Investigator’s Brochure (IB) is one of the critical documents included in the HREC submission package to support the conduct of a clinical trial. As the name suggests, its purpose is to provide investigators with the basic and most up-to-date scientific information on the Investigational Product (IP), including the type and severity of potential adverse reactions as well as risks associated with its use. It provides justification on the approach taken to achieve the proposed clinical trial objectives. To ensure that the information included in the IB is relevant and accurate, the document should be reviewed by subject matter experts. 

ICH E6 GCP (R3) guideline and the regulatory authorities, are explicit on the sections and the type of information that needs to be included in this critical document. The typical structure (at minimum) is as presented below:

1.     TABLE OF CONTENTS

2.     SUMMARY

3.     INTRODUCTION

4.     PHYSICAL, CHEMICAL AND PHARMACEUTICAL PROPERTIES AND FORMULATION

5.     NONCLINICAL STUDIES

• Introduction
  • Nonclinical Pharmacology
  • Pharmacokinetics and Product Metabolism in Animals
  • Toxicology

6.     EFFECTS IN HUMANS

• Introduction
  • Pharmacokinetics and Product Metabolism in Humans
  • Safety and Efficacy
  • Marketing Experience

7.     SUMMARY OF DATA AND GUIDANCE

8.     REFERENCES

Write the IB in a clear, concise and practical style. Use simple language and present summaries in a logical sequence so the reader can easily understand and follow the information. Present all critical data in tables, graphs or summary boxes for clarity. Ensure that all critical statements about the IP (e.g. recommended safe doses) are supported by the available data and evidence (e.g. nonclinical toxicology data).

Based on all the findings and conclusions from non-clinical and clinical studies, including the relevant literature, discuss the safety profile of the IP. This should include IP dose levels considered safe to be used, method of administration, contraindications and precautions. Describe the process for safety monitoring and managing adverse events. At minimum, include all known and potential risks for adverse reactions associated with the administration of the IP, including their possible intensity and frequency.

All information included in the IB must be supported by verifiable sources, such as nonclinical or clinical study reports, relevant data, published literature and Chemistry, Manufacturing and Control (CMC) information. Reference should be provided in the document, and the original data sources must be available and traceable.  

If placebo is planned to be used in the proposed clinical trial, the IB should include a section on the placebo IP material. This section should include the name and describe the characteristics of the placebo that justify its use, such as its composition, appearance, method of administration, packaging, etc. It should also discuss any potential risks are associated with the use of the placebo IP material.

In the guidance section of the IB, include summary of key information the investigator should be aware of, including potential adverse reactions following administration of the IP, recommended management and treatment strategies (including overdose) and any necessary precautions to be taken.

As more data on the IP becomes available (e.g. completion of relevant clinical or nonclinical studies, publications or other sources), the sponsor is responsible for updating the IB and notifying the investigator and all relevant parties of any changes, along with providing a copy of the revised and updated IB. Any changes that may affect the safety or efficacy profile of the IP such as changes in the IP manufacturing process or its formulation, should also be reported.   

The sponsor is responsible to review and update the IB at least once every 12 months or as required, to ensure that any new safety information that may have become available is assessed and incorporated as appropriate.  

The IB is more than a regulatory document. It serves as a key reference tool for the Investigator, supporting decision made to protect the safety of the trial participants.