Pre-Market Clinical Evaluations of Innovative High-Risk Medical Devices in Europe

Abstract

Objectives: High-quality clinical evidence is most often lacking when novel high-risk devices enter the European market. At the same time, a randomized controlled trial (RCT) is often initiated as a requirement for obtaining market access in the US. Should coverage in Europe be postponed until RCT data are available? We studied the premarket clinical evaluation of innovative high-risk medical devices in Europe compared with the US, and with medicines, where appropriate. Methods: The literature and regulatory documents were checked. Representatives from industry, Competent Authorities, Notified Bodies, Ethics Committees, and HTA agencies were consulted. We also discuss patient safety and the transparency of information. Results: In contrast to the US, there is no requirement in Europe to demonstrate the clinical efficacy of high-risk devices in the premarket phase. Patients in Europe can thus have earlier access to a potentially lifesaving device, but at the risk of insufficiently documented efficacy and safety. Variations in the stringency of clinical reviews, both at the level of Notified Bodies and Competent Authorities, do not guarantee patient safety. We tried to document the design of premarket trials in Europe and number of patients exposed, but failed as this information is not made public. Furthermore, the Helsinki Declaration is not followed with respect to the registration and publication of premarket trials. Conclusions: For innovative high-risk devices, new EU legislation should require the premarket demonstration of clinical efficacy and safety, using an RCT if possible, and a transparent clinical review, preferably centralized.

A cost-utility analysis of transcatheter aortic valve implantation in Belgium: focusing on a well-defined and identifiable population

“…These observations once more put into question the appropriateness for the European regulators granting the transapical Sapien valve a CE label in 2007. 12 It also shows the importance of performing high-quality randomised trials with clinically relevant endpoints prior to granting marketing approval of innovative high-risk devices. 12 The contrast between the USA and EU regulation is striking.…”

“…12 It also shows the importance of performing high-quality randomised trials with clinically relevant endpoints prior to granting marketing approval of innovative high-risk devices. 12 The contrast between the USA and EU regulation is striking. Evidence of clinical efficacy is required before market entry in the USA but not in Europe.…”

A framework for the evaluation of new interventional procedures

“…As discussed above many interventional procedures also involve the use of a medical device and although there is an European Directive by which the biomedical industry must comply, [27] the process of approving medical devices in Europe is considered flawed, lacks information, lacks transparency and patient safety may be put at risk. [28] The approval process of high risk (category III) medical devices in Europe now includes an assessment and analysis of clinical data to verify the clinical safety (absence of unacceptable clinical risks) and the performance (ability to achieve intended purpose) of the device when used as intended by the manufacturer. [28] Such clinical investigations do not, however, evaluate efficacy or effectiveness.…”

“…[28] The approval process of high risk (category III) medical devices in Europe now includes an assessment and analysis of clinical data to verify the clinical safety (absence of unacceptable clinical risks) and the performance (ability to achieve intended purpose) of the device when used as intended by the manufacturer. [28] Such clinical investigations do not, however, evaluate efficacy or effectiveness. The current approval process of medical devices in Europe implies that the benefit is estimated before clinical effectiveness is confirmed [29] and it dangerously assumes that the benefit for the rapid availability of the medical device outweighs the consequences.…”

Transcatheter aortic valve implantation (TAVI): risky and costly

“…Patients may be at risk if the high risk device is routinely used outside those indications. Payers may have an interest in limiting reimbursement of such high risk devices only to those indications for which there is a high level of evidence of efficacy and cost effectiveness 25. …”