Regulatory Challenges in Biomaterials: Focus on Medical Devices - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 242

to assess the performance of the medical product (drug, device, biologic) after
being tested during the laboratory and pre-clinical stages of development. As
stated previously, clinical trials are required in PMA submissions that apply
for high-risk devices (Class III) and in some cases for 510k submissions as
well. The reason behind this is that high-risk devices or Class II devices sub-
mitting a 510k require more evidence that supports what the manufacturer
alleges about the product. Preclinical data may not be enough for the FDA to
classify a product as safe and effective, and therefore, in addition to preclini-
cal and bench data, the FDA requires clinical data. A recent search in the pub-
lic clinical trials database clinical trials.gov showed that there are currently
more than 1,000 ongoing clinical trials involving medical devices [34].
Clinical Trials Protocol
In order to perform a clinical trial, a clinical protocol should be written to
provide the following information:
a) The idea that justifies the clinical trial: In clinical research as well as
in other fields of science, researchers want to test ideas. These ideas
could be expressed in terms of a question or research hypothesis
that the researchers aim to demonstrate (as in any other experiment).
There are different kinds of hypotheses:
• Explanatory vs. Pragmatic : The study may be explanatory of some
physiopathological hypotheses (such as the biofouling of implant-
able devices related to macrophage activation and inflammatory
response around the implant) or be pragmatic (biofouling could be
avoided by bio-inert materials that avoid protein adhesion) [35, 36].
• Efficacy vs. Effectiveness : The material was effective in decreasing
biofouling (efficacy), or the material achieved the goal of reduc-
ing biofouling by decreasing the thickness of the fibrous capsule
around the implant by 50% against the current best available
material ( effectiveness ).
• Superiority vs. Equivalence : Treatment A is superior to treatment B
( superiority ) or treatment A is as effective as treatment B ( equiva-
lence ). Equivalence studies are common in drug trials assessing
generic drugs vs. brand name drugs.
b) The purpose of the study: The protocol should state in a single
phrase what the condition the researchers intend to treat is (what
the patient population target is) and what the clinical outcomes are
that they expect to achieve through the proposed intervention.
c) Exclusion/inclusion criteria for patient enrollment: When enrolling
patients in the clinical trial, the researcher will select those patient
conditions that will allow the assessment of the effectiveness of the
proposed treatment ( inclusion criteria ) and will exclude others that
could interfere in the assessment ( exclusion criteria ).