Investigator Brochure Submissions

The Investigator's Brochure (IB) is a compilation of the clinical and non-clinical data on the investigational product(s) that are relevant to the study of the product(s) in human subjects.

In order to approve research studies under the Common Rule (45 CFR 46) or FDA regulations (21 CFR56), the IRB must receive sufficient information about the effects of any drug under study to assess whether the risks to participants are reasonable in relation to anticipated benefits and are adequately minimized.

For studies conducted under an investigational new drug (IND) application, an investigator's drug brochure (IB) is usually required. The FDA provides flexibility to IRBs regarding when IBs are required to be submitted, the format for submission, and how the IRB assesses the brochures.

If an IB was required at the time of the initial review of the study, updated IBs must also be submitted to the IRB. How and when IBs are submitted to the IRB depends on the type of revisions included in the new IB.

Modifications

If the new IB contains revisions that meet any of the following criteria, the revised IB and the accompanying changes to the study documents should be submitted to the IRB via a Modification:

  • affect the risk-to-benefit ratio of the study by requiring a change to the study documents
  • affect alternatives available to study participants; and/or
  • represent new information that should be provided to participants

The modification submission should include:

  • a summary of the changes included in the IB
  • versions of the new study documents marked with tracked changes (NOTE: Use the tracking feature!  Do not highlight or modify the font to indicate the changes.)
  • any additional documents being created to convey new information to participants (e.g., letters, pamphlets)

The revised IB should be uploaded in the Drug Section of the IRB application, replacing the version provided to the IRB previously.

Modification / Continuing Reviews

If an IB is revised for administrative reasons only and the 3 criteria listed above are not applicable, the IRB will accept the revised brochure at the time of continuing review. The PI should submit a combination Mod/CR to upload the IB and include the following information:

The Mod/CR submission should include:

  • a copy of the new IB uploaded in the Drug Section replacing the version provided to the IRB previously
  • an explanation from the PI that states:
  1. s/he has reviewed the revised Investigator's Brochure and believes that the risk-to-benefit ratio remains acceptable to continue the study in its current configuration, and
  2. the information in the revised brochure does not require a change to the protocol and/or the consent document(s).
New Information Reports (RNIs)

In the rare scenario where a revised IB will affect the risk-to-benefit ratio of the study, but the associated revised study documents are not yet available to the PI,

  • the IRB should be informed of the revised IB by submitting an RNI within 5 business days of receiving the new IB.  An explanation should be included stating that once the revised documents are released by the sponsor, a modification will be submitted.