Provide a protocol and informed consent document for each planned study.
Refer to 21 CFR 312.23(6) for complete protocol requirements. The general summary of the overall research plan should be followed by the "Executive Summary" section(s) of the protocol template (or some similar brief protocol summary) for each protocol to be included in this IND application. The actual full protocol(s) is/are to be included as an attachment to this application (see last section below describing attachments).
Due to the unpredictable nature of Phase 1 studies, Phase 1 protocols can be flexible and more focused on providing a general outline of the clinical investigation (dosing plan, safety precautions). Additionally, following IND approval, changes to Phase 1 protocols that do not affect the safety of subjects need only be included in IND annual reports, not more frequent amendments.
The main components of a clinical protocol are described in Guidance for Industry – E6 Good Clinical Practice: Consolidated Guidance . Some of the information listed in this guidance document may be contained in other protocol referenced documents, such as the IB.
The NIH-FDA Protocol Template is a highly recommended template that guides investigators through the information that should be included in a protocol.
Informed consent documents (ICD) do not need to be included in the IND submission. If a sponsor does not submit an ICD as part of its IND submission, the review division may request and review the ICD at any time. The request will reference 21 CFR 312.23(a)(11), which states that if requested by the FDA, the sponsor must submit "any other relevant information needed for review of the application."
Include a statement here that informed consent will be obtained by all study participants in accordance with 21 CFR Part 50 Protection of Human Subjects.
If the investigation involves an exception from informed consent requirements, this should be stated in this section and the reasoning explained.
Informed consent documents are institution-specific but all forms will address the same required topics. Some guidelines are listed below to assist in drafting an informed consent document:
Informed Consent Checklist
- Required Elements
- A statement that the study involves research
- An explanation of the purposes of the research
- The expected duration of the subject's participation
- A description of the procedures to be followed
- Identification of any procedures which are experimental (i.e., not standard of care)
- A description of any reasonably foreseeable risks or discomforts to the subject (ideally subdivided by frequency and severity)
- A description of any benefits to the subject or to others which may reasonably be expected from the research
- A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject
- A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained
- For research involving more than minimal risk, an explanation as to whether any compensation, and an explanation as to whether any medical treatments are available, if injury occurs and, if so, what they consist of, or where further information may be obtained
- An explanation of whom to contact for answers to pertinent questions about research subjects' rights, about the research and in the event of research-related injury.
- A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits, to which the subject is otherwise entitled
- Include clinicaltrials.gov language
- FDA-regulated clinical investigations: Subjects must be informed that the FDA may inspect the records of the study.
- Additional elements
- A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant), which are currently unforeseeable
- Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent
- Any additional costs to the subject that may result from participation in the research
- The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject
- Statement that significant new findings developed during the course of the research, which may relate to the subject's willingness to continue participation, will be provided to the subject
- The approximate number of subjects involved in the study
- For bio-specimen collection consider including the following in the informed consent documents
- A clear description of the operation of the bio-specimen resource. This description could include details that may be of interest to human research participants, such as whether identifiable information will be maintained by the bio-specimen resource and/or whether research results will be linked to the bio-specimen.
- The conditions under which samples and data will be released to recipient investigators. Procedures for protecting the privacy of human research participants and confidentiality of data.
- Specific descriptions of the nature and purpose of the research.
- Information about the consequences of DNA typing if human genetic research is anticipated.
- Core Elements of HIPAA Authorization
- Specific and meaningful description of what will be used or disclosed.
- The name or other specific identification of the person, or class of persons, authorized to make the use or disclosure.
- The name or other specific identification of the person, or class of persons, to whom the covered entity may make the requested use or disclosure.
- A description of each purpose of the requested use or disclosure.
- An expiration date/expiration event that relates to the individual or the purpose of the use or disclosure.
- Statement regarding the right of the individual to revoke the authorization in writing, and the limits of that right.
- Statement regarding the right of the individual to refuse to sign authorization
- Statement regarding ability or inability to condition treatment, payment, enrollment or eligibility for benefits on the authorization
- Re-disclosure Statement - Information disclosed to others not subject to the Privacy Rule may be re-disclosed by them without the Privacy Rule protections (cannot promise that information will definitely be protected)
This information is designed to provide general guidance to you on the elements of human research consent. Always follow the specific requirements/forms/documents of the IRB to which you are planning to submit your proposal.
Informed Consent documents should be written in such a way that they can be understood by the general public. Language should be targeted at a 5th grade reading level. It is advisable to keep the document concise for the benefit of the reader.
If the investigation involves an exception from informed consent requirements, this should be stated and the reasoning explained.
For more detailed information on informed consent regulations, check Guide to Informed Consent - Information Sheet .
Investigator and Facilities Data
Provide the name, address, and a statement of the qualifications (curriculum vitae or other statement of qualifications) of each investigator as well as the name of each sub-investigator (i.e., research fellow, resident) working under the supervision of the investigator. Also needed are the name(s) and address(es) of the research facility(ies) to be used as well as the name and address of each reviewing Institutional Review Board (IRB).
The information needed for this section is provided to the FDA on the Form FDA 1572 along with copies of the Sponsor-Investigator's CV, medical license, and financial disclosure forms (Form FDA 3454 and Form FDA 3455; see below for additional guidance). While not required, the Sponsor-Investigator may also provide copies of the CVs, medical or other professional licenses (if applicable), and financial disclosure forms (Form FDA 3454 and Form FDA 3455) for all sub-investigators listed in Box 6 of the 1572. If the Sponsor-Investigator chooses not provide the sub-investigators' information in the application, the applicant MUST maintain copies of this documentation in an IND regulatory binder. Additional guidance on the completion of the FDA forms for this section as well the website where fillable PDF forms can be found are provided below.
The FDA forms, CVs, and licenses may either 1) be placed after the appropriate subheading in this section or 2) placed in the Attachments.
Form FDA 1572
Insert completed Form FDA 1572, or indicate "Signed and dated Form FDA 1572 in Attachments."
Disclosure of Financial Interests
IND sponsors are not required to submit information regarding clinical investigator financial interests or arrangements in IND applications. They are, however, required to collect this information before a clinical investigator participates in a clinical study and clinical investigators are required to disclose financial information to sponsors. The information does not need to be submitted to FDA until a marketing application is submitted containing the results of the covered clinical study.