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The medical monitor and the CSR
The last phase of the trial, the study close-out phase, holds major significance as patient data from the study is extracted, organized, evaluated, and formulated in the Clinical Study Report (CSR). This CSR aims to provide a comprehensive presentation of the study results. Insight from the medical monitor is needed at this critical juncture to generate evaluable data, and to structure the data presentation in such a way as to support the assessment of study objectives.
The CSR represents a major milestone in the clinical development program and is a crucial document for any investigational drug or device. The structure and contents of the CSR are dictated by the ICH E3 guideline, where it is defined as “an integrated report of a study of any therapeutic, prophylactic or diagnostic agent in which the clinical and statistical description, presentations and analyses are provided in a single report, incorporating tables and figures into the main text of the report and in appendices”.
Once the TLFs and narratives have been finalized, the multidisciplinary team comprising the medical writer, project manager, medical monitor, the responsible statistician, and others, follow the established plan with the associated timelines for the development of the CSR. An established CSR template, where available, would be used by the medical writer to prepare an initial draft of the CSR that is subsequently distributed for review by the various team members.
The medical monitor’s review should take into consideration the objectives of the study while focusing on the efficacy and safety analyses and the conclusions drawn from the respective data. During review, the medical monitor should pay considerable attention to the various sections of the CSR, including the synopsis, that should ideally provide a concise and comprehensive summary of the study and its results. Additionally, all observations and analyses need to be explained in the discussion section, along with the arguments that justify the conclusions derived from the study data. Background information and relevant literature on competitive products should also be incorporated to provide a comparative analysis in the discussion, followed by a brief summary of the efficacy and safety findings outlined in the concluding section.
In applicable cases, the medical monitor should keep the position of the current study with respect to the study drug development plan in mind during the review so that the study observations are evaluated as per the overall strategy of the program. When required, a comments review, or resolution, meeting (CRM) is scheduled where the core study team, including the medical monitor, discuss the review findings, agree on resolutions for conflicting review comments and provide guidance to the writer on the final contents of the CSR.
Following the availability of the study results, additional contributions from the responsible medical monitor may be required with regard to the publication plan. The plan may include the necessary review of study abstracts, poster presentations, or complete manuscripts for publication in a scientific journal.
In this recent series of short articles, we have seen that significant activities are required from the medical monitor during this close-out phase of clinical trials. Clinical data is the single most pertinent product of a study that serves as the basis of the interpretation of the analyses and results; due diligence is therefore expected during the final data review process.
Understanding the design concept, the strategic positioning and study objectives with their endpoints are essential for performing the medical monitoring tasks during this phase.
In this series of articles on the medical management of clinical trials, we wanted to share with our fellow Medics and Industry professionals several operational aspects of the daily practices that, from our significant experience in this sector, have proven to be effective. The complexity of clinical trials during drug development is steadily increasing and, as we have seen, the medical monitor plays a pivotal and challenging role in steering the team and the study towards the finish line.
Mohamed El Malt MD, PhD, Vijayanand Rajendran, MD, Kelechi K. Olu MD, MSc (2016) Medical management in clinical trials: A roadmap to operational excellence (Part 4 – Close-out Phase). Journal for Clinical Studies 8(6): 22-25.
European Medicines Agency. ICH Topic E3 Structure and Content of Clinical Study Reports. Note for guidance on structure and content of clinical study reports (CPMP/ICH/137/95). 1996. Available Online PDF (Accessed: 12 Apr 2021)
Medical Management in Clinical Trials:
A Roadmap to Operational Excellence
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