A physician working in industry may be given the job of writing or updating an Investigator’s Brochure (IB). The Investigator's Brochure (IB) is a compilation of clinical and nonclinical data about an investigational product to provide guidance to clinical investigators. You may have sole responsibility for the drafting of the document or may work with a medical writer or editor.
Usually a member of the Regulatory Affairs staff provides the physician with copies of the preclinical and clinical reports that need to be included in the IB. If this is the first IB for a product, most of the reports are the same one that you are using to prepare for a pre-IND meeting. You will need to include the IB and the first clinical protocol in the IND submission. If the job is to update an existing IB, Regulatory Affairs will provide copies of preclinical and clinical studies and SAE reports completed since the last IB was written.
The IB uses information from chemistry and manufacturing, from nonclinical studies, and from any previous clinical studies to provide the rationale for the key features of the protocol. The IB serves as the Prescribing Information for the investigational product during development.
The IB should include a summary of all relevant nonclinical chemistry, toxicology, pharmacology, pharmacokinetic, and metabolism studies, discuss the methodology used and the results. The writer of the IB should discuss the relevance of nonclinical findings to clinical studies and describe the possible adverse and unintended effects in humans.
For example the IB should include:
Writing an IB should go beyond just cutting and pasting sections from toxicology or pharmacology reports; it should discuss how the results of these studies need to be taken into consideration in running a clinical study. The IB should stress the importance of these findings to an investigator. A medically qualified person should participate in the editing of the IB. This could be the Medical Director for the study or a medical writer who is also a physician. The draft of the IB should be reviewed and approved by representatives of the disciplines that generated the data to make sure the results have been explained appropriately. This usually includes toxicologists, animal and clinical pharmacologists, and chemists.
The IB must be written in a clear, concise, objective, balanced, and non-promotional way to enable a potential investigator to understand the data and make an informed assessment decision about enrolling and monitoring subjects in the clinical trial.
For more detailed information about the contents of an IB, you may want to review the Chapter 7 of the ICH E6 Guidance for Good Clinical Practice: Consolidated Guidance 1996 https://www.fda.gov/downloads/drugs/guidances/ucm073122.pdf
Usually a member of the Regulatory Affairs staff provides the physician with copies of the preclinical and clinical reports that need to be included in the IB. If this is the first IB for a product, most of the reports are the same one that you are using to prepare for a pre-IND meeting. You will need to include the IB and the first clinical protocol in the IND submission. If the job is to update an existing IB, Regulatory Affairs will provide copies of preclinical and clinical studies and SAE reports completed since the last IB was written.
The IB uses information from chemistry and manufacturing, from nonclinical studies, and from any previous clinical studies to provide the rationale for the key features of the protocol. The IB serves as the Prescribing Information for the investigational product during development.
The IB should include a summary of all relevant nonclinical chemistry, toxicology, pharmacology, pharmacokinetic, and metabolism studies, discuss the methodology used and the results. The writer of the IB should discuss the relevance of nonclinical findings to clinical studies and describe the possible adverse and unintended effects in humans.
For example the IB should include:
- A description of the formulation to be used, including excipients, should be provided and justified if clinically relevant. Instructions for the storage and handling of the investigational product should be given.
- If there are no previous clinical studies, what preclinical studies suggest that your product will be useful in treating the indication that has been chosen.
- If the toxicology studies showed a risk of adverse effects in a particular organ system, describe what tests will be conducted to monitor subjects in the clinical studies.
- Describe how pharmacokinetics studies (animal or human) will guide dose selection for the clinical study.
- The IB should provide a description of adverse drug reactions that might be anticipated based on prior experiences with the investigational product and/or with related products. The IB should identify precautions or special monitoring needed during the clinical studies. This adverse event section is important because the adverse events listed in the IB are used to evaluate “relatedness” and “expectedness” of serious adverse events (SAEs) observed in the clinical studies and to guide which SAEs must be reported in an expedited manner.
Writing an IB should go beyond just cutting and pasting sections from toxicology or pharmacology reports; it should discuss how the results of these studies need to be taken into consideration in running a clinical study. The IB should stress the importance of these findings to an investigator. A medically qualified person should participate in the editing of the IB. This could be the Medical Director for the study or a medical writer who is also a physician. The draft of the IB should be reviewed and approved by representatives of the disciplines that generated the data to make sure the results have been explained appropriately. This usually includes toxicologists, animal and clinical pharmacologists, and chemists.
The IB must be written in a clear, concise, objective, balanced, and non-promotional way to enable a potential investigator to understand the data and make an informed assessment decision about enrolling and monitoring subjects in the clinical trial.
For more detailed information about the contents of an IB, you may want to review the Chapter 7 of the ICH E6 Guidance for Good Clinical Practice: Consolidated Guidance 1996 https://www.fda.gov/downloads/drugs/guidances/ucm073122.pdf