Medical Management Series
Study Design and the role of the Medical Monitor
Medical management plays a key role in the development phase of a clinical trial. In addition to focusing on the strategic objectives of the development program, the medical monitor needs to ensure that the study design takes into consideration everything that is currently known about the product and the disease under study. This knowledge should include findings from any earlier phase studies of the investigational drug and preclinical data.
By analyzing the information currently available and the development plan for the product, the medical monitor will be in the best position to help define the targeted patient population, indicate both the study’s primary and secondary objectives and also provide direction for specific, relevant endpoints. Core aspects of the study should be developed with the medical monitor such as the objectives, target patient population, study treatment, and endpoints.
The deliverable in this study design stage is a comprehensive and viable protocol synopsis that reflects the key elements of the planned study. During the development of this protocol synopsis, a culmination of expertise from a cross-functional team, including medical, clinical operations, data management, and statistics, is required. Depending on the nature of the study, contributions from other team members, such as the pharmacology expert, and the toxicologist or medical device specialist, may also be needed.
During the design stage, it is also crucial to explore the current clinical practices relevant to the disease indication and study population. Special attention should be provided to the anticipated study requirements that may be in conflict with applicable international or local treatment guidelines or the standards of care at the targeted countries and sites. This is an issue that might hinder recruitment of subjects into the study and their treatment plan.
Alignment of goals and guidelines can be achieved efficiently by well-organized discussions held between the medical monitor, key opinion leaders, and prospective investigators on the study design and methodology. Up-to-date knowledge of applicable clinical and laboratory practices should also be obtained at this stage, all of which will aid the development of key components of the protocol synopsis.
Targeting the patient population
The target patient population needs to be well-defined with specific inclusion and exclusion criteria to ensure the enrolment of a homogenous patient group that reflects the targeted disease indication. In addition to the disease specifications, the following should also be taken into consideration in the specific patient population: diagnostic criteria, methodologies, current treatment practices, the pharmacological and safety profile of the investigational drug, and the potential impact of associated comorbidities.
The selection criteria should be carefully reviewed by the medical monitor to assess any medically conflicting points that may adversely affect the expected patient enrolment. The medical monitor should also pay attention to the prevalence of the disease under investigation and the standards of care in each of the potential study centers.
Identifying the treatments and assessments
The study treatments and clinical assessments should be evaluated carefully by the medical monitor to ensure the safety and wellbeing of participating patients and the ethical conduct of the study as a whole.
The route and dose of study drugs, and any premedication or prophylaxis required is to be decided based on available data from previous development steps. Careful assessment of anticipated concomitant medications is needed with due consideration given to their respective safety profiles, potential effects, and potential drug-drug interactions with the study drug. The medical monitor will then be able to define the lists of allowed and prohibited medications that might impact either the safety of the trial subjects or the scientific integrity of the study results.
A close collaboration between the medical monitor and the responsible statistician is also essential during the design stage to define the hypothesis to be tested. A complete understanding of all underlying assumptions will be needed, including the:
- Anticipated treatment effect,
- Number of treatment arms,
- Study-specific endpoints,
- Associated outcome measures.
This joint effort will guide the power calculation and the adoption of specific statistical methodologies.
Guideline for good clinical practice E6(R2): Online PDF (Accessed 12 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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