Medical Management Series
Essential Documents and the Medical Monitor
Following the establishment of the study design and the finalization of the protocol synopsis, the focus of the study team should then be directed towards the development of the essential documents required for setting up the study.
These documents include the Investigator Brochure (IB), the Clinical Study Protocol and the Informed Consent Form (ICF). These key documents needed for regulatory and Institutional Review Board approvals, serve as the basis for developing all other relevant medical and operational documents/plans that form the framework for study initiation. In this short article we shall look at what the IB should contain and the essential elements the medical monitor should review.
Helping to develop the Investigator Brochure
The regulation ICH E6 defines the IB as a compilation of the clinical and non-clinical data on the investigational medicinal product that are relevant to the study of the product in human subjects.
The IB needs to be developed or updated before starting up a study. As the IB is intended to guide the investigators in assessing the risks and benefits of using the investigational drug, all the safety and efficacy data so far available should be presented in concise summaries. These data on the investigational drug and its metabolites, when applicable, should be discussed and presented in an easily referenceable format by the investigators as the IB serves as the reference document to evaluate expectedness in case of adverse events.
The IB should highlight the anticipated risks involved with the use of the investigational drug by elucidating the safety experience and incidence of adverse events in prior clinical and pre-clinical studies. This should also include the risks associated with the related pharmacological class of investigational drugs. When multiple clinical trials have been completed, the safety and efficacy summaries from all these trials should be presented across the disease indications. The regulation ICH E6 states that the IB is a living document with periodic updates required at least annually.
Reviewing the Investigator Brochure
During the review of the IB, the medical monitor should ensure that relevant safety information is completely and clearly reflected within. The IB should allow the investigator to comprehensively assess the expectedness and causality of adverse events to ensure sponsor compliance with the applicable pharmacovigilance reporting regulations.
The medical monitor should also ensure that the IB would provide investigators with sufficient information to allow appropriate assessment of the risks and benefits for the patients participating in the study and, when available, the recommended risk management relevant to the study drug.
Further Reading
Guideline for good clinical practice E6(R2): Online PDF (Accessed 21 Oct 2020)
Mohamed El Malt, MD, PhD and Vijayanand Rajendran, MD. (2016) Medical management in clinical trials: A roadmap to operational excellence. Journal for Clinical Studies 8(2): 28-33.
Medical Management in Clinical Trials:
A Roadmap to Operational Excellence
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