For applicable clinical trials regulated by the U.S. Food and Drug Administration (FDA) that are initiated on or after March 7, 2012, sponsors, investigators and institutional review boards will have to assure compliance with an additional informed consent requirement.¹ A revision of FDA regulations requires investigators and sponsors of such clinical trials to include the following statement in informed consents:

A description of this clinical trial will be available onhttp://www.ClinicalTrials.gov, as required by U.S. Law. This Website 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.

ClinicalTrials.gov is the National Institutes of Health (NIH) website where all “applicable clinical trials” must be registered and trial results posted in accordance with the U.S. Food Drug Administration Amendment Act of 2007 (FDAAA).² Registration must occur no later than 21 days after the first subject enrolls, and study results must be posted within 12 months of completion of the data collection for the primary outcome.³ The new informed consent regulation comes on the heels of recent criticism raised by U.S. House of Representatives Henry Waxman, D-CA, Ed Markey, D-MA, and Diana DeGette, D-CO, directed to the FDA Commissioner and to the NIH related to alleged non-compliance with ClinicalTrials.gov registration and data posting requirements.

The discussion below addresses practical questions relating to implementation of the new regulatory requirements.

What is an “applicable clinical trial”?

Under the FDAAA, an “applicable clinical trial”⁴ includes clinical studies on human subjects that:

>> Are interventional (i.e., a prospective study);

>> Are controlled (i.e., has one or more arms); and

>> Involve the use of a drug, device or biologic being tested in the United States or its territories or is conducted under an investigational new drug application (IND) or investigational device exemption (IDE).

The definition of “applicable clinical trial” excludes Phase I drug trials and device studies aimed at obtaining feasibility data as opposed to health outcomes. In addition, studies using de-identified human specimens as defined under the HIPAA Privacy Rule would not be considered “human subject research” and thus would not be considered an “applicable clinical trial.”

Can the informed consent language quoted above be modified?

No. Any deviation from the language above would be deemed to be out of compliance with requirements of the FDAAA. Additional language may be included in the consent to further explain the purpose and nature of the statement, provided that the language quoted above is not modified.

Is the requirement retroactive?

The regulations require the specified informed consent statement to be included in the consent documents for all applicable clinical trials initiated on or after March 7, 2012. A study is considered “initiated” on the date that final approval of an informed consent was granted by the reviewing institutional review board (IRB). Accordingly, if a study (including its consent form) was approved March 6, 2012, the requirement would not apply. Multi-center study consent documents that do not include the statement are not out of compliance if at least one of the study site’s informed consent documents was approved by an IRB prior to March 7, 2012. 

Re-consent of subjects enrolled in clinical trials initiated prior to March 7, 2012 is not required. From a practical perspective, however, investigators and sponsors may choose to include the required language in consent forms for “applicable clinical trials” even if study initiation will occur prior to March 7, 2012.

Must studies outside of the U.S. comply with the new informed consent requirements?

Studies conducted outside of the U.S. should include the required statement in consent documents if study results will be used for a U.S. regulatory submission. The FDA’s acceptance of data from foreign “applicable clinical trials” may be conditioned on compliance with the ClinicalTrials.gov registration and posting requirement and the new informed consent requirement. 

Who is responsible for inclusion of the statement in the informed consent document?

The sponsor and investigator are responsible and should make the determination as to whether the clinical trial is an “applicable clinical trial,” to which the new informed consent requirements would apply.

What is the IRB’s role in reviewing the informed consent language, and how does the new regulation impact the IRB’s ability to waive elements of informed consent?

The IRB’s role includes reviewing the informed consent document to assure compliance with the new informed consent requirements. Applicable law permits waiver of informed consent in very limited circumstances involving life threatening emergency, public health emergencies and military operations (21 C.F.R. § 50.23), and in emergency research (21 C.F.R. § 50.24). If the IRB were to waive written consent under 21 C.F.R. § 56.109(c) (1), it should be expected that the investigator and sponsor would include the required statement in the oral presentation provided to a subject in such a situation.

_{1 75 Fed. Reg. 259 (Jan. 4, 2011)}

_{2 See § 801(b)(3)(A) of the FDA Amendments Act of 2007 (Pub. L. 110-85, Sept. 27, 2007).}

_{3 Id.}

_{4 See definition of “applicable clinical trial” at 42 U.S.C. § 282(j)(1)(A).}