Abstract
Following recent progress in political negotiations, revised legislation of medical devices across the European Union is expected soon to be ready for its First Reading by the European Parliament (consolidated text agreed in June 2015). One of the main objectives of its revisions is to provide a high level of health and safety protection for EU citizens using medical devices (EC, 2015). To this end, the legislative proposals aim to strengthen the role of clinical evaluation and of clinical investigation in regulatory decision-making (Council of the European Union, 2015a).
While expanding the scope of regulation to include new types of medical technological advance, it retains the traditional classification of devices based on risk, which typically require more clinical investigation (clinical trials) to demonstrate safety and efficacy to market higher-risk devices. However, many devices are developed by incremental innovation, making it possible, in principle, to draw on the clinical experience and literature reviews of the safety and performance of ‘equivalent’ devices to satisfy requirements for clinical evidence. The need for clinical investigation (or clinical trials) of specific devices is thus still thought to be reduced, even for high-risk products (Article 49). On its own, we might worry that potential unforeseen adverse events from what are initially regarded as technically equivalent (based on merely incremental) innovations, and their relative safety and efficacy, will never be established against previous generations of these products. Biomechanical design, even when tested in the laboratory, does not always translate well into clinical outcomes.
Clinical data outside formal investigations are rarely thought appropriate to support the evidential case for marketing high-risk devices. Brand new high-risk devices are sometimes offered on humanitarian grounds (off-label) when there are no viable alternatives, yet ‘anecdotal’ clinical data outside formal investigations are not regarded as ‘evidence’ by the enduring Commission’s Guidelines (EC, 2009: 13). A series of these compassionate cases, however, may form recognized first-in-man studies (unlike at a similar stage in early pharmaceutical development), leading on to similarly recognized feasibility and pilot work, before clinical investigations are undertaken (Council of the European Union, 2015b: Annex XIII). The full clinical investigation and ensuing marketing application is likely to take many years, and the old problem providing very poorly patients with early access to investigational devices of high risk remains unresolved.
It is up to the manufacturer to specify and justify the level of clinical evidence necessary to demonstrate safety and performance. The design of clinical investigation should, though, consider currently available alternative treatment options for the same intended purpose, if any, no matter which the manufacturer (EC, 2015: Article 49). The manufacturer’s development plan is that reviewed assessments are independently undertaken while maintaining commercial confidentiality.
The role of Notifiable Bodies which provide these independent assessments of ‘conformity’ with general safety and performance requirements is critical. The legislative proposals claim to have bolstered their responsibilities in this regard and are expected to be more closely monitored by regulatory authorities despite already having strong Codes of Conduct. As lack of regulatory enforcement was blamed for the French breast implant scandal in 2010, when industrial grade silicone was fraudulently used for cosmetic breast implants, the role of Notifiable Bodies as well as of named individuals responsible for regulatory compliance will become more prominent. It remains to be seen how well these new measures work in counterbalancing commercial interests. A missed chance to lend greater weight to independence is in the new expert panels introduced to review and to advise manufacturers on their development plans and on the clinical evaluation of the device. The views of these expert panels, however, need only be considered by the manufacturer, although they should be documented for review by the Notified Body and Regulatory Agency.
Finally, in line with the US Food and Drug Administration, there is new emphasis on the ‘lifecycle’ of a new device with greater provisions for post-market surveillance. Data on high-risk devices are required to be updated at least annually. There is also a central electronic database, EUDAMED, with publicly available information on all CE-marked medical devices. The amount of information to be made publicly available will follow the European Commission’s evolving transparency policy, which currently assumes partial transparency allowing commercially sensitive information to be redacted. How long the Commission can sustain such a policy remains unclear.