent documents for applicable clinical trials:

“A description of this clinical trial will be available on, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”

This statement does not have to be located in any particular section of the consent form. It may be translated if potential participants are non-English speaking.

If an IRB has already approved any informed consent documents for the applicable clinical trial prior to March 7, 2012, then the trial will be considered “initiated” before the compliance date, and the new statement will not be required. Even if documentation of informed consent is waived under the applicable regulations (e.g., the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside the research context), to the extent the IRB requires the investigator to provide subjects with a written statement regarding the research, the written statement is considered a part of the documentation of ensuring the informed consent of the participant and, thus, must include the new statement. Similarly, if an IRB requires the investigator to provide subjects with an oral presentation of the research, the statement should be made to subjects.

The trial is an “applicable clinical device trial” if (i) the trial prospectively compares a device-based intervention subject to FDA regulation against a control in human subjects; or (ii) the trial is a pediatric post-market surveillance trial. The trial is an “applicable clinical drug trial” if the trial is a controlled clinical investigation, other than a Phase I clinical investigation, of a drug subject to FDA regulation. For the purposes of this definition, a “clinical investigation” is “any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects.”

Currently excluded from the definition of “applicable clinical device trials” are:

  1. small feasibility trials and larger clinical trials of prototype devices with a primary measure of feasibility rather than health outcomes; and
  2. a device trial in which the trial includes only de-identified human specimens and does not include “human subjects.”

Currently excluded from the definition of “applicable clinical drug trials” are:

  1. Phase 1 clinical investigations; and
  2. uncontrolled clinical investigations of drugs or devices.

FDA’s elaboration on the definition of “applicable clinical trial” is available at: http://prsinfo.clinicaltrials. gov/ElaborationsOnDefinitions.pdf. The full text of the Guidance is available at: downloads/RegulatoryInformation/Guidances/UCM291085.pdf?source=govdelivery.