Medical Management Series
The Clinical Study Protocol and the Medical Monitor
A diverse variety of stakeholders will need to use the Clinical Study Protocol and so it is essential that it is clearly written and easily understandable. An experienced medical writer can help to achieve this.
The protocol should be systematically developed while adhering to applicable guidelines, standard operating procedures, and the evidence-based and objective medical information. The protocol should then be reviewed holistically by the cross-functional study team. This review should focus on the study objectives, endpoints, material and methods, safety and efficacy assessments and their reporting, and ethical considerations.
Optimization of study design and developing the best protocol achievable are the primary duties of a medical monitor during the study development phase. It is the responsibility of the medical monitor to carefully review the various sections of the protocol and pay special attention to the parts that might lead to mismanagement of patients or the occurrence of protocol deviations.
Consistency between the various sections of the protocol and the schedule of assessments is a key requirement to avoid misinterpretation of the protocol instructions by investigational site staff. A clear description of required assessments and their timing and the protocol-mandated methodologies is essential and the significant variabilities between sites and countries that are expected to participate in the study should be taken into consideration.
Safety reporting requirements need to be clearly described. This includes the applicable severity grading reference, the reporting timeframe, and the methods to be implemented to report the various types of incidents such as adverse events (AEs), serious AEs, AEs of special interest, pregnancies and laboratory abnormalities. When applicable, and as per study specifications, events that are not required to be reported as AEs or SAEs should also be clearly stated, such as death caused solely by disease progression in oncology studies, or patient hospitalization taking place solely due to social factors.
The medical monitor needs to ensure that all aspects of the protocol inclusion and exclusion criteria are sufficiently clear to guide site staff during the selection of patients for screening in the study and to avoid major protocol deviations in the case of potential misinterpretation.
There are several factors that should be taken into account when defining the enrolment criteria. These include the:
- Turnaround time for the assessments,
- Target population,
- Applicable diagnostic procedures,
- Safety profile of the investigational drug,
- Prognosis of the underlying condition.
Another key element that should be reviewed carefully by the medical monitor is the guidance that will be provided via the study protocol with regard to withdrawal of subjects from the study or the discontinuation of treatment. This should be considered in tandem with the safety indicators of the study drug, the prognosis of the disease under study, and the patient’s compliance with regard to the study treatments and procedures.
Guideline for good clinical practice E6(R2): Online PDF (Accessed 10 Nov 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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