Welcome back to the Hart GCP knowledge series. In our last glossary series post, we reviewed the definition of essential documents found in the Good Clinical Practice (GCP) guidelines. In today’s post, we will dive a bit deeper into the Investigator brochure (IB).
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The guideline defines an IB as “a compilation of the clinical and nonclinical data on the investigational product(s) that is relevant to the study of the investigational product(s) in human subjects”. Section 7 of the guideline provides the minimum information that should be included in an IB and suggests options for its layout. The scope of the IB is dependent on the stage of development of the investigational produce, whether it is marketed currently, and under what regulatory agency the study will be conducted. For some studies, in some regulatory regions, a package insert, or product information brochure may be an appropriate alternative to an IB. In others, an expanded background section of the study protocol may be acceptable.
Following development, an IB should be reviewed at least annually to ensure continued compliance with regulations and the sponsor’s operating procedures, and also to incorporate relevant new information as it becomes available
At a minimum, an IB should include the following:
- Title page and confidentiality statement;
- Table of contents;
- Brief summary in less than two pages;
- An introduction section;
- Description of the investigational product’s composition including its relevant physical, chemical, and pharmaceutical properties;
- Non-clinical study results including results of all laboratory and animal testing and development, including any pharmacology, metabolic, and toxicology studies;
- A thorough discussion of the known effects in humans;
- Known safety and efficacy including known and suspected risks and adverse reactions;
- Review of prior marketing experience including where the product is currently marketed; and
- Discussion of data and guidance for the investigator.
In the US, the IB is submitted to the FDA with the IND or IDE package, and is usually submitted to the IRB to support protocol review. While there is no specific requirement that a document named as an IB needs to be submitted to the IRB, much of the information contained in the IB is required for submission nevertheless. The IRB is responsible for confirming that the risks to participants are reasonable given the anticipated benefits and it can only do that with information about previous studies included in the IB. Therefore, many sponsors choose to use the IB for both FDA and IRB submission instead of duplicating the information elsewhere. The sponsor is responsible for providing a current IB to investigators and the investigators are responsible for submitting said IB to their IRB.
For further details on the preparation of an IB, please see the E6 guideline, here.
Thank you for reading HCC’s glossary series! Next time we will continue to examine key essential documents.