As previously blogged, it looks like the European medical device regulatory system is heading for a more pharmaceutical like approval system. What are the differences from clinical research perspective and why does that matter? A white paper on that topic you can find here, but in short and more tuned towards the European market:
More investigational studies
When bringing a new drug to market, clinical trials proving drug safety and efficacy are always required. Typically multiple trials are needed with different objectives and different types of subjects, ranging from safety studies in healthy volunteers to efficacy studies in the target patient population. Under the current Medical Device Directive an investigational trial may not be necessary at all, depending on the type of device, the existing clinical evidence and how that evidence translates to the device in question.
Larger, more complex studies
Pharmaceutical trials before market entry are divided in 3 phases: phase I – small scale safety studies in healthy volunteers, phase II – small scale safety and efficacy studies in patients, and phase III – large scale safety and efficacy studies, mostly randomized controlled trials. Medical devices studies have no phase I, and in Europe are divided in small scale first in man safety studies and small to medium scale safety and performance studies in patients. Clinical data on medical device efficacy is typically collected after market release. Clinical trials on efficacy are more complex, for example due to randomization, and are larger. Performing these before market release will delay market access and require more clinical funding similar to Pharma.
Higher training demands
Physician/ study site training is a pre-requisite for a successful outcome of your medical device study. Whereas in case of drug studies typically the effect of physician technique on the study outcome is minimal, a faulty application of the medical device in a study can ruin your study results. Therefore a thorough training on the device including hands-on and/ or cadaver workshops is a key investment in your medical device trial. In addition the protocol of a medical device trial requires more attention as each is unique in contrast with drug trials where protocols are much more standardized.
More stringent Adverse Event reporting
The standard for pharmaceutical studies is ICH-GCP, whereas the European standard for medical device trials is ISO 14155. In essence these standards are similar, but ISO is more tuned towards medical devices and has different requirements with respect to Adverse Event reporting. Mind that the devil is in the details, as for both drug as well medical device investigational studies all Adverse Events need to be collected, but the ISO 14155 definition of Adverse Event and Adverse Device Effect is much broader, and for example include medical occurrences in users or other persons besides those happening in trial subjects. For postmarket studies the differences are even bigger differ. Information on postmarket study adverse event reporting in medical devices you find here, and I will also speak to at a Themeday of the Mikrocentrum regarding the new medical device regulation. Bottom-line is that Adverse Event reporting in medical device trials is much more labor-intensive.
Answering the question in the title of this blog: Yes, drug studies are different from medical device studies.
Applying the pharmaceutical regulatory approval system to medical devices will require more, larger, and more complex clinical trials before market release.
Together with the higher demands with respect to trial training and safety reporting requirements in medical device studies this will not only lead to a delay in market access but also to a higher demand on clinical budget.
Nobody knows what the European Medical Device regulatory environment will look like in time, especially not with the Tsunami of amendments following Roth Behrendt’s report as aptly formulated by Vollebregt, but for sure things will become more demanding. A schedule of events can be found on the Website of MHRA. Stay tuned …