|The art and science of monitoring|
A quick and dirty how-to for the uninitiated.
So youre new to monitoring clinical research trials? Well, welcome. Youre probably starting out with little formal training (see the feature article Surviving the tide of trials), some knowledge of relevant FDA regulations, and a sense that the rules are just the tip of the iceberg. In addition, its likely that you arent certain what questions you should even ask about your new job. You are, however, not alone. Most monitors start their jobs in a similar state of confusion. Unfortunately, the job is difficult to delineate, since it is more art than science, more luck than skill, and more experience-driven than textbook-learned. Nevertheless, there are questions that can help you get started in the right direction. For example, what do monitors do and how do they go about doing it? What are the best ways to manage research sites, coordinators, and investigators? And most importantly, what is a monitors day-to-day job really like?
What is the job; How is it done?
It goes without saying that monitors must know both the CFR and their assigned research protocols. After all, a large part of the monitors job is to advise and assist sites in conforming to FDA regulations while also helping them meet the requirements of particular research studies. Thus, a monitor should resolve general questions of patient eligibility, the use of concomitant medications, and problems with filing FDA and investigational review board (IRB) documents. It is also important that monitors anticipate upcoming study-related hurdles and necessary regulatory filings to help researchers meet those challenges.
Lets now take a step beyond the regulations to consider a monitors other responsibilities. Generally, monitors help select research sites, train coordinators and investigators, review and collect research data, serve as patient recruitment consultants, verify the dispensation of study medications, and report the ongoing status of research trials. In essence, monitors serve both as communication conduits between sites and sponsors and as managers for individual research centers.
The meat of a monitoring visit, of course, involves the verification of a signed, IRB-approved, informed consent document along with a complete review of all research data collected for every enrolled patient. The data verification process involves comparing sources with case report form (CRF) documents. The source consists of a patients chart and contains every piece of medical information obtained before and during a research trial. The CRF, then, exists as a repository of information collected during, and specific to, a single research trial. So, it is the monitors responsibility to verify that the source data is precisely transcribed into the CRF. Two additional aspects of data review involve drug accountability and patient eligibility. The former requires monitors to physically count and compare all remaining study drugs with the sites dispensation logs. The latter involves matching study participants medical histories with the inclusion and exclusion criteria relevant for a specified trial.
Beyond reviewing patient records, a good monitor will also take a global snapshot of how each patient is progressing during the trial. This snapshot is useful for confirming that a patient is receiving adequate care, the collected data is coherent, and the trial is progressing satisfactorily. If any of the elements of a snapshot seem questionable, however, it then becomes the monitors responsibility to discuss those concerns with investigators, coordinators, and even sponsors.
An unfortunate and often tedious part of any monitors job is making certain that the CRF data are entered according to the rigid requirements of a clinical database. By design, databases are unforgiving, and sites can easily wreak havoc simply by entering data improperly. For example, if the database is designed so that each patient is associated with a three-digit number, then entering a patient as 15 rather than 015 could result in hundreds of data queries. Therefore, monitors must be sufficiently familiar with both the clinical database and the CRF to help sites capture patient data in a way that is accurate but also meets the electronic specifications.
Finally, monitors must complete a written report of each visit for the sponsors files. The purpose of this report is to notify the project management team of the activities conducted, progress being made, difficulties encountered, and any issues of concern at each visited site. The reports are often in check-box format, with space for comments at the end. These comments, like any scientific paper, should be written in the third person past tense, and they should include only facts: no guesses, no thoughts, and no theories. This is extremely important as these reports become a part of a sponsors official study file, may be used to affect investigator payments, and are commonly considered when choosing sites for participation in future research projects. In addition, site visit reports are legal documents that provide the FDA with verification of a sponsors diligence in monitoring investigative trials. As a result, monitors must word these reports carefully and seriously.
Managing a research center
The most difficult situations to manage fall into two categories: site personnel issues and study conduct issues. Personnel issues predominate, and generally, all other concerns eventually devolve into them. These problems are political and delicate. They may involve an untrained coordinator or an investigator who cant get along with the staff. Unfortunately, the monitor often gets caught in the middle of these disputes, and it is here, more than anywhere else, that the monitors management skills must come forcefully into play. Rapport, communication, training, and patience are usually the keys to resolving these situations. Often, monitors must bring their concerns directly to the principal investigator. Although this may be uncomfortable at times (especially if the investigator appears to be the problem), ultimately, it is the monitor who is in charge of each study, and issues that can
Extreme issues that require strong action occasionally occur. The worst of these, of course, involve investigative negligence or fraud. In these situations, the keys are to watch, listen, document, and discuss: watch what is happening at the sites (maybe youve misinterpreted something); listen to what research staff tell you (maybe theyll confirm your suspicions); document everything you see so that both you and your superiors have records to back up any claims; and always discuss the problems you see with the coordinators, investigators, and project managers. It is important to avoid jumping to false conclusions. But it is equally important to express legitimate concerns. Chances are that if you feel something is amiss, it probably is.
Monitoring as a lifestyle
Cullen T. Vogelson is an assistant editor of Modern Drug Discovery. Send your comments or questions regarding this article to firstname.lastname@example.org or the Editorial Office by fax at 202-776-8166 or by post at 1155 16th Street, NW; Washington, DC 20036.