Good Monitoring Practices: FDA versus ISO

ISO/FDIS 14155 (2010) to Change Your Life
A Whitepaper and Workshop by Nancy J Stark, PhD
Wednesday, 10 February 2010, 11 AM Central; or OnDemand soon after.
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Learning Objective
The objective of this workshop is to learn the responsibilities of monitors throughout the four stages of study implementation.

The New ISO Standard and the Old FDA Guidance
Long, long ago in 1988 FDA issued the Guideline for the Monitoring of Clinical Investigations. This guideline has remained the standard of practice in the United States ever since then. Sometime within the next year ISO, the International Standards Organization, will publish a new standard for medical device clinical trials with the intention that it will become good clinical practice for medical devices. It is possible that FDA may recognize the standard when it is published, giving it powerful international standing.

The fundamentals of monitoring have not changed between the 1988 FDA guidance and the 2010 ISO/DIS standard, but the depth and breadth of monitoring responsibilities have. The biggest changes are that the ISO standard frames study implementation within a project management context, there is heavy emphasis on quality management of trials (ISO 13485), and there is a devout commitment to risk management (ISO 14971). Monitoring responsibilities follow along naturally with these new requirements.

It should be stated that, technically, monitors have no legal responsibilities. Monitoring is a "non-delegatable duty" of the sponsor. While the sponsor may hire an employee or CRO to conduct various monitoring tasks, the responsibility for those tasks remains with the sponsor. The ISO/DIS standard speaks about sponsor responsibilities and monitoring tasks, acknowledging that it is the sponsor who is responsible for these activities.

Project Management Approach
FDA's guidance document discusses: [A] the selection of monitors (trained and qualified individuals), [B] the need for written monitoring procedures, [C] the need for preinvestigation visits, [D] the need for periodic monitoring visits, [E] how to review subject records, and [F] maintaining a record of on-site visits. But it is only six pages long (five if we discount the cover page) and it's economy of words does not offer a lot of detail.

The new ISO/DIS 2009 standard can be thought of as being presented in three parts. The first part, aside from scope and definitions, presents the concepts of monitoring within the classic context of project management: formulate, plan, implement, manage, and report. The second part presents the specific duties of the parties. The third part consists of several annexes with detailed how-to information. Sometimes the standard may seem redundant, but it achieves its goal of a teaching document for start-up firms as well as a standard of practice.

Prestudy Process
Pre-investigation or assessment visits to select investigators and prepare sites for the study are much too complex to be accomplished in a single visit. It is better perceived as a process in which the capabilities and business relationship of the sponsor and investigator are established.

Both FDA and ISO envision this as a time for sponsors to assure that investigators understand the investigational nature of the device, the requirement to wait for IRB approval, the need for informed consent, agreement that records will be created and made available for monitoring, and that contractual obligations are mutually understood and agreed to. This period of time may take several months, visits, phone calls, and email messages and can be thought of as spanning from project conception to first subject consented. In the workshop you'll learn how to evaluate sites and prepare them for study initiation.

Initiation Process
The primary focus of the initiation process is getting the device on the subject. Exposure to the investigational device isn't necessarily automatic or immediate just because a subject is consented. In many studies, subsequent screening procedures may disqualify the subject from study participation. FDA feels strongly that consent and enrollment are the same thing. Whether you agree or not, what is important is that every patient who is consented must be accounted for in the final report.

The supporting focus of the initiation process is investigator and study staff training. Training may begin with an investigator's meeting if there are many investigators involved in the study. Or investigative sites may be trained one at a time. As protocols and data collection become more complex, more and more time is dedicated to reviewing the study steps and special IRB and FDA requirements. The importance of training the investigator to device use cannot be over-emphasized. Even investigators familiar with your type of device will need to review special features, materials, software, hardware, or instructions for use. Misuse of an investigational device by an investigator may come back on the sponsor as a failure to adequately train the user and may be considered an adverse event.

In the workshop you'll learn how to set up study record-keeping by building Investigator Regulatory Binders, Coordinator's Study Manuals, Subject Binders, and Source Document Verification Logs.

Routine Monitoring Visits
A routine monitoring visit is an on-site visit in which the monitor observes the progress of the study, compliance to protocol, compliance to regulations, completeness of documentation, and verifies accuracy of data on the case report forms against source information. You should monitor on a periodic basis, but I suggest you allow no more than 2-3 days of work to accumulate at a site.

Monitoring requires an extensive skill set: a knowledge of regulations, a knowledge of company practices, and a knowledge of the special requirements of the study at hand. In this workshop you'll learn tricks for email management, action item control, the cost of database queries and how to prevent them, and many other valuable techniques in order to implement "well-controlled" clinical studies.

Monitoring also requires a special kind of personality. Monitors should be people who love data, people who can sift through pieces of information and fit them together, people who do not leave details unaddressed, and people who cannot tolerate an unbalanced checkbook.

Close-out Visits
A close-out visit deals with ending issues and has the goal of making the site inspection-ready. Close-out visits are like filing income taxes, if you've done a good job of record-keeping the close-out visit will go quickly; if not, it could take days. You'll learn the requirements of close-out visits in the workshop.

A quiz, of course
The five-hour workshop is following by a half-hour online quiz, taken on your own time within the following two weeks. The quiz is designed to test your learning of the concepts discussed in the lecture and your ability to apply those concepts to real-life issues.

Course level
This is an intermediate level course. Participants are expected to have a basic knowledge of clinical research and device regulations.

You will receive
[x] One computer connection for one learner (each learner must log-in individually).
[x] Printable PowerPoint slides.
[x] Clear example distinguishing intended use, indications, claims and warning.
[x] Monitoring procedures and templates.
[x] Recent monitoring warning letters.
[x] A graded quiz with immediate test results.
[x] Certificate of Attendance and 0.55 CEUs.

Who should attend
[x] Monitors.
[x] Clinical research associates.
[x] Managers and directors of clinical research.
[x] Anyone needing to learn about ISO/DIS 14155.

Presenter
Dr. Nancy J Stark is President and Founder of Clinical Device Group, a CRO and consulting firm that has been in business since 1990. Her curriculum vitae can be found at www.nancystark.com.

System requirements
[x] Personal computer.
[x] Internet Access.
[x] Telephone.

Date, time, registration
The 5 hour workshop was presented on Wednesday, 10 February 2010 and is available today OnDemand. Sign up at registration.

Best Regards,
Nancy J Stark, PhD
President, Clinical Device Group Inc