Shanna Ford is an Associate in our Miami office and Christopher O'Brien a Partner in our Washington, D.C. office
Effective March 7, 2012, provisions of the Food and Drug Administration Amendments Act of 2007 (FDAAA) will require new and specific language to be included in the informed consent document of most U.S. interventional studies of FDA-regulated medications and medical devices.1 The language pertains to the requirement of ClinicalTrials.gov postings, and must be replicated word-for-word. The FDA recently issued a guidance document concerning the new rule and its requirements.2
New Mandatory Language in Certain Informed Consent Documents
In accordance with Section 801 of the FDAAA, the informed consent regulations of 21 CFR 50.25 were amended3 to require informed consent documents and processes for applicable drug (including biologic products) and device clinical trials initiated on or after March 7, 2012. The following statement must be included, word-for-word:
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, 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.4
The statement is considered the means by which investigators and sponsors will inform the participants of applicable clinical trials of the availability of information about the clinical trial in the clinical trial registry databank. It is necessary for the statement to be reproduced word-for-word since doing so avoids the following:
- clinical trial investigators and sponsors performing individual analysis to determine what statement needs to be included in the informed consent documents
- the use of different statements for different clinical trials
However, it is permissible for investigators, sponsors and institutional review boards (IRBs) to provide additional explanation of the statement in the informed consent documents if they deem it necessary. Furthermore, there is no requirement for the statement to be located in any particular section of the informed consent form. Investigators and IRBs can place the language where they believe it is most beneficial to serve the trial participant's best interest. Also, if the clinical trial participants are not English speaking or if the consent interviews will be conducted in a language other than English, the institutional review board should require a translation of the statement into the applicable language and should ensure that such a translation is prepared by a qualified individual.
There is no statutory waiver of the requirements to include the statement in the informed consent documents and processes. As a general matter, FDA regulations allow waiver from requiring informed consent for participation in FDA-regulated clinical investigations only under limited circumstances.5 Even if there is a waiver to the documentation of informed consent,6 the trial participant must still provide consent, so the statement is required during the oral presentation of the clinical trial research and/or in the written statement regarding the research, if, as permitted by the regulations, it is required by the IRB.7 Consequences for not complying with the new requirement include administrative, civil and criminal penalties.8
Initiation Date
The required statement must be included in informed consent documents and processes of applicable clinical trials initiated after March 7, 2012. It is the responsibility of the trial sponsor to determine the initiation date. "Initiation" means the clearance of any informed consent documents by an institutional review board or other ethics review committee. Therefore, if the applicable clinical trial is a multi-site clinical trial and the informed consent documents for at least one site have been approved before March 7, 2012, then all of the informed consent documents for the applicable clinical trial are deemed to have been initiated before March 7, 2012. In such a situation, the new statement is not required in any of the informed consent documents (even those for other sites) nor do applicable clinical trial subjects who consented prior to March 7, 2012, need to consent again. Furthermore, if there are any revisions to the informed consent documents, the revised informed consent documents do not need to contain the required statement.
Applicable Clinical Trial
Since the new regulations pertain to "applicable clinical trials,"9 it is important to understand what clinical trials are considered "applicable clinical trials" within the meaning of the regulation. It is the responsibility of the clinical trial sponsors and investigators to make such a determination. According to the FDA guidance document, applicable clinical trials generally include "controlled interventional studies (with one or more arms) of drugs, biological products, or devices that are subject to FDA regulation, meaning that the trial has one or more sites in the United States, involves a drug, biologic, or device that is manufactured in the United States (or its territories), or is conducted under an investigational new drug application (IND) or investigational device exemption (IDE)." There is further distinguishing between applicable clinical device trials and applicable clinical drug trials. An applicable clinical device trial is a trial that (i) prospectively compares a device-based intervention subject to FDA regulation against a control in human subjects; or (ii) is a pediatric post-market surveillance trial.10 An applicable clinical drug trial is a trial that is a controlled clinical investigation, other than a phase I clinical investigation, of a drug subject to FDA regulation.11
It is important to note that "applicable clinical trials" do not include, for devices, "small feasibility trials and larger clinical trials of prototype devices with a primary measure of feasibility rather than health outcomes"12 nor trials including only de-identified human specimens and not "human subjects."13 For drugs, phase I clinical investigations are not considered "applicable clinical trials." For both devices and drugs, "applicable clinical trials" also does not include uncontrolled clinical investigations. If the clinical trial is not an applicable clinical trial, then the statement is not necessary, however even if it is not an applicable clinical trial, there is nothing in the new regulation prohibiting clinical trial investigators or sponsors from voluntarily reporting data on ClinicalTrials.gov and informing participants of such reporting.
The new statement is also required in informed consent documents — even if the applicable clinical trial is conducted in a foreign country. However, the requirement does not preclude the insertion of mandatory or recommended language from governments other than the United States nor does it preclude reference to other clinical trial registries or regulatory bodies.
Additional Considerations
The requirement for the new statement has not altered the institutional review board process. As such, institutional review boards continue to have the responsibility to review and approve informed consent documents.14 In the event an error is made and the statement is not included in the informed consent documents and processes of applicable clinical trials, the clinical trial investigator or sponsor should notify the institutional review board as soon as possible and submit a revised informed consent form that includes the statement to the institutional review board for review and approval. It should also be noted that parent or guardian permission for children to participate in clinical trials must include elements of informed consent,15 therefore parent and guardian consent forms must also contain the required statement.
Footnotes
1 Food and Drug Administration Amendments Act of 2007, Pub L. No. 110-85 § 801, 121 Stat. 904 (2007).
2 Guidance for Sponsors, Investigators, and Institutional Review Boards: Questions and Answers on Informed Consent Elements, 21 CFR § 50.25(c), February 2012, http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM291085.pdf
3 Informed Consent Elements, 76 Fed. Reg. 256 (Jan. 4, 2011) (to be codified at 21 CFR § 50.25(c)).
4 21 CFR § 50.25(c).
5 See 21 CFR §§ 50.23, 50.24.
6 See 21 CFR § 56.109(c)(1).
7 See 21 CFR §56.109(d).
8 See 21 U.S.C. § 303(a); 21 CFR §§ 312.44(b)(1)(ix), 312.70(a), 812.30(b)(4), 812.119(a), 56.121(b).
9 42 USC § 282(j)(1)(A).
10 42 USC § 282(j)(1)(A)(ii).
11 42 USC § 282(j)(1)(A)(iii)(I). A "clinical investigation" is "any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects." 21 CFR § 312.3.
12 42 USC § 282(j)(1)(A)(ii).
13 Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable, April 2006, http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM071265.pdf
14 21 CFR § 56.109(b).
15 21 CFR § 50.3(r).
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