Survey of Safety Information in the Investigator’s Brochure: Inconsistencies and Recommendations

Abstract

A survey was undertaken to gain an understanding of current industry practices in the preparation of the safety information for the Investigator's Brochure (IB). Sixteen of a potential 25 respondents completed a survey (64% response rate). Five respondents represented pharmaceutical and biotech companies, and 11 were consultants or worked at contract research organizations for such companies. The results showed a lack of uniformity of practices. This may be due to the lack of harmonized regulations and guidelines, the lack of standardized terminology and definitions, and the lack of clarity regarding the purpose and content of the various safety-related sections of the IB. These sections, although interrelated, have different purposes, and the criteria and methodology used have to be appropriate for these purposes. It is recommended that regulations, guidelines, and terminology be harmonized worldwide to enable consistent reporting to regulatory authorities across regions, minimize duplication of work for companies that operate in different regions, and to provide meaningful safety information both to the investigator and regulatory authorities. Recently published information regarding the format and the content of a "Reference Safety Information" section provides clarity for this element of the IB, which can hopefully be adopted globally. Until further regulatory clarity is provided for other safety sections, recommended approaches are provided.

How to Interpret an Investigator’s Brochure for Meaningful Risk Assessment: Results of an AGAH Discussion Forum

“…When debating their involvement in the production of IBs, the majority of participants (61%) indicated that they preferred to locate the RSI as a separate section, Section 8, rather than as a subsection of Section 7. These results are in line with data from a previous web-based survey that was conducted to understand current industry practices in the preparation of safety information for the IB [16].…”

“…Where necessary, the RSI section of the IB is to be updated annually after the Development Safety Update Report data-lock point by a substantial amendment. All other safety information comprising a detailed overview on the safety profile of the IMP should be provided in the subsection on the 'Effects in Humans' and in the 'Summary of Data and Guidance to the Investigator' (Section 7) [14,16].…”

Reporting of prior clinical studies in Investigator's Brochures did not adhere to the basic principles of evidence synthesis: a cross-sectional study

“…Klepper and Fontaine (2018) conducted a survey among individuals working in pharmaceutical and biotech companies or at contract research organizations that assess the compilation of safety information in IBs. The survey showed a lack of uniformity of practices that ''may be due to the lack of harmonized regulations and guidelines'' [15]. Recently, our research team published findings of a cross-sectional study investigating the reporting quality of preclinical efficacy studies compiled in IBs [16].…”

The new Good Clinical Practice-2020 in China: Views from ethical perspective

“…Ethics Committees should establish a safety management system to enable clinical trial investigators to conveniently and systematically manage SAEs and SUSARs on site. Investigators could then comprehensively analyze and evaluate the risks of subjects, produce a periodic risk evaluation report, and report to the Ethics Committee on a timely basis [6] .…”

“…Reference safety information (RSI) in the investigators’ brochure is the main source of information regarding an unexpected SAE [6] . However, as regulated in GCP-2020, sponsors need only update the investigators’ brochure once a year during the clinical trial.…”