Key Issues in Clinical Development for Interventional CV Devices | Page 3

Key Issue #1: Regulatory Considerations »

Figure 2. Regulatory Considerations

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Clearly, one of the first steps in creating a development program is
deciding where the device will be marketed. The United States (US)
and European Union (EU) are the largest markets for medical devices,4
but the substantial differences between the two approval processes
require strategic thinking and up front planning to design an efficient,
streamlined program. For high-risk interventional CV devices, current
EU procedures are almost certainly faster and require less clinical and
safety data than the more rigorous US Food and Drug Administration
(FDA) technical standards and requirements. 3 For readers unfamiliar
with the device approval processes in the US and EU, we include an
overview in the appendix. The less stringent requirements in the EU
(and other parts of the world) prompt some sponsors to seek ex-US
approval first and then use accumulated safety and efficacy data to
support the initiation of a clinical development program in the US.3
With careful planning, it is also possible to gain FDA approval for a
device using data collected entirely outside of the US. In an analysis of
78 CV devices approved via the FDA premarketing authorization (PMA)

sham procedures, are more complex than in pharmaceutical trials.
With high-risk CV devices, each trial must be evaluated to balance
the risk of the sham control with the benefit that might be obtained
from careful evaluation of the procedure itself. While the risk
borne by research subjects exposed to sham control may not be

process between 2000 and 2007, 36% had no US study sites. Of course,

insignificant, the aggregate risk to control subjects in a clinical

data generated in the US also may be used for device approval in

trial may be less that the aggregate risk borne by patients who

other countries.

receive an untested device that is ultimately shown not to be

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beneficial after rigorous assessment in a controlled trial.
When planning your regulatory strategy, consider the following:

• Despite widespread compliance with the International Conference

• In general, using FDA standards for safety monitoring, data quality, on Harmonization/Good Clinical Practices (ICH-GCP) requirement
endpoint definitions, sample size calculations, and duration of

that every trial be reviewed and approved by an institutional

follow-up is likely to be acceptable to regulatory bodies in other

review board or ethics committee, there may be additional local

nations. Be aware, however, that these standards are constantly

requirements regarding provisions for standard of care, post-study

in flux. Trials started today will need to meet the regulatory

access to medications, and minimum insurance coverage levels for

expectations of the future.

each enrolled patient.6-8

• In device trials, the pros and cons of various types of control

• Some countries, including China and Japan, require clinical testing

groups, including no intervention, standard-of-care treatment, or

in local patient populations prior to product registration.

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