Investigator’s Brochure

The investigator’s brochure is 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.” (ICH E6, 1.36). In general, the investigator’s brochure provides more complete background information on the investigational product than is provided in the protocol. The investigator’s brochure assists the investigator in interpreting and implementing the study protocol, and may be of particular importance in helping the investigator determine whether specific adverse events are unanticipated, and accordingly, when and how such events should be reported to the sponsor, IEC/ IRB, and regulators.

Distinction between “quality control” and “quality assurance”.

“Quality control”means the steps taken during the generation of a product or service to ensure product/service quality. For a clinical trial, “quality control” encompasses steps taken during the clinical trial (e.g., investigator supervision, sponsor monitoring, and any ongoing review by regulatory authorities) to ensure that the trial meets protocol and procedural requirements and is reproducible.

“Quality assurance” refers to a systematic process to determine whether the quality control system is working and effective. Most often, quality assurance in clinical trials is implemented by the sponsor through independent auditing of quality control activities and, where applicable, by regulatory authorities through inspection of quality control systems and activities. Quality assurance audits may be performed during the course of the clinical trial and/or upon trial completion.


“The purpose of a sponsor’s audit, which is independent of and separate from routine monitoring or quality control functions, should be to evaluate trial conduct and compliance with the protocol, SOPs, GCP,
and the applicable regulatory requirements.”

Understand the SAE process

When an SAE report arrives in-house from an investigator, health worker, or employee (clinical research associate or customer service representative, for example), it is immediately assigned a number and reviewed to determine whether the event is a reportable SAE. If it is reportable, the company needs to send the SAE to FDA by one of the following methods.
• Form 3500A only (can be filed manually or electronically via the AERS system)
•A narrative report
• VAERS form (vaccines only)
• CIOMS I form (foreign reports only).

A company’s culture and experience dictate the way it meets these reporting requirements. Whatever the method it uses, a company must keep an audit trail, either manual or electronic, that shows
• the initial receipt date of the SAE
• all changes made to the original SAE by any personnel.
• all supporting documentation requested and sent in from the site.
• any internal or external correspondence.
• any internal notes, such as medical review.
• all attempts to get additional information regarding the event.
• whether the event is open or closed.

We need to code the SAEs in such a way that they become categorical in nature, such as assigning a code for the event and a MedDRA term