By Harriet Gray Stephens, BMBCh, MA (Oxon), Boyds
It is a regulatory requirement, under ICH Good Clinical Practice, that all clinical studies have medical monitoring support when they are being conducted. Medical monitors ensure the safety of trial patients and integrity of study data throughout the trial, from the initial design of the study to the study close-out. They act as the main point of contact for members of the study team and investigative sites, providing opinions and advice during the start-up phase regarding the feasibility of study conduct, including evaluation of safety events within a clinical trial.
The role is not just about the monitoring of patients; it encompasses a wide range of responsibilities, from the review of study documents, including the investigator brochure, informed consent, and the adverse event and safety plan, to ensure data is adequately reported using standardized procedures. Acting as the bridge between the sponsor and investigator, medical monitors also have strong links with industry and academic bodies, such as the UK’s Faculty of Pharmaceutical Medicine, which provides access to an extensive network of knowledge and skills.
During a study, medical monitors — both external and internal — are contracted to be available 24 hours a day, seven days a week for emergency contact, with a backup monitor provided. This enables monitors to rapidly address any time-sensitive questions, particularly relating to patient safety, medical aspects such as eligibility for enrollment in the study, and information relating to the investigational product.
Indeed, optimizing patient engagement is key to the role of a medical monitor. This includes involving patients in the process at an early stage, reviewing protocols or patient materials, providing insight into the burden of study visits or procedures to help patient recruitment and retention, and promoting patient centricity.
What To Look For In A Medical Monitor
Medical monitors must be medically trained doctors, holding an active licence, such as with the General Medical Council (GMC) or U.S. State Medical Boards, with proven training and experience in clinical research and drug development.
Having in-depth knowledge of pharmaceutical medicine enables a medical monitor to provide expert input on pharmacovigilance, regulatory affairs, and clinical development strategies. This level of knowledge can be developed through training, such as that provided by the Faculty of Pharmaceutical Medicine and Kings College London, or clinical experience gained through years of work within the pharmaceutical industry. Medical monitors often gain experience as an investigator or in academic roles prior to progressing to become a medical monitor.
It is also beneficial to identify medical monitors who hold additional post-graduate qualifications — not only within pharmaceutical medicine, but also in other medical specialities. This provides knowledge of both the relevant speciality and the practical experience of patient factors and expectations within the target therapeutic area. For this reason, sponsors often choose independent medical monitors with experience within the therapeutic area of interest.
The chosen medical monitor should be experienced in overseeing different types of studies, including those relevant to the proposed clinical trial. Human challenge studies, for example, have different safety considerations than other early phase study types, particularly in terms of design features and benefit/risk balance. Medical monitors should be experienced in the conduct of the individual study types to be able to provide maximum value during study setup, conduct, and close-out.
The attitude of a medical monitor is also important. Look for someone who is happy to listen, is knowledgeable, asks the right questions, and provides consistent support to the study team and the investigators. Medical monitors can be helpful in providing guidance and practical advice to junior members of the investigative team, who are often junior doctors just starting out in their careers within the pharmaceutical industry, regarding issues relating to patient safety.
In addition, the monitor should be focused on problem-solving and achieving optimal data collection throughout the study process.
How To Integrate Medical Monitors Effectively
Medical monitors work best when they become an integral part of the study team. Reviewing study-related documents, attending or conducting site initiation visits, and gaining the opportunity to review facilities and get to know the investigator team can assist with this process. Being known by both the investigator and sponsor teams can make it easier for all involved parties to raise and adequately address queries.
Maximum benefit can be derived from collaborative involvement of the medical monitor early on during the study set-up process to ensure the provision of relevant medical input. This is often combined with strategic consulting on aspects such as study design and feasibility to optimize recruitment strategies, balance the burden of study visits and assessments, as well as provide input at ethics meetings and optimize patient information documents such as the informed consent form.
Granting your (external) medical monitor sufficient authority to work with various in-house groups will help them to deliver the best clinical trial package to the site and be fully equipped to keep in-house teams informed of all activities.
As discussed, external medical monitors are contractually employed by the sponsor team to act as the interface between the sponsor and the investigative site and being able to work in collaboration with internal sponsor clinical operations and strategic activities is often key to this.
Establish Strong Communication
Setting up strong lines of communication between the study team and the medical monitor is essential. Before kicking off the study, all team members should be fully briefed on the medical monitoring plan, the expectations and responsibilities of a medical monitor, and the project’s key events and milestones. While the medical monitoring plan is not a study-mandated document, it provides a key contractual base for the methods of communication as well as expectations and responsibilities of all involved parties. This is core to setting up a strong foundation, from which the team relationships and communication can evolve.
As well as holding introductory calls, regular catchups with the medical monitor should take place. This will allow the monitor to exchange important information and developments, such as updates on site activities, country-specific protocol amendments, and new advances or developments in the clinical landscape.
Regular interaction enables medical monitors to integrate both within the sponsor team and investigative sites, complementing work undertaken by clinical research associates while assuring that patient safety is central to clinical trial conduct.
The Value Of Medical Monitors
Having an experienced and subject-knowledgeable medical monitor on-board can often be pivotal to timely study success. Good medical monitors possess a unique combination of clinical and research experience to add significant value at all stages of trial conduct to both the investigative and sponsor teams, including strategic evaluation to optimize study design, enabling teams to minimize delays to study initiation, and — most importantly — providing an additional layer of reassurance with regard to patient safety and study conduct in line with regulations such as ICH-GCP.
About The Author:
Harriet Gray Stephens is a pharmaceutical physician on Boyds’ clinical and medical affairs team. A member of the Faculty of Pharmaceutical Medicine (MFPM) and a Pharmaceutical Medicine Specialist Trainee (PMST), Stephens provides medical and strategic input into clients’ product development programs, as well as pharmacovigilance and medical monitoring expertise.