Version Date: May 21, 2018
In order to approve research studies under the Common Rule (45 CFR 46) or FDA regulations (21 CFR 56), an IRB must receive sufficient information about the effects of any drug under study to assess whether the risks to subjects are reasonable in relation to anticipated benefits and adequately minimized. For studies conducted under an investigational new drug (IND) application FDA guidance notes that an investigator's drug brochure (IDB) is usually required by the FDA (21 CFR 312.23(a)(5) and 312.55). In addition, FDA guidance states that even though 21 CFR 56 does not mention the investigator's brochure by name, much of the information contained in such brochures is "clearly required to be reviewed by the IRB" (FDA Information Sheets at http://www.fda.gov/oc/ohrt/irbs/faqs.html). The FDA provides flexibility to IRBs regarding when IDBs are required to be submitted, the format for submission, and how the IRB assesses the brochures.
When to Submit IDBs Versus Package Inserts
If a research study involves testing or evaluating drug(s) and their use in the research is covered under an IND, an IDB should be provided to the IRB. For any drugs being tested or evaluated as part of the research that are FDA-approved and an IND is not required for their use in the research, the study team should provide the IRB with package inserts rather than IDBs.
Note: Many studies involve using a combination of drugs, some of which may be covered by an IND and some of which may not be.
Many studies involve other FDA-approved drugs used within their approved indication but which are not the focus of the investigation. Examples include drugs to mitigate side effects, eye drops used in a standard eye exam, or lidocaine. The IRB may request package inserts or other documentation in these cases, so that the IRB is able to assess whether there are additional risks to study participation.
Finally, there may be cases where Sponsors require specific documentation related to drug(s) under investigation to be submitted for IRB review (e.g. the Sponsor may require investigators to submit an IDB for a drug, even though it is FDA approved and not covered by an IND). The IRB typically accepts such documentation when it is a Sponsor requirement.
Please see the IDB and Package Insert Decision Tree for assistance in determining which documents should be provided to the IRB.
When to Submit Revised IDBs or Package Inserts as a Change of Protocol
If a study team was required to submit an IDB and/or package insert at the time of the initial review of the research study, updates to the IDBs and/or package inserts also must be submitted to the IRB. How and when study teams should submit these IDBs and/or package inserts to the IRB depend on the whether the document(s) includes revisions that:
If the revised IDB/Package Insert contains revisions that meet any of the criteria listed above, the revised IDB/Package Insert AND the accompanying changes to the study documents generally should be submitted to the IRB via a change of protocol within 60 days of receipt by the study team.
The change of protocol form should describe the revisions to consent documents and/or protocol as well as any documents that provide new information to subjects (e.g., letters to participants). The revised IDB and/or package insert should be uploaded in the IRB application, replacing the version provided to the IRB previously.
With the change of protocol, research teams should submit the IDB and/or package insert that triggered the change as well as any prior versions of IDBs and/or package inserts that had been updated, but not yet submitted to the IRB for review. For example, a research team may have received updated IDBs after the study's initial approval but not submitted them to the IRB yet, as they met the exception for submission noted below and were waiting until the next continuing review.
When to Submit Revised IDBs or Package Inserts at Continuing Review
Revised IDBs/Package Inserts may be submitted at continuing review if:
In these cases, research teams will be required to upload an IDB and Package Insert Log to the continuing review form in ARROW. For IDBs: The log should include a brief summary of the revised information in the IDB as compared to the most recent version of the IDB the IRB has on file; as well as an explanation why the IDB did not meet any of the criteria noted above that would require submission prior to continuing review.
For Package Inserts: If a summary of the changes is not available, the study team should provide confirmation (in the IDB/Package Insert Log) that the Principal Investigator has made a local assessment of the revised package insert and confirm it does not meet any of the criteria noted above that would require submission prior to continuing review.
When to Submit Revised IDBs/Package Inserts as a New Information Report
In the rare case where a revised IDB and/or package insert meets the criteria to be submitted as a change of protocol, but the associated revised study documents are not yet available, the study team should alert the IRB via a new information report within 14 business days of receipt of the IDB/Package Insert. The associated revised study documents and accompanying IDB and/or package insert would then be submitted, together, as a full change of protocol within 60 days of receiving the revised study documents.