Regulatory Challenges in Biomaterials: Focus on Medical Devices - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 246

population that will be using drugs, the number of patients enrolled
in a device trial is usually smaller than the number of patients
enrolled in a drug trial.
Phase III, or post-marketing trials , which are performed to assess the
long-term safety of the device up to 5 years after it has been launched
onto the market. Post-marketing trials of medical devices represent
a very important part of the device development pathway, mainly
because many medical devices are approved without being tested
in clinical trials. Moreover, even when clinical trials are performed,
there are some adverse events that could not be detected owing to
the small number of subjects enrolled (300 to 3,000) or the limited
time during which these clinical trials are run, which preclude the
detection of rare or long-term adverse events. As an example, we can
mention the need of device post-market surveillance in drug-eluting
stents for detection of very late stent thrombosis (which has been
associated with the polymer used in these stents) [27, 39, 40].
To achieve this goal, FDA has developed special programs for post-
market surveillance of medical devices. This program is called
the Medical Device Report (for manufacturers that are required to
submit reports of adverse events that could be related to a medi-
cal device produced by them) or Med Watch, which is a voluntary
adverse-event report system that the FDA has developed for con-
sumers who want to report an adverse event that they think might
be caused by a medical device they are using. In spite of these
efforts, adverse events are still sub-reported. In 1986, a report from
the General Accounting Office of the FDA said that the number of
adverse events caused by medical devices reported in hospitals was
less than 1% and that, what was even worse, the more serious the
adverse event, the less likely it was to be reported [41].
2) Number of patients : Drug trials could involve between 1,000 and 3,000
patients, whereas medical device trials could involve between 500
and 1,000 patients (since more people will be using the drugs, as
already explained above).
3) Time to the market : While it could take from 10 to 15 years for a drug
to enter the market, it could take only between 5 to 10 years for a
medical device to be commercialized [14, 42, 43]. Some of the reasons
behind these differences are based on the fact that medical devices
are dynamically improved during the development process, and
the regulatory process to approve such incremental modifications
needs to be less stringent. Moreover, medical device trials do not
need to evaluate pharmacokinetics, which represents an important
component of drugs trials. It is relevant to note that there are excep-
tions in both cases. For instance, HIV protease inhibitors, which are
drugs developed for the treatment of AIDS, were developed at a