Medical Monitors: Unsung heroes of drug development

Few years back, there was no much compartmentalization in clinical research departments of majority of pharmaceutical companies. One person used to write protocol & related documents, select sites, manage clinical operations, patient safety and prepare clinical study report. There was no difference between clinical monitors and medical monitors if that person was medically qualified. Being trained in that era, it gave me tremendous edge when I was acting exclusively as medical monitor in more sophisticated setups. Currently, many medical doctors, who aspire to develop career in clinical research asks me, what is the role of medical monitor? If we go back, none of the regulatory authorities provides us the definition of a medical monitor. The only FDA document in which the term “medical monitor” is found is the compliance program for the inspection of sponsor/monitors/contract research organizations. (This compliance program is available at  https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/fda-bioresearch-monitoring-information/part-iii-inspectional  and the term is found in section III, item F(2).) This compliance program is the directive to the FDA investigators as to how to inspect the entities listed in its title. The particular reference to medical monitor is within an example for the investigator of the different types of monitors that may be involved in monitoring a study. The medical monitor is defined in this reference as the monitor responsible for medical aspects of the study and the document notes that this individual may be a physician. While FDA regulations pertinent to clinical trials (21 CFR Part 312 for pharmaceuticals and Part 812 for devices) require that a sponsor adequately monitor all trials, there is no description of these individuals other than that they be qualified by training and experience. Only HSA (Singapore) Good Clinical Practice emphasizes requirement of clinical trial oversight by a medically qualified person. The sponsor should designate appropriately qualified medical personnel who will be readily available to advise on trial related medical questions or problems. If necessary, outside consultant(s) may be appointed for this purpose. Something closely related to medical monitor.

So, where the role of a medical monitor starts? In current organizational structures, when study comes on the floor. But is it ideal situation? Role of a medical lead starts from the inception of molecule development. It is a conglomeration of transnational medicine, medical writing and site management.

Medical monitors support the entire clinical trial, from protocol design to study close out. During protocol preparation, the medical monitor reviews the protocol in light with therapeutic area, indication of interest and study objectives. They also weigh the efficacy and safety assessments of the protocol, including how the efficacy of the drug in question will be determined and how adverse events will be assessed and collected. They also help in initial feasibility to conduct the trial in different geographies and determining broad recruitment rate.

In the start up phase, the medical monitor may help to select site from medical competency perspective and accompany CRA for Study Initiation Visit. The purpose of this visit is to have a detailed discussion about the study procedures and sponsor expectations for a given clinical trial, including ensuring each member of the trial is clear about their role. It is the final step in a series of preparations that should occur before a clinical study begins enrollment.

Once a study is commencing, the medical monitor provides 24*7 support to site teams and internal teams for any medical or safety related queries. They may be called on for medical review of safety information, categorization of protocol deviations, determining analysis populations etc. before reports are submitted to the regulatory authorities.

Medical monitors are responsible for verifying/assuring the rights and well-being of human subjects are protected and the trial data is compliance with the approved protocol, good clinical practice (GCP) and other regulatory requirements. They must assure that reported trial data are accurate, complete, and verifiable from the source documents, among other things.

Medical monitoring is an essential function of the clinical trial process.  If not done, or not done well, there exists the potential for huge fines and legal penalties.

In the current era of risk based monitoring, medical monitors play vital role in clinical trial success. By remote data review, they can have a hawk eye on the data trends and dedicated need of thorough onsite monitoring for controlling clinical trial expenditures and get focused outcomes. Medical monitors are synonymous with medical study directors if properly equipped.

Traditionally, these are the persons who remains in the background ( please read “backbone”), act as trouble shooters and take the blame if any mishap happens (What was medical team doing when this was happening?)

Kudos to these unsung heroes of drug development for their silent support in bringing all these innovator and generic drugs in the market and benefit millions of patients!