Regulatory Challenges in Biomaterials: Focus on Medical Devices - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 245

In drug development, there are the following phases:
Phase I , which is usually carried out in human volunteers, and is
aimed at studying pharmacokinetic parameters such as metabolism,
clearance, maximum dose tolerated, and safety issues. Phase I tri-
als are the first stage of testing in human subjects, and, normally, a
small number (20 to 100) of healthy volunteers are selected.
Phase II , which is designed to assess therapeutic efficacy, and is thus
carried out with volunteer patients with the condition to be treated.
Some pharmacokinetic parameters such as dose range also are stud-
ied in this phase in a selected group of patients. Phase II trials are per-
formed in larger populations (100 to 300 patients) than Phase I trials.
Phase II studies are sometimes divided into Phase IIA and Phase IIB:
• Phase IIA is specifically designed to address dosing requirements
(i.e., how much drug should be given).
• Phase IIB is specifically designed to study efficacy (i.e., how well
the drug works at the prescribed dose(s)).
Some trials, however, combine Phase I and Phase II , and test both
efficacy and toxicity in the same study.
Phase III , which is the phase during which the drug of interest is
compared against the best management treatment currently avail-
able, or in some situations, and if ethically approved, against a pla-
cebo. These are usually randomized controlled multicenter trials
in a large population of patients (300-3000 or more) to mimic the
real population. Phase III trials are intended to obtain an additional
information about drug efficacy and to evaluate the overall benefit-
risk ratio of the investigational drug.
Phase IV , which is carried out to collect safety information once the
drug is in the market and is being used in the general population,
although, in some cases, used solely for marketing purposes [38].
On the other hand, in medical device development, trials are con-
ducted in the following phases:
Phase I, or the feasibility trial , during which the design and operating
features of the devices are evaluated. This stage is carried out in a
patient population of 20-50 (here we can try to see some analogy with
Phase I drug trials, where the operating features of the device could
be thought as equivalent to pharmacokinetic optimization of drugs).
Phase II, or the pivotal trial , which is usually a multicenter randomized
controlled trial in which the effectiveness and safety of the device
is being assessed. Usually, large populations (300-800) of patients
are enrolled to mimic the real population. Still, as the number of
patients that will be using a device is significantly smaller than the