Investigator's Brochure: Content & Regulation
Content of the Investigator’s Brochure
According to the EU requirements for good clinical practice in clinical trials (Note for guidance on Good Clinical Practice (CPMP/ICH/135/95), the information in an investigator brochure (IB) should be:
‘… presented in a concise, simple, objective, balanced and non-promotional form that enables a clinician or potential investigator to understand it and make an unbiased benefit-risk assessment of the appropriateness of the proposed clinical trial.'
The content should be approved by the scientists that generated the data in different disciplines (pharmacology, toxicology, etc.). It should also be reviewed and updated at least once a year, or upon receipt of significant new data. The IB must include:
- Information about the sponsor’s name and identity of each IMP (trial number, international non-proprietary name -INN (generic name) and trade name).
- Confidentiality statement, with instructions to treat the document as confidential for the exclusive use of the investigator’s team and review boards and ethics committees.
- Compilation of results gathered from non-clinical and clinical studies of the medicine.
- Background information on the properties and history of the medicine.
Table of Contents
The IB must include the following sections:
- Table of contents.
- Summary - guidance for the investigator, highlighting the important information relevant to the stage of clinical development of the product.
- Introduction - background information, containing the chemical and international non-proprietary name - INN (generic name) of the active substance, and the trade name (when approved) of the IMP. This should also include the base for performing research and what the medicine is intended to treat (the indication). Additionally, it should provide the general approach to evaluate the IMP.
- Physical, chemical and pharmaceutical properties and formulation - relevant properties of the investigational product (active substance and excipients (inactive ingredients)), including any similarity to any other known compound. Instructions for the storage and handling of the dosage forms should also be given.
- Non-clinical studies - including the results of pharmacology, toxicology, pharmacokinetic and metabolism studies. The methodology used, results and relevance of findings should be explained, and when appropriate, there should also be information about animals and doses.
- Effects in humans - including toxicological results, pharmacokinetics, metabolism, safety, efficacy and when possible, summaries of each clinical trial with the IMP. This section should identify any information from previous marketing experience, including the countries where the investigational product has or has not been approved.
- Summary of data and guidance for the investigators – an overall discussion of the non-clinical and clinical data so they have the most informative interpretation of available data. This will help investigators to anticipate adverse drug reactions (ADRs) or other problems in clinical trials.
Regulation of Investigator's Brochure
Authorities (EMA, NCA, etc.) require an up-to-date IB for any medicine in development or on the market (if applicable). They also review the updates to the IB and compare it to previous versions to ensure it is accurate, complete, and impartial.
If the investigational product has already been issued with a marketing authorisation and its pharmacology is widely understood by medical practitioners, an extensive IB may not be necessary. The Summary of Product Characteristics (SmPC) may be used instead - this is the document containing product information for healthcare professionals that is provided with an authorised medicine. Where permitted by Regulatory Authorities, a basic product information brochure, package leaflet, or labelling may be an appropriate alternative. However, it must include current, comprehensive, and detailed information on all aspects of the investigational product that might be of importance to the investigator.
If a marketed product is being studied for a new use (i.e. a new indication), an IB specific to that new use should be prepared. When relevant new information is available, the investigators and Research Ethics Committees (RECs) should be informed. Where possible, these parties should be told before this information is included in the revised IB.
In cases where preparation of a formal IB is impractical, the sponsor should provide, as a substitute, an expanded background information section.
34-38. International Conference on Harmonisation (ICH) Guidance for Industry E6: Good Clinical Practice, Section