Percutane hartklep implantatie bij congenitale en ... - KCE

18 Percutaneous Heart Valves KCE Reports 95
Unlike the pharmaceutical sector, where new drugs have to undergo series of
regulatory clinical trials during development, the evaluation and timing of health
technologies such as medical devices is less demarcated. For instance, no pre-market
clinical trials are required for obtaining “CE marking” of medical devices. 42 The
regulation of medical devices is different in the US as compared to the European Union.
The most remarkable difference with EU countries is the requirements for placing
devices on the market. As in the EU, in the US medical devices are classified into classes
depending on the intended use of the device, indications for use, and risk. In the US
there are three classes for which regulatory control increases from Class I to Class III.
Most Class I devices are exempt from Pre-market Notification 510(k); most Class II
devices require Pre-market Notification 510(k); and most Class III devices require Premarket
Approval (PMA). An investigational device exemption (IDE) can be provided to
allow the investigational device to be used in a clinical study in order to collect safety
and effectiveness data required to support a PMA application or a Pre-market
Notification (510(k)) submission to FDA. The 510(k) is a pre-marketing submission
made to FDA to demonstrate that the device to be marketed is as safe and effective to
a legally marketed device that is not subject to PMA. In contrast with the EU system
FDA’s PMA requires the demonstration of a medical device’s clinical effectiveness as a
precondition for marketing. This is not the case with CE marking. 42
The technical CE label does by no means provide evidence for the clinical effectiveness
nor the clinical safety and potential long term adverse events in the patient populations
concerned. For class III implants clinical data on conformity with the ‘essential
requirements’ (i.e. characteristics and performance of the device) or the justification
why clinical data are not necessary, is required. This requirement is part of the
assessment of the technical file by the notified bodies. It is unclear by which
methodology these clinical data are critically appraised. Several implants and invasive
devices easily obtained their CE label in the past, while there were at most ongoing
clinical trials. For some devices, only several years later the first trials were published,
possibly not showing clear clinical benefits. vi This highly questions the extent and the
rigour of the CE labelling process. It can be regarded as a necessary first step to
guarantee technical safety and good manufacturing of a device, but its value in health
technology assessment for health insurance is limited. 42
In the US, an exemption on the effectiveness requirements is possible for Humanitarian
Use Device (HUD). A HUD is a medical device intended to benefit patients in the
treatment or diagnosis of a disease or condition that affects or is manifested in fewer
than 4,000 individuals in the United States per year. FDA may authorize a company to
market their HUD by approving a Humanitarian Device Exemption (HDE), which is
similar to a pre-market approval (PMA) application, but exempt from the effectiveness
requirements. vii Reasonable evidence of safety and only probability of benefit are
required for this exemption. 43
2.3.2 Ongoing studies
The FDA has placed PHV in class III, the highest risk class for devices, exhibiting the
most serious consequences to patients in case of device failure. Pre-market approval for
these devices in the US require scientific evidence for safety and effectiveness, after
reasonable assurance of feasibility and preliminary safety has been demonstrated. 43
vi ‘In Belgium for example, aortic endovascular devices were reimbursed by social security during several
years in seventy hospitals outside a clinical trial setting. Endovascular stentgrafts were used to repair
abdominal aorta aneurysms (EVAR). The rationale behind EVAR is to offer an alternative for otherwise
inoperable patients and to reduce the severe postoperative mortality and morbidity of open repair, speed
up recovery, and reduce costs through decreased length of stay in hospital and intensive care. Later on,
clinical trials in other countries demonstrated that this technique offered only limited added (clinical)
value, depending on the patient population. 44-50. Several of the EVAR devices were withdrawn from the
market in the past decade. Furthermore, there were elaborate discussions in the Belgian health insurance
bodies on the reimbursement of carotid stenting. These stents are already being used in several Belgian
hospitals outside a randomized clinical trial (RCT) setting. The SPACE and EVA-3S trials were halted early
for reasons of safety and futility. 51, 52 In both trials, there were more strokes and higher mortality than in
the control group with carotid endarterectomy.’ (from Vinck et al. 53)
vii http://www.fda.gov/cdrh/ode/guidance/1381.html#f1 (accessed September 15, 2008)