A Whitepaper and Workshop by Nancy J Stark, PhD
Workshop available OnDemand or on CD.
It's hard to discuss the global consensus on monitoring in a way that is brief, to-the-point, and meaningful. But in a nutshell: ISO/FDIS 14155 (and hence the European Union), is more like the United States than ever before in their expectations of monitoring a clinical investigation.
Clinical research, clinical investigations, and generalizable knowledge
On more than one occasion, a sponsor has decided that some activity they are doing in the field is not clinical research and doesn't have to be monitored. So let's get the definition of clinical research out of the way now: clinical research is the medical care of a patient for the purpose of gathering generalizable knowledge. Americans know this from the Belmont Report.
Said medical care might involve standard-of-care procedures and tests, following the natural course of a disease, or the study of a medical device. If the medical device is not yet cleared for sale (or does not have a Certificate of Conformance in the EU), and the purpose is to gather generalizable knowledge, then the activity is a clinical investigation. Note that two criteria must be met: 1) the device is not yet cleared by 510k or PMA, and 2) the purpose is to gather generalizable knowledge.
This is so because FDA does not have authority to regulate medical practice. Medical practice is 'regulated' by professional societies such as the American Medical Association. FDA regulates interstate commerce.
Manufacturers and sponsors
Still, things can get dicey if a manufacturer puts an uncleared device in a physician's hands and allows the physician to use it. The manufacturer is still in the legal zone if they don't accept data or information about the device, but as soon as they accept an opinion (It worked great!) they have been transformed from manufacturer to sponsor of a clinical trial.
Manufacturers get caught in one other way, in my experience. They don't accept information about their device, instead they accept money. And because there are are only three ways for a device to be "out there" in the world: commercial, custom, or investigational; our hypothetical manufacturer finds himself the unwitting sponsor of a clinical trial.
More than one manufacturer has been surprised to get a warning letter from FDA accusing them of failing to get IRB approval, failing to get informed consent, and sponsoring a clinical trials of an investigational device.
ONLY THREE WAYS TO BE "OUT THERE"
Commercial, Custom, or Investigational
All sponsors must monitor all clinical trials. But the sponsor and monitor may be the same individual; in other words, a one-person firm is perfectly within the legal zone if they monitor an investigation themselves. In early developmental situations, this overlap of responsibilities makes good economic sense.
As a device moves from early development to late development, where you want the resulting data to persuade another party (such as a venture capitalist, an FDA reviewer, a customer, or a third-party payer) of the device's safety, effectiveness, or performance, then you'll want the data to have more credibility. Creditability comes from independent review, enter the monitor.
Who's the sponsor?
Once a client got into a battle with the investigative site over who was the sponsor of the study. There were data-ownership and publishing rights at stake and the site was possessive because they were not accepting payment for the study. The manufacturer was merely providing software free-of-charge.
I asked regulators from the US, UK, and Sweden how to know for certain who was the sponsor: "The sponsor is the guy who is liable if things go south," they said.
My client was in a tricky situation: they wanted to maintain control of their unapproved software and the data generated from it, but they had already installed it on the site's computers. Buyer beware: get it clear up-front in a research contract who owns what, who can publish what, who will pay for what, who is the sponsor, and who is the investigator. There is no substitute for prior understanding.
Now that our hypothetical manufacturer of a hypothetically investigational device has accepted the fact that their on-site activities are clinical trials; and they've come to a understanding that monitoring and credibility go hand-in-hand, who should do the monitoring?
Monitors are usually employees of the sponsor or they may be independently contracted. Employee or contractor, the monitor reports to the sponsor and is the sponsor's agent. So we find an interesting absence in Part 812 and ISO/FDIS 14155: there are no regulatory responsibilities of the monitor. There are only regulatory responsibilities of the sponsor to assure an investigation is monitored.
When the light-bulb first went on, I felt left out.
Convergence between US and ISO/FDIS
When we make a line-by-line comparison between the sponsor's monitoring responsibilities in the US and ISO/FDIS 14155 we find a happy thing: monitors do the same things on both sides of the pond.
If you liked the whitepaper, take the workshop
If you liked this whitepaper, then take the upcoming workshop. The learning objective is to compare the requirements of monitoring in the US and ISO/DIS 14155 in order to help assure quality in clinical trials. In this intermediate level course participants are expected to have a basic knowledge of clinical research and device regulations. Buy the recording here or phone us at 773-489-5706.
A quiz, of course
The five-hour workshop is followed 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.
You will receive, we will discuss
[x] Printable PowerPoint slides.
[x] Comparison of monitoring requirements between US and ISO/FDIS 14155
[x] Clear example distinguishing intended use, indications, claims and warning.
[x] Selected 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.
[x] One computer connection for one learner (each learner must log-in individually).
Who should attend
[x] Clinical research associates.
[x] Managers and directors of clinical research.
[x] Start-up companies planning their first clinical trial.
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 for OnDemand or CD
[x] Personal computer.
[x] Internet Access for OnDemand.
[x] Windows Media Player for CD.
Nancy J Stark, PhD
President, Clinical Device Group Inc